The Eukaryotic Linear Motif resource for
Functional Sites in Proteins

ELM Switches

ELM class Sequence Id Start/Stop Switch Id Description
LIG_SH2_STAT5 O43561 161-164 SWTI000001 Phosphorylation of Y161 in the SH2-binding motif of Linker for activation of T-cells family member 1 (LAT) induces binding to the 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1) protein.
DOC_AGCK_PIF_1 P31749 469-474 SWTI000002 Phosphorylation of S473 in the PIF motif of RAC-alpha serine/threonine-protein kinase (AKT1) by Serine/threonine-protein kinase mTOR (MTOR) (as part of mTORC2 complex) induces intramolecular interaction with the PIF-binding pocket, resulting in cis-activation of RAC-alpha serine/threonine-protein kinase (AKT1). Dephosphorylation of the PIF motif by PHLPP1/2 (PHLPP1 for Akt2/3 and PHLPP2 for Akt1/3) results in reduced Akt activity, probably by disrupting the interaction with the Akt PIF pocket and thus cis-activation.
DOC_AGCK_PIF_1 P05771-2 656-661 SWTI000003 Dephosphorylation of the PIF motif by PHLPP1/2 results in reduced stability and increased degradation of PKC. This is countered by autophosphorylation of the PIF motif, but mTORC2 might also contribute.
DOC_WW_Pin1_4 Q12800 326-331 SWTI000004 Phosphorylation of T329 in the Pin1-binding motif of Alpha-globin transcription factor CP2 (TFCP2) induces binding to Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), which isomerises the peptide bonds at the nearby-phosphorylated SP motifs (S291 and S309) to the trans configuration, thereby facilitating their dephosphorylation, which is required for the transcriptional activity of Alpha-globin transcription factor CP2 (TFCP2).
LIG_PLK P30307 129-131 SWTI000005 Phosphorylation of T130 in the PLK-docking motif of M-phase inducer phosphatase 3 (CDC25C) by Cyclin-dependent kinase 1 (CDK1)-Cyclin AB subfamily generates a recruitment site for Serine/threonine-protein kinase PLK1 (PLK1), which then phosphorylates M-phase inducer phosphatase 3 (CDC25C). This results in inactivation of the NES of M-phase inducer phosphatase 3 (CDC25C), thereby promoting its nuclear localization.
LIG_PLK P30305 49-51 SWTI000006 Phosphorylation of S50 in the PLK-docking motif of M-phase inducer phosphatase 2 (CDC25B) by Cyclin-dependent kinase 1 (CDK1)-Cyclin AB subfamily generates a recruitment site for Serine/threonine-protein kinase PLK1 (PLK1), which then phosphorylates and activates M-phase inducer phosphatase 2 (CDC25B).
LIG_FHA_1 P64897 19-25 SWTI000007 Phosphorylation of T21 in the FHA-binding motif of Uncharacterized protein Rv1827/MT1875 (Rv1827) by Probable serine/threonine-protein kinase pknG (pknG) results in auto-inhibition due to an intramolecular interaction with the FHA domain. As a result, phosphorylation-independent interactions of the FHA domain with metabolic enzymes, which regulate the catalytic activity of these enzymes, are blocked (See also switch details).
LIG_14-3-3_3 P30307 213-218 SWTI000008 Phosphorylation of S216 in a 14-3-3-binding motif of M-phase inducer phosphatase 3 (CDC25C) by Serine/threonine-protein kinase Chk1 (CHEK1) induces binding to 14-3-3 protein beta/alpha (YWHAB), which negatively regulates M-phase inducer phosphatase 3 (CDC25C).
TRG_ENDOCYTIC_2 P11117 413-416 SWTI000009 Phosphorylation of T156 in AP-2 complex subunit mu (AP2M1) by AP2-associated protein kinase 1 (AAK1) upon clathrin recruitment strengthens the interaction between AP-2 complex subunit mu (AP2M1) and cargo proteins.
LIG_SH2_SRC P12931 530-533 SWTI000010 Phosphorylation of Y530 in the SH2-binding motif of Proto-oncogene tyrosine-protein kinase Src (SRC) induces an intramolecular interaction with the SH2 domain of Proto-oncogene tyrosine-protein kinase Src (SRC) resulting in inhibition of its activity and preventing intermolecular interactions of its SH2 domain.
MOD_GSK3_1 O95644 287-294 SWTI000011 Phosphorylation of S294 adjacent to the NLS of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) by cAMP subfamily primes Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) for subsequent phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which results in inhibition of nuclear import of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1).
MOD_GSK3_1 O95644 238-245 SWTI000012 Phosphorylation of S245 adjacent to the NLS of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) by cAMP subfamily primes Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) for subsequent phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which results in inhibition of nuclear import of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1).
LIG_TKB P00533 1069-1074 SWTI000013 Phosphorylation of Y1069 in Epidermal growth factor receptor (EGFR) is necessary for binding to the TKB domain of E3 ubiquitin-protein ligase CBL (CBL).
LIG_TKB O43597 55-60 SWTI000014 Phosphorylation of Y55 in Protein sprouty homolog 2 (SPRY2) is necessary for binding to the TKB domain of E3 ubiquitin-protein ligase CBL (CBL).
MOD_GSK3_1 P01106 55-62 SWTI000015 Phosphorylation of Myc proto-oncogene protein (MYC) at S62 primes the protein for phosphorylation at T58 by Glycogen synthase kinase-3 beta (GSK3B).
MOD_GSK3_1 P04637 30-37 SWTI000016 Phosphorylation of Cellular tumor antigen p53 (TP53) at S37 primes the protein for phosphorylation at S33 by Glycogen synthase kinase-3 beta (GSK3B).
MOD_GSK3_1 P05412 236-243 SWTI000017 Phosphorylation of Transcription factor AP-1 (JUN) at S243 primes the protein for phosphorylation at T239 by Glycogen synthase kinase-3 beta (GSK3B).
MOD_GSK3_1 P24864 392-399 SWTI000018 Phosphorylation of G1/S-specific cyclin-E1 (CCNE1) at S399 by Cyclin-dependent kinase 2 (CDK2) primes the protein for subsequent phosphorylation at T395 by Glycogen synthase kinase-3 beta (GSK3B).
MOD_GSK3_1 P54252 253-260 SWTI000019 Phosphorylation of Ataxin-3 (ATXN3) at S260 primes the protein for subsequent phosphorylation at S256 by Glycogen synthase kinase-3 beta (GSK3B).
DEG_SCF_FBW7_2 P03070 699-705 SWTI000020 Phosphorylation of T701 in the degron of Large T antigen induces binding to the F-box/WD repeat-containing protein 7 (FBXW7) protein, which recruits it to the SCF ubiquitin ligase complex where it is marked for degradation.
DEG_SCF_FBW7_2 P46531 2508-2515 SWTI000021 Phosphorylation of T2511 in the degron of Neurogenic locus notch homolog protein 1 (NOTCH1) induces binding to the F-box/WD repeat-containing protein 7 (FBXW7) protein, which recruits it to the SCF ubiquitin ligase complex where it is marked for degradation.
DEG_ODPH_VHL_1 Q16665 400-413 SWTI000022 Hydroxylation of P402 in the VHL-binding motif of Hypoxia-inducible factor 1-alpha (HIF1A) induces binding to the Von Hippel-Lindau disease tumor suppressor (VHL) protein.
DEG_ODPH_VHL_1 Q16665 562-574 SWTI000023 Hydroxylation of P564 in the VHL-binding motif of Hypoxia-inducible factor 1-alpha (HIF1A) induces binding to the Von Hippel-Lindau disease tumor suppressor (VHL) protein.
DEG_ODPH_VHL_1 Q99814 403-416 SWTI000024 Hydroxylation of P405 in the VHL-binding motif of Endothelial PAS domain-containing protein 1 (EPAS1) induces binding to the Von Hippel-Lindau disease tumor suppressor (VHL) protein.
DEG_ODPH_VHL_1 Q99814 529-542 SWTI000025 Hydroxylation of P531 in the VHL-binding motif of Endothelial PAS domain-containing protein 1 (EPAS1) induces binding to the Von Hippel-Lindau disease tumor suppressor (VHL) protein.
DEG_ODPH_VHL_1 Q9Y2N7 490-502 SWTI000026 Hydroxylation of P492 in the VHL-binding motif of Hypoxia-inducible factor 3-alpha (HIF3A) induces binding to the Von Hippel-Lindau disease tumor suppressor (VHL) protein.
DOC_WW_Pin1_4 O15350 409-414 SWTI000027 Phosphorylation of S412 in the Pin1-binding motif of Tumor protein p73 (TP73) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 O15350 439-444 SWTI000028 Phosphorylation of T442 in the Pin1-binding motif of Tumor protein p73 (TP73) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 O15350 479-484 SWTI000029 Phosphorylation of T482 in the Pin1-binding motif of Tumor protein p73 (TP73) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 O54918 62-67 SWTI000030 Phosphorylation of S65 in the Pin1-binding motif of Bcl-2-like protein 11 (Bcl2l11) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 P01101 229-234 SWTI000031 Phosphorylation of T232 in the Pin1-binding motif of Proto-oncogene c-Fos (Fos) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 P01101 322-327 SWTI000032 Phosphorylation of T325 in the Pin1-binding motif of Proto-oncogene c-Fos (Fos) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 P01101 328-333 SWTI000033 Phosphorylation of T331 in the Pin1-binding motif of Proto-oncogene c-Fos (Fos) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 P01101 371-376 SWTI000034 Phosphorylation of S374 in the Pin1-binding motif of Proto-oncogene c-Fos (Fos) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 P01106 55-60 SWTI000035 Phosphorylation of T58 in the Pin1-binding motif of Myc proto-oncogene protein (MYC) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P03409 157-162 SWTI000036 Phosphorylation of S160 in the Pin1-binding motif of Protein Tax-1 (tax) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P04637 30-35 SWTI000037 Phosphorylation of S33 in the Pin1-binding motif of Cellular tumor antigen p53 (TP53) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P04637 312-317 SWTI000038 Phosphorylation of S315 in the Pin1-binding motif of Cellular tumor antigen p53 (TP53) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P04637 78-83 SWTI000039 Phosphorylation of T81 in the Pin1-binding motif of Cellular tumor antigen p53 (TP53) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P05412 60-65 SWTI000040 Phosphorylation of S63 in the Pin1-binding motif of Transcription factor AP-1 (JUN) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P05412 70-75 SWTI000041 Phosphorylation of S73 in the Pin1-binding motif of Transcription factor AP-1 (JUN) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P06876 525-530 SWTI000042 Phosphorylation of S528 in the Pin1-binding motif of Transcriptional activator Myb (Myb) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 P10276 74-79 SWTI000043 Phosphorylation of S77 in the Pin1-binding motif of Retinoic acid receptor alpha (RARA) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P14598 342-347 SWTI000044 Phosphorylation of S345 in the Pin1-binding motif of Neutrophil cytosol factor 1 (NCF1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P22736 137-142 SWTI000045 Phosphorylation of S140 in the Pin1-binding motif of Nuclear receptor subfamily 4 group A member 1 (NR4A1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P22736 428-433 SWTI000046 Phosphorylation of S431 in the Pin1-binding motif of Nuclear receptor subfamily 4 group A member 1 (NR4A1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P22736 92-97 SWTI000047 Phosphorylation of S95 in the Pin1-binding motif of Nuclear receptor subfamily 4 group A member 1 (NR4A1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P25322 283-288 SWTI000048 Phosphorylation of T286 in the Pin1-binding motif of G1/S-specific cyclin-D1 (Ccnd1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 P29590 400-405 SWTI000049 Phosphorylation of S403 in the Pin1-binding motif of Protein PML (PML) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P29590 502-507 SWTI000050 Phosphorylation of S505 in the Pin1-binding motif of Protein PML (PML) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P29590 515-520 SWTI000051 Phosphorylation of S518 in the Pin1-binding motif of Protein PML (PML) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P29590 524-529 SWTI000052 Phosphorylation of S527 in the Pin1-binding motif of Protein PML (PML) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P31749 447-452 SWTI000053 Phosphorylation of T450 in the Pin1-binding motif of RAC-alpha serine/threonine-protein kinase (AKT1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P31749 89-94 SWTI000054 Phosphorylation of T92 in the Pin1-binding motif of RAC-alpha serine/threonine-protein kinase (AKT1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P33242 200-205 SWTI000055 Phosphorylation of S203 in the Pin1-binding motif of Steroidogenic factor 1 (Nr5a1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 P35222 243-248 SWTI000056 Phosphorylation of S246 in the Pin1-binding motif of Catenin beta-1 (CTNNB1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P35568 431-436 SWTI000057 Phosphorylation of S434 in the Pin1-binding motif of Insulin receptor substrate 1 (IRS1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P35991 112-117 SWTI000058 Phosphorylation of S115 in the Pin1-binding motif of Tyrosine-protein kinase BTK (Btk) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 P35991 18-23 SWTI000059 Phosphorylation of S21 in the Pin1-binding motif of Tyrosine-protein kinase BTK (Btk) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 P40763 724-729 SWTI000060 Phosphorylation of S727 in the Pin1-binding motif of Signal transducer and activator of transcription 3 (STAT3) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P46527 184-189 SWTI000061 Phosphorylation of T187 in the Pin1-binding motif of Cyclin-dependent kinase inhibitor 1B (CDKN1B) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P46531 2118-2123 SWTI000062 Phosphorylation of S2121 in the Pin1-binding motif of Neurogenic locus notch homolog protein 1 (NOTCH1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P46531 2129-2134 SWTI000063 Phosphorylation of T2132 in the Pin1-binding motif of Neurogenic locus notch homolog protein 1 (NOTCH1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P46531 2133-2138 SWTI000064 Phosphorylation of S2136 in the Pin1-binding motif of Neurogenic locus notch homolog protein 1 (NOTCH1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P54274 146-151 SWTI000065 Phosphorylation of T149 in the Pin1-binding motif of Telomeric repeat-binding factor 1 (TERF1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P69713 38-43 SWTI000066 Phosphorylation of S41 in the Pin1-binding motif of Protein X (X) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P78543 144-149 SWTI000067 Phosphorylation of S147 in the Pin1-binding motif of Protein BTG2 (BTG2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P84022 176-181 SWTI000068 Phosphorylation of T179 in the Pin1-binding motif of Mothers against decapentaplegic homolog 3 (SMAD3) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P84022 201-206 SWTI000069 Phosphorylation of S204 in the Pin1-binding motif of Mothers against decapentaplegic homolog 3 (SMAD3) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P84022 205-210 SWTI000070 Phosphorylation of S208 in the Pin1-binding motif of Mothers against decapentaplegic homolog 3 (SMAD3) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 P84022 210-215 SWTI000071 Phosphorylation of S213 in the Pin1-binding motif of Mothers against decapentaplegic homolog 3 (SMAD3) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 Q01860 9-14 SWTI000072 Phosphorylation of S12 in the Pin1-binding motif of POU domain, class 5, transcription factor 1 (POU5F1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 Q04206 251-256 SWTI000073 Phosphorylation of T254 in the Pin1-binding motif of Transcription factor p65 (RELA) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 Q05397 907-912 SWTI000074 Phosphorylation of S910 in the Pin1-binding motif of Focal adhesion kinase 1 (PTK2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 Q14653 336-341 SWTI000075 Phosphorylation of S339 in the Pin1-binding motif of Interferon regulatory factor 3 (IRF3) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 Q3U182 133-138 SWTI000076 Phosphorylation of S136 in the Pin1-binding motif of CREB-regulated transcription coactivator 2 (Crtc2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 Q61457 382-387 SWTI000077 Phosphorylation of S385 in the Pin1-binding motif of G1/S-specific cyclin-E1 (Ccne1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 Q80Z64 49-54 SWTI000078 Phosphorylation of S52 in the Pin1-binding motif of Homeobox protein NANOG (Nanog) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 Q80Z64 62-67 SWTI000079 Phosphorylation of S65 in the Pin1-binding motif of Homeobox protein NANOG (Nanog) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 Q8BT07 420-425 SWTI000080 Phosphorylation of S423 in the Pin1-binding motif of Centrosomal protein of 55 kDa (Cep55) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 Q8BT07 423-428 SWTI000081 Phosphorylation of S426 in the Pin1-binding motif of Centrosomal protein of 55 kDa (Cep55) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 Q8BUV3 185-190 SWTI000082 Phosphorylation of S188 in the Pin1-binding motif of Gephyrin (Gphn) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 Q8BUV3 191-196 SWTI000083 Phosphorylation of S194 in the Pin1-binding motif of Gephyrin (Gphn) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 Q8BUV3 197-202 SWTI000084 Phosphorylation of S200 in the Pin1-binding motif of Gephyrin (Gphn) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 Q8CFN5 107-112 SWTI000085 Phosphorylation of S110 in the Pin1-binding motif of Myocyte-specific enhancer factor 2C (Mef2c) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 Q8CFN5 95-100 SWTI000086 Phosphorylation of S98 in the Pin1-binding motif of Myocyte-specific enhancer factor 2C (Mef2c) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 Q92945 178-183 SWTI000087 Phosphorylation of S181 in the Pin1-binding motif of Far upstream element-binding protein 2 (KHSRP) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 Q99K48 409-414 SWTI000088 Phosphorylation of T412 in the Pin1-binding motif of Non-POU domain-containing octamer-binding protein (Nono) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 Q99K48 427-432 SWTI000089 Phosphorylation of T430 in the Pin1-binding motif of Non-POU domain-containing octamer-binding protein (Nono) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 Q99K48 449-454 SWTI000090 Phosphorylation of T452 in the Pin1-binding motif of Non-POU domain-containing octamer-binding protein (Nono) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 Q99MK8 667-672 SWTI000091 Phosphorylation of S670 in the Pin1-binding motif of Beta-adrenergic receptor kinase 1 (Adrbk1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 Q9BR01 5-10 SWTI000092 Phosphorylation of T8 in the Pin1-binding motif of Sulfotransferase 4A1 (SULT4A1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 Q9BR01 8-13 SWTI000093 Phosphorylation of T11 in the Pin1-binding motif of Sulfotransferase 4A1 (SULT4A1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 Q9ERA0 288-293 SWTI000094 Phosphorylation of S291 in the Pin1-binding motif of Alpha-globin transcription factor CP2 (Tcfcp2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 Q9ERA0 306-311 SWTI000095 Phosphorylation of S309 in the Pin1-binding motif of Alpha-globin transcription factor CP2 (Tcfcp2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 Q9ERA0 326-331 SWTI000096 Phosphorylation of T329 in the Pin1-binding motif of Alpha-globin transcription factor CP2 (Tcfcp2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
DOC_WW_Pin1_4 Q9HC98 212-217 SWTI000097 Phosphorylation of S215 in the Pin1-binding motif of Serine/threonine-protein kinase Nek6 (NEK6) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 Q9HC98 242-247 SWTI000098 Phosphorylation of S245 in the Pin1-binding motif of Serine/threonine-protein kinase Nek6 (NEK6) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 Q9NY61 143-148 SWTI000099 Phosphorylation of T146 in the Pin1-binding motif of Protein AATF (AATF) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 Q9UER7 175-180 SWTI000100 Phosphorylation of S178 in the Pin1-binding motif of Death domain-associated protein 6 (DAXX) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 Q9Y618 1238-1243 SWTI000101 Phosphorylation of T1241 in the Pin1-binding motif of Nuclear receptor corepressor 2 (NCOR2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 Q9Y618 1441-1446 SWTI000102 Phosphorylation of T1444 in the Pin1-binding motif of Nuclear receptor corepressor 2 (NCOR2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 Q9Y6H5 208-213 SWTI000103 Phosphorylation of S211 in the Pin1-binding motif of Synphilin-1 (SNCAIP) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
DOC_WW_Pin1_4 Q9Y6H5 212-217 SWTI000104 Phosphorylation of S215 in the Pin1-binding motif of Synphilin-1 (SNCAIP) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
LIG_14-3-3_1 O35147 134-139 SWTI000105 Phosphorylation of S137 by RAC-alpha serine/threonine-protein kinase (Akt1) in the 14-3-3-binding motif of Bcl2 antagonist of cell death (Bad) induces binding to the 14-3-3 protein beta/alpha (YWHAB) protein. This interaction inhibits the pro-apoptotic activity of Bcl2 antagonist of cell death (Bad).
LIG_14-3-3_1 P03076 254-259 SWTI000106 Phosphorylation of S257 in the 14-3-3-binding motif of Middle T antigen induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein.
LIG_14-3-3_1 P54253 772-777 SWTI000107 Phosphorylation of S775 by RAC-alpha serine/threonine-protein kinase (AKT1) in the 14-3-3-binding motif of Ataxin-1 (ATXN1) induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein.
LIG_14-3-3_1 Q99683 963-968 SWTI000108 Phosphorylation of S966 in the 14-3-3-binding motif of Mitogen-activated protein kinase kinase kinase 5 (MAP3K5) induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein. This interaction inhibits the pro-apoptotic activity of Mitogen-activated protein kinase kinase kinase 5 (MAP3K5).
LIG_14-3-3_2 A2ALK8 355-361 SWTI000109 Phosphorylation of S359 in the 14-3-3-binding motif of Tyrosine-protein phosphatase non-receptor type 3 (Ptpn3) induces binding to the 14-3-3 protein beta/alpha (Ywhab) protein.
LIG_14-3-3_2 P32418 388-394 SWTI000110 Phosphorylation of S392 in the 14-3-3-binding motif of Sodium/calcium exchanger 1 (SLC8A1) induces binding to the 14-3-3 protein epsilon (YWHAE) protein. This interaction inhibits the activity of Sodium/calcium exchanger 1 (SLC8A1).
LIG_14-3-3_2 P98177 193-199 SWTI000111 Phosphorylation of S197 by in the 14-3-3-binding motif of Forkhead box protein O4 (FOXO4) induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein.
LIG_14-3-3_2 Q04206 41-47 SWTI000112 Phosphorylation of S45 by in the 14-3-3-binding motif of Transcription factor p65 (RELA) induces binding to the 14-3-3 protein eta (YWHAH) protein.
LIG_14-3-3_2 Q14432 424-430 SWTI000113 Phosphorylation of S428 by in the 14-3-3-binding motif of cGMP-inhibited 3\',5\'-cyclic phosphodiesterase A (PDE3A) induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein.
LIG_14-3-3_2 Q63572 435-441 SWTI000114 Phosphorylation of S439 in the 14-3-3-binding motif of Dual specificity testis-specific protein kinase 1 (Tesk1) induces binding to the 14-3-3 protein beta/alpha (Ywhab) protein. This interaction inhibits the kinase activity of Dual specificity testis-specific protein kinase 1 (Tesk1).
LIG_14-3-3_3 P43565 1072-1077 SWTI000115 Phosphorylation of T1075 in the 14-3-3-binding motif of Serine/threonine-protein kinase RIM15 (RIM15) induces binding to the Protein BMH2 (BMH2) protein. This interaction sequesters Serine/threonine-protein kinase RIM15 (RIM15) in the cytoplasm, thereby inhibiting its function.
LIG_14-3-3_3 P56524 629-634 SWTI000116 Phosphorylation of S632 in the 14-3-3-binding motif of Histone deacetylase 4 (HDAC4) induces binding to the 14-3-3 protein beta/alpha (YWHAB) protein. This interaction sequesters Histone deacetylase 4 (HDAC4) in the cytoplasm, thereby inhibiting their transcription repression activity.
LIG_BRCT_BRCA1_1 Q13085 1262-1266 SWTI000117 Phosphorylation of S1263 in the BRCT-binding motif of Acetyl-CoA carboxylase 1 (ACACA) induces binding to the Breast cancer type 1 susceptibility protein (BRCA1) protein.
LIG_BRCT_BRCA1_1 Q6UWZ7 405-409 SWTI000118 Phosphorylation of S406 in the BRCT-binding motif of BRCA1-A complex subunit Abraxas (FAM175A) induces binding to the Breast cancer type 1 susceptibility protein (BRCA1) protein.
LIG_BRCT_BRCA1_1 Q8WXE1 238-242 SWTI000119 Phosphorylation of S239 in the BRCT-binding motif of ATR-interacting protein (ATRIP) induces binding to the Breast cancer type 1 susceptibility protein (BRCA1) protein.
LIG_BRCT_BRCA1_1 Q99708 326-330 SWTI000120 Phosphorylation of S327 in the BRCT-binding motif of DNA endonuclease RBBP8 (RBBP8) induces binding to the Breast cancer type 1 susceptibility protein (BRCA1) protein.
LIG_BRCT_BRCA1_1 Q9BX63 989-993 SWTI000121 Phosphorylation of S990 in the BRCT-binding motif of Fanconi anemia group J protein (BRIP1) induces binding to the Breast cancer type 1 susceptibility protein (BRCA1) protein.
LIG_BRCT_BRCA1_2 Q9BX63 989-995 SWTI000122 Phosphorylation of S990 in the BRCT-binding motif of Fanconi anemia group J protein (BRIP1) induces binding to the Breast cancer type 1 susceptibility protein (BRCA1) protein.
LIG_BRCT_MDC1_1 P16104 139-143 SWTI000123 Phosphorylation of S140 in the BRCT-binding motif of Histone H2A.x (H2AFX) induces binding to the Mediator of DNA damage checkpoint protein 1 (MDC1) protein.
LIG_FHA_1 O96017 66-72 SWTI000124 Phosphorylation of T68 in the FHA-binding motif of Serine/threonine-protein kinase Chk2 (CHEK2) induces binding to the Serine/threonine-protein kinase Chk2 (CHEK2) protein.
LIG_FHA_1 P14737 601-607 SWTI000125 Phosphorylation of T603 in the FHA-binding motif of DNA repair protein RAD9 (RAD9) induces binding to the Serine/threonine-protein kinase RAD53 (RAD53) protein.
LIG_FHA_1 P34217 303-309 SWTI000126 Phosphorylation of T305 in the FHA-binding motif of RNA-binding protein PIN4 (PIN4) induces binding to the Serine/threonine-protein kinase RAD53 (RAD53) protein.
LIG_FHA_1 Q9SYQ8 866-872 SWTI000127 Phosphorylation of T868 in the FHA-binding motif of Receptor protein kinase CLAVATA1 (CLV1) induces binding to the Protein phosphatase 2C 70 (KAPP) protein.
LIG_FHA_2 P14737 153-159 SWTI000128 Phosphorylation of T155 in the FHA-binding motif of DNA repair protein RAD9 (RAD9) induces binding to the Serine/threonine-protein kinase RAD53 (RAD53) protein.
LIG_FHA_2 P14737 190-196 SWTI000129 Phosphorylation of T192 in the FHA-binding motif of DNA repair protein RAD9 (RAD9) induces binding to the Serine/threonine-protein kinase RAD53 (RAD53) protein.
LIG_FHA_2 P18887 521-527 SWTI000130 Phosphorylation of T523 in the FHA-binding motif of DNA repair protein XRCC1 (XRCC1) by Casein kinase II subunit alpha (CSNK2A1) induces binding to the Aprataxin (APTX) protein.
LIG_FHA_2 Q13426 231-237 SWTI000131 Phosphorylation of T233 in the FHA-binding motif of DNA repair protein XRCC4 (XRCC4) by Casein kinase II subunit alpha (CSNK2A1) induces binding to the Bifunctional polynucleotide phosphatase/kinase (PNKP) protein.
LIG_FHA_2 Q924T3 229-235 SWTI000132 Phosphorylation of T231 in the FHA-binding motif of DNA repair protein XRCC4 (Xrcc4) induces binding to the Bifunctional polynucleotide phosphatase/kinase (Pnkp) protein.
LIG_FHA_2 Q9P7T4 643-649 SWTI000133 Phosphorylation of T645 in the FHA-binding motif of Mediator of replication checkpoint protein 1 (mrc1) induces binding to the Serine/threonine-protein kinase cds1 (cds1) protein.
LIG_PTB_Phospho_1 P00533 1104-1110 SWTI000134 Phosphorylation of Y1110 in the PTB-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Docking protein 1 (DOK1) protein.
LIG_PTB_Phospho_1 P21860 1322-1328 SWTI000135 Phosphorylation of Y1328 in the PTB-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the SHC-transforming protein 1 (SHC1) protein.
LIG_PTB_Phospho_1 P14784 358-364 SWTI000136 Phosphorylation of Y364 in the PTB-binding motif of Interleukin-2 receptor subunit beta (IL2RB) induces binding to the SHC-transforming protein 1 (SHC1) protein.
LIG_PTB_Phospho_1 P24394 491-497 SWTI000137 Phosphorylation of Y497 in the PTB-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Insulin receptor substrate 1 (IRS1) protein.
LIG_PTB_Phospho_1 P06213 993-999 SWTI000138 Phosphorylation of Y999 in the PTB-binding motif of Insulin receptor (INSR) induces binding to the SHC-transforming protein 1 (SHC1) protein.
LIG_PTB_Phospho_1 P05106 767-773 SWTI000139 Phosphorylation of Y773 in the PTB-binding motif of Integrin beta-3 (ITGB3) induces binding to the Docking protein 1 (DOK1) protein.
LIG_PTB_Phospho_1 P05106 779-785 SWTI000140 Phosphorylation of Y785 in the PTB-binding motif of Integrin beta-3 (ITGB3) induces binding to the SHC-transforming protein 1 (SHC1) protein.
LIG_PTB_Phospho_1 P16144 1590-1596 SWTI000141 Phosphorylation of Y1596 in the PTB-binding motif of Integrin beta-4 (ITGB4) induces binding to the SHC-transforming protein 1 (SHC1) protein.
LIG_PTB_Phospho_1 Q07954 4501-4507 SWTI000142 Phosphorylation of Y4507 in the PTB-binding motif of Prolow-density lipoprotein receptor-related protein 1 (LRP1) induces binding to the SHC-transforming protein 1 (SHC1) protein.
LIG_PTB_Phospho_1 P03077 244-250 SWTI000143 Phosphorylation of Y250 in the PTB-binding motif of Middle T antigen induces binding to the SHC-transforming protein 1 (Shc1) protein.
LIG_PTB_Phospho_1 Q61006 547-553 SWTI000144 Phosphorylation of Y553 in the PTB-binding motif of Muscle, skeletal receptor tyrosine-protein kinase (Musk) induces binding to the Protein Dok-7 (Dok7) protein.
LIG_PTB_Phospho_1 P04629 490-496 SWTI000145 Phosphorylation of Y496 in the PTB-binding motif of High affinity nerve growth factor receptor (NTRK1) induces binding to the SHC-transforming protein 1 (SHC1) protein.
LIG_PTB_Phospho_1 P35546 1057-1063 SWTI000146 Phosphorylation of Y1063 in the PTB-binding motif of Proto-oncogene tyrosine-protein kinase receptor Ret (Ret) induces binding to the Docking protein 1 (Dok1) protein.
LIG_PTB_Phospho_1 Q92835 1016-1022 SWTI000147 Phosphorylation of Y1022 in the PTB-binding motif of Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 (INPP5D) induces binding to the SHC-transforming protein 1 (SHC1) protein.
LIG_PTB_Phospho_1 Q92835 909-915 SWTI000148 Phosphorylation of Y915 in the PTB-binding motif of Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 (INPP5D) induces binding to the SHC-transforming protein 1 (SHC1) protein.
DOC_AGCK_PIF_1 O00141 418-423 SWTI000149 Phosphorylation of S422 by Serine/threonine-protein kinase mTOR (MTOR) (as part of mTORC2 complex) in the PIF pocket-binding motif of Serine/threonine-protein kinase Sgk1 (SGK1) induces intramolecular binding and kinase cis-activation.
DOC_AGCK_PIF_1 P11792 733-738 SWTI000150 Phosphorylation of T737 by Serine/threonine-protein kinase TOR1 (TOR1) in the PIF pocket-binding motif of Serine/threonine-protein kinase SCH9 (SCH9) induces intramolecular binding and kinase cis-activation.
DOC_AGCK_PIF_1 P18654 382-387 SWTI000151 Auto-phosphorylation of S386 in the PIF pocket-binding motif of Ribosomal protein S6 kinase alpha-3 (Rps6ka3) induces intramolecular binding and kinase cis-activation.
DOC_AGCK_PIF_1 P31751 470-475 SWTI000152 Phosphorylation of S474 in the PIF pocket-binding motif of RAC-beta serine/threonine-protein kinase (AKT2) induces intramolecular binding and kinase cis-activation.
DOC_AGCK_PIF_1 P67999 408-413 SWTI000153 Phosphorylation of T412 in the PIF pocket-binding motif of Ribosomal protein S6 kinase beta-1 (Rps6kb1) induces intramolecular binding and kinase cis-activation.
DOC_AGCK_PIF_1 Q13464 394-399 SWTI000154 Phosphorylation of T398 in the PIF pocket-binding motif of Rho-associated protein kinase 1 (ROCK1) induces intramolecular binding and kinase cis-activation.
DOC_AGCK_PIF_1 Q96BR1 482-487 SWTI000155 Phosphorylation of S486 in the PIF pocket-binding motif of Serine/threonine-protein kinase Sgk3 (SGK3) induces intramolecular binding and kinase cis-activation.
DOC_AGCK_PIF_1 Q9ERE3 482-487 SWTI000156 Phosphorylation of S486 in the PIF pocket-binding motif of Serine/threonine-protein kinase Sgk3 (Sgk3) induces intramolecular binding and kinase cis-activation.
DEG_SCF_TRCP1_1 O00221 156-161 SWTI000157 Dual phosphorylation of S157 and S161 in the TrCP1-binding motif of NF-kappa-B inhibitor epsilon (NFKBIE) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation.
DEG_SCF_TRCP1_1 P03230 210-215 SWTI000158 Dual phosphorylation of S211 and S215 in the TrCP1-binding motif of Latent membrane protein 1 (LMP1) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation.
DEG_SCF_TRCP1_1 P05923 51-56 SWTI000159 Dual phosphorylation of S52 and S56 in the TrCP1-binding motif of Protein Vpu (vpu) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation.
DEG_SCF_TRCP1_1 P16471 348-353 SWTI000160 Dual phosphorylation of S349 and S353 in the TrCP1-binding motif of Prolactin receptor (PRLR) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation.
DEG_SCF_TRCP1_1 P18848 218-224 SWTI000161 Dual phosphorylation of S219 and S224 in the TrCP1-binding motif of Cyclic AMP-dependent transcription factor ATF-4 (ATF4) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation.
DEG_SCF_TRCP1_1 P19838 926-932 SWTI000162 Dual phosphorylation of S927 and S932 in the TrCP1-binding motif of Nuclear factor NF-kappa-B p105 subunit (NFKB1) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation.
DEG_SCF_TRCP1_1 P25963 31-36 SWTI000163 Dual phosphorylation of S32 and S36 in the TrCP1-binding motif of NF-kappa-B inhibitor alpha (NFKBIA) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation.
DEG_SCF_TRCP1_1 Q12959 597-602 SWTI000164 Dual phosphorylation of S598 and S602 in the TrCP1-binding motif of Disks large homolog 1 (DLG1) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation.
DEG_SCF_TRCP1_1 Q15653 18-23 SWTI000165 Dual phosphorylation of S19 and S23 in the TrCP1-binding motif of NF-kappa-B inhibitor beta (NFKBIB) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation.
DEG_SCF_TRCP1_1 Q53EL6 70-76 SWTI000166 Dual phosphorylation of S71 and S76 in the TrCP1-binding motif of Programmed cell death protein 4 (PDCD4) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation.
DEG_SCF_TRCP1_1 Q6PGQ7 496-501 SWTI000167 Dual phosphorylation of S497 and T501 in the TrCP1-binding motif of Protein aurora borealis (BORA) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation.
DEG_SCF_TRCP1_1 Q9HAW4 29-34 SWTI000168 Dual phosphorylation of S30 and S34 in the TrCP1-binding motif of Claspin (CLSPN) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation.
DEG_SCF_TRCP1_1 Q9UKT4 144-149 SWTI000169 Dual phosphorylation of S145 and S149 in the TrCP1-binding motif of F-box only protein 5 (FBXO5) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation.
DOC_WW_Pin1_4 Q8QGV2 183-188 SWTI000170 Phosphorylation of T186 in the Pin1-binding motif of Wee1-like protein kinase 1-B (wee1-b) induces binding to the pin1 protein.
DOC_WW_Pin1_4 Q90Z80 7-12 SWTI000171 Phosphorylation of S10 in the Pin1-binding motif of F-box only protein 5-A (fbxo5-a) induces binding to the pin1 protein.
DOC_WW_Pin1_4 P35210 651-656 SWTI000172 Phosphorylation of S654 in the Pin1-binding motif of Protein SPT23 (SPT23) induces binding to the Peptidyl-prolyl cis-trans isomerase ESS1 (ESS1) protein.
DOC_WW_Pin1_4 O64645 192-197 SWTI000173 Phosphorylation of S195 in the Pin1-binding motif of MADS-box protein SOC1 (SOC1) induces binding to the Peptidyl-prolyl cis-trans isomerase Pin1 (PIN1) protein.
DOC_WW_Pin1_4 O64645 46-51 SWTI000174 Phosphorylation of S49 in the Pin1-binding motif of MADS-box protein SOC1 (SOC1) induces binding to the Peptidyl-prolyl cis-trans isomerase Pin1 (PIN1) protein.
DOC_WW_Pin1_4 O82794 199-204 SWTI000175 Phosphorylation of T202 in the Pin1-binding motif of MADS-box protein AGL24 (AGL24) induces binding to the Peptidyl-prolyl cis-trans isomerase Pin1 (PIN1) protein.
DOC_WW_Pin1_4 P34152-3 907-912 SWTI000176 Phosphorylation of S910 in the Pin1-binding motif of Isoform 3 of Focal adhesion kinase 1 (Ptk2) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein.
LIG_TYR_ITIM P31994 290-295 SWTI000177 Phosphorylation of Y292 in the ITIM motif of Low affinity immunoglobulin gamma Fc region receptor II-b (FCGR2B) induces binding of Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 (INPP5D) via its SH2 domain.
LIG_TYR_ITIM P43630 396-401 SWTI000178 Phosphorylation of Y398 in the ITIM motif of Killer cell immunoglobulin-like receptor 3DL2 (KIR3DL2) induces binding of Tyrosine-protein phosphatase non-receptor type 6 (PTPN6) via one of its SH2 domains.
LIG_TYR_ITSM Q13291 277-284 SWTI000179 Phosphorylation of Y281 in the ITSM motif of Signaling lymphocytic activation molecule (SLAMF1) induces binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) via one of its SH2 domains.
LIG_TYR_ITSM Q13291 323-330 SWTI000180 Phosphorylation of Y327 in the ITSM motif of Signaling lymphocytic activation molecule (SLAMF1) induces binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) via one of its SH2 domains.
LIG_SH2_GRB2 P35570 895-898 SWTI000181 Phosphorylation of Y895 in the SH2-binding motif of Insulin receptor substrate 1 (Irs1) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein.
LIG_SH3_2 P01106 60-65 SWTI000182 Phosphorylation of S62 in the SH3-binding motif of Myc proto-oncogene protein (MYC) by GSK-3 subfamily disrupts its interaction with Myc box-dependent-interacting protein 1 (BIN1).
TRG_NLS_MonoExtN_4 P09959 161-167 SWTI000183 Phosphorylation of S160 adjacent to the NLS of Regulatory protein SWI6 (SWI6) decreases nuclear import of this protein by decreasing the affinity for Importin subunit alpha (SRP1).
TRG_NLS_MonoExtC_3 P07270 156-161 SWTI000184 Phosphorylation of S152 adjacent to the NLS of Phosphate system positive regulatory protein PHO4 (PHO4) by the Pho80-Pho85 CDK-Cyclin complex inhibits nuclear import this protein by blocking its interaction with Importin subunit beta-3 (PSE1). Upon phosphate starvation, Pho81 inhibits the Pho80-Pho85 complex, leading to translocation of Phosphate system positive regulatory protein PHO4 (PHO4) to the nucleus, where it regulates expression of phosphate-responsive genes.
LIG_HP1_1 Q62318 486-490 SWTI000185 Phosphorylation of S473 close to the Chromo shadow domain-binding motif of Transcription intermediary factor 1-beta (Trim28) by Protein kinase C delta type (Prkcd) negatively regulates its interaction with Chromobox protein homolog 1 (Cbx1), which is crucial for heterochromatin formation and maintenance. This results in relief of transcription repression and promotion of cell cycle progression.
TRG_NES_CRM1_1 P30307 189-203 SWTI000186 Phosphorylation of S198 in the NES of M-phase inducer phosphatase 3 (CDC25C) by Serine/threonine-protein kinase PLK1 (PLK1) inhibits binding to Exportin-1 (XPO1), thus promoting nuclear localization of M-phase inducer phosphatase 3 (CDC25C).
LIG_TAZ1 Q16665 792-795 SWTI000187 Under normoxic conditions interaction of Hypoxia-inducible factor 1-alpha (HIF1A) with transcriptional coactivators such as CREB-binding protein (Crebbp) is inhibited by hydroxylation of N803.
TRG_NLS_Bipartite_1 P12272 124-144 SWTI000188 Phosphorylation of T121 adjacent to the NLS of Parathyroid hormone-related protein (PTHLH) by Cyclin-dependent kinase 2 (CDK2) disrupts the interaction with Importin subunit beta-1 (KPNB1) and down-regulates nuclear import.
LIG_14-3-3_1 P04049 256-261 SWTI000189 Phosphorylation of S257 in the 14-3-3-binding motif of RAF proto-oncogene serine/threonine-protein kinase (RAF1) abolishes binding of the motif, phosphorylated at S259, to 14-3-3 protein zeta/delta (YWHAZ).
LIG_14-3-3_3 P30305 320-325 SWTI000190 Phosphorylation of S321 in the 14-3-3-binding motif of M-phase inducer phosphatase 2 (CDC25B) by Cyclin-dependent kinase 1 (CDK1) during mitosis abolishes binding of the motif, phosphorylated at S323, to 14-3-3 protein beta/alpha (YWHAB), thereby maintaining active Cdc25B.
LIG_Glycolytic_Aldolase Q9Y5X1 165-169 SWTI000191 Phosphorylation of the LC4 region of Sorting nexin-9 (SNX9) abolishes its interaction with Fructose-bisphosphate aldolase A (ALDOA). However, the exact position of the residues that are phosphorylated and regulate binding is not known.
LIG_PTB_Talin O60331 650-653 SWTI000192 Phosphorylation of S650 in the PTB-binding motif of Phosphatidylinositol-4-phosphate 5-kinase type-1 gamma (PIP5K1C) blocks its interaction with Talin-1 (TLN1). Phosphorylation of Y649 by Src kinase enhances the interaction, possibly indirectly by inhibiting S650 phosphorylation.
CLV_C14_caspase-8-10 P42574 172-175 SWTI000193 Phosphorylation of S176 adjacent to the cleavage motif of Caspase-3 (CASP3) by CK2 subfamily prevents cleavage by Caspase-8 (CASP8) and thus activation of Caspase-3 (CASP3).
CLV_C14_Caspase3-7 P60484 381-385 SWTI000194 Phosphorylation of S385 adjacent to the cleavage motif of Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) by CK2 subfamily prevents cleavage by Caspase-3 (CASP3).
TRG_ER_diArg_1 Q05586 893-895 SWTI000195 Phosphorylation of S896 adjacent to the ER retention motif of Glutamate [NMDA] receptor subunit zeta-1 (GRIN1) by PKC subfamily (and possibly S897 by PKA) inactivates the motif and promotes delivery of the receptor to the plasma membrane. Optimal trafficking upon dual phosphorylation of S896 and S897 allows regulation of receptor trafficking by coordinated PKA and PKC signaling.
TRG_NLS_MonoExtN_4 O95644 262-269 SWTI000196 Phosphorylation of S241 and S290 adjacent to the NLS of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) by Glycogen synthase kinase-3 beta (GSK3B) and Glycogen synthase kinase-3 beta (GSK3B) inhibits nuclear import of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) by disrupting its interaction with Importin subunit alpha-2 (KPNA2). Calcium-dependent dephosphorylation by calcineurin promotes nuclear import.
LIG_SH3_2 Q13153 13-18 SWTI000197 Phosphorylation of S21 adjacent to the SH3-binding motif of Serine/threonine-protein kinase PAK 1 (PAK1) by RAC subfamily inhibits binding to Cytoplasmic protein NCK1 (NCK1), which regulates its localization to focal contacts.
LIG_SH3_3 P10636 530-536 SWTI000198 Phosphorylation of S527 adjacent to the SH3-binding motif of Microtubule-associated protein tau (MAPT) inhibits binding to Tyrosine-protein kinase Fyn (FYN).
LIG_PDZ_Class_2 P18827 305-310 SWTI000199 Phosphorylation of Y309 in the PDZ-binding motif of Syndecan-1 (SDC1) prevents binding to the PDZ domain of Syntenin-1 (SDCBP), an interaction involved in the formation of cellular protrusions.
LIG_PDZ_Class_1 O88602 318-323 SWTI000200 Phosphorylation of T321 in the PDZ-binding motif of Voltage-dependent calcium channel gamma-2 subunit (Cacng2) by cAMP subfamily prevents binding to the PDZ domain of Disks large homolog 4 (Dlg4), an interaction involved in regulating synaptic targeting of AMPA-selective glutamate receptors.
LIG_PTB_Apo_2 P05067 756-763 SWTI000201 Phosphorylation of T743 adjacent to the PTB-binding motif of Amyloid beta A4 protein (APP) reduces the affinity for Amyloid beta A4 precursor protein-binding family B member 1 (APBB1).
LIG_PTB_Phospho_1 P05106 779-785 SWTI000202 Phosphorylation of T779 in the PTB-binding motif of Integrin beta-3 (ITGB3) inhibits its interaction with SHC-transforming protein 1 (SHC1).
LIG_SxIP_EBH_1 Q99661 93-104 SWTI000203 Phosphorylation of S95 and S109 and S111 adjacent to the EB1-binding motif of Kinesin-like protein KIF2C (KIF2C) by Aurora kinase B (AURKB) and Aurora kinase B (AURKB) and Aurora kinase B (AURKB) inhibits its interaction with Microtubule-associated protein RP/EB family member 1 (MAPRE1), thereby inhibiting microtubule tip tracking.
LIG_SxIP_EBH_1 O75122 515-525 SWTI000204 Phosphorylation of several serine residues surrounding the EB1-binding motifs of CLIP-associating protein 2 (CLASP2) by Glycogen synthase kinase-3 beta (GSK3B) and Glycogen synthase kinase-3 beta (GSK3B) and Glycogen synthase kinase-3 beta (GSK3B) and Glycogen synthase kinase-3 beta (GSK3B) and Glycogen synthase kinase-3 beta (GSK3B) inhibits its interaction with Microtubule-associated protein RP/EB family member 1 (MAPRE1).
LIG_RhoGAP_OCRL_1 Q9UKG1 403-415 SWTI000205 Phosphorylation of S403 in the RhoGAP-binding motif of DCC-interacting protein 13-alpha (APPL1), possibly by PKA, inhibits its interaction with Inositol polyphosphate 5-phosphatase OCRL-1 (OCRL).
LIG_RhoGAP_OCRL_1 Q9UKG1 403-415 SWTI000206 Phosphorylation of S410 in the RhoGAP-binding motif of DCC-interacting protein 13-alpha (APPL1) inhibits its interaction with Inositol polyphosphate 5-phosphatase OCRL-1 (OCRL).
LIG_PDZ_Class_1 P48050 440-445 SWTI000207 Phosphorylation of S443 in the PDZ-binding motif of Inward rectifier potassium channel 4 (KCNJ4) by inhibits its interaction with the Disks large homolog 4 (DLG4) protein.
LIG_PDZ_Class_1 P07550 408-413 SWTI000208 Phosphorylation of S411 in the PDZ-binding motif of Beta-2 adrenergic receptor (ADRB2) by inhibits its interaction with the Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (SLC9A3R1) protein.
LIG_PDZ_Class_1 P11274 1266-1271 SWTI000209 Phosphorylation of T1269 in the PDZ-binding motif of Breakpoint cluster region protein (BCR) inhibits its interaction with the Afadin (MLLT4) protein.
LIG_GBD_WASP_1 P42768 466-476 SWTI000210 Phosphorylation of Wiskott-Aldrich syndrome protein (WAS) at Y291 by Src kinases, e.g., destabilises the auto-inhibitory intramolecular interaction of Wiskott-Aldrich syndrome protein (WAS).
LIG_GBD_WASP_1 O00401 467-477 SWTI000211 Phosphorylation of Neural Wiskott-Aldrich syndrome protein (WASL) at Y256 destabilises the auto-inhibitory intramolecular interaction of Neural Wiskott-Aldrich syndrome protein (WASL).
TRG_ENDOCYTIC_2 P19814 350-353 SWTI000212 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (Ap2m1) subunit for recruitment of Trans-Golgi network integral membrane protein TGN38 (Ttgn1) via an endocytosis motif.
LIG_SH3_5 P07766 184-188 SWTI000213 Ligand binding to the T cell receptor complex TCR-CD3 results in a conformational change that exposes an SH3-binding motif in T-cell surface glycoprotein CD3 epsilon chain (CD3E), resulting in recruitment of Cytoplasmic protein NCK2 (NCK2), involved in T cell activation.
LIG_ALG2 Q8WUM4 801-810 SWTI000214 Binding of 29108" target="_blank">calcium(2+) to Programmed cell death protein 6 (PDCD6) opens a hydrophobic pocket on Programmed cell death protein 6 (PDCD6) that is required for binding of Programmed cell death 6-interacting protein (PDCD6IP).
LIG_MAD2 Q12834 129-137 SWTI000215 Binding of Mad1-bound Closed (C-) Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1) to Open (O-) Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1) switches conformation of the latter to the C conformation, making the binding site for Cell division cycle protein 20 homolog (CDC20) available. This sequesters Cell division cycle protein 20 homolog (CDC20) to the spindle assembly checkpoint and prevents onset of anaphase.
TRG_AP2beta_CARGO_1 P49407 385-395 SWTI000216 Binding of Beta-arrestin-1 (ARRB1) to ligand-induced, phosphorylated GPCRs results in a conformational change that makes the AP2-beta interaction motif in Beta-arrestin-1 (ARRB1) accessible for binding to AP-2 complex subunit beta (AP2B1), which mediates internalization of the GPCR.
TRG_LysEnd_APsAcLL_1 P01730 434-439 SWTI000217 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of T-cell surface glycoprotein CD4 (CD4) via an endocytosis motif.
LIG_PDZ_Class_1 P35222 776-781 SWTI000218 Binding of Ezrin (EZR) via its FERM domain to the EB domain of Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (SLC9A3R1) results in allosteric coupling to the second PDZ domain of Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (SLC9A3R1), which results in relief of the intramolecular interaction with the PDZ binding ligand, thereby increasing the affinity of the PDZ domain for other ligands, including Catenin beta-1 (CTNNB1).
MOD_NMyristoyl P21457 1-7 SWTI000219 Binding of 29108" target="_blank">calcium(2+) to Recoverin (RCVRN) results in a conformational change in Recoverin that makes the myristoyl moiety available for binding to the membrane.
MOD_NMyristoyl P17612 1-7 SWTI000220 Phosphorylation of cAMP-dependent protein kinase catalytic subunit alpha (PRKACA) at S11 shifts the conformational equilibrium to the myristoyl-out conformation, making the myristoyl moiety available for interaction with the membrane.
TRG_ENDOCYTIC_2 P00533 998-1001 SWTI000221 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Epidermal growth factor receptor (EGFR) via an endocytosis motif.
TRG_ENDOCYTIC_2 P02786 20-23 SWTI000222 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Transferrin receptor protein 1 (TFRC) via an endocytosis motif.
TRG_ENDOCYTIC_2 P03383 477-480 SWTI000223 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Envelope glycoprotein gp63 (env) via an endocytosis motif.
TRG_ENDOCYTIC_2 P03522 501-504 SWTI000224 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Glycoprotein G (G) via an endocytosis motif.
TRG_ENDOCYTIC_2 P04578 712-715 SWTI000225 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Envelope glycoprotein gp160 (env) via an endocytosis motif.
TRG_ENDOCYTIC_2 P05884 723-726 SWTI000226 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Envelope glycoprotein gp160 (env) via an endocytosis motif.
TRG_ENDOCYTIC_2 P07306 5-8 SWTI000227 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Asialoglycoprotein receptor 1 (ASGR1) via an endocytosis motif.
TRG_ENDOCYTIC_2 P11279 414-417 SWTI000228 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Lysosome-associated membrane glycoprotein 1 (LAMP1) via an endocytosis motif.
TRG_ENDOCYTIC_2 P16410 201-204 SWTI000229 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Cytotoxic T-lymphocyte protein 4 (CTLA4) via an endocytosis motif.
TRG_ENDOCYTIC_2 P32004 1176-1179 SWTI000230 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Neural cell adhesion molecule L1 (L1CAM) via an endocytosis motif.
TRG_ENDOCYTIC_2 P51519 487-490 SWTI000231 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Envelope glycoprotein (env) via an endocytosis motif.
TRG_ENDOCYTIC_2 Q9J3M8 582-585 SWTI000232 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit mu (AP2M1) subunit for recruitment of Envelope glycoprotein E (gE) via an endocytosis motif.
TRG_LysEnd_APsAcLL_1 O15118 1271-1276 SWTI000233 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of Niemann-Pick C1 protein (NPC1) via an endocytosis motif.
TRG_LysEnd_APsAcLL_1 P04233 19-24 SWTI000234 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of HLA class II histocompatibility antigen gamma chain (CD74) via an endocytosis motif.
TRG_LysEnd_APsAcLL_1 P04235 138-143 SWTI000235 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (Ap2s1) subunit for recruitment of T-cell surface glycoprotein CD3 delta chain (Cd3d) via an endocytosis motif.
TRG_LysEnd_APsAcLL_1 P04601 160-165 SWTI000236 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of Nef protein (nef) via an endocytosis motif.
TRG_LysEnd_APsAcLL_1 P05855 159-164 SWTI000237 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of Protein Nef (nef) via an endocytosis motif.
LIG_14-3-3_1 P46938 109-114 SWTI000238 Phosphorylation of S112 in the 14-3-3 binding motif of Yorkie homolog (Yap1) induces binding to the 14-3-3 protein epsilon (Ywhae) protein. 14-3-3 retains phosphorylated YAP in the cytosol, negatively regulating its function.
TRG_LysEnd_APsAcLL_1 P11942 149-154 SWTI000239 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (Ap2s1) subunit for recruitment of T-cell surface glycoprotein CD3 gamma chain (Cd3g) via an endocytosis motif.
TRG_LysEnd_APsAcLL_1 P16070 708-713 SWTI000240 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of CD44 antigen (CD44) via an endocytosis motif.
TRG_LysEnd_APsAcLL_1 P41143 241-246 SWTI000241 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of Delta-type opioid receptor (OPRD1) via an endocytosis motif.
TRG_LysEnd_APsAcLL_1 P50895 604-609 SWTI000242 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of Basal cell adhesion molecule (BCAM) via an endocytosis motif.
TRG_LysEnd_APsAcLL_1 P51519 463-468 SWTI000243 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of Envelope glycoprotein (env) via an endocytosis motif.
TRG_LysEnd_APsAcLL_1 P56817 495-500 SWTI000244 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of Beta-secretase 1 (BACE1) via an endocytosis motif.
TRG_LysEnd_APsAcLL_1 Q04656 1483-1488 SWTI000245 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to the AP-2 complex alpha, beta and mu subunits exposes a binding site on the AP-2 complex subunit sigma (AP2S1) subunit for recruitment of Copper-transporting ATPase 1 (ATP7A) via an endocytosis motif.
LIG_CORNRBOX O75376 2051-2059 SWTI000246 Binding of the 15367" target="_blank">all-trans-retinoic acid ligand to the nuclear Retinoic acid receptor alpha (RARA) makes the binding site for the CORNRBOX motif of Nuclear receptor corepressor 1 (NCOR1) inaccessible.
LIG_CORNRBOX O75376 2263-2271 SWTI000247 Binding of the 15367" target="_blank">all-trans-retinoic acid ligand to the nuclear Retinoic acid receptor alpha (RARA) makes the binding site for the CORNRBOX motif of Nuclear receptor corepressor 1 (NCOR1) inaccessible.
LIG_CORNRBOX Q9Y618 2143-2151 SWTI000248 Binding of the 28666" target="_blank">leukotriene D4 ligand to the nuclear Peroxisome proliferator-activated receptor alpha (PPARA) makes the binding site for the CORNRBOX motif of Nuclear receptor corepressor 2 (NCOR2) inaccessible.
LIG_CORNRBOX Q9Y618 2350-2358 SWTI000249 Binding of the 28666" target="_blank">leukotriene D4 ligand to the nuclear Peroxisome proliferator-activated receptor alpha (PPARA) makes the binding site for the CORNRBOX motif of Nuclear receptor corepressor 2 (NCOR2) inaccessible.
LIG_NRBOX P48552 132-138 SWTI000250 Binding of the 50114" target="_blank">estrogen ligand to the nuclear Estrogen receptor (ESR1) makes the binding site for the NRBOX motif of Nuclear receptor-interacting protein 1 (NRIP1) accessible.
LIG_NRBOX P48552 184-190 SWTI000251 Binding of the 50114" target="_blank">estrogen ligand to the nuclear Estrogen receptor (ESR1) makes the binding site for the NRBOX motif of Nuclear receptor-interacting protein 1 (NRIP1) accessible.
LIG_NRBOX P48552 20-26 SWTI000252 Binding of the 50114" target="_blank">estrogen ligand to the nuclear Estrogen receptor (ESR1) makes the binding site for the NRBOX motif of Nuclear receptor-interacting protein 1 (NRIP1) accessible.
LIG_NRBOX P48552 265-271 SWTI000253 Binding of the 50114" target="_blank">estrogen ligand to the nuclear Estrogen receptor (ESR1) makes the binding site for the NRBOX motif of Nuclear receptor-interacting protein 1 (NRIP1) accessible.
LIG_NRBOX P48552 379-385 SWTI000254 Binding of the 50114" target="_blank">estrogen ligand to the nuclear Estrogen receptor (ESR1) makes the binding site for the NRBOX motif of Nuclear receptor-interacting protein 1 (NRIP1) accessible.
LIG_NRBOX P48552 499-505 SWTI000255 Binding of the 50114" target="_blank">estrogen ligand to the nuclear Estrogen receptor (ESR1) makes the binding site for the NRBOX motif of Nuclear receptor-interacting protein 1 (NRIP1) accessible.
LIG_NRBOX P48552 500-506 SWTI000256 Binding of the 50114" target="_blank">estrogen ligand to the nuclear Estrogen receptor (ESR1) makes the binding site for the NRBOX motif of Nuclear receptor-interacting protein 1 (NRIP1) accessible.
LIG_NRBOX P48552 712-718 SWTI000257 Binding of the 50114" target="_blank">estrogen ligand to the nuclear Estrogen receptor (ESR1) makes the binding site for the NRBOX motif of Nuclear receptor-interacting protein 1 (NRIP1) accessible.
LIG_NRBOX P48552 818-824 SWTI000258 Binding of the 50114" target="_blank">estrogen ligand to the nuclear Estrogen receptor (ESR1) makes the binding site for the NRBOX motif of Nuclear receptor-interacting protein 1 (NRIP1) accessible.
LIG_NRBOX P48552 935-941 SWTI000259 Binding of the 50114" target="_blank">estrogen ligand to the nuclear Estrogen receptor (ESR1) makes the binding site for the NRBOX motif of Nuclear receptor-interacting protein 1 (NRIP1) accessible.
LIG_NRBOX Q15596 640-646 SWTI000260 Binding of the 24261" target="_blank">glucocorticoid ligand to the nuclear Glucocorticoid receptor (NR3C1) makes the binding site for the NRBOX motif of Nuclear receptor coactivator 2 (NCOA2) accessible.
LIG_NRBOX Q15596 689-695 SWTI000261 Binding of the 24261" target="_blank">glucocorticoid ligand to the nuclear Glucocorticoid receptor (NR3C1) makes the binding site for the NRBOX motif of Nuclear receptor coactivator 2 (NCOA2) accessible.
LIG_NRBOX Q15596 744-750 SWTI000262 Binding of the 24261" target="_blank">glucocorticoid ligand to the nuclear Glucocorticoid receptor (NR3C1) makes the binding site for the NRBOX motif of Nuclear receptor coactivator 2 (NCOA2) accessible.
LIG_NRBOX Q15648 603-609 SWTI000263 Binding of the 18258" target="_blank">3,3\',5-triiodo-L-thyronine ligand to the nuclear Thyroid hormone receptor alpha (THRA) makes the binding site for the NRBOX motif of Mediator of RNA polymerase II transcription subunit 1 (MED1) accessible.
LIG_NRBOX Q15648 644-650 SWTI000264 Binding of the 18258" target="_blank">3,3\',5-triiodo-L-thyronine ligand to the nuclear Thyroid hormone receptor alpha (THRA) makes the binding site for the NRBOX motif of Mediator of RNA polymerase II transcription subunit 1 (MED1) accessible.
LIG_NRBOX Q9JL19 1494-1500 SWTI000265 Binding of the 34159" target="_blank">15-deoxy-Delta(12,14)-prostaglandin J2 ligand to the nuclear Peroxisome proliferator-activated receptor gamma (Pparg) makes the binding site for the NRBOX motif of Nuclear receptor coactivator 6 (Ncoa6) accessible.
LIG_GBD_WASP_1 P42768 466-476 SWTI000266 Binding of Cell division control protein 42 homolog (CDC42) to Wiskott-Aldrich syndrome protein (WAS) allosterically relieves an auto-inhibitory intramolecular interaction in Wiskott-Aldrich syndrome protein (WAS), which becomes active.
LIG_GBD_WASP_1 P42768 466-476 SWTI000267 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to Wiskott-Aldrich syndrome protein (WAS) allosterically relieves an auto-inhibitory intramolecular interaction in Wiskott-Aldrich syndrome protein (WAS), which becomes active.
LIG_GBD_WASP_1 O00401 467-477 SWTI000268 Binding of Cell division control protein 42 homolog (CDC42) to Neural Wiskott-Aldrich syndrome protein (WASL) allosterically relieves an auto-inhibitory intramolecular interaction in Neural Wiskott-Aldrich syndrome protein (WASL), which becomes active.
LIG_GBD_WASP_1 O00401 467-477 SWTI000269 Binding of 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to Neural Wiskott-Aldrich syndrome protein (WASL) allosterically relieves an auto-inhibitory intramolecular interaction in Neural Wiskott-Aldrich syndrome protein (WASL), which becomes active.
LIG_PH_Tfb1 P04637 50-56 SWTI000270 Multisite phosphorylation of S46 and T55 in the PH-like binding motif of Cellular tumor antigen p53 (TP53) gradually enhances its affinity for General transcription factor IIH subunit 1 (GTF2H1), an interaction involved in activation of transcription initiation and elongation by Cellular tumor antigen p53 (TP53).
LIG_TKB P00533 1069-1074 SWTI000271 While phosphorylation of Y1069 induces binding, additional phosphorylation of S1070 and S1071 in the TKB-binding motif of Epidermal growth factor receptor (EGFR) gradually lowers its binding affinity for E3 ubiquitin-protein ligase CBL (CBL).
LIG_TKB O43597 55-60 SWTI000272 While phosphorylation of Y55 induces binding, additional phosphorylation of T56 in the TKB-binding motif of Protein sprouty homolog 2 (SPRY2) lowers its binding affinity for E3 ubiquitin-protein ligase CBL (CBL).
LIG_FHA_2 P18887 517-523 SWTI000273 Two Bifunctional polynucleotide phosphatase/kinase (PNKP) molecules interact with two FHA-binding motifs in DNA repair protein XRCC1 (XRCC1) upon phosphorylation of T519 and T523 in the motifs. Additional phosphorylation of S518 and S525 further increases the affinity of the interaction. S518 and T523 are consensus CK2 phosphorylation sites, T519 and S525 atypical.
LIG_FHA_2 P18887 521-527 SWTI000273 Two Bifunctional polynucleotide phosphatase/kinase (PNKP) molecules interact with two FHA-binding motifs in DNA repair protein XRCC1 (XRCC1) upon phosphorylation of T519 and T523 in the motifs. Additional phosphorylation of S518 and S525 further increases the affinity of the interaction. S518 and T523 are consensus CK2 phosphorylation sites, T519 and S525 atypical.
LIG_SH2_GRB2 P05067 757-760 SWTI000274 While phosphorylation of Y757 in the SH2-binding motif of Amyloid beta A4 protein (APP) induces binding to Growth factor receptor-bound protein 2 (GRB2), additional phosphorylation of T743 further increases the strength of the interaction.
LIG_PTB_Phospho_1 P05106 779-785 SWTI000275 While phosphorylation of Y785 in the PTB-binding motif of Integrin beta-3 (ITGB3) induces binding to SHC-transforming protein 1 (SHC1), additional phosphorylation of Y773 further increases the strength of the interaction.
LIG_SxIP_EBH_1 P25054 2801-2811 SWTI000276 Phosphorylation of S2789 and S2793 adjacent to the EBH-binding motif of Adenomatous polyposis coli protein (APC), by, respectively, gradually reduces the affinity of its interaction with Microtubule-associated protein RP/EB family member 1 (MAPRE1).
LIG_PTB_Apo_2 P05106 767-774 SWTI000277 Phosphorylation of Y773 in Integrin beta-3 (ITGB3) switches the specificity of ITGB3 from Talin-1 (TLN1) to Docking protein 1 (DOK1), with a 2-fold decrease of the affinity for TLN1 and close to a 400-fold increase of the affinity for DOK1. This switch results in negative regulation of integrin activation.
LIG_PTB_Phospho_1 P05106 767-773 SWTI000277 Phosphorylation of Y773 in Integrin beta-3 (ITGB3) switches the specificity of ITGB3 from Talin-1 (TLN1) to Docking protein 1 (DOK1), with a 2-fold decrease of the affinity for TLN1 and close to a 400-fold increase of the affinity for DOK1. This switch results in negative regulation of integrin activation.
MOD_GSK3_1 P24864-3 377-384 SWTI000278 Phosphorylation of Isoform E-S of G1/S-specific cyclin-E1 (CCNE1) at S384 by CDK2 primes CCNE1 for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B) at S380, which creates a recognition site for F box proteins of the SCF ubiquitin ligase complex (F-box/WD repeat-containing protein 7 (FBXW7)) that target CCNE1 for degradation.
DEG_SCF_FBW7_1 P24864-3 378-384 SWTI000278 Phosphorylation of Isoform E-S of G1/S-specific cyclin-E1 (CCNE1) at S384 by CDK2 primes CCNE1 for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B) at S380, which creates a recognition site for F box proteins of the SCF ubiquitin ligase complex (F-box/WD repeat-containing protein 7 (FBXW7)) that target CCNE1 for degradation.
DOC_WW_Pin1_4 P84022 176-181 SWTI000279 CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details.
MOD_GSK3_1 P84022 201-208 SWTI000279 CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details.
LIG_WW_Nedd4L P84022 203-210 SWTI000279 CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details.
LIG_WW_1 P84022 181-184 SWTI000279 CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. See also switch details and switch details.
TRG_ENDOCYTIC_2 P09793 201-204 SWTI000280 Dephosphorylation of Y201 of Cytotoxic T-lymphocyte protein 4 (Ctla4) switches the specificity of Ctla4 from SH2 domain-containing proteins like Tyrosine-protein phosphatase non-receptor type 11 (Ptpn11) to the AP-2 complex mu subunit (AP-2 complex subunit mu (Ap2m1)), thereby switching from inhibitory signal transmission and negative regulation of T cell responses to internalization and inactivation of Ctla4.
LIG_SH2_STAT5 P09793 201-204 SWTI000280 Dephosphorylation of Y201 of Cytotoxic T-lymphocyte protein 4 (Ctla4) switches the specificity of Ctla4 from SH2 domain-containing proteins like Tyrosine-protein phosphatase non-receptor type 11 (Ptpn11) to the AP-2 complex mu subunit (AP-2 complex subunit mu (Ap2m1)), thereby switching from inhibitory signal transmission and negative regulation of T cell responses to internalization and inactivation of Ctla4.
LIG_WW_1 Q14118 889-892 SWTI000281 Adhesion-dependent phosphorylation of Y892 in Dystroglycan (DAG1) by Src kinase (Proto-oncogene tyrosine-protein kinase Src (SRC)) switches the specificity of DAG1 from the WW domain containing cytoskeletal linker Dystrophin (DMD) to the SH2 domain containing Tyrosine-protein kinase Fyn (FYN).
LIG_SH2_SRC Q14118 892-895 SWTI000281 Adhesion-dependent phosphorylation of Y892 in Dystroglycan (DAG1) by Src kinase (Proto-oncogene tyrosine-protein kinase Src (SRC)) switches the specificity of DAG1 from the WW domain containing cytoskeletal linker Dystrophin (DMD) to the SH2 domain containing Tyrosine-protein kinase Fyn (FYN).
MOD_GSK3_1 P98174 280-287 SWTI000282 Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 1 (FGD1), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD1 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD1 for degradation.
DEG_SCF_TRCP1_1 P98174 282-287 SWTI000282 Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 1 (FGD1), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD1 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD1 for degradation.
MOD_GSK3_1 Q5JSP0 77-84 SWTI000283 Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 3 (FGD3), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD3 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD3 for degradation.
MOD_GSK3_1 Q5JSP0 73-80 SWTI000283 Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 3 (FGD3), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD3 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD3 for degradation.
DEG_SCF_TRCP1_1 Q5JSP0 75-80 SWTI000283 Phosphorylation of FYVE, RhoGEF and PH domain-containing protein 3 (FGD3), a GEF for CDC42 small effector protein 2 (CDC42SE2), by Glycogen synthase kinase-3 beta (GSK3B) targets FGD3 to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks FGD3 for degradation.
MOD_CDK Q9BYG3 235-241 SWTI000284 Phosphorylation of T238 of MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP) by Cyclin-dependent kinase 1 (CDK1) primes for phosphorylation of T234 by Glycogen synthase kinase-3 beta (GSK3B), which primes for phosphorylation of S230 by GSK3B. Triple-phosphorylated hNIFK (MKI67IP) binds strongly to Antigen KI-67 (MKI67).
MOD_GSK3_1 Q9BYG3 231-238 SWTI000284 Phosphorylation of T238 of MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP) by Cyclin-dependent kinase 1 (CDK1) primes for phosphorylation of T234 by Glycogen synthase kinase-3 beta (GSK3B), which primes for phosphorylation of S230 by GSK3B. Triple-phosphorylated hNIFK (MKI67IP) binds strongly to Antigen KI-67 (MKI67).
MOD_GSK3_1 Q9BYG3 227-234 SWTI000284 Phosphorylation of T238 of MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP) by Cyclin-dependent kinase 1 (CDK1) primes for phosphorylation of T234 by Glycogen synthase kinase-3 beta (GSK3B), which primes for phosphorylation of S230 by GSK3B. Triple-phosphorylated hNIFK (MKI67IP) binds strongly to Antigen KI-67 (MKI67).
LIG_FHA_2 Q9BYG3 238-244 SWTI000284 Phosphorylation of T238 of MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP) by Cyclin-dependent kinase 1 (CDK1) primes for phosphorylation of T234 by Glycogen synthase kinase-3 beta (GSK3B), which primes for phosphorylation of S230 by GSK3B. Triple-phosphorylated hNIFK (MKI67IP) binds strongly to Antigen KI-67 (MKI67).
MOD_ProDKin_1 P01106 59-65 SWTI000285 Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation.
MOD_GSK3_1 P01106 55-62 SWTI000285 Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation.
DEG_SCF_FBW7_1 P01106 55-62 SWTI000285 Phosphorylation of Myc proto-oncogene protein (MYC) at S62 by Mitogen-activated protein kinase 1 (MAPK1) primes MYC for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets MYC to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks MYC for degradation.
MOD_GSK3_1 P05412 236-243 SWTI000286 Transcription factor AP-1 (JUN) is primed by an unknown kinase for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets JUN to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks JUN for degradation. In v-Jun (Viral jun-transforming protein (JUN)) the residue corresponding to S243 is mutated to phenylalanine, which protects v-Jun (JUN) from degradation.
DEG_SCF_FBW7_1 P05412 236-243 SWTI000286 Transcription factor AP-1 (JUN) is primed by an unknown kinase for phosphorylation by Glycogen synthase kinase-3 beta (GSK3B), which targets JUN to the SCF ubiquitin ligase complex, F-box/WD repeat-containing protein 7 (FBXW7) that marks JUN for degradation. In v-Jun (Viral jun-transforming protein (JUN)) the residue corresponding to S243 is mutated to phenylalanine, which protects v-Jun (JUN) from degradation.
LIG_SH3_5 P07766 184-188 SWTI000287 Phosphorylation of T-cell surface glycoprotein CD3 epsilon chain (CD3E) by Lck (Tyrosine-protein kinase Lck (LCK)) during T cell activation switches the specificity of CD3E from SH3 domain containing proteins like Epidermal growth factor receptor kinase substrate 8-like protein 1 (EPS8L1) to SH2 domain containing proteins like Tyrosine-protein kinase ZAP-70 (ZAP70).
LIG_TYR_ITAM P07766 185-202 SWTI000287 Phosphorylation of T-cell surface glycoprotein CD3 epsilon chain (CD3E) by Lck (Tyrosine-protein kinase Lck (LCK)) during T cell activation switches the specificity of CD3E from SH3 domain containing proteins like Epidermal growth factor receptor kinase substrate 8-like protein 1 (EPS8L1) to SH2 domain containing proteins like Tyrosine-protein kinase ZAP-70 (ZAP70).
LIG_Filamin P05107 753-763 SWTI000288 Phosphorylation of T758 in Integrin beta-2 (ITGB2) switches the specificity of ITGB2 from Filamin-A (FLNA) to 14-3-3 proteins (e.g. 14-3-3 protein zeta/delta (YWHAZ)).
LIG_14-3-3_3 P05107 755-760 SWTI000288 Phosphorylation of T758 in Integrin beta-2 (ITGB2) switches the specificity of ITGB2 from Filamin-A (FLNA) to 14-3-3 proteins (e.g. 14-3-3 protein zeta/delta (YWHAZ)).
LIG_WW_1 Q14118 889-892 SWTI000289 Adhesion-dependent phosphorylation of Y892 in Dystroglycan (DAG1) by c-Src (SRC) switches the specificity of DAG1 from WW domain containing proteins like Utrophin (UTRN) to SH2 domain containing proteins like Tyrosine-protein kinase CSK (CSK).
LIG_SH2_SRC Q14118 892-895 SWTI000289 Adhesion-dependent phosphorylation of Y892 in Dystroglycan (DAG1) by c-Src (SRC) switches the specificity of DAG1 from WW domain containing proteins like Utrophin (UTRN) to SH2 domain containing proteins like Tyrosine-protein kinase CSK (CSK).
LIG_WW_1 Q15303 1053-1056 SWTI000290 Phosphorylation-dependent binding of Receptor tyrosine-protein kinase erbB-4 (ERBB4) to the SH2 domains of Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1) results in signaling activation, while binding to the WW domains of E3 ubiquitin-protein ligase Itchy homolog (ITCH) to unphopshorylated ERBB4 results in ubiquitylation, endocytosis and ultimately degradation of ERBB4.
LIG_SH2_STAT5 Q15303 1056-1059 SWTI000290 Phosphorylation-dependent binding of Receptor tyrosine-protein kinase erbB-4 (ERBB4) to the SH2 domains of Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1) results in signaling activation, while binding to the WW domains of E3 ubiquitin-protein ligase Itchy homolog (ITCH) to unphopshorylated ERBB4 results in ubiquitylation, endocytosis and ultimately degradation of ERBB4.
LIG_ULM_U2AF65_1 P54253 770-775 SWTI000291 Phosphorylation of S775 switches binding specificity of Ataxin-1 (ATXN1) from the splicing factor Splicing factor U2AF 65 kDa subunit (U2AF2) to 14-3-3 proteins (e.g. 14-3-3 protein zeta/delta (YWHAZ)). While association with the spliceosome protects ATXN1 from self-association, its phosphorylation-dependent recruitment to 14-3-3 proteins (e.g. YWHAZ) might result in aggregation.
LIG_14-3-3_1 P54253 772-777 SWTI000291 Phosphorylation of S775 switches binding specificity of Ataxin-1 (ATXN1) from the splicing factor Splicing factor U2AF 65 kDa subunit (U2AF2) to 14-3-3 proteins (e.g. 14-3-3 protein zeta/delta (YWHAZ)). While association with the spliceosome protects ATXN1 from self-association, its phosphorylation-dependent recruitment to 14-3-3 proteins (e.g. YWHAZ) might result in aggregation.
LIG_PTB_Apo_2 P05067 756-763 SWTI000292 Phosphorylation of Y757 in APP (Amyloid beta A4 protein (APP)) switches its specificity from PTB domain containing proteins, like Amyloid beta A4 precursor protein-binding family B member 1 (APBB1), which is involved in trafficking and processing of APP, to SH2 domain containing proteins, such as Growth factor receptor-bound protein 2 (GRB2).
LIG_SH2_GRB2 P05067 757-760 SWTI000292 Phosphorylation of Y757 in APP (Amyloid beta A4 protein (APP)) switches its specificity from PTB domain containing proteins, like Amyloid beta A4 precursor protein-binding family B member 1 (APBB1), which is involved in trafficking and processing of APP, to SH2 domain containing proteins, such as Growth factor receptor-bound protein 2 (GRB2).
LIG_PTB_Apo_2 P05106 779-786 SWTI000293 Phosphorylation of Integrin beta-3 (ITGB3) at Y785 switches the specificity of integrin from Kindlin-2 (Fermitin family homolog 2 (FERMT2)) to the adaptor protein SHC-transforming protein 1 (SHC1).
LIG_PTB_Phospho_1 P05106 779-785 SWTI000293 Phosphorylation of Integrin beta-3 (ITGB3) at Y785 switches the specificity of integrin from Kindlin-2 (Fermitin family homolog 2 (FERMT2)) to the adaptor protein SHC-transforming protein 1 (SHC1).
MOD_GSK3_1 P24864 392-399 SWTI000294 Phosphorylation of G1/S-specific cyclin-E1 (CCNE1) at S399 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of CCNE1 by Glycogen synthase kinase-3 beta (GSK3B) at T395 switches the specificity of CCNE1 to the F-box/WD repeat-containing protein 7 (FBXW7), which recruits CCNE1 to the SCF ubiquitin ligase complex to mark CCNE1 for degradation.
DEG_SCF_FBW7_1 P24864 393-399 SWTI000294 Phosphorylation of G1/S-specific cyclin-E1 (CCNE1) at S399 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of CCNE1 by Glycogen synthase kinase-3 beta (GSK3B) at T395 switches the specificity of CCNE1 to the F-box/WD repeat-containing protein 7 (FBXW7), which recruits CCNE1 to the SCF ubiquitin ligase complex to mark CCNE1 for degradation.
MOD_GSK3_1 P36956 422-430 SWTI000295 Phosphorylation of SREBP-1 (Sterol regulatory element-binding protein 1 (SREBF1)) at S430 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of SREBP-1 (SREBF1) by GSK3B at T426 switches the specificity of SREBP-1 (SREBF1) to the F-box/WD repeat-containing protein 7 (FBXW7), which recruits SREBP-1 (SREBF1) to the SCF ubiquitin ligase complex to mark SREBP-1 (SREBF1) for degradation.
DEG_SCF_FBW7_1 P36956 425-430 SWTI000295 Phosphorylation of SREBP-1 (Sterol regulatory element-binding protein 1 (SREBF1)) at S430 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of SREBP-1 (SREBF1) by GSK3B at T426 switches the specificity of SREBP-1 (SREBF1) to the F-box/WD repeat-containing protein 7 (FBXW7), which recruits SREBP-1 (SREBF1) to the SCF ubiquitin ligase complex to mark SREBP-1 (SREBF1) for degradation.
MOD_GSK3_1 P35222 30-37 SWTI000296 Phosphorylation of Catenin beta-1 (CTNNB1) at T41 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B), which then phosphorylates S37, thereby generating a new docking site for GSK3B. Subsequent phosphorylation of S33 by GSK3B switches the specificity of CTNNB1 to the F-box/WD repeat-containing protein 1A (BTRC), which recruits CTNNB1 to the SCF ubiquitin ligase complex.
DEG_SCF_TRCP1_1 P35222 32-37 SWTI000296 Phosphorylation of Catenin beta-1 (CTNNB1) at T41 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B), which then phosphorylates S37, thereby generating a new docking site for GSK3B. Subsequent phosphorylation of S33 by GSK3B switches the specificity of CTNNB1 to the F-box/WD repeat-containing protein 1A (BTRC), which recruits CTNNB1 to the SCF ubiquitin ligase complex.
MOD_GSK3_1 O95863 93-100 SWTI000297 Phosphorylation of Zinc finger protein SNAI1 (SNAI1) at S100 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of S96 by GSK3B targets Zinc finger protein SNAI1 (SNAI1) to the SCF ubiquitin ligase complexes F-box/WD repeat-containing protein 1A (BTRC), which marks it for degradation.
DEG_SCF_TRCP1_1 O95863 95-100 SWTI000297 Phosphorylation of Zinc finger protein SNAI1 (SNAI1) at S100 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of S96 by GSK3B targets Zinc finger protein SNAI1 (SNAI1) to the SCF ubiquitin ligase complexes F-box/WD repeat-containing protein 1A (BTRC), which marks it for degradation.
LIG_RGD O43854 96-98 SWTI000298 Binding of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand.
LIG_RGD P62384 51-53 SWTI000299 Binding of Disintegrin albolabrin to integrin receptors depends on pre-assembly of Integrin alpha-IIb (ITGA2B)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand.
LIG_RGD P02751 1524-1526 SWTI000300 Binding of Fibronectin (FN1) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand.
LIG_RGD P03305 869-871 SWTI000301 Binding of Genome polyprotein to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand.
LIG_RGD P04004 64-66 SWTI000302 Binding of Vitronectin (VTN) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand.
LIG_RGD P04275 2507-2509 SWTI000303 Binding of von Willebrand factor (VWF) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand.
LIG_RGD P10451 159-161 SWTI000304 Binding of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand.
LIG_RGD P11276 1614-1616 SWTI000305 Binding of Fibronectin (Fn1) to integrin receptors depends on pre-assembly of Integrin alpha-5 (Itga5)-Integrin beta-1 (Itgb1) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand.
LIG_RGD P17349 459-461 SWTI000306 Binding of Zinc metalloproteinase/disintegrin to integrin receptors depends on pre-assembly of Integrin alpha-IIb (ITGA2B)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand.
LIG_RGD P17495 51-53 SWTI000307 Binding of Disintegrin trigramin-beta-2 to integrin receptors depends on pre-assembly of Integrin alpha-IIb (ITGA2B)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand.
LIG_RGD P21404 858-860 SWTI000308 Binding of Genome polyprotein to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-6 (ITGB6) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand.
LIG_RGD P29788 64-66 SWTI000309 Binding of Vitronectin (Vtn) to integrin receptors depends on pre-assembly of Integrin alpha-V (Itgav)-Integrin beta-3 (Itgb3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand.
LIG_RGD Q66578 764-766 SWTI000310 Binding of Genome polyprotein to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-6 (ITGB6) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand.
LIG_Integrin_isoDGR_1 P02751 263-265 SWTI000311 Binding of Fibronectin (FN1) to integrin receptors depends on pre-assembly of Integrin alpha-V (ITGAV)-Integrin beta-3 (ITGB3) heterodimers, since association of the integrin alpha and beta subunits results in the formation of a composite binding site for the RGD motif in the ligand.
MOD_CDK_1 P46527 184-190 SWTI000312 Binding of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (p27) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p27 (CDKN1B) at T187, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p27 (CDKN1B). While some residues, including the phosphorylated T187, bind to CKS1B and others to SKP2, the E185 makes contact with residues of both CKS1B and SKP2.
DEG_SCF_Skp2-Cks1_1 P46527 183-190 SWTI000312 Binding of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (p27) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p27 (CDKN1B) at T187, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p27 (CDKN1B). While some residues, including the phosphorylated T187, bind to CKS1B and others to SKP2, the E185 makes contact with residues of both CKS1B and SKP2.
MOD_CDK_1 P49918 307-313 SWTI000313 Binding of Cyclin-dependent kinase inhibitor 1C (CDKN1C) (p57) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p57 (CDKN1C) at T310, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p57 (CDKN1C).
DEG_SCF_Skp2-Cks1_1 P49918 306-313 SWTI000313 Binding of Cyclin-dependent kinase inhibitor 1C (CDKN1C) (p57) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p57 (CDKN1C) at T310, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p57 (CDKN1C).
MOD_CDK_1 P49919 339-345 SWTI000314 Binding of Cyclin-dependent kinase inhibitor 1C (Cdkn1c) (p57) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p57 (Cdkn1c) at T342, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p57 (Cdkn1c).
DEG_SCF_Skp2-Cks1_1 P49919 338-345 SWTI000314 Binding of Cyclin-dependent kinase inhibitor 1C (Cdkn1c) (p57) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p57 (Cdkn1c) at T342, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p57 (Cdkn1c).
TRG_NLS_MonoExtN_4 P03070 126-132 SWTI000315 Inhibition of nuclear import of Large T antigen by phosphorylation-dependent (T124) binding of BRCA1-associated protein (BRAP).
TRG_NLS_MonoExtN_4 P16790 425-432 SWTI000316 Inhibition of nuclear import of DNA polymerase processivity factor (UL44) by phosphorylation-dependent (T427) binding of BRCA1-associated protein (BRAP).
LIG_14-3-3_3 Q9P0K1 831-836 SWTI000317 Phosphorylation-induced binding of dimeric 14-3-3 protein beta/alpha (YWHAB) to Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) blocks ER retention motifs in Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) and regulates transport of this protein to the membrane.
LIG_14-3-3_3 Q9P0K1 854-859 SWTI000317 Phosphorylation-induced binding of dimeric 14-3-3 protein beta/alpha (YWHAB) to Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) blocks ER retention motifs in Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) and regulates transport of this protein to the membrane.
TRG_ER_diArg_1 Q9P0K1 829-831 SWTI000317 Phosphorylation-induced binding of dimeric 14-3-3 protein beta/alpha (YWHAB) to Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) blocks ER retention motifs in Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) and regulates transport of this protein to the membrane.
TRG_ER_diArg_1 Q9P0K1 851-854 SWTI000317 Phosphorylation-induced binding of dimeric 14-3-3 protein beta/alpha (YWHAB) to Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) blocks ER retention motifs in Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) and regulates transport of this protein to the membrane.
LIG_Actin_RPEL_3 Q8K4J6 17-36 SWTI000318 Hiding of the NLS of MKL/myocardin-like protein 1 (Mkl1) by binding of G-actin to the RPEL motifs of MKL/myocardin-like protein 1 (Mkl1) prevents translocation of this transcription factor to the nucleus.
LIG_Actin_RPEL_3 Q8K4J6 61-80 SWTI000318 Hiding of the NLS of MKL/myocardin-like protein 1 (Mkl1) by binding of G-actin to the RPEL motifs of MKL/myocardin-like protein 1 (Mkl1) prevents translocation of this transcription factor to the nucleus.
LIG_Actin_RPEL_3 Q8K4J6 105-124 SWTI000318 Hiding of the NLS of MKL/myocardin-like protein 1 (Mkl1) by binding of G-actin to the RPEL motifs of MKL/myocardin-like protein 1 (Mkl1) prevents translocation of this transcription factor to the nucleus.
TRG_NLS_MonoExtN_4 Q8K4J6 62-67 SWTI000318 Hiding of the NLS of MKL/myocardin-like protein 1 (Mkl1) by binding of G-actin to the RPEL motifs of MKL/myocardin-like protein 1 (Mkl1) prevents translocation of this transcription factor to the nucleus.
TRG_NLS_MonoExtN_4 Q8K4J6 95-101 SWTI000318 Hiding of the NLS of MKL/myocardin-like protein 1 (Mkl1) by binding of G-actin to the RPEL motifs of MKL/myocardin-like protein 1 (Mkl1) prevents translocation of this transcription factor to the nucleus.
LIG_14-3-3_3 P49685 356-360 SWTI000319 Phosphorylation-induced binding of 14-3-3 protein beta/alpha (YWHAB) promotes cell surface expression of G-protein coupled receptor 15 (GPR15) by releasing the receptor from the ER retrieval/retention pathway that is mediated by the interaction of its ER retention motif with Coatomer subunit beta (COPB1).
TRG_ER_diArg_1 P49685 352-354 SWTI000319 Phosphorylation-induced binding of 14-3-3 protein beta/alpha (YWHAB) promotes cell surface expression of G-protein coupled receptor 15 (GPR15) by releasing the receptor from the ER retrieval/retention pathway that is mediated by the interaction of its ER retention motif with Coatomer subunit beta (COPB1).
LIG_14-3-3_3 P04233 5-10 SWTI000320 The basic ER retention motif of HLA class II histocompatibility antigen gamma chain (CD74) is blocked from binding to Coatomer subunit beta (COPB1) by phosphorylation-induced binding of 14-3-3 protein beta/alpha (YWHAB), regulating its release from the ER and trafficking to the plasma membrane.
TRG_ER_diArg_1 P04233 3-5 SWTI000320 The basic ER retention motif of HLA class II histocompatibility antigen gamma chain (CD74) is blocked from binding to Coatomer subunit beta (COPB1) by phosphorylation-induced binding of 14-3-3 protein beta/alpha (YWHAB), regulating its release from the ER and trafficking to the plasma membrane.
TRG_ER_diArg_1 Q9UBS5 923-926 SWTI000321 Interaction of the GABA receptor R2 subunit (Gamma-aminobutyric acid type B receptor subunit 2 (GABBR2)) with the R1 subunit (Gamma-aminobutyric acid type B receptor subunit 1 (GABBR1)) via coiled-coil forming domains masks the ER retention motif in the R1 subunit (Gamma-aminobutyric acid type B receptor subunit 1 (GABBR1)), thereby promoting surface expression of fully assembled GABA receptors.
LIG_PDZ_Class_1 Q8R4T5 389-394 SWTI000322 Binding of the PDZ-binding motif of General receptor for phosphoinositides 1-associated scaffold protein (Grasp) (Tamalin) to the Tamalin Grasp PDZ domain locks this protein in an auto-inhibited conformation. Binding of the PDZ-binding motif of Metabotropic glutamate receptor 5 (Grm5) to the Tamalin GraspPDZ domain results in disruption of the weaker intramolecular Tamalin (Grasp) interactions. The PDZ-binding motif of Tamalin (General receptor for phosphoinositides 1-associated scaffold protein (Grasp)) becomes available to interact with the PDZ domain of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (Magi2) (S-SCAM), which functions as a receptor for kinesin motor proteins. See also switch details.
LIG_14-3-3_1 Q96PU5-8 465-470 SWTI000323 Phosphorylation of Isoform Nedd4-2a of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) by Serine/threonine-protein kinase Sgk1 (SGK1) induces binding to 14-3-3 protein eta (YWHAH). This inhibits (whether allosterically or sterically is not known) interactions of NEDD4L via its WW domains with the PY motif in Amiloride-sensitive sodium channel subunit gamma (SCNN1G) (ENaC). As a result, ENaC does not get degraded and ENaC-mediated Na+ currents increase.
LIG_WW_1 P51170 624-627 SWTI000323 Phosphorylation of Isoform Nedd4-2a of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) by Serine/threonine-protein kinase Sgk1 (SGK1) induces binding to 14-3-3 protein eta (YWHAH). This inhibits (whether allosterically or sterically is not known) interactions of NEDD4L via its WW domains with the PY motif in Amiloride-sensitive sodium channel subunit gamma (SCNN1G) (ENaC). As a result, ENaC does not get degraded and ENaC-mediated Na+ currents increase.
LIG_SH3_3 O00499-6 305-311 SWTI000324 An intramolecular interaction of an SH3 binding motif, encoded by exon 12A, in Isoform II2 of Myc box-dependent-interacting protein 1 (BIN1) with the SH3 domain of Bin1 prevents interaction of the Bin1 SH3 domain with the SH3 binding motif of Myc proto-oncogene protein (MYC).
LIG_SH3_2 P01106 60-65 SWTI000324 An intramolecular interaction of an SH3 binding motif, encoded by exon 12A, in Isoform II2 of Myc box-dependent-interacting protein 1 (BIN1) with the SH3 domain of Bin1 prevents interaction of the Bin1 SH3 domain with the SH3 binding motif of Myc proto-oncogene protein (MYC).
LIG_SH2_STAT5 P06213 1361-1364 SWTI000325 PIP3 (16618" target="_blank">1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate), a product of PI3-kinase, binds to the SH2 domains of PI3K (Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1)) and thereby blocks its interaction with tyrosine-phosphorylated SH2 motif containing proteins.
LIG_14-3-3_1 P08965 435-440 SWTI000326 Binding of meiRNA meiotic non-coding RNA (meiRNA) to the RRM domains of Meiosis protein mei2 (mei2) is essential for promotion of premeiotic DNA synthesis and meiosis I and is blocked by Pat1-mediated phosphorylation-induced binding of the 14-3-3 protein DNA damage checkpoint protein rad24 (rad24) to 2 14-3-3 binding motifs in mei2.
LIG_14-3-3_1 P08965 523-529 SWTI000326 Binding of meiRNA meiotic non-coding RNA (meiRNA) to the RRM domains of Meiosis protein mei2 (mei2) is essential for promotion of premeiotic DNA synthesis and meiosis I and is blocked by Pat1-mediated phosphorylation-induced binding of the 14-3-3 protein DNA damage checkpoint protein rad24 (rad24) to 2 14-3-3 binding motifs in mei2.
LIG_14-3-3_2 P08965 435-440 SWTI000326 Binding of meiRNA meiotic non-coding RNA (meiRNA) to the RRM domains of Meiosis protein mei2 (mei2) is essential for promotion of premeiotic DNA synthesis and meiosis I and is blocked by Pat1-mediated phosphorylation-induced binding of the 14-3-3 protein DNA damage checkpoint protein rad24 (rad24) to 2 14-3-3 binding motifs in mei2.
LIG_14-3-3_2 P08965 523-529 SWTI000326 Binding of meiRNA meiotic non-coding RNA (meiRNA) to the RRM domains of Meiosis protein mei2 (mei2) is essential for promotion of premeiotic DNA synthesis and meiosis I and is blocked by Pat1-mediated phosphorylation-induced binding of the 14-3-3 protein DNA damage checkpoint protein rad24 (rad24) to 2 14-3-3 binding motifs in mei2.
LIG_PDZ_Class_2 Q02410 832-837 SWTI000327 An intramolecular interaction of the C-terminal PDZ binding motif of Amyloid beta A4 precursor protein-binding family A member 1 (APBA1) (also known as X11alpha/Mint1) with the PDZ domain tandem of APBA1 results in an auto-inhibited conformation of APBA1, where binding of ligands containing a PDZ binding motif such as Presenilin-1 (PSEN1) is blocked. Binding of these ligands might be regulated by phosphorylation of Y836 in the APBA1 PDZ-binding motif, as its mutation to glutamate releases autoinhibition and enhances the interaction of the APBA1 PDZ tandem with presenilin.
LIG_PDZ_Class_2 P49768 462-467 SWTI000327 An intramolecular interaction of the C-terminal PDZ binding motif of Amyloid beta A4 precursor protein-binding family A member 1 (APBA1) (also known as X11alpha/Mint1) with the PDZ domain tandem of APBA1 results in an auto-inhibited conformation of APBA1, where binding of ligands containing a PDZ binding motif such as Presenilin-1 (PSEN1) is blocked. Binding of these ligands might be regulated by phosphorylation of Y836 in the APBA1 PDZ-binding motif, as its mutation to glutamate releases autoinhibition and enhances the interaction of the APBA1 PDZ tandem with presenilin.
LIG_SH3_8 O00499-8 265-268 SWTI000328 An intramolecular interaction of a Bin1 SH3 binding motif, encoded by exon 10, with the Dynamin-2 (DNM2) SH3 domain prevents binding of dynamin2 to the Bin1 SH3 domain. Binding of PI(4,5)P2 to the overlapping PI(4,5)P2 binding motif encoded by exon 10 relieves the intramolecular auto-inhibitory interaction and allows the Bin1 SH3 domain to interact with the dynamin2 PxxP motif
LIG_SH3_2 P50570 829-834 SWTI000328 An intramolecular interaction of a Bin1 SH3 binding motif, encoded by exon 10, with the Dynamin-2 (DNM2) SH3 domain prevents binding of dynamin2 to the Bin1 SH3 domain. Binding of PI(4,5)P2 to the overlapping PI(4,5)P2 binding motif encoded by exon 10 relieves the intramolecular auto-inhibitory interaction and allows the Bin1 SH3 domain to interact with the dynamin2 PxxP motif
TRG_NLS_Bipartite_1 Q02821 44-58 SWTI000329 An intramolecular interaction between the importin beta-binding (IBB) domain and the NLS-binding pocket of Importin subunit alpha (SRP1) prevents binding of NLS cargo (e.g. Large T antigen) in the absence of Importin subunit beta-1 (KAP95) by hiding of the NLS-binding pocket. Binding of the IBB of Importin subunit alpha (SRP1) to Importin subunit beta-1 (KAP95) relieves this auto-inhibitory interaction and increases the affinity of Importin subunit alpha (SRP1) for NLS cargo.
TRG_NLS_MonoExtN_4 P03070 126-132 SWTI000329 An intramolecular interaction between the importin beta-binding (IBB) domain and the NLS-binding pocket of Importin subunit alpha (SRP1) prevents binding of NLS cargo (e.g. Large T antigen) in the absence of Importin subunit beta-1 (KAP95) by hiding of the NLS-binding pocket. Binding of the IBB of Importin subunit alpha (SRP1) to Importin subunit beta-1 (KAP95) relieves this auto-inhibitory interaction and increases the affinity of Importin subunit alpha (SRP1) for NLS cargo.
DOC_CYCLIN_1 P46527 30-33 SWTI000330 Binding of the CDK-cyclin inhibitor p27 (Cyclin-dependent kinase inhibitor 1B (CDKN1B)) blocks the substrate recruitment site on Cyclin-A2 (CCNA2).
DOC_CYCLIN_1 Q99741 94-98 SWTI000330 Binding of the CDK-cyclin inhibitor p27 (Cyclin-dependent kinase inhibitor 1B (CDKN1B)) blocks the substrate recruitment site on Cyclin-A2 (CCNA2).
LIG_EABR_CEP55_1 Q7M6U3 791-797 SWTI000331 The switch from cytokinesis to intracellular bridge formation in differentiating male germ cells is mediated by Testis-expressed protein 14 (Tex14). Binding of Tex14 to Centrosomal protein of 55 kDa (Cep55) prevents binding of ALIX (Programmed cell death 6-interacting protein (Pdcd6ip)) and Tumor susceptibility gene 101 protein (Tsg101) to Cep55, which is required for abscission at the end of cytokinesis. Tex14 uses the same site on Cep55 as ALIX (Pdcd6ip) and Tsg101. The strong interaction between Tex14 and Cep55 together with the avidity effect that results from interaction of MKLP1 with both Tex14 and Cep55 prevent recruitment of ALIX (Pdcd6ip) and Tsg101 for abscission.
LIG_EABR_CEP55_1 Q61187 158-164 SWTI000331 The switch from cytokinesis to intracellular bridge formation in differentiating male germ cells is mediated by Testis-expressed protein 14 (Tex14). Binding of Tex14 to Centrosomal protein of 55 kDa (Cep55) prevents binding of ALIX (Programmed cell death 6-interacting protein (Pdcd6ip)) and Tumor susceptibility gene 101 protein (Tsg101) to Cep55, which is required for abscission at the end of cytokinesis. Tex14 uses the same site on Cep55 as ALIX (Pdcd6ip) and Tsg101. The strong interaction between Tex14 and Cep55 together with the avidity effect that results from interaction of MKLP1 with both Tex14 and Cep55 prevent recruitment of ALIX (Pdcd6ip) and Tsg101 for abscission.
LIG_EABR_CEP55_1 Q7M6U3 791-797 SWTI000332 The switch from cytokinesis to intracellular bridge formation in differentiating male germ cells is mediated by Testis-expressed protein 14 (Tex14). Binding of Tex14 to Centrosomal protein of 55 kDa (Cep55) prevents binding of ALIX (Programmed cell death 6-interacting protein (Pdcd6ip)) and Tumor susceptibility gene 101 protein (Tsg101) to Cep55, which is required for abscission at the end of cytokinesis. Tex14 uses the same site on Cep55 as ALIX (Pdcd6ip) and Tsg101. The strong interaction between Tex14 and Cep55 together with the avidity effect that results from interaction of MKLP1 with both Tex14 and Cep55 prevent recruitment of ALIX (Pdcd6ip) and Tsg101 for abscission.
LIG_EABR_CEP55_1 Q9WU78 801-807 SWTI000332 The switch from cytokinesis to intracellular bridge formation in differentiating male germ cells is mediated by Testis-expressed protein 14 (Tex14). Binding of Tex14 to Centrosomal protein of 55 kDa (Cep55) prevents binding of ALIX (Programmed cell death 6-interacting protein (Pdcd6ip)) and Tumor susceptibility gene 101 protein (Tsg101) to Cep55, which is required for abscission at the end of cytokinesis. Tex14 uses the same site on Cep55 as ALIX (Pdcd6ip) and Tsg101. The strong interaction between Tex14 and Cep55 together with the avidity effect that results from interaction of MKLP1 with both Tex14 and Cep55 prevent recruitment of ALIX (Pdcd6ip) and Tsg101 for abscission.
LIG_PDZ_Class_1 O14745 353-358 SWTI000333 Binding of Ezrin via its FERM domain to the EB domain of Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (SLC9A3R1) results in allosteric coupling to the second PDZ domain of SLC9A3R1. This relieves the intramolecular interaction with the SLC9A3R1 PDZ-binding ligand and increases the affinity of the PDZ domain for other ligands including Catenin beta-1 (CTNNB1).
LIG_PDZ_Class_1 P35222 776-781 SWTI000333 Binding of Ezrin via its FERM domain to the EB domain of Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (SLC9A3R1) results in allosteric coupling to the second PDZ domain of SLC9A3R1. This relieves the intramolecular interaction with the SLC9A3R1 PDZ-binding ligand and increases the affinity of the PDZ domain for other ligands including Catenin beta-1 (CTNNB1).
LIG_PDZ_Class_1 P31424 1198-1203 SWTI000334 Binding of the PDZ-binding motif of General receptor for phosphoinositides 1-associated scaffold protein (Grasp) (Tamalin) to the Tamalin (Grasp) PDZ domain locks this protein in an auto-inhibited conformation. Binding of the PDZ-binding motif of Metabotropic glutamate receptor 5 (Grm5) to the Tamalin (Grasp) PDZ domain results in disruption of the weaker intramolecular Tamalin (Grasp) interactions. The PDZ-binding motif of Tamalin (Grasp) becomes available to interact with the PDZ domain of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (Magi2) (S-SCAM), which functions as a receptor for kinesin motor proteins. See also switch details.
LIG_PDZ_Class_1 Q8R4T5 389-394 SWTI000334 Binding of the PDZ-binding motif of General receptor for phosphoinositides 1-associated scaffold protein (Grasp) (Tamalin) to the Tamalin (Grasp) PDZ domain locks this protein in an auto-inhibited conformation. Binding of the PDZ-binding motif of Metabotropic glutamate receptor 5 (Grm5) to the Tamalin (Grasp) PDZ domain results in disruption of the weaker intramolecular Tamalin (Grasp) interactions. The PDZ-binding motif of Tamalin (Grasp) becomes available to interact with the PDZ domain of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (Magi2) (S-SCAM), which functions as a receptor for kinesin motor proteins. See also switch details.
LIG_Talin P26010 770-779 SWTI000335 The integrin regulator Talin-1 (TLN1) and the actin-crosslinking Filamins Filamin-A (FLNA) use overlapping binding sites on the cytoplasmic tails of beta integrin subunits Integrin beta-7 (ITGB7), which makes their interaction with beta integrin mutually exclusive.
LIG_Filamin P26010 776-787 SWTI000335 The integrin regulator Talin-1 (TLN1) and the actin-crosslinking Filamins Filamin-A (FLNA) use overlapping binding sites on the cytoplasmic tails of beta integrin subunits Integrin beta-7 (ITGB7), which makes their interaction with beta integrin mutually exclusive.
LIG_WRPW_1 Q14469 275-280 SWTI000336 The Transducin-like enhancer protein 1 (TLE1) can recruit a wide range of transcriptional repressors via its WD domain, to which the WRPW motif of Transcription factor HES-1 (HES1) and the EH1 motif of Homeobox protein goosecoid (GSC) can bind using overlapping sites.
LIG_EH1_1 P56915 5-13 SWTI000336 The Transducin-like enhancer protein 1 (TLE1) can recruit a wide range of transcriptional repressors via its WD domain, to which the WRPW motif of Transcription factor HES-1 (HES1) and the EH1 motif of Homeobox protein goosecoid (GSC) can bind using overlapping sites.
LIG_GYF P06729 295-303 SWTI000337 T-cell surface antigen CD2 (CD2) uses overlapping motifs to bind to CD2 antigen cytoplasmic tail-binding protein 2 (CD2BP2) and Fyn, which makes their interactions mutually exclusive. Since CD2BP2 and Tyrosine-protein kinase Fyn (FYN) reside in different subcellular locations, the specificity of CD2 for the two competitors is switched by changing its cellular localization, from non-raft membranes to lipid raft membranes.
LIG_SH3_3 P06729 294-300 SWTI000337 T-cell surface antigen CD2 (CD2) uses overlapping motifs to bind to CD2 antigen cytoplasmic tail-binding protein 2 (CD2BP2) and Fyn, which makes their interactions mutually exclusive. Since CD2BP2 and Tyrosine-protein kinase Fyn (FYN) reside in different subcellular locations, the specificity of CD2 for the two competitors is switched by changing its cellular localization, from non-raft membranes to lipid raft membranes.
DOC_CYCLIN_1 P38936 19-22 SWTI000338 Cyclin-dependent kinase inhibitor 1 (CDKN1A) (p21) and the M-phase inducer phosphatase 1 (CDC25A) bind the same site on Cyclin proteins (e.g. G1/S-specific cyclin-E1 (CCNE1)), making their interactions mutually exclusive.
DOC_CYCLIN_1 P30304 11-15 SWTI000338 Cyclin-dependent kinase inhibitor 1 (CDKN1A) (p21) and the M-phase inducer phosphatase 1 (CDC25A) bind the same site on Cyclin proteins (e.g. G1/S-specific cyclin-E1 (CCNE1)), making their interactions mutually exclusive.
DOC_CYCLIN_1 P06400 873-877 SWTI000339 The docking sites for PP1 (e.g. Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PPP1CA)) and Cdk-Cyclins (e.g. Cyclin-A2 (CCNA2)) on Retinoblastoma-associated protein (RB1) overlap, which makes their binding to RB1 mutually exclusive. Hypophosphorylated RB1 blocks E2F-dependent transcription, while hyperphosphorylation inactivates RB1 as a repressor, thereby promoting cell cycle progression.
DOC_PP1 P06400 872-878 SWTI000339 The docking sites for PP1 (e.g. Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PPP1CA)) and Cdk-Cyclins (e.g. Cyclin-A2 (CCNA2)) on Retinoblastoma-associated protein (RB1) overlap, which makes their binding to RB1 mutually exclusive. Hypophosphorylated RB1 blocks E2F-dependent transcription, while hyperphosphorylation inactivates RB1 as a repressor, thereby promoting cell cycle progression.
LIG_Glycolytic_Aldolase Q9Y5X1 165-169 SWTI000340 Sorting nexin-9 (SNX9) and fructose-1,6-bisphosphate (16905" target="_blank">D-fructose 1,6-bisphosphate) bind mutually exclusive and with similar affinities to Fructose-bisphosphate aldolase A (ALDOA).
LIG_WW_1 Q14118 889-892 SWTI000341 The WW-binding motif for Dystrophin (DMD) and the SH3-binding motif for Growth factor receptor-bound protein 2 (GRB2) on Dystroglycan (DAG1) overlap, making their interactions mutually exclusive and competitive.
LIG_SH3_3 Q14118 888-894 SWTI000341 The WW-binding motif for Dystrophin (DMD) and the SH3-binding motif for Growth factor receptor-bound protein 2 (GRB2) on Dystroglycan (DAG1) overlap, making their interactions mutually exclusive and competitive.
LIG_PDZ_Class_1 P13569 1475-1480 SWTI000342 The PDZ domains of Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (SLC9A3R1) and SH3 and multiple ankyrin repeat domains protein 2 (SHANK2) compete for the PDZ-binding motif of Cystic fibrosis transmembrane conductance regulator (CFTR). SLC9A3R1 positively regulates CFTR activity by recruiting a PKA-containing complex, while SH3 and multiple ankyrin repeat domains protein 2 (SHANK2) negatively affects CFTR activity by recruiting PDE4D.
LIG_FHA_2 P18887 517-523 SWTI000343 Hierarchical cooperative binding of two Bifunctional polynucleotide phosphatase/kinase (PNKP) molecules to one DNA repair protein XRCC1 (XRCC1) molecule upon phosphorylation of a primary and secondary FHA-binding motif in DNA repair protein XRCC1 (XRCC1) by Casein kinase II subunit alpha (CSNK2A1).
LIG_FHA_2 P18887 521-527 SWTI000343 Hierarchical cooperative binding of two Bifunctional polynucleotide phosphatase/kinase (PNKP) molecules to one DNA repair protein XRCC1 (XRCC1) molecule upon phosphorylation of a primary and secondary FHA-binding motif in DNA repair protein XRCC1 (XRCC1) by Casein kinase II subunit alpha (CSNK2A1).
LIG_TYR_ITAM P20963 69-86 SWTI000344 Phosphorylation of Y72 and Y83 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70).
LIG_TYR_ITAM P11911 179-196 SWTI000345 Phosphorylation of Y182 and Y193 in the ITAM motif of B-cell antigen receptor complex-associated protein alpha chain (Cd79a) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (Syk). Maximal Syk activation requires both Syk SH2 domains and phosphorylation of both ITAM tyrosine residues.
LIG_TYR_ITAM P07766 185-202 SWTI000346 Phosphorylation of Y188 and Y199 in the ITAM motif of T-cell surface glycoprotein CD3 epsilon chain (CD3E) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK).
LIG_TYR_ITAM P20963 108-126 SWTI000347 Phosphorylation of Y111 and Y123 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70).
LIG_TYR_ITAM P20963 139-156 SWTI000348 Phosphorylation of Y142 and Y153 in the ITAM motif of T-cell surface glycoprotein CD3 zeta chain (CD247) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70).
LIG_TYR_ITAM P09693 157-174 SWTI000349 Phosphorylation of Y160 and Y171 in the ITAM motif of T-cell surface glycoprotein CD3 gamma chain (CD3G) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase ZAP-70 (ZAP70).
LIG_TYR_ITSM O43613 79-86 SWTI000350 Orexin-A induced phosphorylation of the ITSM and ITIM motifs in Orexin receptor type 1 (HCRTR1) allows binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) via its two SH2 domains. Mutation of either tyrosine in the motifs abolishes binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11).
LIG_TYR_ITIM O43613 356-361 SWTI000350 Orexin-A induced phosphorylation of the ITSM and ITIM motifs in Orexin receptor type 1 (HCRTR1) allows binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) via its two SH2 domains. Mutation of either tyrosine in the motifs abolishes binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11).
LIG_TYR_ITAM P12318 285-307 SWTI000351 Phosphorylation of Y288 and Y304 in the ITAM motif of Low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK).
LIG_TYR_ITAM P30273 62-79 SWTI000352 Phosphorylation of Y65 and Y76 in the ITAM motif of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) induces high-avidity binding to the tandem SH2 domains of Tyrosine-protein kinase SYK (SYK).
LIG_14-3-3_3 Q02156 343-348 SWTI000353 Phosphorylation of two 14-3-3-binding motifs in Protein kinase C epsilon type (PRKCE) induces high-avidity binding to dimeric 14-3-3 protein zeta/delta (YWHAZ).
LIG_14-3-3_3 Q02156 365-370 SWTI000353 Phosphorylation of two 14-3-3-binding motifs in Protein kinase C epsilon type (PRKCE) induces high-avidity binding to dimeric 14-3-3 protein zeta/delta (YWHAZ).
LIG_14-3-3_1 P04049 256-261 SWTI000354 Phosphorylation of two 14-3-3-binding motifs in RAF proto-oncogene serine/threonine-protein kinase (RAF1) in response to growth factors induces high-avidity binding to dimeric 14-3-3 protein zeta/delta (YWHAZ), with pS621 being the high-affinity interaction site. This interaction locks RAF proto-oncogene serine/threonine-protein kinase (RAF1) in an inhibited conformation.
LIG_14-3-3_1 P04049 618-623 SWTI000354 Phosphorylation of two 14-3-3-binding motifs in RAF proto-oncogene serine/threonine-protein kinase (RAF1) in response to growth factors induces high-avidity binding to dimeric 14-3-3 protein zeta/delta (YWHAZ), with pS621 being the high-affinity interaction site. This interaction locks RAF proto-oncogene serine/threonine-protein kinase (RAF1) in an inhibited conformation.
LIG_14-3-3_3 O43524 250-255 SWTI000355 Phosphorylation of two 14-3-3-binding motifs in Forkhead box protein O3 (FOXO3) by RAC-alpha serine/threonine-protein kinase (AKT1) induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (YWHAB). This interaction results in cytoplasmic retention and inactivation of Forkhead box protein O3 (FOXO3).
LIG_14-3-3_3 O43524 29-34 SWTI000355 Phosphorylation of two 14-3-3-binding motifs in Forkhead box protein O3 (FOXO3) by RAC-alpha serine/threonine-protein kinase (AKT1) induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (YWHAB). This interaction results in cytoplasmic retention and inactivation of Forkhead box protein O3 (FOXO3).
LIG_14-3-3_3 P26045 356-361 SWTI000356 Phosphorylation of two 14-3-3-binding motifs in Tyrosine-protein phosphatase non-receptor type 3 (PTPN3) induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (YWHAB).
LIG_14-3-3_3 P26045 832-837 SWTI000356 Phosphorylation of two 14-3-3-binding motifs in Tyrosine-protein phosphatase non-receptor type 3 (PTPN3) induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (YWHAB).
LIG_14-3-3_3 Q61097 294-299 SWTI000357 Phosphorylation of two 14-3-3-binding motifs in Kinase suppressor of Ras 1 (Ksr1) by Q03141 induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (Ywhab). This interaction prevents Kinase suppressor of Ras 1 (Ksr1) to localise to the membrane where it is involved in activation of MAP kinases by Q99N57 in response to growth factors.
LIG_14-3-3_3 Q61097 389-394 SWTI000357 Phosphorylation of two 14-3-3-binding motifs in Kinase suppressor of Ras 1 (Ksr1) by Q03141 induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (Ywhab). This interaction prevents Kinase suppressor of Ras 1 (Ksr1) to localise to the membrane where it is involved in activation of MAP kinases by Q99N57 in response to growth factors.
LIG_14-3-3_3 Q8IPH9 51-56 SWTI000358 Phosphorylation of two 14-3-3-binding motifs in Slowpoke-binding protein (Slob) by Calcium/calmodulin-dependent protein kinase type II alpha chain (CaMKII) induces high-avidity binding to dimeric 14-3-3 protein zeta (14-3-3zeta). This interaction recruits 14-3-3 protein zeta (14-3-3zeta) to Calcium-activated potassium channel slowpoke (slo) in the presynapse of neuromuscular junctions.
LIG_14-3-3_3 Q8IPH9 76-81 SWTI000358 Phosphorylation of two 14-3-3-binding motifs in Slowpoke-binding protein (Slob) by Calcium/calmodulin-dependent protein kinase type II alpha chain (CaMKII) induces high-avidity binding to dimeric 14-3-3 protein zeta (14-3-3zeta). This interaction recruits 14-3-3 protein zeta (14-3-3zeta) to Calcium-activated potassium channel slowpoke (slo) in the presynapse of neuromuscular junctions.
LIG_14-3-3_3 P35568 371-376 SWTI000359 Phosphorylation of two 14-3-3-binding motifs in Insulin receptor substrate 1 (IRS1) induces high-avidity binding to dimeric 14-3-3 protein epsilon (YWHAE).
LIG_14-3-3_3 P35568 638-643 SWTI000359 Phosphorylation of two 14-3-3-binding motifs in Insulin receptor substrate 1 (IRS1) induces high-avidity binding to dimeric 14-3-3 protein epsilon (YWHAE).
LIG_SH2_IC A9UF02 174-180 SWTI000360 Phosphorylation of Y177 in the SH2-binding motif of BCR/ABL fusion induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein.
LIG_SH2_IC O15530 376-379 SWTI000361 Phosphorylation of Y376 in the SH2-binding motif of 3-phosphoinositide-dependent protein kinase 1 (PDPK1) induces binding to the Tensin-1 (TNS1) protein.
LIG_SH2_IC O43561 198-203 SWTI000362 Phosphorylation of Y200 in the SH2-binding motif of Linker for activation of T-cells family member 1 (LAT) induces binding to the GRB2-related adaptor protein 2 (Grap2) protein.
LIG_SH2_IC O43561 218-223 SWTI000363 Phosphorylation of Y220 in the SH2-binding motif of Linker for activation of T-cells family member 1 (LAT) induces binding to the GRB2-related adaptor protein 2 (Grap2) protein.
LIG_SH2_GRB2 O54957 175-178 SWTI000364 Phosphorylation of Y175 in the SH2-binding motif of Linker for activation of T-cells family member 1 (Lat) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein.
LIG_SH2_GRB2 O54957 195-198 SWTI000365 Phosphorylation of Y195 in the SH2-binding motif of Linker for activation of T-cells family member 1 (Lat) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein.
LIG_SH2_GRB2 O54957 235-238 SWTI000366 Phosphorylation of Y235 in the SH2-binding motif of Linker for activation of T-cells family member 1 (Lat) induces binding to the Growth factor receptor-bound protein 2 (Grb2) protein.
LIG_SH2_IC O60496 402-405 SWTI000367 Phosphorylation of Y402 in the SH2-binding motif of Docking protein 2 (DOK2) induces binding to the Tensin-1 (TNS1) protein.
LIG_SH2_IIB O60674 804-823 SWTI000368 Phosphorylation of Y813 in the SH2-binding motif of Tyrosine-protein kinase JAK2 (JAK2) induces binding to the SH2B adapter protein 1 (SH2B1) protein.
LIG_SH2_IB O75553 211-230 SWTI000369 Phosphorylation of Y220 in the SH2-binding motif of Disabled homolog 1 (DAB1) induces binding to the Adapter molecule crk (CRK) protein.
LIG_SH2_IC P00533 1092-1100 SWTI000370 Phosphorylation of Y1092 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein.
LIG_SH2_IE P00533 1011-1020 SWTI000371 Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Ras and Rab interactor 1 (RIN1) protein.
LIG_SH2_IE P00533 1191-1200 SWTI000372 Phosphorylation of Y1197 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Ras and Rab interactor 1 (RIN1) protein.
LIG_SH2_IE P00533 1008-1024 SWTI000373 Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Tyrosine-protein kinase JAK1 (JAK1) protein.
LIG_SH2_IE P00533 1008-1024 SWTI000374 Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Tyrosine-protein kinase JAK2 (JAK2) protein.
LIG_SH2_ID P00533 1008-1024 SWTI000375 Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the SH2 domain-containing protein 3C (SH2D3C) protein.
LIG_SH2_ID P00533 1008-1024 SWTI000376 Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the SH2 domain-containing protein 3A (SH2D3A) protein.
LIG_SH2_III P00533 1008-1024 SWTI000377 Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Signal transducer and activator of transcription 6 (STAT6) protein.
LIG_SH2_IC P04626 1135-1144 SWTI000378 Phosphorylation of Y1139 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-2 (ERBB2) induces binding to the Growth factor receptor-bound protein 7 (GRB7) protein.
LIG_SH2_IE P04626 1015-1031 SWTI000379 Phosphorylation of Y1023 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-2 (ERBB2) induces binding to the Tyrosine-protein kinase JAK1 (JAK1) protein.
LIG_SH2_IE P04626 1015-1031 SWTI000380 Phosphorylation of Y1023 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-2 (ERBB2) induces binding to the Tyrosine-protein kinase JAK2 (JAK2) protein.
LIG_SH2_ID P04626 1131-1147 SWTI000381 Phosphorylation of Y1139 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-2 (ERBB2) induces binding to the Breast cancer anti-estrogen resistance protein 3 (BCAR3) protein.
LIG_SH2_ID P04626 1015-1031 SWTI000382 Phosphorylation of Y1023 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-2 (ERBB2) induces binding to the SH2 domain-containing protein 3A (SH2D3A) protein.
LIG_SH2_III P04626 1131-1147 SWTI000383 Phosphorylation of Y1139 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-2 (ERBB2) induces binding to the Signal transducer and activator of transcription 6 (STAT6) protein.
LIG_SH2_IIB P04629 782-796 SWTI000384 Phosphorylation of Y791 in the SH2-binding motif of High affinity nerve growth factor receptor (NTRK1) induces binding to the SHC-transforming protein 1 (SHC1) protein.
LIG_SH2_IB P04629 783-796 SWTI000385 Phosphorylation of Y791 in the SH2-binding motif of High affinity nerve growth factor receptor (NTRK1) induces binding to the Megakaryocyte-associated tyrosine-protein kinase (MATK) protein.
LIG_SH2_IIB P07949 976-985 SWTI000386 Phosphorylation of Y981 in the SH2-binding motif of Proto-oncogene tyrosine-protein kinase receptor Ret (RET) induces binding to the SH2B adapter protein 1 (SH2B1) protein.
LIG_SH2_IC P08581 1351-1360 SWTI000387 Phosphorylation of Y1356 in the SH2-binding motif of Hepatocyte growth factor receptor (MET) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein.
LIG_SH2_IIA P09619 751-755 SWTI000388 Phosphorylation of Y751 in the SH2-binding motif of Platelet-derived growth factor receptor beta (PDGFRB) induces binding to the Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1) protein.
LIG_SH2_IIA P09619 1018-1029 SWTI000389 Phosphorylation of Y1021 in the SH2-binding motif of Platelet-derived growth factor receptor beta (PDGFRB) induces binding to the 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1) protein.
LIG_SH2_IIA P10912 591-600 SWTI000390 Phosphorylation of Y595 in the SH2-binding motif of Growth hormone receptor (GHR) induces binding to the Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) protein.
LIG_SH2_III P10912 428-444 SWTI000391 Phosphorylation of Y436 in the SH2-binding motif of Growth hormone receptor (GHR) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein.
LIG_SH2_IA P14784 409-428 SWTI000392 Phosphorylation of Y418 in the SH2-binding motif of Interleukin-2 receptor subunit beta (IL2RB) induces binding to the Tyrosine-protein kinase Lck (LCK) protein.
LIG_SH2_III P14784 531-540 SWTI000393 Phosphorylation of Y536 in the SH2-binding motif of Interleukin-2 receptor subunit beta (IL2RB) induces binding to the Signal transducer and activator of transcription 5A (STAT5A) protein.
LIG_SH2_IIB P14784 361-370 SWTI000394 Phosphorylation of Y364 in the SH2-binding motif of Interleukin-2 receptor subunit beta (IL2RB) induces binding to the SHC-transforming protein 1 (SHC1) protein.
LIG_SH2_III P14784 528-544 SWTI000395 Phosphorylation of Y536 in the SH2-binding motif of Interleukin-2 receptor subunit beta (IL2RB) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein.
LIG_SH2_III P15260 457-461 SWTI000396 Phosphorylation of Y457 in the SH2-binding motif of Interferon gamma receptor 1 (IFNGR1) induces binding to the Signal transducer and activator of transcription 1-alpha/beta (STAT1) protein.
LIG_SH2_IIB P15498 165-180 SWTI000397 Phosphorylation of Y174 in the SH2-binding motif of Proto-oncogene vav (VAV1) induces binding to the SH2 domain-containing adapter protein B (SHB) protein.
LIG_SH2_IIB P16234 705-729 SWTI000398 Phosphorylation of Y720 in the SH2-binding motif of Platelet-derived growth factor receptor alpha (PDGFRA) induces binding to the SH2 domain-containing adapter protein F (SHF) protein.
LIG_SH2_IE P17181 458-474 SWTI000399 Phosphorylation of Y466 in the SH2-binding motif of Interferon alpha/beta receptor 1 (IFNAR1) induces binding to the Non-receptor tyrosine-protein kinase TYK2 (TYK2) protein.
LIG_SH2_IE P17181 473-489 SWTI000400 Phosphorylation of Y481 in the SH2-binding motif of Interferon alpha/beta receptor 1 (IFNAR1) induces binding to the Non-receptor tyrosine-protein kinase TYK2 (TYK2) protein.
LIG_SH2_III P19235 360-376 SWTI000401 Phosphorylation of Y368 in the SH2-binding motif of Erythropoietin receptor (EPOR) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein.
LIG_SH2_III P19235 418-434 SWTI000402 Phosphorylation of Y426 in the SH2-binding motif of Erythropoietin receptor (EPOR) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein.
LIG_SH2_III P19235 496-508 SWTI000403 Phosphorylation of Y504 in the SH2-binding motif of Erythropoietin receptor (EPOR) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein.
LIG_SH2_ID P21860 860-876 SWTI000404 Phosphorylation of Y868 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Breast cancer anti-estrogen resistance protein 3 (BCAR3) protein.
LIG_SH2_ID P21860 1268-1284 SWTI000405 Phosphorylation of Y1276 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Breast cancer anti-estrogen resistance protein 3 (BCAR3) protein.
LIG_SH2_ID P21860 1281-1297 SWTI000406 Phosphorylation of Y1289 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Breast cancer anti-estrogen resistance protein 3 (BCAR3) protein.
LIG_SH2_ID P21860 1320-1336 SWTI000407 Phosphorylation of Y1328 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Breast cancer anti-estrogen resistance protein 3 (BCAR3) protein.
LIG_SH2_ID P21860 1320-1336 SWTI000408 Phosphorylation of Y1328 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the SH2 domain-containing protein 3A (SH2D3A) protein.
LIG_SH2_III P21860 1320-1336 SWTI000409 Phosphorylation of Y1328 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Signal transducer and activator of transcription 6 (STAT6) protein.
LIG_SH2_IB P22681 770-780 SWTI000410 Phosphorylation of Y774 in the SH2-binding motif of E3 ubiquitin-protein ligase CBL (CBL) induces binding to the Adapter molecule crk (CRK) protein.
LIG_SH2_III P24394 566-585 SWTI000411 Phosphorylation of Y575 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Signal transducer and activator of transcription 6 (STAT6) protein.
LIG_SH2_III P24394 594-613 SWTI000412 Phosphorylation of Y603 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Signal transducer and activator of transcription 6 (STAT6) protein.
LIG_SH2_III P24394 622-641 SWTI000413 Phosphorylation of Y631 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Signal transducer and activator of transcription 6 (STAT6) protein.
LIG_SH2_IIA P24394 706-721 SWTI000414 Phosphorylation of Y713 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) protein.
LIG_SH2_IIB P24394 706-721 SWTI000415 Phosphorylation of Y713 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the SHC-transforming protein 1 (SHC1) protein.
LIG_SH2_IIB P24394 706-721 SWTI000416 Phosphorylation of Y713 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 (INPP5D) protein.
LIG_SH2_IA P29320 597-606 SWTI000417 Phosphorylation of Y602 in the SH2-binding motif of Ephrin type-A receptor 3 (EPHA3) induces binding to the Cytoplasmic protein NCK1 (NCK1) protein.
LIG_SH2_IC P29353 423-435 SWTI000418 Phosphorylation of Y427 in the SH2-binding motif of SHC-transforming protein 1 (SHC1) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein.
LIG_SH2_IA P30273 75-79 SWTI000419 Phosphorylation of Y76 in the SH2-binding motif of High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) induces binding to the Tyrosine-protein kinase SYK (SYK) protein.
LIG_SH2_IC Q8WU20 191-200 SWTI000420 Phosphorylation of Y196 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein.
LIG_SH2_IC Q8WU20 301-310 SWTI000421 Phosphorylation of Y306 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein.
LIG_SH2_IC Q8WU20 345-355 SWTI000422 Phosphorylation of Y349 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein.
LIG_SH2_IC Q8WU20 385-395 SWTI000423 Phosphorylation of Y392 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Growth factor receptor-bound protein 2 (GRB2) protein.
LIG_SH2_IIA Q8WU20 431-440 SWTI000424 Phosphorylation of Y436 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) protein.
LIG_SH2_IIA Q8WU20 465-475 SWTI000425 Phosphorylation of Y471 in the SH2-binding motif of Fibroblast growth factor receptor substrate 2 (FRS2) induces binding to the Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) protein.
LIG_SH2_IIB Q92918 372-391 SWTI000426 Phosphorylation of Y381 in the SH2-binding motif of Mitogen-activated protein kinase kinase kinase kinase 1 (MAP4K1) induces binding to the B-cell linker protein (BLNK) protein.
LIG_SH2_IIA Q99062 747-758 SWTI000427 Phosphorylation of Y752 in the SH2-binding motif of Granulocyte colony-stimulating factor receptor (CSF3R) induces binding to the Suppressor of cytokine signaling 3 (SOCS3) protein.
LIG_SH2_IIB Q99704 203-206 SWTI000428 Phosphorylation of Y203 in the SH2-binding motif of Docking protein 1 (DOK1) induces binding to the Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 (INPP5D) protein.
LIG_SH2_IB Q99704 447-454 SWTI000429 Phosphorylation of Y449 in the SH2-binding motif of Docking protein 1 (DOK1) induces binding to the SH2 domain-containing protein 1A (SH2D1A) protein.
LIG_SH2_IA Q05397 389-405 SWTI000430 Phosphorylation of Y397 in the SH2-binding motif of Focal adhesion kinase 1 (PTK2) induces binding to the Cytoplasmic protein NCK2 (NCK2) protein.
LIG_SH2_IIB Q13094 105-118 SWTI000431 Phosphorylation of Y113 in the SH2-binding motif of Lymphocyte cytosolic protein 2 (LCP2) induces binding to the SH2 domain-containing adapter protein B (SHB) protein.
LIG_SH2_IIB Q13094 120-133 SWTI000432 Phosphorylation of Y128 in the SH2-binding motif of Lymphocyte cytosolic protein 2 (LCP2) induces binding to the SH2 domain-containing adapter protein B (SHB) protein.
LIG_SH2_IIB Q13094 137-150 SWTI000433 Phosphorylation of Y145 in the SH2-binding motif of Lymphocyte cytosolic protein 2 (LCP2) induces binding to the SH2 domain-containing adapter protein B (SHB) protein.
LIG_SH2_IB Q13291 276-286 SWTI000434 Phosphorylation of Y281 in the SH2-binding motif of Signaling lymphocytic activation molecule (SLAMF1) induces binding to the SH2 domain-containing protein 1A (SH2D1A) protein.
LIG_SH2_IB Q13291 273-286 SWTI000435 Phosphorylation of Y281 in the SH2-binding motif of Signaling lymphocytic activation molecule (SLAMF1) induces binding to the SH2 domain-containing protein 1B (Sh2d1b) protein.
LIG_SH2_IB Q14289 394-410 SWTI000436 Phosphorylation of Y402 in the SH2-binding motif of Protein-tyrosine kinase 2-beta (PTK2B) induces binding to the Megakaryocyte-associated tyrosine-protein kinase (MATK) protein.
LIG_SH2_IA Q16620 714-730 SWTI000437 Phosphorylation of Y727 in the SH2-binding motif of BDNF/NT-3 growth factors receptor (NTRK2) induces binding to the Cytoplasmic protein NCK2 (NCK2) protein.
LIG_SH2_IA Q60787 143-148 SWTI000438 Phosphorylation of Y145 in the SH2-binding motif of Lymphocyte cytosolic protein 2 (Lcp2) induces binding to the Tyrosine-protein kinase ITK/TSK (Itk) protein.
LIG_SH2_III Q62120 804-820 SWTI000439 Phosphorylation of Y813 in the SH2-binding motif of Tyrosine-protein kinase JAK2 (Jak2) induces binding to the Signal transducer and activator of transcription 5B (Stat5b) protein.
LIG_SH2_IB P56945 358-368 SWTI000440 Phosphorylation of Y362 in the SH2-binding motif of Breast cancer anti-estrogen resistance protein 1 (BCAR1) induces binding to the Adapter molecule crk (CRK) protein.
LIG_SH2_IA P63245 241-250 SWTI000441 Phosphorylation of Y246 in the SH2-binding motif of Guanine nucleotide-binding protein subunit beta-2-like 1 (Gnb2l1) induces binding to the Proto-oncogene tyrosine-protein kinase Src (SRC) protein.
LIG_SH2_IA P81605 15-25 SWTI000442 Phosphorylation of Y20 in the SH2-binding motif of Dermcidin (DCD) induces binding to the Cytoplasmic protein NCK1 (NCK1) protein.
LIG_SH2_IA P97318 212-228 SWTI000443 Phosphorylation of Y220 in the SH2-binding motif of Disabled homolog 1 (Dab1) induces binding to the Cytoplasmic protein NCK2 (NCK2) protein.
LIG_SH2_IIA Q00560 750-764 SWTI000444 Phosphorylation of Y757 in the SH2-binding motif of Interleukin-6 receptor subunit beta (Il6st) induces binding to the Suppressor of cytokine signaling 3 (Socs3) protein.
LIG_SH2_III P42229 686-702 SWTI000445 Phosphorylation of Y694 in the SH2-binding motif of Signal transducer and activator of transcription 5A (STAT5A) induces binding to the Signal transducer and activator of transcription 5B (STAT5B) protein.
LIG_SH2_IIC P43403 284-300 SWTI000446 Phosphorylation of Y292 in the SH2-binding motif of Tyrosine-protein kinase ZAP-70 (ZAP70) induces binding to the E3 ubiquitin-protein ligase CBL-B (CBLB) protein.
LIG_SH2_IIC P43405 315-331 SWTI000447 Phosphorylation of Y323 in the SH2-binding motif of Tyrosine-protein kinase SYK (SYK) induces binding to the E3 ubiquitin-protein ligase CBL-B (CBLB) protein.
LIG_SH2_IB P54763 601-610 SWTI000448 Phosphorylation of Y604 in the SH2-binding motif of Ephrin type-B receptor 2 (Ephb2) induces binding to the Adapter molecule crk (CRK) protein.
LIG_SH2_IB P54763 606-620 SWTI000449 Phosphorylation of Y610 in the SH2-binding motif of Ephrin type-B receptor 2 (Ephb2) induces binding to the Adapter molecule crk (CRK) protein.
LIG_SH2_III P48356 1129-1148 SWTI000450 Phosphorylation of Y1138 in the SH2-binding motif of Leptin receptor (Lepr) induces binding to the Signal transducer and activator of transcription 3 (STAT3) protein.
LIG_SH2_IE P21860 1320-1336 SWTI000451 Phosphorylation of Y1328 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Tyrosine-protein kinase JAK1 (JAK1) protein.
LIG_SH2_IE P21860 1320-1336 SWTI000452 Phosphorylation of Y1328 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Tyrosine-protein kinase JAK2 (JAK2) protein.
LIG_SH2_IE P21860 1268-1284 SWTI000453 Phosphorylation of Y1276 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Tyrosine-protein kinase JAK2 (JAK2) protein.
LIG_SH2_IE P21860 1268-1284 SWTI000454 Phosphorylation of Y1276 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the Tyrosine-protein kinase JAK3 (JAK3) protein.
LIG_SH2_IIA P24394 706-721 SWTI000455 Phosphorylation of Y713 in the SH2-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Tyrosine-protein phosphatase non-receptor type 6 (PTPN6) protein.
DEG_MDM2_1 P04637 19-26 SWTI000456 Phosphorylation of Cellular tumor antigen p53 (TP53) on T18 (in vitro by Casein kinase I subfamily, requiring prior phosphorylation of S15) inhibits its binding to E3 ubiquitin-protein ligase Mdm2 (MDM2). In vivo, T18 is phosphorylated in response to DNA damage.
LIG_TAZ2 P04637 19-25 SWTI000457 Multisite phosphorylation of S15 and T18 and S20 and S33 and S37 and S46 in the TAD region of Cellular tumor antigen p53 (TP53) additively enhances its affinity for CREB-binding protein (CREBBP).
LIG_SUMO_SBM_1 Q9UER7 733-740 SWTI000458 Multisite phosphorylation of S737 and S739 in the SUMO-binding motif of Death domain-associated protein 6 (DAXX) by CK2 subfamily and CK2 subfamily increases the strength of the interaction with Small ubiquitin-related modifier 1 (SUMO1).
LIG_14-3-3_1 P08965 435-440 SWTI000459 Phosphorylation of two 14-3-3-binding motifs in Meiosis protein mei2 (mei2) by Negative regulator of sexual conjugation and meiosis (ran1) induces high-avidity binding to dimeric DNA damage checkpoint protein rad24 (rad24), with pT527 being the high-affinity interaction site.
LIG_14-3-3_2 P08965 523-529 SWTI000459 Phosphorylation of two 14-3-3-binding motifs in Meiosis protein mei2 (mei2) by Negative regulator of sexual conjugation and meiosis (ran1) induces high-avidity binding to dimeric DNA damage checkpoint protein rad24 (rad24), with pT527 being the high-affinity interaction site.
LIG_FHA_2 Q9BYG3 238-244 SWTI000460 Phosphorylation of T238 in MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP) by Cyclin-dependent kinase 1 (CDK1) primes for phosphorylation of T234 by Glycogen synthase kinase-3 beta (GSK3B), which primes for phosphorylation of S230 by Glycogen synthase kinase-3 beta (GSK3B). Triple-phosphorylated hNIFK (MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP)) binds strongly to Antigen KI-67 (MKI67). See also switch details
TRG_ENDOCYTIC_2 P32004 1176-1179 SWTI000461 Phosphorylation of Y1176 by Proto-oncogene tyrosine-protein kinase Src (SRC) in the endocytosis motif of Neural cell adhesion molecule L1 (L1CAM) inhibits binding to AP-2 complex subunit mu (AP2M1).
LIG_Dynein_DLC8_1 O43521-2 50-56 SWTI000462 Phosphorylation of T56 by Mitogen-activated protein kinase 8 (MAPK8) in the Dynein-binding motif of Isoform Bim(L) of Bcl-2-like protein 11 (BCL2L11) inhibits binding to Dynein light chain 1, cytoplasmic (DYNLL1). Most Bim in healthy cells is sequestered away bound to light chain dynein molecules. Cells exposed to environmental stress up-regulate c-Jun NH(2)-terminal kinase (JNK) that phosphorylates both Bim and Bmf, releasing them from motor complexes and promoting apoptosis.
LIG_WW_1 Q4VCS5 239-242 SWTI000463 Alternative splicing removes the WW-binding motif of Angiomotin (AMOT), abrogating binding to Yorkie homolog (YAP1). The splice specific Isoform p130 of AMOT works within the Hippo pathway to sequester the transcription coactivator YAP1 away at tight junction. In contrast Isoform p80 of AMOT lacks WW-binding motif.
LIG_WW_1 Q4VCS5 239-242 SWTI000464 Alternative splicing removes the WW-binding motif of Angiomotin (AMOT), abrogating binding to WW domain-containing transcription regulator protein 1 (WWTR1). The splice specific Isoform p130 of AMOT works within the Hippo pathway to sequester the transcription coactivator YAP1 away at tight junction. In contrast Isoform p80 of AMOT lacks WW-binding motif.
LIG_PDZ_Class_1 Q9P0K1 901-906 SWTI000466 Alternative splicing removes the PDZ-binding motif of Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22), abrogating binding to Disks large homolog 4 (DLG4). The motif-containing Isoform Epsilon of Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) forms part of a complex containing Leucine-rich glioma-inactivated protein 1 (LGI1), AMPA-R (e.g. Glutamate receptor 1 (GRIA1)) and AMPA-R regulatory proteins (e.g. Voltage-dependent calcium channel gamma-2 subunit (CACNG2)), and is closely associated with epilepsy.
DEG_APCC_KENbox_2 P30305 191-195 SWTI000467 Alternative splicing removes the APC/C KEN-box degron motif of M-phase inducer phosphatase 2 (CDC25B), abrogating binding to Fizzy-related protein homolog (FZR1). The motif-lacking Isoform CDC25B2 is not degraded during mitosis, unlike other isoforms.
DOC_PP1 P51955 380-387 SWTI000468 Alternative splicing removes the PP1-docking motif of Serine/threonine-protein kinase Nek2 (NEK2), abrogating binding to Serine/threonine-protein phosphatase PP1-gamma catalytic subunit (PPP1CC). Isoform Nek2A is localised at centrosomes and causes centrosome splitting. Isoform Nek2B is expressed at a different point in the cell cycle and is required for assembly/maintenance of centrosomes.
DOC_PP1 P51955 380-387 SWTI000469 Alternative splicing removes the PP1-docking motif of Serine/threonine-protein kinase Nek2 (NEK2), abrogating binding to Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PPP1CA). Isoform Nek2A is localised at centrosomes and causes centrosome splitting. Isoform Nek2B is expressed at a different point in the cell cycle and required for assembly/maintenance of centrosomes.
DEG_APCC_Dbox_3 P51955 423-445 SWTI000470 Alternative splicing removes the extended D-box degron motif of Serine/threonine-protein kinase Nek2 (NEK2), abrogating binding to Cell division cycle protein 20 homolog (CDC20). NEK2-A is targeted by APC/C-Cdc20 in early mitosis whereas Isoform Nek2B persists into late mitosis. Degradation of Isoform Nek2A may be necessary to allow re-establishment of the intercentriolar linkage in late mitosis.
LIG_SCF-TrCP1_2 O43521 93-98 SWTI000471 Alternative splicing removes the extended SCF-TrCP degron motif of Bcl-2-like protein 11 (BCL2L11), abrogating binding to F-box/WD repeat-containing protein 1A (BTRC). Upon mitogen survival signals, RPS6KA1 and RPS6KA2 kinases are up-regulated and rapidly phosphorylate the three serines of Isoform Bim(EL). This facilitates the binding of betaTrCP and subsequent ubiquitination and degradation of Isoform Bim(EL).
TRG_MLS P43155 1-21 SWTI000472 Alternative splicing removes the mitochondrial localisation signal (MLS) motif of Carnitine O-acetyltransferase (CRAT), abrogating binding to Mitochondrial import receptor subunit TOM70 (TOMM70A). As a result, Isoform SM-1200 of Carnitine O-acetyltransferase (CRAT), which lacks the MLS, is located in peroxisomes due to a PTS1 motif in its C-terminus.
LIG_Talin P05556-5 775-785 SWTI000473 Alternative splicing alters the flanking regions of the PTB-binding motif of Isoform Beta-1D of Integrin beta-1 (ITGB1), inducing higher affinity binding to Talin-1 (TLN1). Alteration of residue 788 from G to Q and alteration of residue 786 from A to P increases the binding affinity from 491 micromolar in the canonical Isoform Beta-1A to 95 micromolar in Isoform Beta-1D.
LIG_Talin P05556-5 775-785 SWTI000474 Alternative splicing alters the flanking regions of the PTB-binding motif of Isoform Beta-1D of Integrin beta-1 (ITGB1), inducing higher affinity binding to Talin-2 (TLN2). The alteration of residue 788 from G to Q and alteration of residue 786 from A to P increases the binding affinity from 652 micromolar in the canonical Isoform Beta-1A to 36 micromolar in Isoform Beta-1D.
LIG_Filamin_2 P05556 783-791 SWTI000475 Alternative splicing strongly inhibits the binding of the filamin-binding motif of Integrin beta-1 (ITGB1) to Filamin-A (FLNA), primarily due to the alteration of A to P it seems.
LIG_Filamin_2 P05556 783-791 SWTI000476 Alternative splicing strongly inhibits the binding of the filamin-binding motif of Integrin beta-1 (ITGB1) to Filamin-B (FLNB), primarily due to the alteration of A to P it seems. Splicing of FLNB also affects this interaction.
LIG_Clathr_ClatBox_1 O00499 390-394 SWTI000477 Alternative splicing removes the Clathrin I-binding motif of Myc box-dependent-interacting protein 1 (BIN1), abrogating binding to Clathrin heavy chain 1 (CLTC).
LIG_Clathr_ClatBox_2 O00499 415-420 SWTI000478 Alternative splicing removes the Clathrin II-binding motif of Myc box-dependent-interacting protein 1 (BIN1), abrogating binding to Clathrin heavy chain 1 (CLTC).
LIG_SH3_8 O00499-8 265-268 SWTI000479 Alternative splicing removes the SH3-binding motif of Isoform BIN1 of Myc box-dependent-interacting protein 1 (BIN1), abrogating binding to the SH3 domain of Isoform BIN1 of Myc box-dependent-interacting protein 1 (BIN1). Splice-specific motifs in Isoform BIN1 of Myc box-dependent-interacting protein 1 (BIN1) engage in an intra-molecular interaction with its own SH3 domain. Auto-inhibition is relieved at the plasma membrane when an overlapping lipid-binding motif outcompetes the SH3-binding motif. This means that the SH3 domain is only available for inter-molecular interactions at the plasma membrane.
LIG_PI(4,5)P2 O00499-8 258-266 SWTI000480 Alternative splicing removes the PI(4,5)P2-binding motif of Isoform BIN1 of Myc box-dependent-interacting protein 1 (BIN1), abrogating binding to 18348" target="_blank">1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate. Splice-specific motifs in Isoform BIN1 of Myc box-dependent-interacting protein 1 (BIN1) engage in an intra-molecular interaction with its own SH3 domain. Auto-inhibition is relieved at the plasma membrane when an overlapping lipid-binding motif outcompetes the SH3-binding motif. This means that the SH3 domain is only available for inter-molecular interactions at the plasma membrane.
LIG_NRBOX Q16881 144-150 SWTI000481 Alternative splicing removes the NRBOX motif of Thioredoxin reductase 1, cytoplasmic (TXNRD1), abrogating binding to Estrogen receptor (ESR1). Unlike splice variants without the NRBOX motif, TrxR1b (also known as Isoform TXNRD1_v2) is identified within the nucleus. TrxR1b enhanced the transcriptional activity of the estrogen receptors ESR1 and ESR2, possibly by providing a reduced environment in the immediate vicinity of the ERs.
LIG_NRBOX Q16881 144-150 SWTI000482 Alternative splicing removes the NRBOX motif of Thioredoxin reductase 1, cytoplasmic (TXNRD1), abrogating binding to Estrogen receptor beta (ESR2). Unlike splice variants without the NRBOX motif, TrxR1b (also known as Isoform TXNRD1_v2) is identified within the nucleus. TrxR1b enhanced the transcriptional activity of the estrogen receptors ESR1 and ESR2, possibly by providing a reduced environment in the immediate vicinity of the ERs.
LIG_PDZ_Class_1 Q01814 1238-1243 SWTI000483 Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 2 (ATP2B2), abrogating binding to Na(+)/H(+) exchange regulatory cofactor NHE-RF2 (SLC9A3R2), altering the location of this Ca2+ pump. Despite the similarity in C-terminal between the \'b\' splice variants of Plasma membrane calcium-transporting ATPase 4 (ATP2B4) (-ETSV) and Plasma membrane calcium-transporting ATPase 2 (ATP2B2) (-ETSL), \'b\' splice variants of ATP2B4 did not interact with either of the NHERFs whereas PMCA2b selectively preferred Na(+)/H(+) exchange regulatory cofactor NHE-RF2 (SLC9A3R2) over Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (SLC9A3R1). NHERFs have been previously implicated in the targeting, retention and regulation of membrane proteins including the \xce\xb22-adrenergic receptor, cystic fibrosis transmembrane conductance regulator, and Trp4 Ca2+channel. This study suggests Plasma membrane calcium-transporting ATPase 2 (ATP2B2) may be under similar regulation.
LIG_PDZ_Class_1 P23634 1236-1241 SWTI000484 Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 4 (ATP2B4), abrogating binding to Nitric oxide synthase, brain (NOS1). PMCA4b acts as a negative regulator of Nitric oxide synthase, brain (NOS1), reducing production of nitric oxide in heart tissue. This negative regulation was not dependent on a conformational change due to binding of the PDZ ligand, but on Ca2+ depletion in close proximity of the enzyme. Nitric oxide production by NOS1 is known to be important in the regulation of excitation-contraction (EC) coupling and subsequently contractility.
LIG_PDZ_Class_1 P23634 1236-1241 SWTI000485 Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 4 (ATP2B4), abrogating binding to Disks large homolog 3 (DLG3). Disks large homolog 3 (DLG3) did not bind to \'b\' isoform of PMCA2. There is therefore an interaction selectivity between \'b\' isoforms of ATP2B4 and DLG3 as opposed to the promiscuity of \'b\' isoforms of ATP2B2 and ATP2B4 in interacting with other SAPs. Same study DLG4, DLG2 and DLG1 shown to bind to PDZ-binding motifs in \'b\' isoforms of ATP2B4 and ATP2B2.
LIG_PDZ_Class_1 P23634 1236-1241 SWTI000486 Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 4 (ATP2B4), abrogating binding to Disks large homolog 1 (DLG1). A much lower affinity was recorded for the third PDZ domain of DLG1 (in in the micromolar range (KD = 1.2 microM) compared to nanomolar affinity (KD = 1.6 nM)). PMCA4b and DLG1 are co-expressed in kidney and intestinal epithelial cells as well as in several areas of the brain. Should be noted that the \'b\' isoforms of Plasma membrane calcium-transporting ATPase 2 (ATP2B2) bind much more weakly to all PDZ domains of DLG1
LIG_PDZ_Class_1 P23634 1236-1241 SWTI000487 Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 4 (ATP2B4), abrogating binding to Peripheral plasma membrane protein CASK (CASK). The PDZ domain-containing protein CASK and PMCA4b co-precipitate in kidney and brain. Similar to NOS1, binding to PMCA4b allows Ca2+ dependent regulation. Depletion of local Ca2+ by PMCA4b in close proximity to CASK may inhibit Ca2+/calmodulin binding. This can subsequently inhibit binding to T-box brain protein 1 (TBR1) and/or translocation of CASK or the CASK/TBR1 complex to the nucleus.
TRG_ENDOCYTIC_2 P32004 1176-1179 SWTI000488 Alternative splicing removes the endocytosis motif of Neural cell adhesion molecule L1 (L1CAM), abrogating binding to AP-2 complex subunit mu (AP2M1). This motif is required for sorting of L1CAM to the axonal growth cone of neurons and its clathrin-mediated internalisation. Non-neuronal cells, such as Schwann cells, do not require these motifs, probably because these cells are not highly polarised.
LIG_SH3_2 Q13444 767-772 SWTI000489 Alternative splicing removes the SH3-binding motif of Disintegrin and metalloproteinase domain-containing protein 15 (ADAM15), abrogating binding to Proto-oncogene tyrosine-protein kinase Src (SRC). The overexpression of this splice variant has been linked to clinical aggressiveness of breast cancer.
LIG_WW_1 Q15303 1053-1056 SWTI000490 Alternative splicing removes the WW-binding motif of Receptor tyrosine-protein kinase erbB-4 (ERBB4), abrogating binding to E3 ubiquitin-protein ligase Itchy homolog (ITCH). The presence of a WW-binding motif mediates ERBB4 mono-ubiquitination and endocytosis by the WW domain-containing HECT-type E3 ubiquitin ligase ITCH.
MOD_NMyristoyl O00408 1-7 SWTI000491 Alternative splicing removes the myristoylation motif of cGMP-dependent 3\',5\'-cyclic phosphodiesterase (PDE2A). The soluble Isoform PDE2A1 is expressed in a variety of peripheral tissues, whereas the membrane-associated Isoform PDE2A3 is found exclusively in the brain. Isoform PDE2A3 requires N-myristoylation together with palmitoylation to be targeted to synapses, allowing control and crosstalk of cyclic nucleotides.
MOD_PKA_2 Q01082-2 2157-2162 SWTI000492 Alternative splicing removes the PKA-binding motif of Isoform Short of Spectrin beta chain, brain 1 (SPTBN1), abrogating binding to cAMP-dependent protein kinase catalytic subunit alpha (PRKACA). The phosphorylation of the short C-terminal betaII-spectrin (also known as Isoform Short) by PKA is important in allowing neuritogenesis.
CLV_C14_Caspase3-7 Q05655 326-330 SWTI000493 Alternative splicing inserts exons within the Caspase-3 scission motif of Protein kinase C delta type (PRKCD), abrogating binding to Caspase-3 (CASP3). Cleavage of PKCdeltaI Protein kinase C delta type (PRKCD) by caspase-3 releases a catalytically active C-terminal fragment that is sufficient to induce apoptosis. This inserted exon disrupts scission motifs and therefore the PKCdeltaVIII (GENBANK:DQ516383) splice variant functions as an anti-apoptotic protein in NT2 cells.
LIG_Dynein_DLC8_1 O43521 110-116 SWTI000494 Alternative splicing removes the Dynein-binding motif of Bcl-2-like protein 11 (BCL2L11), abrogating binding to Dynein light chain 1, cytoplasmic (DYNLL1). Most BCL2L11 in healthy cells is sequestered away bound to DYNLL1 (the exception is Bim-S Isoform BCL2-like 11 transcript variant 9). Cells exposed to environmental stress up-regulate c-Jun NH(2)-terminal kinases (JNK) that phosphorylate both BCL2L11 and BMF, releasing them from motor complexes and promoting apoptosis.
TRG_NLS_MonoExtN_4 P13051 15-21 SWTI000495 Alternative splicing removes the nuclear localisation signal (NLS) of Uracil-DNA glycosylase (UNG), abrogating binding to Importin subunit alpha-1 (KPNA1) and import into the nucleus. In Isoform UNG1 of Uracil-DNA glycosylase (UNG) the NLS present in Isoform UNG2 of Uracil-DNA glycosylase (UNG) is replaced with a mitochondrial localisation signal (MLS), promoting different localisations of the different protein isoforms.
LIG_EVH1_2 P23385 1152-1156 SWTI000496 Alternative splicing removes the EVH1-binding motif of Metabotropic glutamate receptor 1 (Grm1), abrogating binding to Homer protein homolog 1 (Homer1), which is important for spatial targeting of Grm1.
LIG_PDZ_Class_1 P97288-2 382-387 SWTI000497 Alternative splicing removes the PDZ-binding motif of Isoform 5-HT4(A) of 5-hydroxytryptamine receptor 4 (Htr4), abrogating binding to Sorting nexin-27 (Snx27). Snx27 is responsible for targeting of the Isoform 5-HT4(A) to early endosomes.
LIG_PDZ_Class_1 P97288-2 382-387 SWTI000498 Alternative splicing removes the PDZ-binding motif of Isoform 5-HT4(A) of 5-hydroxytryptamine receptor 4 (Htr4), abrogating binding to Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (Slc9a3r1). Isoform 5-HT4(A) interacts specifically with a protein complex including Slc9a3r1 and Ezrin (Ezr) that might participate in its targeting to specialised subcellular regions, such as microvilli.
LIG_PDZ_Class_2 P97288-3 368-371 SWTI000499 Alternative splicing removes the PDZ-binding motif of Isoform 5-HT4(E) of 5-hydroxytryptamine receptor 4 (Htr4), abrogating binding to InaD-like protein (Inadl).
LIG_SH2_IIA Q15303 1056-1059 SWTI000500 Alternative splicing removes the SH2-binding motif of Receptor tyrosine-protein kinase erbB-4 (ERBB4), abrogating binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1). The SH2-binding motif overlaps with a WW-binding motif. Binding of these motifs is regulated in a phosphorylation-dependent manner, ensuring ERBB4 is either endocytosed or stabilised.
LIG_FAT_LD_1 P49023 4-12 SWTI000501 Alternative splicing removes the FAK-binding LD motif of Paxillin (PXN), abrogating binding to Focal adhesion kinase 1 (PTK2).
LIG_SH2_IB P49023 118-121 SWTI000502 Alternative splicing removes the SH2-binding motif of Paxillin (PXN), abrogating binding to Ras GTPase-activating protein 1 (RASA1).
LIG_SH2_IB P49023 118-121 SWTI000503 Alternative splicing removes the SH2-binding motif of Paxillin (PXN), abrogating binding to Adapter molecule crk (CRK).
LIG_SH2_IB P49023 31-34 SWTI000504 Alternative splicing removes the SH2-binding motif of Paxillin (PXN), abrogating binding to Adapter molecule crk (CRK).
LIG_EH_1 O43426 1393-1397 SWTI000505 Alternative splicing removes the EH-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to Epidermal growth factor receptor substrate 15 (EPS15). Isoform Synaptojanin-170 is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 is by far the major synaptojanin isoform. Isoform Synaptojanin-145 may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate transport.
LIG_EH_1 O43426 1403-1407 SWTI000506 Alternative splicing removes the EH-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to Epidermal growth factor receptor substrate 15 (EPS15). Isoform Synaptojanin-170 is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 is by far the major synaptojanin isoform. Isoform Synaptojanin-145 may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate receptor transport.
LIG_EH_1 O43426 1414-1418 SWTI000507 Alternative splicing removes the EH-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to Epidermal growth factor receptor substrate 15 (EPS15). Isoform Synaptojanin-170 is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 is by far the major synaptojanin isoform. Isoform Synaptojanin-145 may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate receptor transport.
LIG_AP2alpha_2 O43426 1323-1325 SWTI000508 Alternative splicing removes the AP2alpha-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to AP-2 complex subunit alpha-2 (AP2A2). Isoform Synaptojanin-170 is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 is by far the major synaptojanin isoform. Isoform Synaptojanin-145 may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate transport.
LIG_AP2alpha_2 O43426 1555-1557 SWTI000509 Alternative splicing removes the AP2alpha-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to AP-2 complex subunit alpha-2 (AP2A2). Isoform Synaptojanin-170 is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 is by far the major synaptojanin isoform. Isoform Synaptojanin-145 may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate transport.
LIG_14-3-3_3 Q8IPH9 76-81 SWTI000510 Alternative splicing removes the 14-3-3-binding motif of Slowpoke-binding protein (Slob), abrogating binding to 14-3-3 family. Another 14-3-3 motif exists in this protein (50-RSNS-54) that is not altered by Alternative splicing. The removal of this motif therefore decreases the avidity of the interaction with 14-3-3 proteins.
LIG_Actin_RPEL_3 Q8VIM5 20-39 SWTI000511 Alternative promoter usage removes the RPEL-binding motif of Myocardin (Myocd), abrogating binding to Actin, alpha skeletal muscle (Acta1). 3 RPEL motifs are found in Myocd. The shortened form lacks 2 RPEL motifs but no definitive comparison of binding to actin has been undertaken between isoforms.
LIG_Actin_RPEL_3 Q8VIM5 64-83 SWTI000512 Alternative promoter usage removes the RPEL-binding motif of Myocardin (Myocd), abrogating binding to Actin, alpha skeletal muscle (Acta1). 3 RPEL motifs are found in Myocd. The shortened form lacks 2 RPEL motifs but no definitive comparison of binding to actin has been undertaken between isoforms.
LIG_Actin_DMD P11532-5 5-10 SWTI000513 Alternative splicing removes the actin-binding motif of Isoform Dp71 of Dystrophin (DMD), abrogating binding to Actin, alpha skeletal muscle (ACTA1). The presence of the actin-binding motif in Isoform Dp71 of Dystrophin (DMD) may allow it to participate in the clustering of sodium channels by anchoring the syntrophin/channel complex to the actin cytoskeleton.
DOC_PP1 Q92667 151-158 SWTI000514 Alternative splicing removes the PP1-binding motif of A-kinase anchor protein 1, mitochondrial (AKAP1), abrogating binding to PP-1 subfamily. Isoform AKAP149 may conceivably position PKA and PP1 in close proximity where they can reversibly modulate the phosphorylation of nuclear substrates such as NPP1, DNA-binding cAMP response elements, B-type lamins and inner nuclear membrane proteins LBR and lamina-associated polypeptides, which all harbor PKA phosphorylation sites.
LIG_BIR_internal Q9NR28 56-59 SWTI000515 Alternative splicing removes the BIR-binding motif of Diablo homolog, mitochondrial (DIABLO), abrogating binding to Baculoviral IAP repeat-containing protein 4 (XIAP). Isoform SMAC3 is localised to mitochondria via its mitochondrial localisation signal (MLS). Upon entry in mitochondria the MLS is cleaved and Isoform SMAC3 is found localised with cytochrome-c. During apoptosis, Isoform SMAC3 binds to the second/third BIR domain of Baculoviral IAP repeat-containing protein 4 (XIAP). This interaction disrupts binding of XIAP to processed Caspase-9 (CASP9) and promotes Caspase-3 (CASP3) activation. Isoform SMAC3 also promotes ubiquitination of XIAP and subsequent degradation. Isoform 1 on the other hand did not cause degradation of XIAP.
TRG_MLS Q9NR28 1-55 SWTI000516 Alternative splicing removes the BIR-binding motif of Diablo homolog, mitochondrial (DIABLO), abrogating binding to Mitochondrial import receptor subunit TOM70 (TOMM70A). Isoform SMAC3 is localised to mitochondria via its mitochondrial localisation signal (MLS). Upon entry in mitochondria the MLS is cleaved and Isoform SMAC3 is found localised with cytochrome-c. During apoptosis, Isoform SMAC3 binds to the second/third BIR domain of Baculoviral IAP repeat-containing protein 4 (XIAP). This interaction disrupts binding of XIAP to processed Caspase-9 (CASP9) and promotes Caspase-3 (CASP3) activation. Isoform SMAC3 also promotes ubiquitination of XIAP and subsequent degradation. Isoform 1 on the other hand did not cause degradation of XIAP.
DEG_MDM2_1 P04637 19-26 SWTI000517 Alternative promoter usage and alternative splicing removes the E3 ubiquitin ligase MDM2-binding motif of Cellular tumor antigen p53 (TP53), abrogating binding to E3 ubiquitin-protein ligase Mdm2 (MDM2). The splice variant without this motif is resistant to MDM2-mediated degradation, leading to a longer half-life.
TRG_NES_CRM1_1 P04637 339-352 SWTI000518 Alternative splicing removes the nuclear export signal (NES) of Cellular tumor antigen p53 (TP53), abrogating binding to Exportin-1 (XPO1) and export from the nucleus.
DOC_USP7_1 P04637 359-363 SWTI000519 Alternative splicing removes the deubiquitinating enzyme USP7-binding motif of Cellular tumor antigen p53 (TP53), abrogating binding to Ubiquitin carboxyl-terminal hydrolase 7 (USP7).
DOC_USP7_1 P04637 364-368 SWTI000520 Alternative splicing removes the deubiquitinating enzyme USP7-binding motif of Cellular tumor antigen p53 (TP53), abrogating binding to Ubiquitin carboxyl-terminal hydrolase 7 (USP7).
LIG_PCNA_2 Q9UK53-2 9-15 SWTI000521 Alternative splicing removes the PCNA-binding motif of Isoform Variant A of Inhibitor of growth protein 1 (ING1), abrogating binding to Proliferating cell nuclear antigen (PCNA). P33-ING1b (also known as Isoform Variant A) binds specially to PCNA, resulting in a major change in subcellular localisation and the import of this isoform into the nucleus. This is theorised to act by limiting access to the PCNA-binding domain but eventually it promotes apoptosis (though this may not be its physiological effect).
TRG_ER_diLys_1 P78381 392-396 SWTI000522 Alternative splicing removes the di-lysine ER-retention motif of UDP-galactose translocator (SLC35A2), abrogating binding to Coatomer subunit alpha (COPA). This motif localises Isoform UGT1 exclusively in the Golgi whereas Isoform UGT2 shows dual expression in both the Golgi and the ER. This motif is considered a weak retention signal.
TRG_MLS P13051-2 1-44 SWTI000523 Alternative promoter usage removes the mitochondrial localisation signal (MLS) of Isoform UNG1 of Uracil-DNA glycosylase (UNG), abrogating binding to Mitochondrial import receptor subunit TOM70 (TOMM70A) and import into mitochondria. In Isoform UNG2 of Uracil-DNA glycosylase (UNG) the MLS present in Isoform UNG1 of Uracil-DNA glycosylase (UNG) is replaced with a nuclear localisation signal (NLS), promoting different localisations of the different protein isoforms.
LIG_IQ_2 P20020-3 1114-1128 SWTI000524 Alternative splicing partially removes the IQ motif of Isoform CI of Plasma membrane calcium-transporting ATPase 1 (ATP2B1), partially inhibiting binding to Calmodulin (CALM1).
LIG_WW_1 P84022 181-184 SWTI000525 CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of the E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. Dual phosphorylation of the two NEDD4L-binding sites mediates high-avidity binding of two WW domains of NEDD4L to SMAD3. See also switch details and switch details.
LIG_WW_Nedd4L P84022 203-210 SWTI000525 CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of the E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. Dual phosphorylation of the two NEDD4L-binding sites mediates high-avidity binding of two WW domains of NEDD4L to SMAD3. See also switch details and switch details.
LIG_WW_Nedd4L P84022 203-210 SWTI000526 CDK8/9 phosphorylates Mothers against decapentaplegic homolog 3 (SMAD3) at T179 and S208. Phosphorylation of T179 creates a binding site for the WW domain of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), while phosphorylation of S208 primes SMAD3 for phosphorylation of S204 by Glycogen synthase kinase-3 beta (GSK3B). The pS204-pS208 forms a binding site for the third WW domain of the E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), whose second WW domain will displace the WW domain of PIN1 at the pT179-PY box site of SMAD3. This regulation couples SMAD3 activation to SMAD3 destruction in an ordered fashion. Phosphorylation of S208 in SMAD3 induces binding of the third WW domain of NEDD4L, while additional phosphorylation of S204 in SMAD3 further increases the affinity of this interaction. See also switch details and switch details.
LIG_BIR_III_2 P55211 315-319 SWTI000527 Binding of the BIR domain-binding motif of Caspase-9 (CASP9) to the BIR domains of Baculoviral IAP repeat-containing protein 4 (XIAP) requires cleavage of Caspase-9 (CASP9) at D315, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification.
LIG_BIR_III_2 P55211 315-319 SWTI000528 Binding of the BIR domain-binding motif of Caspase-9 (CASP9) to the BIR domains of Baculoviral IAP repeat-containing protein 2 (BIRC2) requires cleavage of Caspase-9 (CASP9) at D315, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification.
LIG_BIR_III_2 P55210 23-27 SWTI000529 Binding of the BIR domain-binding motif of Caspase-7 (CASP7) to the BIR domains of Baculoviral IAP repeat-containing protein 2 (BIRC2) requires cleavage of Caspase-7 (CASP7) at D23, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification.
LIG_BIR_III_4 O02002 33-37 SWTI000530 Binding of the BIR domain-binding motif of Caspase-1 (Dcp-1) to the BIR domains of Apoptosis 1 inhibitor (th) requires cleavage of Caspase-1 (Dcp-1) at D33, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification.
LIG_BIR_III_4 O01382 28-32 SWTI000531 Binding of the BIR domain-binding motif of Caspase (Ice) to the BIR domains of Apoptosis 1 inhibitor (th) requires cleavage of Caspase (Ice) at D28, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification.
LIG_PDZ_Class_1 P48542 420-425 SWTI000532 Alternative splicing removes the PDZ-binding motif of G protein-activated inward rectifier potassium channel 2 (Kcnj6), abrogating binding to Sorting nexin-27 (Snx27).
TRG_NLS_MonoCore_2 P15791-3 327-332 SWTI000533 Alternative splicing removes the nuclear localisation signal (NLS) of Isoform Delta 3 of Calcium/calmodulin-dependent protein kinase type II subunit delta (Camk2d), abrogating binding to Importin subunit alpha-1 (KPNA1) and nuclear import. This is due to an 11 amino acid insert encoded by exon 14.
TRG_ENDOCYTIC_2 Q8C437-3 38-41 SWTI000534 Alternative splicing removes the endocytosis motif of Isoform 3 of PEX5-related protein (Pex5l), abrogating binding to AP-2 complex subunit mu (Ap2m1). The motif is present in exon 2, and its absence causes a significant increase in channel density of members from the potassium channel HCN family.
TRG_LysEnd_APsAcLL_1 Q8C437 14-19 SWTI000535 Alternative splicing removes the di-leucine endocytosis motif of PEX5-related protein (Pex5l), abrogating binding to AP-2 complex subunit sigma (Ap2s1). The motif is present in exon 5.
MOD_SUMO Q9ULV5 292-295 SWTI000536 Alternative splicing removes the sumoylation motif of Heat shock factor protein 4 (HSF4), abrogating binding to SUMO-conjugating enzyme UBC9 (UBE2I). The phosphorylation-dependent sumoylation of the PDSM (phosphorylation-dependent sumoylation motif) strongly represses Isoform HSF4B activity.
MOD_SUMO Q9ULV5 292-295 SWTI000537 The phosphorylation-dependent sumoylation of the PDSM (phosphorylation-dependent sumoylation motif) strongly represses Isoform HSF4B activity.
DOC_WW_Pin1_4 O15350 479-484 SWTI000538 Alternative splicing removes the WW-binding motif of Tumor protein p73 (TP73), abrogating binding to Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1). Isoforms lacking WW-binding motifs have decreased transcriptional activity.
DOC_WW_Pin1_4 O15350 439-444 SWTI000539 Alternative splicing removes the WW-binding motif of Tumor protein p73 (TP73), abrogating binding to Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1). Isoforms lacking WW-binding motifs have decreased transcriptional activity.
DOC_WW_Pin1_4 O15350 409-414 SWTI000540 Alternative splicing removes the WW-binding motif of Tumor protein p73 (TP73), abrogating binding to Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1). Isoforms lacking WW-binding motifs have decreased transcriptional activity.
LIG_Dynein_DLC8_2 Q9Y4I1 1286-1290 SWTI000541 Alternative splicing removes the dynein-binding motif of Unconventional myosin-Va (MYO5A), abrogating binding to Dynein light chain 2, cytoplasmic (DYNLL2). DYNLL2 (also known as DLC2) globally protects the tail domains of MYO5A against limited proteolysis.
LIG_SCF-TrCP1_2 Q13127 1008-1013 SWTI000542 Alternative splicing removes the beta-TrCP-binding degron of RE1-silencing transcription factor (REST), abrogating binding to F-box/WD repeat-containing protein 1A (BTRC), and therefore altering the half-life of the variant. Up-regulation of the protein isoform without the degron has been linked to cancer.
TRG_NLS_MonoCore_2 Q969H0 10-15 SWTI000543 Alternative splicing removes the nuclear localisation signal (NLS) of F-box/WD repeat-containing protein 7 (FBXW7), abrogating binding to Importin subunit alpha-1 (KPNA1). There are two other NLS motifs in the protein, meaning the isoform can still enter the nucleus.
TRG_NES_CRM1_2 Q969H0-2 19-26 SWTI000544 Alternative splicing removes the nuclear export signal (NES) of Isoform Archipelago beta of F-box/WD repeat-containing protein 7 (FBXW7), abrogating binding to Exportin-1 (XPO1) and export from nucleus. The presence of the NES produces an isoform with a cytoplasmic localisation. The two other isoforms of FBXW7 localise to the nucleus and the nucleolus, respectively.
TRG_LysEnd_APsAcLL_2 Q8WY21-4 1136-1140 SWTI000545 Alternative splicing removes the di-leucine motif of Isoform 4 of VPS10 domain-containing receptor SorCS1 (SORCS1), abrogating binding to AP-2 complex subunit sigma (AP2S1). Human and mouse have completely different C-termini for SorCS1a (also known as Isoform 4 of VPS10 domain-containing receptor SorCS1 (SORCS1)), with only the human splice variant containing the motif.
TRG_ENDOCYTIC_2 Q8WY21-2 1132-1135 SWTI000546 Alternative splicing removes the endocytosis motif of Isoform 2 of VPS10 domain-containing receptor SorCS1 (SORCS1), abrogating binding to AP-2 complex subunit mu (AP2M1). The sequence is conserved in both human and mouse. Different splice variants have different endocytosis motifs.
LIG_TYR_ITSM Q9NQ25 280-287 SWTI000547 Alternative splicing removes the ITSM (immunoreceptor tyrosine-based switch motif) motif of SLAM family member 7 (SLAMF7), abrogating binding to SH2 domain-containing protein 1A (SH2D1A). The full-length isoform (Isoform CS1-L) has 2 ITSM motifs and only one is missing in the shorter splice variant (Isoform 19A24). However, experiments showed only Isoform CS1-L binds to SH2D1A.
MOD_CAAXbox P60953 188-191 SWTI000548 Alternative splicing removes the prenylation motif of Cell division control protein 42 homolog (CDC42), abrogating binding to Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha (FNTA). The canonical, prenylated Cdc42 isoform (Cdc42-pren or Isoform Placental) is expressed in all tissues, the variant, palmitoylated form (Cdc42-palm or Isoform Brain) is expressed only in brain.
MOD_Spalmitoyl P60953-1 188-191 SWTI000549 Alternative splicing removes the palmitoylation motif of Isoform Brain of Cell division control protein 42 homolog (CDC42), abrogating binding to Palmitoyltransferase ZDHHC9 (ZDHHC9). The splice variant with the palmitoylation motif (Isoform Brain) is expressed in brain and is often found within raf-like domain of dendrites. Increased levels of glutamate results in rapid depalmitoylation and dislocation from dendrites.
CLV_CASPASE3_1 P31809 457-460 SWTI000550 Alternative splicing removes the caspase-3 scission site of Carcinoembryonic antigen-related cell adhesion molecule 1 (Ceacam1), preventing cleavage by Caspase-3 (Casp3). The presence of cleavage sites allows production of a stronger adhession molecule.
LIG_SH2_IIA Q9ES52 918-921 SWTI000552 Alternative splicing partially removes the SH2-binding motif of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (Inpp5d), partially inhibiting binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (Pik3r1).
LIG_WW_1 P13285 57-60 SWTI000553 Alternative splicing removes the WW-binding motif of Latent membrane protein 2 (LMP2), abrogating binding to E3 ubiquitin-protein ligase Itchy (Itch).
LIG_WW_1 P13285 98-101 SWTI000554 Alternative splicing removes the WW-binding motif of Latent membrane protein 2 (LMP2), abrogating binding to E3 ubiquitin-protein ligase Itchy (Itch).
LIG_PDZ_Class_1 Q60575-3 1145-1150 SWTI000555 Alternative splicing removes the PDZ-binding motif of Isoform 3 of Kinesin-like protein KIF1B (Kif1b), abrogating binding to PDZ domain-containing protein GIPC1 (Gipc1).
LIG_TRAF2_3 Q80TQ2 449-453 SWTI000556 Alternative splicing removes the TRAF2-binding motif of Ubiquitin carboxyl-terminal hydrolase CYLD (Cyld), abrogating binding to TNF receptor-associated factor 2 (Traf2). Mice expressing solely the alternatively spliced Isoform 3 of Ubiquitin carboxyl-terminal hydrolase CYLD (Cyld) (sCYLD) show an altered B-cell expansion profile and have more stable NF-kB proteins.
LIG_TYR_ITIM Q91Y57 430-435 SWTI000557 Alternative splicing removes the ITIM (immunoreceptor tyrosine-based inhibitory motif) of Sialic acid-binding Ig-like lectin 12 (Siglec12), abrogating binding to Tyrosine-protein phosphatase non-receptor type 6 (Ptpn6).
LIG_TYR_ITIM Q91Y57 430-435 SWTI000558 Alternative splicing removes the ITIM (immunoreceptor tyrosine-based inhibitory motif) of Sialic acid-binding Ig-like lectin 12 (Siglec12), abrogating binding to Tyrosine-protein phosphatase non-receptor type 11 (Ptpn11).
LIG_TYR_ITIM Q86YW5 279-284 SWTI000559 Alternative splicing removes the ITIM (immunoreceptor tyrosine-based inhibitory motif) of Trem-like transcript 1 protein (TREML1), abrogating binding to Tyrosine-protein phosphatase non-receptor type 11 (PTPN11).
LIG_PDZ_Class_1 P22756 945-949 SWTI000560 Alternative splicing removes the PDZ-binding motif of Glutamate receptor, ionotropic kainate 1 (Grik1), abrogating binding to PRKCA-binding protein (Pick1). The ER-retention motif of Grik1 splice variants can be inhibited by PKC phosphorylation and association with a PDZ protein. It has also been shown that the PDZ domain-containing proteins Disks large homolog 4 (Dlg4) and Syntenin-1 (Sdcbp) are able to bind.
LIG_PDZ_Class_1 P22756 945-949 SWTI000561 Alternative splicing removes the PDZ-binding motif of Glutamate receptor, ionotropic kainate 1 (Grik1), abrogating binding to Glutamate receptor-interacting protein 1 (Grip1). The ER retention of Grik1 splice variants can be inhibited by PKC phosphorylation and association with a PDZ domain-containing protein. Also shown that the PDZ-binding containing proteins PSD95 and syntenin are able to bind.
TRG_ER_diArg_2 P22756 937-941 SWTI000562 Alternative splicing removes the di-arginine ER-retention motif of Glutamate receptor, ionotropic kainate 1 (Grik1), abrogating binding to Coatomer subunit beta (COPB1).
MOD_CDK_1 Q5BJF6 817-823 SWTI000563 Alternative splicing removes the cyclin-dependent kinase (CDK) phosphorylation motif of Outer dense fiber protein 2 (ODF2), abrogating binding to Cyclin-dependent kinase 1 (CDK1). This phosphorylation is required for the recruitment of Serine/threonine-protein kinase PLK1 (PLK1). The C-terminal extension of Isoform Cenexin 1 has the ability to distinctly localise to mother centriole whereas the splice variant (e.g. Isoform Cenexin 1), which does not have this extension, permits ODF2 to associate with sperm tail.
TRG_ER_KDEL_1 P15246-2 225-228 SWTI000564 Alternative splicing removes the KDEL ER-retention motif of Isoform 2 of Protein-L-isoaspartate(D-aspartate) O-methyltransferase (PCMT1).
TRG_ER_KDEL_1 Q32P28 733-736 SWTI000565 Alternative splicing removes the KDEL ER-retention motif of Prolyl 3-hydroxylase 1 (LEPRE1).
TRG_NES_CRM1_2 Q13485 142-149 SWTI000566 Alternative splicing removes the nuclear export signal (NES) motif of Mothers against decapentaplegic homolog 4 (SMAD4), thereby inhibiting binding to Exportin-1 (XPO1) and export from the nucleus. A splice variant lacking the NES does not shuttle back and forth between nucleus and cytosol. At present, this particular splice variant is not annotated in UniProtKB.
TRG_MLS P15565 1-16 SWTI000567 Alternative initiation removes the mitochondrial localisation signal (MLS) motif of tRNA (guanine(26)-N(2))-dimethyltransferase, mitochondrial (TRM1), abrogating binding to Mitochondrial import receptor subunit TOM70 (TOMM70A). Both variants contain a weak nuclear localisation signal (NLS) (KKSKKKRC). However, this motif is over-powered by the MLS and therefore the full-length variant is localised to mitochondria. Alternative initiation removes the N-terminus and the MLS motif, resulting in a nuclear localisation for the truncated isoform.
TRG_MLS Q80UN9 1-47 SWTI000568 Alternative splicing removes the mitochondrial localisation signal (MLS) motif of tRNA dimethylallyltransferase, mitochondrial (Trit1), abrogating binding to Mitochondrial import receptor subunit TOM70 (TOMM70A). The IPPT-I isoform (also known as Isoform 1) was found to localise to both the mitochondria and the cytosol whereas the IPPT-II isoform (also known as Isoform 2) is only localised to the cytosol and the nucleus. No nuclear localisation signal (NLS) was identified in either splice variant.
TRG_MLS Q15046-2 1-49 SWTI000569 Alternative splicing removes the mitochondrial localisation signal (MLS) motif of Isoform Mitochondrial of Lysine--tRNA ligase (KARS), abrogating binding to Mitochondrial import receptor subunit TOM70 (TOMM70A) and import into mitochondria. Unusually, the first two exons of Lysine--tRNA ligase (KARS) are non-constitutive. The first exon does not contain a localisation signal (resulting in cytosol localisation) whereas the second exon contains an MLS.
TRG_MLS Q9NS18 1-21 SWTI000570 Alternative splicing removes the mitochondrial localisation signal (MLS) motif of Glutaredoxin-2, mitochondrial (GLRX2), abrogating binding to Mitochondrial import receptor subunit TOM70 (TOMM70A) and import into mitochondria. The Grx2a isoform Isoform Grx2a is localised to the mitochondria whereas the Isoform Grx2b is localised to the perinuclear region.
TRG_NLS_MonoExtN_4 O15527 332-339 SWTI000571 Alternative splicing removes the nuclear localisation signal (NLS) motif of N-glycosylase/DNA lyase (OGG1), abrogating binding to Importin subunit alpha-1 (KPNA1) and import into the nucleus. OGG1-1a (also known as Isoform Alpha) has a C-terminal NLS motif that is absent in OGG1-2a (also known as Isoform Beta) . Both have a weak mitochondrial localisation signal (MLS) in the N-terminal.
TRG_MLS P33316 1-69 SWTI000572 Alternative splicing removes the mitochondrial localisation signal (MLS) motif of Deoxyuridine 5\'-triphosphate nucleotidohydrolase, mitochondrial (DUT), abrogating binding to Mitochondrial import receptor subunit TOM70 (TOMM70A) and import into the mitochondria.
LIG_AP2alpha_2 P98082 293-295 SWTI000573 Alternative splicing removes the AP2alpha-binding motifs of Disabled homolog 2 (DAB2), abrogating binding to AP-2 complex subunit alpha-2 (AP2A2). The p67 splice variant of Dab1 (also known as Isoform 2) does not localise to vesicles as it fails to bind the AP-2 complex.
LIG_AP2alpha_2 P98082 298-300 SWTI000574 Alternative splicing removes the AP2alpha-binding motifs of Disabled homolog 2 (DAB2), abrogating binding to AP-2 complex subunit alpha-2 (AP2A2). The p67 splice variant of Dab1 (also known as Isoform 2) does not localise to vesicles as it fails to bind the AP-2 complex.
TRG_NLS P29590 476-490 SWTI000575 Alternative splicing removes the nuclear localisation signal (NLS) of Protein PML (PML), abrogating binding to Importin subunit alpha-1 (KPNA1) and import into the nucleus.
MOD_SUMO P29590 489-492 SWTI000576 Alternative splicing removes the SUMO motif of Protein PML (PML), abrogating binding to SUMO-conjugating enzyme UBC9 (UBE2I). The study identified a major sumoylation site within the nuclear localisation signal (NLS) of PML. Although they did not determine whether the lysine residue regulates the NLS, they found that sumoylation was not necessary for nuclear localisation and that SUMO-modification only occurs in the nucleus.
TRG_NES_CRM1_1 P29590 702-716 SWTI000577 Alternative splicing removes the nuclear export signal (NES) of Protein PML (PML), abrogating binding to Exportin-1 (XPO1) and export from the nucleus.
TRG_LysEnd_APsAcLL_1 P05710 301-306 SWTI000578 Alternative splicing removes the di-leucine endocytosis motif of Prolactin receptor (Prlr), partially inhibiting binding to AP-2 complex subunit sigma (AP2S1) and the rate of endocytosis. Isoform Long of Prolactin receptor (Prlr) (also known as PRLR-long) has a longer C-terminal tail than the Isoform Short of Prolactin receptor (Prlr) (also known as PRLR-short) splice variant. PRLR-long internalises faster than PRLR-short due to two additional di-leucine motifs in the C-terminus (where the adjacent phenylalanine also plays a role). PRLR-short has two di-leucine motifs whereas PRLR-long has four.
TRG_PTS1 Q9UHK6 379-382 SWTI000579 Alternative splicing removes the type 1 peroxisomal targeting signal (PTS1) of Alpha-methylacyl-CoA racemase (AMACR), abrogating binding to Peroxisomal targeting signal 1 receptor (PEX5) and import into the peroxisome. Only the major AMACR IA (also known as Isoform 1) form localises to the peroxisome.
TRG_NLS_MonoExtN_4 P38398 501-508 SWTI000580 Alternative splicing removes the nuclear localisation signal (NLS) of Breast cancer type 1 susceptibility protein (BRCA1), abrogating binding to Importin subunit alpha-1 (KPNA1) and import into the nucleus. The study compared the full-length Brca1 splice variant (Isoform 1) to the Delta11b isoform (Isoform Delta11b). The shorter isoform is missing exon 11b and differs in a number of ways. Firstly, it lacks an NLS and therefore has a cytoplasmic localisation. Also, when over-expressed, the Delta11b isoform was not toxic, suggesting nuclear localisation is important for Brca1\'s toxic behaviour.
DEG_ODPH_VHL_1 Q9Y2N7 490-502 SWTI000581 Alternative splicing removes the VHL-hydroxyproline-modified binding motif of Hypoxia-inducible factor 3-alpha (HIF3A), abrogating binding to Von Hippel-Lindau disease tumor suppressor (VHL). Other studies have shown that the HIF-3 alpha-4 splice variant (Isoform HIF-3alpha4) can act as a dominant negative form with tumour-suppressive activity (see Maynard et al. (2007) (here)).
LIG_SH2_STAT5 P42229 694-697 SWTI000582 Alternative splicing removes the regulatory Y694 residue of Signal transducer and activator of transcription 5A (STAT5A). The phosphorylation of Y694 by Proto-oncogene tyrosine-protein kinase Src (SRC) has been shown to be essential for DNA binding. This event acts as an important regulatory mechanism (See Clark et al. (2005) (here) and Okutani et al. (2001) (here)). The exact function of Y694 remains uncertain as is binding to STAT5 in dimer. The STAT5A-DeltaE18 does not enter nucleus upon PRLR stimulation.
LIG_14-3-3_4 P54256-2 594-598 SWTI000583 Alternative splicing removes the 14-3-3-binding motif of Isoform Short of Huntingtin-associated protein 1 (Hap1), abrogating binding to 14-3-3 protein zeta/delta (Ywhaz). The association of HAP1A (Isoform Short) with 14-3-3 protein zeta/delta (Ywhaz) inhibits binding of the splice variant to members of the kinesin light chain family and diminishes trafficking of Hap1 to neural processes and neurite tips. The result is a decrease in neurite outgrowth.
LIG_EVH1_1 Q702N8 22-26 SWTI000584 Alternative splicing removes the EVH1-binding motif of Xin actin-binding repeat-containing protein 1 (XIRP1), abrogating binding to Protein enabled homolog (ENAH).
LIG_EVH1_1 Q702N8 22-26 SWTI000585 Alternative splicing removes the EVH1-binding motif of Xin actin-binding repeat-containing protein 1 (XIRP1), abrogating binding to Vasodilator-stimulated phosphoprotein (VASP).
LIG_PDZ_Class_1 Q9Y2T3 449-454 SWTI000586 Alternative splicing removes the PDZ-binding motif of Guanine deaminase (GDA) (Nedasin), abrogating binding to Disks large homolog 3 (DLG3). Isoform 1 of Guanine deaminase (GDA) (Nedasin S) is predominately expressed in neuronal tissues and binds PDZ domains. Isoform 3 of Guanine deaminase (GDA) (Nedasin V1), which is predominately expressed in non-neuronal tissues, does not bind PDZ domains. The presence of Nedasin S inhibits binding of NMDA receptors and K+ channels to PDZ domain-containing proteins such as members of the MAGUK family. This suggests that GDA might modulate the receptor clustering function of the PDZ domains of MAGUK family members, and this modulation is regulated by alternative splicing of GDA transcripts.
LIG_14-3-3_1 Q9GZV5 86-91 SWTI000587 Phosphorylation of S89 in the 14-3-3-binding motif of WW domain-containing transcription regulator protein 1 (WWTR1) induces binding to 14-3-3 protein epsilon (YWHAE), retaining phosphorylated WWTR1 in the cytosol, negatively regulating its function.
LIG_PDZ_Class_1 Q05586-4 917-922 SWTI000588 Alternative splicing removes the PDZ-binding motif of Isoform 4 of Glutamate [NMDA] receptor subunit zeta-1 (GRIN1), abrogating binding to Disks large homolog 4 (DLG4). Binding of the PDZ domain of DLG4 suppresses an ER-retention motif in GRIN1, promoting its cell surface expression in a splice variant-specific manner.
LIG_PDZ_Class_1 Q05586-4 917-922 SWTI000589 Binding of the PDZ domain of Disks large homolog 4 (DLG4) suppresses the ER-retention motif of Isoform 4 of Glutamate receptor subunit zeta-1 (GRIN1) in a splice variant-specific manner, thereby promoting cell surface expression of this particular isoform. This supports the hypothesis that local regulation of receptor exit from neuronal ER plays a role in modifying discrete synaptic receptor number.
TRG_ER_diArg_1 Q05586-4 893-895 SWTI000589 Binding of the PDZ domain of Disks large homolog 4 (DLG4) suppresses the ER-retention motif of Isoform 4 of Glutamate receptor subunit zeta-1 (GRIN1) in a splice variant-specific manner, thereby promoting cell surface expression of this particular isoform. This supports the hypothesis that local regulation of receptor exit from neuronal ER plays a role in modifying discrete synaptic receptor number.
LIG_PDZ_Class_1 O55207-3 1288-1293 SWTI000590 Alternative splicing removes the PDZ-binding motif of Isoform 7.5kb of Synaptojanin-2 (Synj2), abrogating binding to Synaptojanin-2-binding protein (Synj2bp). Isoform 7.5kb (Synaptojanin 2A) is recruited to mitochondria through the interaction with the PDZ domain of the mitochondrial outer membrane protein Synj2bp.
LIG_SH3_2 O55207 1120-1125 SWTI000591 Alternative splicing removes the SH3-binding motif of Synaptojanin-2 (Synj2), abrogating binding to Endophilin-A2 (Sh3gl1). Endophilin-A1 (Sh3gl2) and Endophilin-A3 (Sh3gl3) were also shown to bind in this study.
LIG_PDZ_Class_1 P51790-2 861-866 SWTI000592 Alternative splicing removes the PDZ-binding motif of Isoform ClC-3B of H(+)/Cl(-) exchange transporter 3 (CLCN3), abrogating binding to Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (SLC9A3R1). Isoform ClC-3B of H(+)/Cl(-) exchange transporter 3 (CLCN3) is expressed at the leading edge of membrane ruffles. The interaction of CLCN3 with SLC9A3R1 is important for localising outwardly rectifying chloride channels at the leading edge.
LIG_PDZ_Class_2 P19491 878-883 SWTI000593 Alternative splicing removes the PDZ-binding motif of Glutamate receptor 2 (Gria2), abrogating binding to PRKCA-binding protein (Pick1). The presence of PDZ-binding motifs is also seen in the short isoforms of Gria3 (Isoform Flop) and Gria4 (Isoform 4C flop). PRKCA-binding protein (Pick1) recruits both Protein kinase C alpha type (Prkca) and Gria2 simultaneously, possibly allowing Pick1 to play a role in the selective targeting to and possible anchoring of GluRshort-containing AMPA receptors to intracellular membrane-associated Prkca.
LIG_PDZ_Class_1 Q66T02 1068-1073 SWTI000594 Alternative splicing removes the PDZ-binding motif of Pleckstrin homology domain-containing family G member 5 (Plekhg5), abrogating binding to PDZ domain-containing protein GIPC1 (Gipc1). The PDZ adaptor protein Gipc1 (Synectin) bound the longer splice variant, Isoform SYX1 (Syx1), which was targeted to the plasma membrane in a Synectin-dependent manner. The shorter variant, Isoform SYX2 (Syx2), was diffusely distributed in the cytoplasm. Expression of Syx1 augmented endothelial cell migration and tube formation, whereas Syx2 expression did not. Significant expression of Syx2 was only seen in brain tumour cells, which also exhibited high basal Transforming protein RhoA (Rhoa) activity.
LIG_IQ P38377 13-31 SWTI000595 Binding of 29108" target="_blank">calcium(2+) to Calmodulin (Calm1) exposes a binding site on Calmodulin (Calm1) for the Calmodulin-binding IQ motif of Protein transport protein Sec61 subunit alpha isoform 1 (SEC61A1), an interaction that results in closure of the protein-conducting channel located in the ER.
LIG_PDZ_Class_1 P97924-6 1649-1654 SWTI000597 Alternative splicing removes the PDZ-binding motif of Isoform Kalirin-7 of Kalirin (Kalrn), abrogating binding to Disks large homolog 4 (Dlg4). Isoform Kalirin-7 of Kalirin (Kalrn) is the most prevalent isoform in the adult rat hippocampus where it locates to the postsynaptic density via an interaction with Dlg4 and regulates dendritic morphogenesis.
LIG_PDZ_Class_1 Q9NQ66 1211-1216 SWTI000598 Alternative splicing removes the PDZ-binding motif of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 (PLCB1), abrogating binding to Partitioning defective 3 homolog (PARD3). The G protein-activated PLCB1 can directly interact with cell polarity proteins Partitioning defective 3 homolog (PARD3) and Partitioning defective 6 homolog alpha (PARD6A) to form protein complexes in the cell, which potentially modulate G protein-activated PLCB1 activity in cell polarity formation and asymmetric cell division.
LIG_PDZ_Class_1 Q9Z1B3 1211-1216 SWTI000599 Alternative splicing removes the PDZ-binding motif of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 (Plcb1), abrogating binding to Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (Slc9a3r1). Plcb1 does not bind to Slc9a3r2.
LIG_SH3_3 Q9NQ66-2 1162-1168 SWTI000600 Alternative splicing removes the SH3-binding motif of Isoform B of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 (PLCB1), abrogating binding to SH3 and multiple ankyrin repeat domains protein 3 (SHANK3). PLCB1 associates with a SHANK3 complex in cardiomyocytes via its splice variant-specific C-terminal tail. Studies show that Isoform B selectively mediates downstream responses initiated by Gq-coupled receptors, in particular hypertrophy and apoptosis.
TRG_ENDOCYTIC_2 O70161 644-647 SWTI000601 Alternative splicing removes the endocytosis motif of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c), abrogating binding to AP-2 complex subunit mu (Ap2m1). The direct interaction between the AP-2 complex and Isoform PIPKIgamma661 (PIPKIgamma661) targets this isoform to sites of endocytosis at the plasma membrane. Consequently, this results in the generation of a highly concentrated pool of PI(4,5)P2 at these sites.
LIG_PTB_Talin O70161 645-648 SWTI000602 Alternative splicing removes the PTB domain-binding motif of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c), abrogating binding to Talin-1 (Tln1). Integrin receptors, Tln1 and Isoform PIPKIgamma661 (PIPKIgamma661) are recruited to focal adhesions, inducing synthesis of PI(4,5)P2. The regulated and localised generation of PI(4,5)P2 facilitates the assembly and/or disassembly of focal adhesions.
LIG_PTB_Talin O70161 645-648 SWTI000603 Phosphorylation of S645 in the PTB-binding motif of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c) by Cyclin-dependent kinase 5 (Cdk5) inhibits its interaction with Talin-1 (Tln1).
LIG_PTB_Talin O70161 645-648 SWTI000604 Phosphorylation of Y644 in Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c) promotes its association with Talin-1 (Tln1).
TRG_AP2beta_CARGO_2 O70161 633-644 SWTI000605 Alternative splicing removes the AP-2 beta-appendage-binding motif of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c), abrogating binding to AP-2 complex subunit beta (Ap2b1). With other enzymes (members of the eukaryotic diacylglycerol kinase family, and Synaptojanin-1 (Synj1)), Isoform PIPKIgamma661 (PIPKIgamma661) optimises the regional lipid environment necessary for clathrin coat formation. There are three different C-terminal splice variants of Pip5k1c: one (PIPKIgamma687) can bind selectively to Talin-1 (Tln1) via the C-terminal extension (switch details), one (PIPKIgamma661) can bind to both Talin-1 (Tln1) and AP-2 complex subunit beta (Ap2b1), and one (PIPKIgamma635) can bind to neither protein. This flexibility could impart importantly different biological functions to each isoform. For example, in humans PIP5K1C (PIPKIgamma661 in mouse) is proposed to act upstream of Rac/Rho and the differential regulation of PIP5K-gamma and -alpha might allow them to work in tandem to modulate the actin cytoskeleton during the attachment and ingestion phases of phagocytosis (See (here)).
TRG_AP2beta_CARGO_2 O70161 633-644 SWTI000606 Phosphorylation of S645 in Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c) impedes binding to AP-2 complex subunit beta (Ap2b1), while dephosphorylation by calcineurin promotes binding. These phosphorylation and dephosphorylation events are important for the regulation of clathrin coat formation associated with synaptic vesicles.
TRG_NLS_MonoExtC_3 Q00987 181-187 SWTI000607 Alternative splicing removes the nuclear localisation signal (NLS) of E3 ubiquitin-protein ligase Mdm2 (MDM2), abrogating binding to Importin subunit alpha-1 (KPNA1). The exclusion from the nucleus is not complete however, as another NLS (466-473) is speculated to target splice variants to the nucleus, however, to the annotator it seems more likely that splice variants can dimerise with full-length MDM2 and be simultaneously transported into nucleus.
TRG_NES_CRM1_2 Q00987 190-202 SWTI000608 Alternative splicing removes the nuclear export signal (NES) of E3 ubiquitin-protein ligase Mdm2 (MDM2), abrogating binding to Exportin-1 (XPO1).
TRG_NES_CRM1_1 O60716 942-956 SWTI000609 Alternative splicing removes the nuclear export signal (NES) of Catenin delta-1 (CTNND1), abrogating binding to Exportin-1 (XPO1). Despite demonstration of the importance of the NES for removing Catenin delta-1 (CTNND1) from the nucleus, those isoforms without NES are rarely found in the nucleus.
TRG_NES_CRM1_2 Q14494 251-259 SWTI000610 Alternative splicing removes the nuclear export signal (NES) of Nuclear factor erythroid 2-related factor 1 (NFE2L1), abrogating binding to Exportin-1 (XPO1). Only the full-length variant of NFE2L1 (Isoform 1 of Nuclear factor erythroid 2-related factor 1 (NFE2L1)) contains an NES and shows cytoplasmic localisation. The two other naturally occuring isoforms (of which at present only 1 is annotated in UniProtKB) lack the NES and show exclusive nuclear staining.
LIG_PDZ_Class_1 Q9UQB8-4 516-521 SWTI000611 Alternative splicing removes the PDZ-binding motif of Isoform BAIAP2-alpha of Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2), abrogating binding to Disks large homolog 3 (DLG3). The SH3 domain of Isoform BAIAP2-alpha of Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2) also binds to SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), meaning it can link two prominent proteins of the postsynaptic NMDA-receptor complex, namely SHANK1 and DLG3.
LIG_IQ P27732 1650-1669 SWTI000612 Alternative splicing removes the IQ motif of Voltage-dependent L-type calcium channel subunit alpha-1D (Cacna1d) abrogating binding to Calmodulin (Calm1). CaV1.3IQdelta (IQ-deleted Isoform CACN4B) channels exhibit a lack of calcium-dependent inactivation. CaV1.3IQdelta channel immunoreactivity was preferentially localised to cochlear outer hair cells (OHCs), whereas that of CaV1.3IQfull channels (IQ-possessing Isoform CACN4A) labelled inner hair cells (IHCs).
LIG_SUMO_SBM_1 O75925 457-461 SWTI000613 Phosphorylation of S466 and S467 and S468 in the SUMO-binding motif of E3 SUMO-protein ligase PIAS1 (PIAS1) by CK2 subfamily and CK2 subfamily and CK2 subfamily increases the strength of its interaction with Small ubiquitin-related modifier 1 (SUMO1).
TRG_ENDOCYTIC_2 O60331 649-652 SWTI000614 Phosphorylation of S645 near the AP2-binding motif of Phosphatidylinositol-4-phosphate 5-kinase type-1 gamma (PIP5K1C) by Cyclin-dependent kinase 5 (Cdk5) inhibits its interaction with AP-2 complex subunit mu (AP2M1).
LIG_SH2_IA P97318 220-223 SWTI000615 Alternative splicing removes the SH2-binding motif of Disabled homolog 1 (Dab1), abrogating binding to Cytoplasmic protein NCK2 (NCK2). NCK2-beta has a clear preference for splice variant 2 (with the YQYI motif) over splice variant 3 (with the YQTI motif). The authors theorise that since Adapter molecule crk (Crk) is directly linked to the C3G-Rap1 pathway, and NCK2-beta is linked to the Breast cancer anti-estrogen resistance protein 1 (Bcar1) (p130Cas) pathway, it is likely that isoforms 2 and 3 connect to different downstream cascades. It was suggested that the ability of different Dab1 isoforms to recruit distinct sets of SH2 domains implies a fine-tuning role of Dab1 splicing in the intricate series of events that underlie neuronal migration (Gao et al. (2012) (here)) (See also Katyal and Godbout (2004) (here) and Gao et al. (2010) (here)).
LIG_SH2_IA P97318 232-235 SWTI000616 Alternative splicing removes the SH2-binding motif of Disabled homolog 1 (Dab1), abrogating binding to Cytoplasmic protein NCK2 (NCK2). The NCK2-beta has a clear preference for splice variant 2 (with YQYI motif) over splice variant 3 (with YQTI motif). The authors theorise that since Adapter molecule crk (Crk) is directly linked to the C3G-Rap1 pathway, and NCK2-beta is linked to the Breast cancer anti-estrogen resistance protein 1 (Bcar1) (p130Cas) pathway, it is likely that isoforms 2 and 3 connect to different downstream cascades. It was suggested that the ability of different Dab1 isoforms to recruit distinct sets of SH2 domains implies a fine-tuning role of Dab1 splicing in the intricate series of events that underlie neuronal migration (Gao et al. (2012) (here)) (See also Katyal and Godbout (2004) (here) and Gao et al. (2010) (here)).
LIG_SH2_IA P97318 220-223 SWTI000617 Alternative splicing removes the SH2-binding motif of Disabled homolog 1 (Dab1), abrogating binding to Adapter molecule crk (Crk). Both Adapter molecule crk (Crk) and Crk-like protein (Crkl) bind equally well to variants 2 and 3. The authors theorise that since Adapter molecule crk (Crk) is directly linked to the C3G-Rap1 pathway, and NCK2-beta is linked to the Breast cancer anti-estrogen resistance protein 1 (Bcar1) (p130Cas) pathway, it is likely that isoforms 2 and 3 connect to different downstream cascades. It was suggested that the ability of different Dab1 isoforms to recruit distinct sets of SH2 domains implies a fine-tuning role of Dab1 splicing in the intricate series of events that underlie neuronal migration (Gao et al. (2012) (here)) (See also Katyal and Godbout (2004) (here) and Gao et al. (2010) (here)).
LIG_SH2_IA P97318 232-235 SWTI000618 Alternative splicing removes the SH2-binding motif of Disabled homolog 1 (Dab1), abrogating binding to Adapter molecule crk (Crk). Both Adapter molecule crk (Crk) and Crk-like protein (Crkl) bind equally well to variants 2 and 3. The authors theorise that since Adapter molecule crk (Crk) is directly linked to the C3G-Rap1 pathway, and NCK2-beta is linked to the Breast cancer anti-estrogen resistance protein 1 (Bcar1) (p130Cas) pathway, it is likely that isoforms 2 and 3 connect to different downstream cascades. It was suggested that the ability of different Dab1 isoforms to recruit distinct sets of SH2 domains implies a fine-tuning role of Dab1 splicing in the intricate series of events that underlie neuronal migration (Gao et al. (2012) (here)) (See also Katyal and Godbout (2004) (here) and Gao et al. (2010) (here)).
LIG_SH2_SRC P97318 185-188 SWTI000619 Alternative splicing removes the SH2-binding motif of Disabled homolog 1 (Dab1), abrogating binding to Neuronal proto-oncogene tyrosine-protein kinase Src (Src). Splice variants 2 and 3 (only containing one of the YQxI motifs, i.e. Y185 and Y198) exhibit decreased tyrosine phosphorylation, suggesting both motifs are required for full activation of Dab1. Dab1 is likely to recruit Neuronal proto-oncogene tyrosine-protein kinase Src (Src) via these two YQxI motifs, which subsequently phosphorylates adjacent YxVP motifs (here). This was also suggested for Phosphatidylinositol 3-kinase regulatory subunit alpha (Pik3r1) and Suppressor of cytokine signaling 2 (Socs2). Gao et al. (2012) (here) suggests that the ability of different Dab1 isoforms to recruit distinct sets of SH2 domains allows a fine-tuning role for Dab1 splicing in the intricate series of events that underlie neuronal migration (See also Katyal & Godbout (2004) (here) and Gao et al. (2010) (here)).
LIG_SH2_SRC P97318 198-201 SWTI000620 Alternative splicing removes the SH2-binding motif of Disabled homolog 1 (Dab1), abrogating binding to Neuronal proto-oncogene tyrosine-protein kinase Src (Src). Splice variants 2 and 3 (only containing one of the YQxI motifs, i.e. Y185 and Y198) exhibit decreased tyrosine phosphorylation, suggesting both motifs are required for full activation of Dab1. Dab1 is likely to recruit Neuronal proto-oncogene tyrosine-protein kinase Src (Src) via these two YQxI motifs, which subsequently phosphorylates adjacent YxVP motifs (here). This was also suggested for Phosphatidylinositol 3-kinase regulatory subunit alpha (Pik3r1) and Suppressor of cytokine signaling 2 (Socs2). Gao et al. (2012) (here) suggests that the ability of different Dab1 isoforms to recruit distinct sets of SH2 domains allows a fine-tuning role for Dab1 splicing in the intricate series of events that underlie neuronal migration (See also Katyal & Godbout (2004) (here) and Gao et al. (2010) (here)).
LIG_SH2_IA P97318 232-235 SWTI000621 Phosphorylation of Y232 in the SH2-binding motif of Disabled homolog 1 (Dab1) induces binding to Cytoplasmic protein NCK2 (NCK2).
LIG_SH2_IA P97318 232-235 SWTI000622 Phosphorylation of Y232 in the SH2-binding motif of Disabled homolog 1 (Dab1) induces binding to Adapter molecule crk (Crk).
LIG_SH2_SRC P97318 185-188 SWTI000623 Phosphorylation of Y185 in the SH2-binding motif of Disabled homolog 1 (Dab1) induces binding to Neuronal proto-oncogene tyrosine-protein kinase Src (Src).
LIG_SH2_SRC P97318 198-201 SWTI000624 Phosphorylation of Y198 in the SH2-binding motif of Disabled homolog 1 (Dab1) induces binding to Neuronal proto-oncogene tyrosine-protein kinase Src (Src).
DEG_SCF_TRCP1_1 P16471 348-353 SWTI000625 Alternative Splicing removes the degron motif of Prolactin receptor (PRLR) abrogating binding to F-box/WD repeat-containing protein 11 (FBXW11). SCF-beta-TrCP2 negatively regulates the long isoform of PRLR (Isoform 1). Should be noted that TrCP2 has a predominately cytoplasmic localisation compared to TrCP1 that is located in the nucleus. The mechanism for the down-regulation of the intermediate (Isoform Intermediate) and short (Isoform Short form 1a and Isoform Short form 1b) that lack the TrCP degron is still not known. However it should be noted that the short and intermediate are either partially deficient or entirely deficient in mediating the signal transduction pathways induced by PRL (see Kine et al. (1999) (here) and Ross et al. (1997) (here)). This though is likely due to the missing STAT5-SH2-binding motif.
LIG_SH2_STAT5 P16471 342-345 SWTI000626 Alternative Splicing removes the degron motif of Prolactin receptor (PRLR), abrogating binding to Signal transducer and activator of transcription 5A (STAT5A). The PRLR S1a (Isoform Short form 1a) and S1b and (Isoform Short form 1b) isoforms were unable to mediate the transcriptional activation of the beta-casein promoter via the JAK-STAT5 pathway. Therefore these two splice variants act as dominant negatives on the full-length version LF (Isoform 1). Another study showed that different splice variants of heterodimers (e.g. LF/S1a, LF/S1b) that were able to induce JAK2 phosphorylation but not further signalling events due to lack of STAT recruitment (Qazi et al. (2006) (here)).
MOD_PKA_1 Q24546 3-9 SWTI000627 RNA editing removes the degron motif of Synapsin (Syn), abrogating binding to cAMP-dependent protein kinase catalytic subunit (Pka-C1). A genomic version of the protein sequence contains a canonical PKA-recognition motif that is highly conserved, however in Drosophilia, in all except the embryo sequences this sequence was RNA-edited to RGFS (from RRFS).
LIG_PDZ_Class_1 P23634 1236-1241 SWTI000628 Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 4 (ATP2B4), abrogating binding to Disks large homolog 1 (DLG1). A much lower affinity was recorded for the third PDZ domain of DLG1 (in in the micromolar range (KD = 1.2 microM) compared to nanomolar affinity (KD = 1.6 nM)). PMCA4b and DLG1 are co-expressed in kidney and intestinal epithelial cells as well as in several areas of the brain.
LIG_PDZ_Class_1 P23634 1236-1241 SWTI000629 Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 4 (ATP2B4), abrogating binding to Disks large homolog 3 (DLG3). Disks large homolog 3 (DLG3) did not bind to \'b\' isoform of PMCA2. There is therefore an interaction selectivity between \'b\' isoforms of ATP2B4 and DLG3 as opposed to the promiscuity of \'b\' isoforms of ATP2B2 and ATP2B4 in interacting with other SAPs. Same study DLG4, DLG2 and DLG1 shown to bind to PDZ-binding motifs in \'b\' isoforms of ATP2B4 and ATP2B2.
LIG_PDZ_Class_1 P97924-6 1649-1654 SWTI000630 Alternative splicing removes the PDZ-binding motif of Isoform Kalirin-7 of Kalirin (Kalrn), abrogating binding to Disks large homolog 4 (Dlg4). Isoform Kalirin-7 of Kalirin (Kalrn) is the most prevalent isoform in the adult rat hippocampus where it locates to the postsynaptic density via an interaction with Dlg4 and regulates dendritic morphogenesis.
LIG_PDZ_Class_1 P97924-6 1649-1654 SWTI000631 Alternative splicing removes the PDZ-binding motif of Isoform Kalirin-7 of Kalirin (Kalrn), abrogating binding to Disks large homolog 4 (Dlg4). Isoform Kalirin-7 of Kalirin (Kalrn) is the most prevalent isoform in the adult rat hippocampus where it locates to the postsynaptic density via an interaction with Dlg4 and regulates dendritic morphogenesis.
LIG_FHA_1 P64897 20-26 SWTI000632 Phosphorylation of T22 in the FHA-binding motif of Uncharacterized protein Rv1827/MT1875 (Rv1827) by Serine/threonine-protein kinase pknB (pknB) results in auto-inhibition due to an intramolecular interaction with the FHA domain. As a result, phosphorylation-independent interactions of the FHA domain with metabolic enzymes, which regulate the catalytic activity of these enzymes, are blocked (See also switch details).
LIG_IQ P38377 13-31 SWTI000633 Binding of 29108" target="_blank">calcium(2+) to Calmodulin (Calm1) exposes a binding site on Calmodulin (Calm1) for the Calmodulin-binding IQ motif of Protein transport protein Sec61 subunit alpha isoform 1 (SEC61A1), an interaction that results in closure of the protein-conducting channel located in the ER.
LIG_PDZ_Class_1 Q05586-4 917-922 SWTI000634 Alternative splicing removes the PDZ-binding motif of Isoform 4 of Glutamate [NMDA] receptor subunit zeta-1 (GRIN1), abrogating binding to Disks large homolog 4 (DLG4). Binding of the PDZ domain of DLG4 suppresses an ER-retention motif in GRIN1, promoting its cell surface expression in a splice variant-specific manner.
LIG_PDZ_Class_1 Q05586-4 917-922 SWTI000635 Binding of the PDZ domain of Disks large homolog 4 (DLG4) suppresses the ER-retention motif of Isoform 4 of Glutamate receptor subunit zeta-1 (GRIN1) in a splice variant-specific manner, thereby promoting cell surface expression of this particular isoform. This supports the hypothesis that local regulation of receptor exit from neuronal ER plays a role in modifying discrete synaptic receptor number.
TRG_ER_diArg_1 Q05586-4 893-895 SWTI000635 Binding of the PDZ domain of Disks large homolog 4 (DLG4) suppresses the ER-retention motif of Isoform 4 of Glutamate receptor subunit zeta-1 (GRIN1) in a splice variant-specific manner, thereby promoting cell surface expression of this particular isoform. This supports the hypothesis that local regulation of receptor exit from neuronal ER plays a role in modifying discrete synaptic receptor number.
LIG_PDZ_Class_1 Q05586-4 917-922 SWTI000636 Alternative splicing removes the PDZ-binding motif of Isoform 4 of Glutamate [NMDA] receptor subunit zeta-1 (GRIN1), abrogating binding to Disks large homolog 4 (DLG4). Binding of the PDZ domain of DLG4 suppresses an ER-retention motif in GRIN1, promoting its cell surface expression in a splice variant-specific manner.
LIG_PDZ_Class_1 Q05586-4 917-922 SWTI000637 Binding of the PDZ domain of Disks large homolog 4 (DLG4) suppresses the ER-retention motif of Isoform 4 of Glutamate receptor subunit zeta-1 (GRIN1) in a splice variant-specific manner, thereby promoting cell surface expression of this particular isoform. This supports the hypothesis that local regulation of receptor exit from neuronal ER plays a role in modifying discrete synaptic receptor number.
TRG_ER_diArg_1 Q05586-4 893-895 SWTI000637 Binding of the PDZ domain of Disks large homolog 4 (DLG4) suppresses the ER-retention motif of Isoform 4 of Glutamate receptor subunit zeta-1 (GRIN1) in a splice variant-specific manner, thereby promoting cell surface expression of this particular isoform. This supports the hypothesis that local regulation of receptor exit from neuronal ER plays a role in modifying discrete synaptic receptor number.
LIG_PDZ_Class_1 Q9Y2T3 449-454 SWTI000638 Alternative splicing removes the PDZ-binding motif of Guanine deaminase (GDA) (Nedasin), abrogating binding to Disks large homolog 3 (DLG3). Isoform 1 of Guanine deaminase (GDA) (Nedasin S) is predominately expressed in neuronal tissues and binds PDZ domains. Isoform 3 of Guanine deaminase (GDA) (Nedasin V1), which is predominately expressed in non-neuronal tissues, does not bind PDZ domains. The presence of Nedasin S inhibits binding of NMDA receptors and K+ channels to PDZ domain-containing proteins such as members of the MAGUK family. This suggests that GDA might modulate the receptor clustering function of the PDZ domains of MAGUK family members, and this modulation is regulated by alternative splicing of GDA transcripts.
LIG_TYR_ITIM Q91Y57 430-435 SWTI000639 Alternative splicing removes the ITIM (immunoreceptor tyrosine-based inhibitory motif) of Sialic acid-binding Ig-like lectin 12 (Siglec12), abrogating binding to Tyrosine-protein phosphatase non-receptor type 6 (Ptpn6).
LIG_TYR_ITIM Q91Y57 430-435 SWTI000640 Alternative splicing removes the ITIM (immunoreceptor tyrosine-based inhibitory motif) of Sialic acid-binding Ig-like lectin 12 (Siglec12), abrogating binding to Tyrosine-protein phosphatase non-receptor type 11 (Ptpn11).
LIG_TYR_ITIM Q86YW5 279-284 SWTI000641 Alternative splicing removes the ITIM (immunoreceptor tyrosine-based inhibitory motif) of Trem-like transcript 1 protein (TREML1), abrogating binding to Tyrosine-protein phosphatase non-receptor type 11 (PTPN11).
LIG_SH2_IIA Q9ES52 918-921 SWTI000642 Alternative splicing partially removes the SH2-binding motif of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (Inpp5d), partially inhibiting binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (Pik3r1).
LIG_WW_1 P13285 57-60 SWTI000643 Alternative splicing removes the WW-binding motif of Latent membrane protein 2 (LMP2), abrogating binding to E3 ubiquitin-protein ligase Itchy (Itch).
LIG_BIR_III_2 P55210 23-27 SWTI000644 Binding of the BIR domain-binding motif of Caspase-7 (CASP7) to the BIR domains of Baculoviral IAP repeat-containing protein 2 (BIRC2) requires cleavage of Caspase-7 (CASP7) at D23, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification.
LIG_BIR_III_2 P55210 23-27 SWTI000645 Binding of the BIR domain-binding motif of Caspase-7 (CASP7) to the BIR domains of Baculoviral IAP repeat-containing protein 2 (BIRC2) requires cleavage of Caspase-7 (CASP7) at D23, since this results in a functional neo N-terminal motif. BIR domains are found in Inhibitor of Apoptosis Proteins (IAPs) that suppress the activity of activated caspases, either by directly inhibiting caspase catalytic activity, or by targeting caspases for degradation by ubiquitin modification.
LIG_IQ_2 P20020-3 1114-1128 SWTI000646 Alternative splicing partially removes the IQ motif of Isoform CI of Plasma membrane calcium-transporting ATPase 1 (ATP2B1), partially inhibiting binding to Calmodulin (CALM1).
LIG_BIR_internal Q9NR28 56-59 SWTI000647 Alternative splicing removes the BIR-binding motif of Diablo homolog, mitochondrial (DIABLO), abrogating binding to Baculoviral IAP repeat-containing protein 4 (XIAP). Isoform SMAC3 is localised to mitochondria via its mitochondrial localisation signal (MLS). Upon entry in mitochondria the MLS is cleaved and Isoform SMAC3 is found localised with cytochrome-c. During apoptosis, Isoform SMAC3 binds to the second/third BIR domain of Baculoviral IAP repeat-containing protein 4 (XIAP). This interaction disrupts binding of XIAP to processed Caspase-9 (CASP9) and promotes Caspase-3 (CASP3) activation. Isoform SMAC3 also promotes ubiquitination of XIAP and subsequent degradation. Isoform 1 on the other hand did not cause degradation of XIAP.
LIG_EH_1 O43426 1393-1397 SWTI000648 Alternative splicing removes the EH-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to Epidermal growth factor receptor substrate 15 (EPS15). Isoform Synaptojanin-170 is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 is by far the major synaptojanin isoform. Isoform Synaptojanin-145 may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate transport.
LIG_EH_1 O43426 1403-1407 SWTI000649 Alternative splicing removes the EH-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to Epidermal growth factor receptor substrate 15 (EPS15). Isoform Synaptojanin-170 is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 is by far the major synaptojanin isoform. Isoform Synaptojanin-145 may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate receptor transport.
LIG_EH_1 O43426 1414-1418 SWTI000650 Alternative splicing removes the EH-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to Epidermal growth factor receptor substrate 15 (EPS15). Isoform Synaptojanin-170 is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 is by far the major synaptojanin isoform. Isoform Synaptojanin-145 may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate receptor transport.
LIG_EH_1 O43426 1393-1397 SWTI000651 Alternative splicing removes the EH-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to Epidermal growth factor receptor substrate 15 (EPS15). Isoform Synaptojanin-170 is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 is by far the major synaptojanin isoform. Isoform Synaptojanin-145 may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate transport.
LIG_EH_1 O43426 1403-1407 SWTI000652 Alternative splicing removes the EH-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to Epidermal growth factor receptor substrate 15 (EPS15). Isoform Synaptojanin-170 is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 is by far the major synaptojanin isoform. Isoform Synaptojanin-145 may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate receptor transport.
LIG_EH_1 O43426 1414-1418 SWTI000653 Alternative splicing removes the EH-binding motif of Synaptojanin-1 (SYNJ1), abrogating binding to Epidermal growth factor receptor substrate 15 (EPS15). Isoform Synaptojanin-170 is associated with clathrin-mediated endocytosis as a negative regulator of coat-membrane interaction. This isoform is virtually absent from mature neuronal synapses, where clathrin-mediated endocytosis plays a critical role and where Isoform Synaptojanin-145 is by far the major synaptojanin isoform. Isoform Synaptojanin-145 may be recruited early to clathrin-coated pits of synapses, either indirectly by adaptors that bind clathrin and AP-2, such as Amphiphysin (AMPH), or by interactions of endophilin family dimers with synaptic vesicle cargo, such as the vesicular glutamate receptor transport.
LIG_SH2_IB P49023 118-121 SWTI000654 Alternative splicing removes the SH2-binding motif of Paxillin (PXN), abrogating binding to Ras GTPase-activating protein 1 (RASA1).
LIG_PDZ_Class_1 P97288-2 382-387 SWTI000655 Alternative splicing removes the PDZ-binding motif of Isoform 5-HT4(A) of 5-hydroxytryptamine receptor 4 (Htr4), abrogating binding to Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (Slc9a3r1). Isoform 5-HT4(A) interacts specifically with a protein complex including Slc9a3r1 and Ezrin (Ezr) that might participate in its targeting to specialised subcellular regions, such as microvilli.
LIG_SH2_IIA Q15303 1056-1059 SWTI000656 Alternative splicing removes the SH2-binding motif of Receptor tyrosine-protein kinase erbB-4 (ERBB4), abrogating binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1). The SH2-binding motif overlaps with a WW-binding motif. Binding of these motifs is regulated in a phosphorylation-dependent manner, ensuring ERBB4 is either endocytosed or stabilised.
LIG_WW_1 Q15303 1053-1056 SWTI000657 Alternative splicing removes the WW-binding motif of Receptor tyrosine-protein kinase erbB-4 (ERBB4), abrogating binding to E3 ubiquitin-protein ligase Itchy homolog (ITCH). The presence of a WW-binding motif mediates ERBB4 mono-ubiquitination and endocytosis by the WW domain-containing HECT-type E3 ubiquitin ligase ITCH.
LIG_WW_1 Q4VCS5 239-242 SWTI000658 Alternative splicing removes the WW-binding motif of Angiomotin (AMOT), abrogating binding to Yorkie homolog (YAP1). The splice specific Isoform p130 of AMOT works within the Hippo pathway to sequester the transcription coactivator YAP1 away at tight junction. In contrast Isoform p80 of AMOT lacks WW-binding motif.
LIG_TYR_ITSM O43613 79-86 SWTI000659 Orexin-A induced phosphorylation of the ITSM and ITIM motifs in Orexin receptor type 1 (HCRTR1) allows binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) via its two SH2 domains. Mutation of either tyrosine in the motifs abolishes binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11).
LIG_TYR_ITIM O43613 356-361 SWTI000659 Orexin-A induced phosphorylation of the ITSM and ITIM motifs in Orexin receptor type 1 (HCRTR1) allows binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) via its two SH2 domains. Mutation of either tyrosine in the motifs abolishes binding of Tyrosine-protein phosphatase non-receptor type 11 (PTPN11).
LIG_WW_1 Q14118 889-892 SWTI000660 The WW-binding motif for Dystrophin (DMD) and the SH3-binding motif for Growth factor receptor-bound protein 2 (GRB2) on Dystroglycan (DAG1) overlap, making their interactions mutually exclusive and competitive.
LIG_SH3_3 Q14118 888-894 SWTI000660 The WW-binding motif for Dystrophin (DMD) and the SH3-binding motif for Growth factor receptor-bound protein 2 (GRB2) on Dystroglycan (DAG1) overlap, making their interactions mutually exclusive and competitive.
DOC_WW_Pin1_4 Q969H0 202-207 SWTI000661 Phosphorylation of T205 in the Pin1-binding motif of F-box/WD repeat-containing protein 7 (FBXW7) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. Pin1 interacts with Fbw7 in a phoshorylation-dependent manner and promotes Fbw7 self-ubiquitination and protein degradation by disrupting Fbw7 dimerization. Paper also shows the over-expression of Pin1 suppresses the ability of Fbw7 to inhibit cell transformation and proliferation, suggesting a link between Pin1 overexpression and cancer.
LIG_SUMO_SBM_1 O75925 457-461 SWTI000662 Acetylation of K33 in Small ubiquitin-related modifier 2 (SUMO2) inhibits binding to E3 SUMO-protein ligase PIAS1 (PIAS1). The acetylation counters SUMO-SIM-dependent transcriptional repression processes. An additional interaction is also possible upon acetylation with the Bromodomain of p300 shown to bind the acetylated version of SUMO2. This does not occur with acetylated SUMO1. Acetylation is countered by Histone deacetylase family, HD type 1 subfamily.
LIG_SUMO_SBM_1 O75925 457-461 SWTI000663 Acetylation of K37 in Small ubiquitin-related modifier 1 (SUMO1) inhibits binding to E3 SUMO-protein ligase PIAS1 (PIAS1). The acetylation counters SUMO-SIM-dependent transcriptional repression processes. Acetylation is countered by Histone deacetylase family, HD type 1 subfamily.
LIG_SUMO_SBM_1 O75928 467-471 SWTI000664 Acetylation of K33 in Small ubiquitin-related modifier 2 (SUMO2) inhibits binding to E3 SUMO-protein ligase PIAS2 (PIAS2). The acetylation counters SUMO-SIM-dependent transcriptional repression processes. An additional interaction is also possible upon acetylation with the Bromodomain of p300 shown to bind the acetylated version of SUMO2. This does not occur with acetylated SUMO1. Acetylation is countered by Histone deacetylase family, HD type 1 subfamily.
LIG_SUMO_SBM_1 O75928 467-471 SWTI000665 Acetylation of K37 in Small ubiquitin-related modifier 1 (SUMO1) inhibits binding to E3 SUMO-protein ligase PIAS2 (PIAS2). The acetylation counters SUMO-SIM-dependent transcriptional repression processes. Acetylation is countered by Histone deacetylase family, HD type 1 subfamily.
MOD_GSK3_1 Q92731 5-12 SWTI000668 The GSK3-beta binding site at S12 in Estrogen receptor beta (ESR2) is primed by (most likely) RAC-alpha serine/threonine-protein kinase (AKT1). This enhances the binding of SUMO-conjugating enzyme UBC9 (UBE2I) at the adjacent Sumoylation site. This site is also primed at S6 (most likely) by AKT1. The addition of SUMO at K4 stabilises ESR2 as it prevents the ubiquitination at K4 (see switch details)
MOD_SUMO_PHOS Q92731 4-7 SWTI000668 The GSK3-beta binding site at S12 in Estrogen receptor beta (ESR2) is primed by (most likely) RAC-alpha serine/threonine-protein kinase (AKT1). This enhances the binding of SUMO-conjugating enzyme UBC9 (UBE2I) at the adjacent Sumoylation site. This site is also primed at S6 (most likely) by AKT1. The addition of SUMO at K4 stabilises ESR2 as it prevents the ubiquitination at K4 (see switch details)
MOD_SUMO_PHOS Q92731 4-7 SWTI000669 Sumoylation of K4 in Estrogen receptor beta (ESR2) is inhibited by ubiquitination K4. This destabilises ESR2 increasing its turnover (see also switch details)
TRG_NLS_MonoExtN_4 Q13309 65-72 SWTI000670 Acetylation of S-phase kinase-associated protein 2 (SKP2) in its NLS inhibits binding to the Importin subunit alpha-6 (KPNA5). p300 acetylates SKP2 at K68 and K71 within SKP2\'s nuclear localisation signal, this stabilises SKP2 from Fizzy-related protein homolog (FZR1)-mediated degradation and facilitates its translocation into the cytoplasm. This process can be reversed by NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SIRT3) that specifically deacetylates SKP2 facilitating its translocation back into the nucleus. In the cytosol, SKP2 acts to promote Cadherin-1 (CDH1) degradation in a Casein Kinase I dependent manner to promote cell migration. Casein kinase I recognises the MOD_CK1_1 motif in CDH1 phosphorylating at residues Ser840 and Ser842.
TRG_NLS_MonoExtN_4 Q13309 65-72 SWTI000671 Acetylation of S-phase kinase-associated protein 2 (SKP2) in its NLS inhibits binding to the Importin subunit alpha-7 (KPNA6). p300 acetylates SKP2 at K68 and K71 within SKP2\'s nuclear localisation signal, this stabilises SKP2 from Fizzy-related protein homolog (FZR1)-mediated degradation and facilitates its translocation into the cytoplasm. This process can be reversed by NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SIRT3) that specifically deacetylates SKP2 facilitating its translocation back into the nucleus. In the cytosol, SKP2 acts to promote Cadherin-1 (CDH1) degradation in a Casein Kinase I dependent manner to promote cell migration. Casein kinase I recognises the MOD_CK1_1 motif in CDH1 phosphorylating at residues Ser840 and Ser842.
LIG_TPR_Kinesin_1 Q8IWE5 236-240 SWTI000672 Alternative splicing removes the Kinesin Light Chain-binding motif of Pleckstrin homology domain-containing family M member 2 (PLEKHM2), abrogating binding to Kinesin light chain 2 (KLC2). Pleckstrin homology domain-containing family M member 2 (PLEKHM2) contains kinesin light chain (KLC) binding WD motifs (second motif at 205-210), and these are required for kinesin-1 recruitment and the peripheral movement of lysosomes. ADP-ribosylation factor-like protein 8B (ARL8B) and PLEKHM2 act together to recruit kinesin-1 to lysosomes and hence direct their movement toward microtubule plus ends. A splice variant of PLEKHM2 that lacks a light chain binding motif does not\xc2\xa0stimulate movement, suggesting fine-tuning by alternative splicing.
DOC_PP1 O35867 455-461 SWTI000673 Phosphorylation of S461 in the PP1-binding motif of Neurabin-1 (Ppp1r9a) by cAMP subfamily inhibits binding to the Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (Ppp1ca). Binding of Neurabin-1 (Ppp1r9a) inhibits activity of the phosphatase.
LIG_PDZ_Class_1 P09619 1101-1106 SWTI000674 Phosphorylation of S1104 in the PDZ-binding motif of Platelet-derived growth factor receptor beta (PDGFRB) by Beta-adrenergic receptor kinase 1 (ADRBK1) inhibits binding to Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (SLC9A3R1). Binding of Platelet-derived growth factor receptor beta (PDGFRB) to Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (SLC9A3R1) potentiates dimerisation and signalling of the receptor, while phosphorylation at S1104 desensitises the receptor.
LIG_Clathr_ClatBox_1 P49418 351-355 SWTI000675 Phosphorylation of T350 adjacent to the clathrin-binding motif of Amphiphysin (AMPH) by CK2 subfamily inhibits binding to the Clathrin heavy chain 1 (CLTC). A second clathrin-binding motif in Amphiphysin (AMPH) is regulated in a similar manner (see switch details). Both these motifs cooperate in avidity-based binding to Clathrin heavy chain 1 (CLTC) (see switch details).
LIG_Clathr_ClatBox_2 P49418 380-385 SWTI000676 Phosphorylation of T387 adjacent to the clathrin-binding motif of Amphiphysin (AMPH) by CK2 subfamily inhibits binding to the Clathrin heavy chain 1 (CLTC). A second clathrin-binding motif in Amphiphysin (AMPH) is regulated in a similar manner (see switch details). Both these motifs cooperate in avidity-based binding to Clathrin heavy chain 1 (CLTC) (see switch details).
LIG_Clathr_ClatBox_1 P49418 351-355 SWTI000677 Amphiphysin 1 contains two distinct motifs that bind to distinct sites on N-terminal beta-propeller domain of clathrin, resulting in increased binding strength to free domain. This, in combination with binding of its BAR domain to curved membranes, results in localisation of amphipysin to the periphery of the assembling clathrin lattice. The two clathrin-binding motifs are regulated by phosphorylation of adjacent modification sites (see switch details and switch details).
LIG_Clathr_ClatBox_2 P49418 380-385 SWTI000677 Amphiphysin 1 contains two distinct motifs that bind to distinct sites on N-terminal beta-propeller domain of clathrin, resulting in increased binding strength to free domain. This, in combination with binding of its BAR domain to curved membranes, results in localisation of amphipysin to the periphery of the assembling clathrin lattice. The two clathrin-binding motifs are regulated by phosphorylation of adjacent modification sites (see switch details and switch details).
LIG_WW_1 O15350 484-487 SWTI000678 The transcriptional coactivator YAP1 and the ubiquitin ligase Itch competitively bind to the same WW-binding motif of p73. Binding of YAP1 prevents Itch-mediated ubiquitylation of p73, resulting in stabilisation, and increases trancriptional activity of p73.
LIG_PCNA_PIPBox_1 Q15054 456-465 SWTI000679 Phosphorylation of S458 in the PCNA-binding motif of DNA polymerase delta subunit 3 (POLD3) by cAMP subfamily reduces the affinity of binding to the Proliferating cell nuclear antigen (PCNA) and decreases the processivity of the polymerase complex.
TRG_ENDOCYTIC_2 P32004 1176-1179 SWTI000680 Phosphorylation of Y1176 in the endocytotic motif of Neural cell adhesion molecule L1 (L1CAM) by Proto-oncogene tyrosine-protein kinase Src (SRC) abolishes binding to the AP-2 complex subunit mu (AP2M1) and thereby inhibits internalisation of Neural cell adhesion molecule L1 (L1CAM).
DOC_USP7_1 O15151 398-402 SWTI000681 Phosphorylation of S403 adjacent to the USP7-binding motif of Protein Mdm4 (MDM4) by Serine-protein kinase ATM (ATM) inhibits binding to the Ubiquitin carboxyl-terminal hydrolase 7 (USP7), thereby reducing deubiquitylation of Protein Mdm4 (MDM4). As a result, ubiquitylation by E3 ubiquitin-protein ligase Mdm2 (MDM2) is not countered and Protein Mdm4 (MDM4) is targeted for proteasomal degradation.
LIG_14-3-3_1 O15151 364-369 SWTI000682 Optimal binding of 14-3-3 dimer to Hdmx in response to DNA damage requires phosphorylation of two 14-3-3-binding motifs by Chk2 kinase. Binding of 14-3-3 dimer is involved in inactivation of Hdmx, a negative regulator of p53, in response to DNA damage.
LIG_14-3-3_3 O15151 339-344 SWTI000682 Optimal binding of 14-3-3 dimer to Hdmx in response to DNA damage requires phosphorylation of two 14-3-3-binding motifs by Chk2 kinase. Binding of 14-3-3 dimer is involved in inactivation of Hdmx, a negative regulator of p53, in response to DNA damage.
DOC_CYCLIN_1 Q9WTQ5 501-504 SWTI000683 Phosphorylation of S507 adjacent to the cyclin-binding motif of A-kinase anchor protein 12 (Akap12) by PKC subfamily blocks binding to the G1/S-specific cyclin-D1 (Ccnd1). As a result, the function of A-kinase anchor protein 12 (Akap12) as a scaffold is inhibited and G1/S-specific cyclin-D1 (Ccnd1) is translocated to the nucleus where it regulates progression of the cell cycle from G1 to S phase.
LIG_WW_1 P05627 167-170 SWTI000684 Phosphorylation of Y170 in the WW-binding motif of Transcription factor AP-1 (Jun) by Tyrosine-protein kinase ABL1 (Abl1) blocks binding to the E3 ubiquitin-protein ligase Itchy (Itch). As a result, Transcription factor AP-1 (Jun) is not ubiquitylated by E3 ubiquitin-protein ligase Itchy (Itch), and thus not targeted for proteasomal degradation. Regulation of transcriptional activity of Transcription factor AP-1 (Jun) by Tyrosine-protein kinase ABL1 (Abl1) required translocation of the kinase to the nucleus, which was triggered by T cell activation.
DEG_APCC_KENbox_2 O60566 303-307 SWTI000685 Binding of the second KEN-box motif of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B), a subunit of the Spindle Assembly Checkpoint (SAC), to the substrate recruitment site of Cell division cycle protein 20 homolog (CDC20), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), blocks binding of the Cdc20 substrate G2/mitotic-specific cyclin-B1 (CCNB1). As a result, G2/mitotic-specific cyclin-B1 (CCNB1) is not targeted for proteasomal degradation until metaphase, when the SAC is inhibited. Destruction of G2/mitotic-specific cyclin-B1 (CCNB1) is required for progression to the anaphase of the cell cycle.
DEG_APCC_Dbox_1 P14635 41-49 SWTI000685 Binding of the second KEN-box motif of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B), a subunit of the Spindle Assembly Checkpoint (SAC), to the substrate recruitment site of Cell division cycle protein 20 homolog (CDC20), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), blocks binding of the Cdc20 substrate G2/mitotic-specific cyclin-B1 (CCNB1). As a result, G2/mitotic-specific cyclin-B1 (CCNB1) is not targeted for proteasomal degradation until metaphase, when the SAC is inhibited. Destruction of G2/mitotic-specific cyclin-B1 (CCNB1) is required for progression to the anaphase of the cell cycle.
DEG_APCC_KENbox_2 O60566 303-307 SWTI000686 Binding of the second KEN-box motif of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B), a subunit of the Spindle Assembly Checkpoint (SAC), to the substrate recruitment site of Cell division cycle protein 20 homolog (CDC20), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), blocks binding of the Cdc20 substrate Securin (PTTG1). As a result, Securin (PTTG1) is not targeted for proteasomal degradation until metaphase, when the SAC is inhibited. Destruction of Securin (PTTG1) is required for progression to the anaphase of the cell cycle.
DEG_APCC_Dbox_1 O95997 60-68 SWTI000686 Binding of the second KEN-box motif of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B), a subunit of the Spindle Assembly Checkpoint (SAC), to the substrate recruitment site of Cell division cycle protein 20 homolog (CDC20), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), blocks binding of the Cdc20 substrate Securin (PTTG1). As a result, Securin (PTTG1) is not targeted for proteasomal degradation until metaphase, when the SAC is inhibited. Destruction of Securin (PTTG1) is required for progression to the anaphase of the cell cycle.
DEG_APCC_KENbox_2 Q08981 97-101 SWTI000687 The KEN-box motif of APC/C-CDH1 modulator 1 (ACM1) binds to the substrate recruitment site of APC/C activator protein CDH1 (CDH1), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), and thereby blocks recruitment, and subsequent targeting for proteasomal degradation, of the Cdh1 substrate G2/mitotic-specific cyclin-2 (CLB2). Degradation of G2/mitotic-specific cyclin-2 (CLB2) is required for mitotic exit and maintenance of the G1 phase of the cell cycle and is allowed by Cdc20-dependent degradation of APC/C-CDH1 modulator 1 (ACM1) in anaphase.
DEG_APCC_Dbox_1 P24869 99-103 SWTI000687 The KEN-box motif of APC/C-CDH1 modulator 1 (ACM1) binds to the substrate recruitment site of APC/C activator protein CDH1 (CDH1), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), and thereby blocks recruitment, and subsequent targeting for proteasomal degradation, of the Cdh1 substrate G2/mitotic-specific cyclin-2 (CLB2). Degradation of G2/mitotic-specific cyclin-2 (CLB2) is required for mitotic exit and maintenance of the G1 phase of the cell cycle and is allowed by Cdc20-dependent degradation of APC/C-CDH1 modulator 1 (ACM1) in anaphase.
DEG_APCC_KENbox_2 Q08981 97-101 SWTI000688 The KEN-box motif of APC/C-CDH1 modulator 1 (ACM1) binds to the substrate recruitment site of APC/C activator protein CDH1 (CDH1), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), and thereby blocks recruitment, and subsequent targeting for proteasomal degradation, of the Cdh1 substrate Kinesin-like protein CIN8 (CIN8). Degradation of Kinesin-like protein CIN8 (CIN8) is required for mitotic exit and maintenance of the G1 phase of the cell cycle and is allowed by Cdc20-dependent degradation of APC/C-CDH1 modulator 1 (ACM1) in anaphase.
DEG_APCC_Dbox_1 P27895 931-935 SWTI000688 The KEN-box motif of APC/C-CDH1 modulator 1 (ACM1) binds to the substrate recruitment site of APC/C activator protein CDH1 (CDH1), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), and thereby blocks recruitment, and subsequent targeting for proteasomal degradation, of the Cdh1 substrate Kinesin-like protein CIN8 (CIN8). Degradation of Kinesin-like protein CIN8 (CIN8) is required for mitotic exit and maintenance of the G1 phase of the cell cycle and is allowed by Cdc20-dependent degradation of APC/C-CDH1 modulator 1 (ACM1) in anaphase.
DEG_APCC_KENbox_2 Q08981 97-101 SWTI000689 The KEN-box motif of APC/C-CDH1 modulator 1 (ACM1) binds to the substrate recruitment site of APC/C activator protein CDH1 (CDH1), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), and thereby blocks recruitment, and subsequent targeting for proteasomal degradation, of the Cdh1 substrate Probable serine/threonine-protein kinase HSL1 (HSL1). Degradation of Probable serine/threonine-protein kinase HSL1 (HSL1) is required for mitotic exit and maintenance of the G1 phase of the cell cycle and is allowed by Cdc20-dependent degradation of APC/C-CDH1 modulator 1 (ACM1) in anaphase.
DEG_APCC_Dbox_1 P34244 774-778 SWTI000689 The KEN-box motif of APC/C-CDH1 modulator 1 (ACM1) binds to the substrate recruitment site of APC/C activator protein CDH1 (CDH1), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), and thereby blocks recruitment, and subsequent targeting for proteasomal degradation, of the Cdh1 substrate Probable serine/threonine-protein kinase HSL1 (HSL1). Degradation of Probable serine/threonine-protein kinase HSL1 (HSL1) is required for mitotic exit and maintenance of the G1 phase of the cell cycle and is allowed by Cdc20-dependent degradation of APC/C-CDH1 modulator 1 (ACM1) in anaphase.
LIG_14-3-3_1 P98177 29-34 SWTI000690 Phosphorylation of two 14-3-3-binding motifs in Foxo4 by PKB induces binding of 14-3-3 dimer. In the nucleus, this blocks binding to DNA, while in the cytoplasm it blocks reimport of Foxo4 into the nucleus by blocking its Nuclear Localisation Signal (NLS). Since binding of 14-3-3 to a single motif occurs with an affinity similar to the affinity of Foxo4 for DNA, multivalent binding of 14-3-3 dimer is required for efficient inhibition of DNA binding.
LIG_14-3-3_2 P98177 193-199 SWTI000690 Phosphorylation of two 14-3-3-binding motifs in Foxo4 by PKB induces binding of 14-3-3 dimer. In the nucleus, this blocks binding to DNA, while in the cytoplasm it blocks reimport of Foxo4 into the nucleus by blocking its Nuclear Localisation Signal (NLS). Since binding of 14-3-3 to a single motif occurs with an affinity similar to the affinity of Foxo4 for DNA, multivalent binding of 14-3-3 dimer is required for efficient inhibition of DNA binding.
MOD_LATS_1 P46937-2 376-381 SWTI000691 Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E
MOD_CK1_1 P46937-2 381-387 SWTI000691 Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E
MOD_CK1_1 P46937-2 384-390 SWTI000691 Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E
LIG_SCF-TrCP1_2 P46937-2 383-387 SWTI000691 Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E
TRG_NLS P46527 152-166 SWTI000692 Phosphorylation of a 14-3-3-binding motif in the NLS of Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) induces binding of 14-3-3 protein gamma (YWHAG), which hides the NLS and prevents binding to Importin subunit alpha-1 (KPNA1), thereby mediating cytoplasmic retention of Cyclin-dependent kinase inhibitor 1B (CDKN1B). Binding of 14-3-3 dimer involves an additional C-terminal 14-3-3-binding motif (see switch details).
LIG_14-3-3_3 P46527 154-159 SWTI000692 Phosphorylation of a 14-3-3-binding motif in the NLS of Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) induces binding of 14-3-3 protein gamma (YWHAG), which hides the NLS and prevents binding to Importin subunit alpha-1 (KPNA1), thereby mediating cytoplasmic retention of Cyclin-dependent kinase inhibitor 1B (CDKN1B). Binding of 14-3-3 dimer involves an additional C-terminal 14-3-3-binding motif (see switch details).
PF00244">PF00244 P61981 4-241 SWTI000693 Phosphorylation of two 14-3-3-binding motifs in Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) and ribosomal protein S6 kinases (Ribosomal protein S6 kinase alpha-1 (RPS6KA1), Ribosomal protein S6 kinase alpha-3 (RPS6KA3)) induces binding of 14-3-3 dimer. Binding of 14-3-3 results in cytoplasmic localisation of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (see switch details), thereby alleviating Cyclin-dependent kinase inhibitor 1B (CDKN1B)-mediated inhibition of cyclin-dependent kinases and cell cycle progression.
LIG_14-3-3_3 P46527 154-159 SWTI000693 Phosphorylation of two 14-3-3-binding motifs in Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) and ribosomal protein S6 kinases (Ribosomal protein S6 kinase alpha-1 (RPS6KA1), Ribosomal protein S6 kinase alpha-3 (RPS6KA3)) induces binding of 14-3-3 dimer. Binding of 14-3-3 results in cytoplasmic localisation of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (see switch details), thereby alleviating Cyclin-dependent kinase inhibitor 1B (CDKN1B)-mediated inhibition of cyclin-dependent kinases and cell cycle progression.
LIG_14-3-3_3 P46527 193-198 SWTI000693 Phosphorylation of two 14-3-3-binding motifs in Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) and ribosomal protein S6 kinases (Ribosomal protein S6 kinase alpha-1 (RPS6KA1), Ribosomal protein S6 kinase alpha-3 (RPS6KA3)) induces binding of 14-3-3 dimer. Binding of 14-3-3 results in cytoplasmic localisation of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (see switch details), thereby alleviating Cyclin-dependent kinase inhibitor 1B (CDKN1B)-mediated inhibition of cyclin-dependent kinases and cell cycle progression.
LIG_PCNA_PIPBox_1 P38936 144-153 SWTI000694 Phosphorylation of T145 in the PCNA-binding motif of Cyclin-dependent kinase inhibitor 1 (CDKN1A) by RAC-alpha serine/threonine-protein kinase (AKT1) inhibits binding to Proliferating cell nuclear antigen (PCNA). As a result, Cyclin-dependent kinase inhibitor 1 (CDKN1A) no longer inhibits Proliferating cell nuclear antigen (PCNA) and blocking of DNA replication is relieved.
LIG_PCNA_PIPBox_1 P38936 144-153 SWTI000695 Phosphorylation of S146 in the PCNA-binding motif of Cyclin-dependent kinase inhibitor 1 (CDKN1A) by PKC subfamily inhibits binding to Proliferating cell nuclear antigen (PCNA). As a result, Cyclin-dependent kinase inhibitor 1 (CDKN1A) no longer inhibits Proliferating cell nuclear antigen (PCNA) and blocking of DNA replication is relieved.
LIG_eIF4E_1 Q13541 54-60 SWTI000696 Phosphorylation of S65 flanking the eIF4E-binding motif of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) by Serine/threonine-protein kinase mTOR (MTOR) inhibits binding to Eukaryotic translation initiation factor 4E (EIF4E) in response to growth factors and nutrients. This results in release of Eukaryotic translation initiation factor 4E (EIF4E), which associates with other initiation factors to form the eIF-4F complex that mediates initiation of translation. However, disruption of the interaction between Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) and Eukaryotic translation initiation factor 4E (EIF4E) has been shown to be dependent on hyperphosphorylation of Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) by FRAP/mTOR, PI3K and ERK pathways. According to the current model, Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) is phosphorylated on multiple residues in a well-defined order. Basal phosphorylation of T37 and T46 serves as a priming event for subsequent serum-induced phosphorylation of T70, which primes for subsequent phosphorylation of S65.
LIG_14-3-3_1 Q61337 133-138 SWTI000697 Phosphorylation of S136 in Bcl2 antagonist of cell death (Bad) by RAC-alpha serine/threonine-protein kinase (Akt1) in response to survival and growth signals such as Interleukin-3 (Il3) induces binding to 14-3-3 protein theta (Ywhaq). Binding of 14-3-3 protein theta (Ywhaq) results in dissociation of Bcl2 antagonist of cell death (Bad) from Bcl-2-like protein 1 (Bcl2l1), and thereby inhibits the pro-apoptotic activity of Bcl2 antagonist of cell death (Bad) by allowing liberated Bcl-2-like protein 1 (Bcl2l1) to exert its anti-apoptotic effect on pro-apoptotic proteins like Apoptosis regulator BAX (Bax).
LIG_SH2_SRC P00533 1016-1019 SWTI000698 Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1).
LIG_SH2_SRC P00533 1125-1128 SWTI000699 Phosphorylation of Y1125 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to Adapter molecule crk (CRK).
LIG_SH2_SRC P00533 1016-1019 SWTI000700 Phosphorylation of Y1016 in the SH2-binding motif of Epidermal growth factor receptor (EGFR) induces binding to Cytoplasmic protein NCK1 (NCK1).
LIG_SH2_GRB2 P21860 1262-1265 SWTI000701 Phosphorylation of Y1262 in the SH2-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to Growth factor receptor-bound protein 2 (GRB2).
LIG_SH2_SRC Q05397 397-400 SWTI000702 Phosphorylation of Y397 in the SH2-binding motif of Focal adhesion kinase 1 (PTK2) induces binding to Neuronal proto-oncogene tyrosine-protein kinase Src (Src).
LIG_SH2_STAT5 Q13480 472-475 SWTI000703 Phosphorylation of Y472 in the SH2-binding motif of GRB2-associated-binding protein 1 (GAB1) induces binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1).
LIG_SH2_STAT5 Q13480 447-450 SWTI000704 Phosphorylation of Y447 in the SH2-binding motif of GRB2-associated-binding protein 1 (GAB1) induces binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1).
MOD_SUMO P29590 159-162 SWTI000666 Sumoylation of K160 induces binding to the Protein PML (PML) protein. SUMO-modified forms of PML are essential for the recruitment of Death domain-associated protein 6 (DAXX) to PML nuclear bodies.
LIG_SUMO_SBM_1 Q9UER7 733-740 SWTI000666 Sumoylation of K160 induces binding to the Protein PML (PML) protein. SUMO-modified forms of PML are essential for the recruitment of Death domain-associated protein 6 (DAXX) to PML nuclear bodies.
LIG_SUMO_SBM_1 Q9UER7 733-740 SWTI000705 Acetylation of K33 in the SUMO2 inhibits binding to the Death domain-associated protein 6 (DAXX) protein see switch details. SUMO-modified forms of Protein PML (PML) are essential for the recruitment of Small ubiquitin-related modifier 2 (SUMO2) to PML nuclear bodies. The acetylated versions of SUMO1/2 failed to trigger recruitment of Small ubiquitin-related modifier 2 (SUMO2) into the nuclear bodies. An additional interaction is also possible upon acetylation with the Bromodomain of Histone acetyltransferase p300 (EP300) shown to bind the acetylated version of SUMO2. This does not occur with acetylated SUMO1. Acetylation is countered by Histone deacetylase family, HD type 1 subfamily.
LIG_BROMO P61956 33-33 SWTI000705 Acetylation of K33 in the SUMO2 inhibits binding to the Death domain-associated protein 6 (DAXX) protein see switch details. SUMO-modified forms of Protein PML (PML) are essential for the recruitment of Small ubiquitin-related modifier 2 (SUMO2) to PML nuclear bodies. The acetylated versions of SUMO1/2 failed to trigger recruitment of Small ubiquitin-related modifier 2 (SUMO2) into the nuclear bodies. An additional interaction is also possible upon acetylation with the Bromodomain of Histone acetyltransferase p300 (EP300) shown to bind the acetylated version of SUMO2. This does not occur with acetylated SUMO1. Acetylation is countered by Histone deacetylase family, HD type 1 subfamily.
MOD_SUMO P29590 159-162 SWTI000667 Sumoylation of K160 induces binding to the Protein PML (PML) protein. SUMO-modified forms of PML are essential for the recruitment of Death domain-associated protein 6 (DAXX) to PML nuclear bodies.
LIG_SUMO_SBM_1 Q9UER7 733-740 SWTI000667 Sumoylation of K160 induces binding to the Protein PML (PML) protein. SUMO-modified forms of PML are essential for the recruitment of Death domain-associated protein 6 (DAXX) to PML nuclear bodies.
LIG_SUMO_SBM_1 Q9UER7 733-740 SWTI000706 Acetylation of K37 in the SUMO1 inhibits binding to the Small ubiquitin-related modifier 1 (SUMO1) protein see switch details. SUMO-modified forms of Protein PML (PML) are essential for the recruitment of DAXX to PML nuclear bodies. The acetylated versions of SUMO1/2 failed to trigger recruitment of DAXX into the nuclear bodies. Acetylation is countered by Histone deacetylase family, HD type 1 subfamily.
LIG_SUMO_SBM_1 P29590 556-566 SWTI000707 Alternative splicing removes the Sumoylation interacting motif (SIM) of Protein PML (PML), abrogating binding to Small ubiquitin-related modifier 1 (SUMO1) in Isoform TRIM19epsilon. Isoforms lacking the SIM were resistant to As2O3-induced PML degradation.
MOD_SUMO O95644 701-704 SWTI000708 Alternative splicing removes the Sumoylation motif (SIM) of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1), preventing the sumolyation of Isoform A-alpha. Both the Isoform C-alpha and Isoform A-alpha exert a differential effect upon IL-2 expression. However, the longer isoform, Isoform C-alpha, has a sumoylation motif and is therefore negatively regulated in a sumolyation-dependent manner.
MOD_SUMO O95644 913-916 SWTI000709 Alternative splicing removes the Sumoylation motif (SIM) of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1), preventing the sumolyation of Isoform A-alpha. Both the Isoform C-alpha and Isoform A-alpha exert a differential effect upon IL-2 expression. However, the longer isoform, Isoform C-alpha, has a sumoylation motif and is therefore negatively regulated in a sumolyation-dependent manner.
TRG_NES P21192 122-150 SWTI000710 Phosphorylation of S137 in the NES of Metallothionein expression activator (ACE2) inhibits binding to Exportin-1 (CRM1). Phosphorylation of S137, and to a lesser extent S122, by Cbk1 directly antagonizes the interaction of Ace2 with nuclear export machinery.
TRG_NES P21192 122-150 SWTI000711 Phosphorylation of S122 in the NES of Metallothionein expression activator (ACE2) inhibits binding to Exportin-1 (CRM1). Phosphorylation of S137, and to a lesser extent S122, by Cbk1 directly antagonizes the interaction of Ace2 with nuclear export machinery.
DEG_SCF_TIR1_1 Q38825 82-93 SWTI000712 Binding of Auxin-responsive protein IAA7 (IAA7) to Protein TRANSPORT INHIBITOR RESPONSE 1 (TIR1), an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone 22676" target="_blank">auxin to TIR1, as this pre-assembled complex provides a composite binding site for the degron motif in IAA7. Subsequent ubiquitylation of IAA7 by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to auxin.
DEG_SCF_TIR1_1 P93830 82-93 SWTI000713 Binding of Auxin-responsive protein IAA17 (IAA17) to Protein TRANSPORT INHIBITOR RESPONSE 1 (TIR1), an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone 22676" target="_blank">auxin to TIR1, as this pre-assembled complex provides a composite binding site for the degron motif in IAA17. Subsequent ubiquitylation of IAA17 by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to auxin.
DEG_SCF_TIR1_1 P49677 55-66 SWTI000714 Binding of Auxin-responsive protein IAA1 (IAA1) to Protein TRANSPORT INHIBITOR RESPONSE 1 (TIR1), an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone 22676" target="_blank">auxin to TIR1, as this pre-assembled complex provides a composite binding site for the degron motif in IAA1. Subsequent ubiquitylation of IAA1 by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to auxin.
DEG_SCF_TIR1_1 Q9XFM0 48-59 SWTI000715 Binding of Auxin-responsive protein IAA28 (IAA28) to Protein TRANSPORT INHIBITOR RESPONSE 1 (TIR1), an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone 22676" target="_blank">auxin to TIR1, as this pre-assembled complex provides a composite binding site for the degron motif in IAA28. Subsequent ubiquitylation of IAA28 by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to auxin.
DEG_SCF_TIR1_1 Q38830 69-80 SWTI000716 Binding of Auxin-responsive protein IAA12 (IAA12) to Protein TRANSPORT INHIBITOR RESPONSE 1 (TIR1), an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone 22676" target="_blank">auxin to TIR1, as this pre-assembled complex provides a composite binding site for the degron motif in IAA12. Subsequent ubiquitylation of IAA12 by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to auxin.
DEG_SCF_TIR1_1 Q38822 64-75 SWTI000717 Binding of Auxin-responsive protein IAA3 (IAA3) to Protein TRANSPORT INHIBITOR RESPONSE 1 (TIR1), an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone 22676" target="_blank">auxin to TIR1, as this pre-assembled complex provides a composite binding site for the degron motif in IAA3. Subsequent ubiquitylation of IAA3 by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to auxin.
DEG_SCF_COI1_1 Q9LVI4 303-320 SWTI000718 Binding of Protein TIFY 6B (TIFY6B) to Coronatine-insensitive protein 1 (COI1), an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone jasmonate to COI1, as this pre-assembled complex provides a composite binding site for the degron motif in TIFY6B. Subsequent ubiquitylation of TIFY6B by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to jasmonate.
DEG_SCF_COI1_1 Q9LMA8 203-220 SWTI000719 Binding of Protein TIFY 10A (TIFY10A) to Coronatine-insensitive protein 1 (COI1), an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone jasmonate to COI1, as this pre-assembled complex provides a composite binding site for the degron motif in TIFY10A. Subsequent ubiquitylation of TIFY10A by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to jasmonate.
DEG_SCF_COI1_1 Q8W4J8 221-238 SWTI000720 Binding of Protein TIFY 7 (TIFY7) to Coronatine-insensitive protein 1 (COI1), an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone jasmonate to COI1, as this pre-assembled complex provides a composite binding site for the degron motif in TIFY7. Subsequent ubiquitylation of TIFY7 by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to jasmonate.
DEG_SCF_COI1_1 Q9S7M2 205-222 SWTI000721 Binding of Protein TIFY 10B (TIFY10B) to Coronatine-insensitive protein 1 (COI1), an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone jasmonate to COI1, as this pre-assembled complex provides a composite binding site for the degron motif in TIFY10B. Subsequent ubiquitylation of TIFY10B by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to jasmonate.
DEG_SCF_COI1_1 B2XVS2 251-268 SWTI000723 Binding of to Coi1, an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone jasmonate to COI1, as this pre-assembled complex provides a composite binding site for the degron motif in the JAZ protein. Subsequent ubiquitylation of the JAZ protein by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to jasmonate.
DEG_SCF_COI1_1 A7XXZ0 199-216 SWTI000722 Binding of LOC100134911 to Coi1, an F-box substrate recognition subunit of the SCF E3 ubiquitin ligase, depends on binding of the plant hormone jasmonate to COI1, as this pre-assembled complex provides a composite binding site for the degron motif in the JAZ protein. Subsequent ubiquitylation of the JAZ protein by the SCF targets this transcriptional repressor for proteasomal degradation, a pre-requisite for the transcriptional response to jasmonate.
LIG_SH2_STAT5 Q13480-2 447-450 SWTI000704 Phosphorylation of Y447 in the SH2-binding motif of GRB2-associated-binding protein 1 (GAB1) induces binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1).
LIG_SH2_STAT5 Q13480-2 472-475 SWTI000703 Phosphorylation of Y472 in the SH2-binding motif of GRB2-associated-binding protein 1 (GAB1) induces binding to Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1).
LIG_NRBOX Q16881-4 46-52 SWTI000481 Alternative splicing removes the NRBOX motif of Q16881-4, abrogating binding to Estrogen receptor (ESR1). Unlike splice variants without the NRBOX motif, TrxR1b (also known as Isoform TXNRD1_v2) is identified within the nucleus. TrxR1b enhanced the transcriptional activity of the estrogen receptors ESR1 and ESR2, possibly by providing a reduced environment in the immediate vicinity of the ERs.
LIG_NRBOX Q16881-4 46-52 SWTI000482 Alternative splicing removes the NRBOX motif of Q16881-4, abrogating binding to Estrogen receptor beta (ESR2). Unlike splice variants without the NRBOX motif, TrxR1b (also known as Isoform TXNRD1_v2) is identified within the nucleus. TrxR1b enhanced the transcriptional activity of the estrogen receptors ESR1 and ESR2, possibly by providing a reduced environment in the immediate vicinity of the ERs.
LIG_SH3_3 P10636-8 213-219 SWTI000198 Phosphorylation of S527 adjacent to the SH3-binding motif of Microtubule-associated protein tau (MAPT) inhibits binding to Tyrosine-protein kinase Fyn (FYN).
LIG_PDZ_Class_1 P22756-2 900-905 SWTI000560 Alternative splicing removes the PDZ-binding motif of Glutamate receptor, ionotropic kainate 1 (Grik1), abrogating binding to PRKCA-binding protein (Pick1). The ER-retention motif of Grik1 splice variants can be inhibited by PKC phosphorylation and association with a PDZ protein. It has also been shown that the PDZ domain-containing proteins Disks large homolog 4 (Dlg4) and Syntenin-1 (Sdcbp) are able to bind.
MOD_CDK_1 Q5BJF6-3 793-799 SWTI000563 Alternative splicing removes the cyclin-dependent kinase (CDK) phosphorylation motif of Outer dense fiber protein 2 (ODF2), abrogating binding to Cyclin-dependent kinase 1 (CDK1). This phosphorylation is required for the recruitment of Serine/threonine-protein kinase PLK1 (PLK1). The C-terminal extension of Isoform Cenexin 1 has the ability to distinctly localise to mother centriole whereas the splice variant (e.g. Isoform Cenexin 1), which does not have this extension, permits ODF2 to associate with sperm tail.
DEG_APCC_DBOX_1 P14635 41-49 SWTI000685 Binding of the second KEN-box motif of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B), a subunit of the Spindle Assembly Checkpoint (SAC), to the substrate recruitment site of Cell division cycle protein 20 homolog (CDC20), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), blocks binding of the Cdc20 substrate G2/mitotic-specific cyclin-B1 (CCNB1). As a result, G2/mitotic-specific cyclin-B1 (CCNB1) is not targeted for proteasomal degradation until metaphase, when the SAC is inhibited. Destruction of G2/mitotic-specific cyclin-B1 (CCNB1) is required for progression to the anaphase of the cell cycle.
DEG_APCC_KENBOX_2 O60566 303-307 SWTI000685 Binding of the second KEN-box motif of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B), a subunit of the Spindle Assembly Checkpoint (SAC), to the substrate recruitment site of Cell division cycle protein 20 homolog (CDC20), the substrate recognition subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), blocks binding of the Cdc20 substrate G2/mitotic-specific cyclin-B1 (CCNB1). As a result, G2/mitotic-specific cyclin-B1 (CCNB1) is not targeted for proteasomal degradation until metaphase, when the SAC is inhibited. Destruction of G2/mitotic-specific cyclin-B1 (CCNB1) is required for progression to the anaphase of the cell cycle.
DOC_PP2B_1 Q05193-3 843-849 SWTI000465 Alternative splicing removes the PP2B-binding motif of Isoform 3 of Dynamin-1 (DNM1), abrogating binding to Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform (PPP3CA). This splice-specific motif in Isoform 3 allows the docking of calcineurin phosphatase. The dephosphorylation of DNM1 by calcineurin, upon NGF stimulation, promotes the internalisation of the High affinity nerve growth factor receptor (NTRK1) (TrkA).
LIG_SUMO_SIM_par_1 O75925 458-463 SWTI000662 Acetylation of K33 in Small ubiquitin-related modifier 2 (SUMO2) inhibits binding to E3 SUMO-protein ligase PIAS1 (PIAS1). The acetylation counters SUMO-SIM-dependent transcriptional repression processes. An additional interaction is also possible upon acetylation with the Bromodomain of p300 shown to bind the acetylated version of SUMO2. This does not occur with acetylated SUMO1. Acetylation is countered by Histone deacetylase family, HD type 1 subfamily.
LIG_SUMO_SIM_par_1 O75925 458-463 SWTI000663 Acetylation of K37 in Small ubiquitin-related modifier 1 (SUMO1) inhibits binding to E3 SUMO-protein ligase PIAS1 (PIAS1). The acetylation counters SUMO-SIM-dependent transcriptional repression processes. Acetylation is countered by Histone deacetylase family, HD type 1 subfamily.
LIG_SUMO_SIM_par_1 O75925 458-463 SWTI000613 Phosphorylation of S466 and S467 and S468 in the SUMO-binding motif of E3 SUMO-protein ligase PIAS1 (PIAS1) by CK2 subfamily and CK2 subfamily and CK2 subfamily increases the strength of its interaction with Small ubiquitin-related modifier 1 (SUMO1).
LIG_SUMO_SIM_par_1 O75928 468-473 SWTI000665 Acetylation of K37 in Small ubiquitin-related modifier 1 (SUMO1) inhibits binding to E3 SUMO-protein ligase PIAS2 (PIAS2). The acetylation counters SUMO-SIM-dependent transcriptional repression processes. Acetylation is countered by Histone deacetylase family, HD type 1 subfamily.
LIG_SUMO_SIM_par_1 O75928 468-473 SWTI000664 Acetylation of K33 in Small ubiquitin-related modifier 2 (SUMO2) inhibits binding to E3 SUMO-protein ligase PIAS2 (PIAS2). The acetylation counters SUMO-SIM-dependent transcriptional repression processes. An additional interaction is also possible upon acetylation with the Bromodomain of p300 shown to bind the acetylated version of SUMO2. This does not occur with acetylated SUMO1. Acetylation is countered by Histone deacetylase family, HD type 1 subfamily.
LIG_SUMO_SIM_par_1 P29590 556-566 SWTI000707 Alternative splicing removes the Sumoylation interacting motif (SIM) of Protein PML (PML), abrogating binding to Small ubiquitin-related modifier 1 (SUMO1) in Isoform TRIM19epsilon of Protein PML (PML). Isoforms lacking the SIM were resistant to As2O3-induced PML degradation.
LIG_SUMO_SIM_par_1 Q9UER7 731-740 SWTI000706 Acetylation of K37 in the SUMO1 inhibits binding to the Small ubiquitin-related modifier 1 (SUMO1) protein see switch details. SUMO-modified forms of Protein PML (PML) are essential for the recruitment of DAXX to PML nuclear bodies. The acetylated versions of SUMO1/2 failed to trigger recruitment of DAXX into the nuclear bodies. Acetylation is countered by Histone deacetylase family, HD type 1 subfamily.
LIG_SUMO_SIM_par_1 Q9UER7 731-740 SWTI000458 Multisite phosphorylation of S737 and S739 in the SUMO-binding motif of Death domain-associated protein 6 (DAXX) by CK2 subfamily and CK2 subfamily increases the strength of the interaction with Small ubiquitin-related modifier 1 (SUMO1).
LIG_SUMO_SIM_par_1 Q9UER7 731-740 SWTI000705 Acetylation of K33 in the SUMO2 inhibits binding to the Death domain-associated protein 6 (DAXX) protein see switch details. SUMO-modified forms of Protein PML (PML) are essential for the recruitment of Small ubiquitin-related modifier 2 (SUMO2) to PML nuclear bodies. The acetylated versions of SUMO1/2 failed to trigger recruitment of Small ubiquitin-related modifier 2 (SUMO2) into the nuclear bodies. An additional interaction is also possible upon acetylation with the Bromodomain of Histone acetyltransferase p300 (EP300) shown to bind the acetylated version of SUMO2. This does not occur with acetylated SUMO1. Acetylation is countered by Histone deacetylase family, HD type 1 subfamily.
LIG_SUMO_SIM_par_1 Q9UER7 731-740 SWTI000667 Sumoylation of K160 induces binding to the Protein PML (PML) protein. SUMO-modified forms of PML are essential for the recruitment of Death domain-associated protein 6 (DAXX) to PML nuclear bodies.
LIG_SUMO_SIM_par_1 Q9UER7 731-740 SWTI000666 Sumoylation of K160 induces binding to the Protein PML (PML) protein. SUMO-modified forms of PML are essential for the recruitment of Death domain-associated protein 6 (DAXX) to PML nuclear bodies.
LIG_SUMO_SIM_anti_2 P29590 553-564 SWTI000707 Alternative splicing removes the Sumoylation interacting motif (SIM) of Protein PML (PML), abrogating binding to Small ubiquitin-related modifier 1 (SUMO1) in Isoform TRIM19epsilon of Protein PML (PML). Isoforms lacking the SIM were resistant to As2O3-induced PML degradation.
LIG_SUMO_SIM_par_1 P29590 553-564 SWTI000707 Alternative splicing removes the Sumoylation interacting motif (SIM) of Protein PML (PML), abrogating binding to Small ubiquitin-related modifier 1 (SUMO1) in Isoform TRIM19epsilon of Protein PML (PML). Isoforms lacking the SIM were resistant to As2O3-induced PML degradation.
LIG_ANK_PxLPxL_1 P56524 349-354 SWTI000724 None
LIG_14-3-3_CanoR_1 O15151 364-369 SWTI000682 Optimal binding of 14-3-3 dimer to Hdmx in response to DNA damage requires phosphorylation of two 14-3-3-binding motifs by Chk2 kinase. Binding of 14-3-3 dimer is involved in inactivation of Hdmx, a negative regulator of p53, in response to DNA damage.
LIG_14-3-3_CanoR_1 P54253 772-777 SWTI000291 Phosphorylation of S775 switches binding specificity of Ataxin-1 (ATXN1) from the splicing factor Splicing factor U2AF 65 kDa subunit (U2AF2) to 14-3-3 proteins (e.g. 14-3-3 protein zeta/delta (YWHAZ)). While association with the spliceosome protects ATXN1 from self-association, its phosphorylation-dependent recruitment to 14-3-3 proteins (e.g. YWHAZ) might result in aggregation.
LIG_14-3-3_CanoR_1 P54253 772-777 SWTI000107 Phosphorylation of S775 by RAC-alpha serine/threonine-protein kinase (AKT1) in the 14-3-3-binding motif of Ataxin-1 (ATXN1) induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein.
LIG_14-3-3_CanoR_1 Q63572 435-441 SWTI000114 Phosphorylation of S439 in the 14-3-3-binding motif of Dual specificity testis-specific protein kinase 1 (Tesk1) induces binding to the 14-3-3 protein beta/alpha (Ywhab) protein. This interaction inhibits the kinase activity of Dual specificity testis-specific protein kinase 1 (Tesk1).
LIG_14-3-3_CanoR_1 O43524 29-34 SWTI000355 Phosphorylation of two 14-3-3-binding motifs in Forkhead box protein O3 (FOXO3) by RAC-alpha serine/threonine-protein kinase (AKT1) induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (YWHAB). This interaction results in cytoplasmic retention and inactivation of Forkhead box protein O3 (FOXO3).
LIG_14-3-3_CanoR_1 P98177 29-34 SWTI000690 Phosphorylation of two 14-3-3-binding motifs in Foxo4 by PKB induces binding of 14-3-3 dimer. In the nucleus, this blocks binding to DNA, while in the cytoplasm it blocks reimport of Foxo4 into the nucleus by blocking its Nuclear Localisation Signal (NLS). Since binding of 14-3-3 to a single motif occurs with an affinity similar to the affinity of Foxo4 for DNA, multivalent binding of 14-3-3 dimer is required for efficient inhibition of DNA binding.
LIG_14-3-3_CanoR_1 Q02156 343-348 SWTI000353 Phosphorylation of two 14-3-3-binding motifs in Protein kinase C epsilon type (PRKCE) induces high-avidity binding to dimeric 14-3-3 protein zeta/delta (YWHAZ).
LIG_14-3-3_CanoR_1 Q14432 424-430 SWTI000113 Phosphorylation of S428 by in the 14-3-3-binding motif of cGMP-inhibited 3',5'-cyclic phosphodiesterase A (PDE3A) induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein.
LIG_14-3-3_CanoR_1 P46938 109-114 SWTI000238 Phosphorylation of S112 in the 14-3-3 binding motif of Yorkie homolog (Yap1) induces binding to the 14-3-3 protein epsilon (Ywhae) protein. 14-3-3 retains phosphorylated YAP in the cytosol, negatively regulating its function.
LIG_14-3-3_CanoR_1 Q61337 109-114 SWTI000697 Phosphorylation of S136 in Bcl2 antagonist of cell death (Bad) by RAC-alpha serine/threonine-protein kinase (Akt1) in response to survival and growth signals such as Interleukin-3 (Il3) induces binding to 14-3-3 protein theta (Ywhaq). Binding of 14-3-3 protein theta (Ywhaq) results in dissociation of Bcl2 antagonist of cell death (Bad) from Bcl-2-like protein 1 (Bcl2l1), and thereby inhibits the pro-apoptotic activity of Bcl2 antagonist of cell death (Bad) by allowing liberated Bcl-2-like protein 1 (Bcl2l1) to exert its anti-apoptotic effect on pro-apoptotic proteins like Apoptosis regulator BAX (Bax).
LIG_14-3-3_CanoR_1 Q61337 133-138 SWTI000697 Phosphorylation of S136 in Bcl2 antagonist of cell death (Bad) by RAC-alpha serine/threonine-protein kinase (Akt1) in response to survival and growth signals such as Interleukin-3 (Il3) induces binding to 14-3-3 protein theta (Ywhaq). Binding of 14-3-3 protein theta (Ywhaq) results in dissociation of Bcl2 antagonist of cell death (Bad) from Bcl-2-like protein 1 (Bcl2l1), and thereby inhibits the pro-apoptotic activity of Bcl2 antagonist of cell death (Bad) by allowing liberated Bcl-2-like protein 1 (Bcl2l1) to exert its anti-apoptotic effect on pro-apoptotic proteins like Apoptosis regulator BAX (Bax).
LIG_14-3-3_CanoR_1 O35147 134-139 SWTI000105 Phosphorylation of S137 by RAC-alpha serine/threonine-protein kinase (Akt1) in the 14-3-3-binding motif of Bcl2 antagonist of cell death (Bad) induces binding to the 14-3-3 protein beta/alpha (YWHAB) protein. This interaction inhibits the pro-apoptotic activity of Bcl2 antagonist of cell death (Bad).
LIG_14-3-3_CanoR_1 P56524 629-634 SWTI000116 Phosphorylation of S632 in the 14-3-3-binding motif of Histone deacetylase 4 (HDAC4) induces binding to the 14-3-3 protein beta/alpha (YWHAB) protein. This interaction sequesters Histone deacetylase 4 (HDAC4) in the cytoplasm, thereby inhibiting their transcription repression activity.
LIG_14-3-3_CanoR_1 Q99683 963-968 SWTI000108 Phosphorylation of S966 in the 14-3-3-binding motif of Mitogen-activated protein kinase kinase kinase 5 (MAP3K5) induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein. This interaction inhibits the pro-apoptotic activity of Mitogen-activated protein kinase kinase kinase 5 (MAP3K5).
LIG_14-3-3_CanoR_1 P03076 254-259 SWTI000106 Phosphorylation of S257 in the 14-3-3-binding motif of Middle T antigen induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein.
LIG_14-3-3_CanoR_1 P04049 256-261 SWTI000189 Phosphorylation of S257 in the 14-3-3-binding motif of RAF proto-oncogene serine/threonine-protein kinase (RAF1) abolishes binding of the motif, phosphorylated at S259, to 14-3-3 protein zeta/delta (YWHAZ).
LIG_14-3-3_CanoR_1 P04049 256-261 SWTI000354 Phosphorylation of two 14-3-3-binding motifs in RAF proto-oncogene serine/threonine-protein kinase (RAF1) in response to growth factors induces high-avidity binding to dimeric 14-3-3 protein zeta/delta (YWHAZ), with pS621 being the high-affinity interaction site. This interaction locks RAF proto-oncogene serine/threonine-protein kinase (RAF1) in an inhibited conformation.
LIG_14-3-3_CanoR_1 P04049 618-623 SWTI000354 Phosphorylation of two 14-3-3-binding motifs in RAF proto-oncogene serine/threonine-protein kinase (RAF1) in response to growth factors induces high-avidity binding to dimeric 14-3-3 protein zeta/delta (YWHAZ), with pS621 being the high-affinity interaction site. This interaction locks RAF proto-oncogene serine/threonine-protein kinase (RAF1) in an inhibited conformation.
LIG_14-3-3_CanoR_1 Q9P0K1 854-863 SWTI000317 Phosphorylation-induced binding of dimeric 14-3-3 protein beta/alpha (YWHAB) to Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) blocks ER retention motifs in Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) and regulates transport of this protein to the membrane.
LIG_14-3-3_CanoR_1 Q9P0K1 831-839 SWTI000317 Phosphorylation-induced binding of dimeric 14-3-3 protein beta/alpha (YWHAB) to Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) blocks ER retention motifs in Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) and regulates transport of this protein to the membrane.
LIG_14-3-3_CanoR_1 Q61097 294-302 SWTI000357 Phosphorylation of two 14-3-3-binding motifs in Kinase suppressor of Ras 1 (Ksr1) by Q03141 induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (Ywhab). This interaction prevents Kinase suppressor of Ras 1 (Ksr1) to localise to the membrane where it is involved in activation of MAP kinases by Q99N57 in response to growth factors.
LIG_14-3-3_CanoR_1 Q8IPH9 51-60 SWTI000358 Phosphorylation of two 14-3-3-binding motifs in Slowpoke-binding protein (Slob) by Calcium/calmodulin-dependent protein kinase type II alpha chain (CaMKII) induces high-avidity binding to dimeric 14-3-3 protein zeta (14-3-3zeta). This interaction recruits 14-3-3 protein zeta (14-3-3zeta) to Calcium-activated potassium channel slowpoke (slo) in the presynapse of neuromuscular junctions.
LIG_14-3-3_CanoR_1 O43524 250-255 SWTI000355 Phosphorylation of two 14-3-3-binding motifs in Forkhead box protein O3 (FOXO3) by RAC-alpha serine/threonine-protein kinase (AKT1) induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (YWHAB). This interaction results in cytoplasmic retention and inactivation of Forkhead box protein O3 (FOXO3).
LIG_14-3-3_CanoR_1 P98177 193-199 SWTI000690 Phosphorylation of two 14-3-3-binding motifs in Foxo4 by PKB induces binding of 14-3-3 dimer. In the nucleus, this blocks binding to DNA, while in the cytoplasm it blocks reimport of Foxo4 into the nucleus by blocking its Nuclear Localisation Signal (NLS). Since binding of 14-3-3 to a single motif occurs with an affinity similar to the affinity of Foxo4 for DNA, multivalent binding of 14-3-3 dimer is required for efficient inhibition of DNA binding.
LIG_14-3-3_CanoR_1 P98177 193-199 SWTI000111 Phosphorylation of S197 by in the 14-3-3-binding motif of Forkhead box protein O4 (FOXO4) induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein.
LIG_14-3-3_CanoR_1 P08965 523-529 SWTI000326 Binding of meiRNA meiotic non-coding RNA (meiRNA) to the RRM domains of Meiosis protein mei2 (mei2) is essential for promotion of premeiotic DNA synthesis and meiosis I and is blocked by Pat1-mediated phosphorylation-induced binding of the 14-3-3 protein DNA damage checkpoint protein rad24 (rad24) to 2 14-3-3 binding motifs in mei2.
LIG_14-3-3_CanoR_1 P08965 523-529 SWTI000459 Phosphorylation of two 14-3-3-binding motifs in Meiosis protein mei2 (mei2) by Negative regulator of sexual conjugation and meiosis (ran1) induces high-avidity binding to dimeric DNA damage checkpoint protein rad24 (rad24), with pT527 being the high-affinity interaction site.
LIG_14-3-3_CanoR_1 P32418 388-398 SWTI000110 Phosphorylation of S392 in the 14-3-3-binding motif of Sodium/calcium exchanger 1 (SLC8A1) induces binding to the 14-3-3 protein epsilon (YWHAE) protein. This interaction inhibits the activity of Sodium/calcium exchanger 1 (SLC8A1).
LIG_14-3-3_CanoR_1 P26045 356-361 SWTI000356 Phosphorylation of two 14-3-3-binding motifs in Tyrosine-protein phosphatase non-receptor type 3 (PTPN3) induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (YWHAB).
LIG_14-3-3_CanoR_1 A2ALK8 355-365 SWTI000109 Phosphorylation of S359 in the 14-3-3-binding motif of Tyrosine-protein phosphatase non-receptor type 3 (Ptpn3) induces binding to the 14-3-3 protein beta/alpha (Ywhab) protein.
LIG_14-3-3_CanoR_1 Q9GZV5 86-91 SWTI000587 Phosphorylation of S89 in the 14-3-3-binding motif of WW domain-containing transcription regulator protein 1 (WWTR1) induces binding to 14-3-3 protein epsilon (YWHAE), retaining phosphorylated WWTR1 in the cytosol, negatively regulating its function.
LIG_14-3-3_CanoR_1 P32418 388-394 SWTI000110 Phosphorylation of S392 in the 14-3-3-binding motif of Sodium/calcium exchanger 1 (SLC8A1) induces binding to the 14-3-3 protein epsilon (YWHAE) protein. This interaction inhibits the activity of Sodium/calcium exchanger 1 (SLC8A1).
LIG_14-3-3_CanoR_1 A2ALK8 355-361 SWTI000109 Phosphorylation of S359 in the 14-3-3-binding motif of Tyrosine-protein phosphatase non-receptor type 3 (Ptpn3) induces binding to the 14-3-3 protein beta/alpha (Ywhab) protein.
LIG_14-3-3_CanoR_1 Q02156 365-370 SWTI000353 Phosphorylation of two 14-3-3-binding motifs in Protein kinase C epsilon type (PRKCE) induces high-avidity binding to dimeric 14-3-3 protein zeta/delta (YWHAZ).
LIG_14-3-3_CanoR_1 Q9P0K1 831-836 SWTI000317 Phosphorylation-induced binding of dimeric 14-3-3 protein beta/alpha (YWHAB) to Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) blocks ER retention motifs in Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) and regulates transport of this protein to the membrane.
LIG_14-3-3_CanoR_1 Q9P0K1 854-859 SWTI000317 Phosphorylation-induced binding of dimeric 14-3-3 protein beta/alpha (YWHAB) to Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) blocks ER retention motifs in Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) and regulates transport of this protein to the membrane.
LIG_14-3-3_CanoR_1 P43565 1072-1077 SWTI000115 Phosphorylation of T1075 in the 14-3-3-binding motif of Serine/threonine-protein kinase RIM15 (RIM15) induces binding to the Protein BMH2 (BMH2) protein. This interaction sequesters Serine/threonine-protein kinase RIM15 (RIM15) in the cytoplasm, thereby inhibiting its function.
LIG_14-3-3_CanoR_1 Q8IPH9 51-56 SWTI000358 Phosphorylation of two 14-3-3-binding motifs in Slowpoke-binding protein (Slob) by Calcium/calmodulin-dependent protein kinase type II alpha chain (CaMKII) induces high-avidity binding to dimeric 14-3-3 protein zeta (14-3-3zeta). This interaction recruits 14-3-3 protein zeta (14-3-3zeta) to Calcium-activated potassium channel slowpoke (slo) in the presynapse of neuromuscular junctions.
LIG_14-3-3_CanoR_1 Q61097 389-394 SWTI000357 Phosphorylation of two 14-3-3-binding motifs in Kinase suppressor of Ras 1 (Ksr1) by Q03141 induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (Ywhab). This interaction prevents Kinase suppressor of Ras 1 (Ksr1) to localise to the membrane where it is involved in activation of MAP kinases by Q99N57 in response to growth factors.
LIG_14-3-3_CanoR_1 Q61097 294-299 SWTI000357 Phosphorylation of two 14-3-3-binding motifs in Kinase suppressor of Ras 1 (Ksr1) by Q03141 induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (Ywhab). This interaction prevents Kinase suppressor of Ras 1 (Ksr1) to localise to the membrane where it is involved in activation of MAP kinases by Q99N57 in response to growth factors.
LIG_Rb_LxCxE_1 Q99708 153-157 certain None
LIG_Rb_LxCxE_1 Q9R002 416-420 certain None
MOD_Plk_1 O14920 750-755 LOW None
MOD_Plk_1 O14920 750-755 PHOSPHORYLATION None
MOD_Plk_1 O14920 750-755 LEVEL None
MOD_Plk_2-3 P37840 129-134 X None
MOD_Plk_2-3 P37840 129-134 S None
MOD_Plk_2-3 P37840 129-134 E None
MOD_Plk_2-3 P37840 129-134 D None
MOD_Plk_2-3 P37840 129-134 T None
Please cite: ELM-the Eukaryotic Linear Motif resource-2024 update. (PMID:37962385)

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