ELM candidate motifs
ELM annotation process is a tedious and time-consuming process involving critical reading of primary and secondary literature, finding motif instances,
generating multiple sequence alignments and more.
In order not to loose track of possible annotations, we keep the following list of candidate motifs.
We invite researchers to send us their feedback and expert opinion on these
classes and to contribute novel motif classes that will be added to the candidate page and ultimately be turned into full ELM classes.
Minimum requirements are at least one literature reference as well as a short description. In addition, a draft regular expression or a 3D structure showing the relevant interaction would also be helpful.
Currently 384 candidates need annotation: (Add a new candidate)
Detailed Status:first draft: | 234 |
undergoing annotation: | 18 |
fully annotated: | 106 |
not annotatable: | 2 |
deleted: | 22 |
annotatable: | 2 |
Identifier | Model | References | Description | Notes | Status | |
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DEG_FEM1B_FNIP1Cys3_2 | R...C.CkYC.H | 7ROY 32941802 34562363 |
Remarkable Triple-Cys Degron binding via Zn++ coordination to E3 ligase FEM1B. Is used as part of oxidation-reduction monitoring in the cell. Binds a different surface to the FEM1B C-degrons. |
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LIG_FERM_ERM_2 | MDW[^P][^P][^P][^P][^P][LI]F[^P][^P][LF] | 16615918;15020681 2D10;2YVC; |
The C-terminal helical motif that mediates binding to the FERM domain of Radixin, is found in NHERF-1 and NHERF-2. Binds different sites to PSGL-1, NEP, CD44 and CD43. Nice mutational analysis in the paper. Seems quite conserved in vertebrates. First two residues Met and Asp don't make direct contact. Trp is buried deep in the pocket, and Phe engaged in the second pocket with stacking interactions. Lys seems important in the +2 and +3 sites after conserved Trp and makes H-bonds with E244, additional interaction with F240 (2D10). C-terminus main chain carboxyl from Leu forms H-bond with T214 and N210 from the binding partner. | switches.elm:SWTI000333 overlaps with the motif. |
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LIG_FERM_ERM_1 | [KRQ]...Y..[ILV] | 12554651,18076570,18753140, 2YVC, 2EMS, 2ZPY, 2EMT | Motif that mediates binding to the FERM domain of Radixin found in PSGL-1, NEP, CD44 and CD43. Difficult consensus but all structures overlap the same binding site. |
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TRG_NES_CRM1rev_2 | #.#.[^P]{1,2}#[^P]{2,3}#([^P]{2,3}#) | Fung,2015 Fung,2017 35995566 5DIF 5DHA 5DHF 5DI9 |
Some CRM1-binding nuclear export motifs bind in the reverse orientation to the usual motifs. Reverse NESes include Rio4 and CPEB4 The known reverse motifs (Class 2) bind mainly as an alpha helix. There are four or five hydrophobic residues entering a hydrophobic groove of CRM1. The first two hydrophobic residues must have exact #x# spacing for reverse orientation. By contrast, for the forward orientation Class 1 motifs, the last two hydrophobic residues must have the exact #x# spacing. Class 3 forward motifs are helical and are shifted with respect to Class 1 and do not need to occupy one of the hydrophobic pockets. |
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DEG_Kelch_KLHL20_1 | LPDLV | 31279627, 6GY5 |
BTB-Kelch E3 ligase degrading DAPK1, PML, and ULK1. Structure for DAPK1 peptide. Unusually, the bound peptide is within the DAPK1 Death Domain. |
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LIG_HBOX_DDB1 | nx[VLtp][^P][^P][Lvfh][^P][^P][Rvahs][^P][LIVRk][^p] | 19966799 35938868 7ukn |
~13aa structural motif, that must be located inside a disordered region, and which binds to DDB1. The most important interacting residues are not fully conserved but are either hydrophobic or basic. Found in many DDB1-binding proteins such as DCAFs but also in viral proteins, such as Hepatitis B virus protein X and parainfluenza virus 5 (formerly called simian virus 5 or SV5) protein V and hCMV pUL145 which use it to hijack DDB1. Viral motifs tend to have higher affinities than cellular ones. |
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DOC_PP2A_B55_2 | [kr]v..[vi]r | 34661528 | Docking site required for the regulatory subunit B55 of PP2A for protein dephosphorylation. |
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DOC_PP2B_TxxP_1 | ([ST].[RK]P)|([ST][RK].P) | Li,2020, Hendus-Altenburger,2019 | Calcineurin (PP2B) preferred dephosphorylation of serine/threonine phosphorylation sites |
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DEG_MAGE_A11_1 | [LFYW]..[^P][VIMACL][^P][^P][IV[RK][^P][LVMI][LFWY] | 33004795 6WJH |
MAGE proteins are a class of substrate adaptors for E3 ligases. MAGE-A11 recognises a helical hydrophobic degron with one key positively charged residue |
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LIG_LxxPTP_EBH_2 | [LIVM]..PTP[ILTV] | 28552577, 29576319; 5N74 |
The LxxPTP motif is found in some +TIP proteins that bind to the EBH domain of the EB1 microtubule end-binding protein. It binds the same surface as the SxIP motif but with some EBH domain rearrangement. |
Sequence conservation is very poor and it is not clear that this motif can be annotated. |
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TRG_ER_KDEL_2 | [KRHQSAP][DENQT][ED]L[K]{0,1}$ | 9914159 | Same as previous TRG_ER_KDEL_1 but modified to recognize the C-terminal motif in Exotoxin A in Pseudomonas as well as its closely related species. | The Lys at the C-terminal position is conserved in all Exotoxin As from P. aeruginosa as well as in Cholix toxin from V. cholerae. The position -3, counting from the C-terminal, in Exotoxin A from P. aeruginosa has a conserved Asp while all the Cholix toxins have a Glu. An exotoxin from Aeromonas hydrophila does not contain the same Lys at the last position (resembling the canonical KDEL motif) but half of the sequences (11 out of 26) have an Asp at the position -2 counting from the C-terminal. Not clear that this can be annotated as cellular KDEL motifs are not seen to tolerate c-terminal extensions. |
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TRG_Kap121pNLS_IxK_1 | ..[IV].K.{1,2}[KRH] | 26022122, 23541588, 26173234, 15367670, 3W3X, 3W3W, 3W3Y, 4ZJ7, |
The yeast importin beta, Karyopherin 121 (Kap121p) can import proteins to the nucleus that have an NLS with a core of [IV]xK. A few ligand proteins are reliably known, including structures for the IxK motif in Nup53, Ste12, Pho4, Cdc14. | The pattern around the core needs to be defined to make a motif entry. It has a positive charge preference. |
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LIG_CAF40_CBM_1 | LgFDPf[^P][^P][STC][^P][^P][^P]L[^P][^P]ll[^P][^P]E | 30692204 28165457 29255063 |
CBM is a long, mainly helical, linear motif in proteins which bind to the CAF40 subunit of the CCR4-NOT mRNA deadenylase complex. CBM is found in NOT4, Roquin and Bag of Marbles. |
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MOD_CAAXbox_PGGT_1 | (([KR]{2,9})|([KR]{1,6}.[KR]{1,3})).{0,2}C.[VIL].$ | 8811180 | Specific case of prenylation by Protein Geranylgeranyl Transferase I (PGGT) |
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LIG_SH2_IC | (Y).N | Huang,2008 | Subgroup IC, identifiable by a strong proclivity for an Asn residue at P+2, forms the second largest subgroup within group I with 18 members. It includes not only the GRB2/GRAP/GADS family but also the GRB7/10/14 family, the tensin family, and the Fes/Fer family. |
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MOD_P4H_1 | PPG | 10428773 12824157 19553701 27129244 14698617 26368022 |
Extracellular motif that undergoes proline hydroxylation by P4H | Particular version of XYP repeats |
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MOD_Ime2_RPxS_1 | RP.[ST] | 17198398, 17349956, 16776651, 25310241, 24710277, 25243405, 22356909, 16954377 |
Ime2 is a yeast meiotic kinase. Although related to the CDK group, it does not recognise SPxK sites. Instead, it recognises RPxS/T sites. Substrates include CDH1. The related mammalian kinases are ICK/MRK, MAK and MOK. ICK has also been shown to preferentially phosphorylate RPxS/T sites. These three kinases are required for proper ciliary function. |
Mutations in ICK cause Endocrine-cerebro-osteodysplasia ECO). Mutations in MAK cause retinitis pigmentosa 62 (RP62). |
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LIG_ET_KIKL_1 | [LVI][K][IFL][KR].{0,1}[LFIV] | 29567837 27291650 26858406 6BGG 2NCZ 6BGH 2ND0 2N3K |
The KIKL motif is found in proteins such as CHD4, SMCA4 and NSD3 that bind to the small three-helix ET (or NET) domain of BET proteins. This interaction creates a two-stranded sheet by beta-augmentation to a loop region. Most of the KIKL-containing proteins are themselves part of protein complexes which usually have chromatin remodelling functions. Viral proteins such as KSHV LANA and MLV-Integrase also have KIKL motifs. | ET is homologous to the AHD domain of AF9 which also binds a linear motif by beta-augmentatioN (23260655). |
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MOD_Cx3Xbox | C....$ | 29282289 | Extension of the CAAX box. Showed to work as substrate of both FTase and GGTase-I in both yeast and mammals. | Expected instances: Sushi, nidogen and EGF-like domain-containing protein 1; Putative glycosylation-dependent cell adhesion molecule 1; Sorting nexin 4 |
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DOC_ULK3_MIT_1 | F..L[^P][^P]L[^P][^P]RF[^P][^P]L[KR] | Caballe,2015 4WZX |
Docking motif in ESCRT-III IST1 that binds to ULK3 MIT domain enabling ULK3 to phosphorylate IST1. Part of abscission delay checkpoint for lagging chromosomes |
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LIG_VCP_VBM_2 | [MILVAK][RK][^P][^P]R[LFWE][^P][^P][FLI][^P] | Lim,2016 18208387 5EPP |
Helical motif binding a groove in the N-terminal domain of the VCP/P97/Segregase ATPase involved in transitional ER formation and other processes including ubiquitin-proteasome targeting. The VIM motif binds the same pocket in reverse orientation. |
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LIG_VCP_VIM_1 | R[^P](5)AA[^P](2)R[^P] | Hanzelmann,2011, 18208387, Stapf,2011, 3TIW |
Helical motif binding a groove in the N-terminal domain of the VCP/P97/Segregase ATPase involved in transitional ER formation and other processes including ubiquitin-proteasome targeting. The VBM motif binds the same pocket in reverse orientation |
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LIG_14-3-3_5 | IRLNNAIWRAWY | Ge,2012,Sato,2016 |
A newly identified 14-3-3 binding motif identified in ChREBP protein. Unlike other 14-3-3 binding proteins, here 14-3-3 binds to a non-phosphorylated site in ChREBP with high affinity and the interaction can be activated by a free sulfate or phosphate molecules provided by the metabolites like AMP or ketone bodies.AMP binds directly to ChREBP and allosterically induces conformational changes resulting in increased affinity of ChREBP for 14-3-3and stabilization of the heterodimer in the cytoplasm of hepatocytes thus inhibiting fat synthesis during periods of ketosis. The main interaction interaction interface is between the α2 helix of the ChREBP and the positively charged patch containing a Arg-Arg-Tyr triad on the binding groove on 14-3-3. Motif is highly conserved in mammals. |
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RTX_motif | G..G.[DN].[LVIFY]. | 19015266 27058787 17728256 8253063 |
This motif is present in several bacterial toxins, usually in 5 to 50 repeats, and are highly common in effector proteins from the type one secretion system (T1SS) (19015266). In CyaA from Bordetella pertussis, the motifs are located in a predominantly disordered region at the C-terminal of the protein. Under nanomolar concentrations of Ca2+ (as in the bacterial cytosol) the C-terminal region lacks a terciary and secondary structures. After CyaA is transported through the T1SS, the protein gets in contact with Ca2+ which is sequestered and induces the folding of CyaA into β-Rolls Ratchets (27058787). The motif has also been described in extracellular lipase from Serratia marcescens (2QUA; 2QUB), Serralysin from Pseudomonas aeruginosa, triacylglycerol lipase from P. aeruginosa (1EX9), Hemolysin from Escherichia coli, triacylglycerol lipase from Brukholderia cepacia (1OIL) and in the fungal lipase from Thermomyces lanuginosus (1EIN; 1DT3) (17728256; 8253063). |
CyaA has PDB structures: 5CVW and 5CXL |
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LIG_Vh1_VBS_2 | DD[VMIL][MILFYPA].[TASKHCR][AVSCT]..[ILVM]...[LMTVI]..[LMV][ILVMAT]..[AIVLMT] | Park,2011 | Surface cell antigen 4 (sca4) is a protein from R. rickettsii that contains two VBSs, sca4-VBS-N and sca4-VBS-C, where the former resembles the binding of the talin or IpaA VBSs The later contains a Pro at position +14 causing a kink in the helix structure. The crystal structure of sca4-VBS-C with vinculin (3TJ6) shows that the position of the alpha-helix alpha1 in the Vh1 domain of vinculin has a dramatic movement compared to its corresponding position in other structures containing non-kinked helices (Park,2011), therefore exemplifying a new variant of a Vh1 binding-motif. |
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LIG_IRF3_1 | [DEN]L.I(S)|[DE]{2}.[DE]L.IS | Zhao,2016 Structural and functional studies about the pLxIS motif in cellular and viral proteins. Structures of STING (5JEJ), MAVS (5JEK), TRIF (5JEK) and NSP1 (5JEO; 5JER) with IRF-3. Structure of the IRF-3 dimer (5JEM). Liu,2015 Phosphorylation of the pLxIS motif. Barro,2005 The C-terminal region of NSP1 binds IRF-3 and mediates its degradation. |
The recognition of pathogen-associated molecular patters (PAMPs) involves different pathways that can trigger convergent antimicrobial responses. Microbial double-stranded (ds)DNA in the cytosol is sensed by cGAS whcih produces the second messenger cGAMP, cGAMP binds to the adaptor protein STING which is located at the endoplasmic reticulum (ER) surface. Viral dsRNA is sensed in the cytosol by RLRs which activates the adaptor protein MAVS which is located at the mitochondria surface. Membrane anchored toll-like receptors (TLRs) 3 and 4, which recognize viral dsRNA and bacterial LPS, respectively, when activated recruit the adaptor protein TRIF. The three adaptor proteins STING, MAVS and TRIG contain a conserved motif previously refered as pLxIS that is phosphorylated by TBK1 or IKKepsilon (Liu,2015). Once phosphorylated, it binds to the transcription factor IRF-3 resulting in TBK1-dependent phosphorylation of an additional pLxIS motif in IRF-3. Phosphorylated IRF-3 forms a dimer that activates the protein (Zhao,2016). IRF-3 dimer translocates to the nucleus and positively regulates the trasncription of IFN-beta (Honda,2006). Interestingly, rotavirus is able to escape innate immune recognition by interfering with the IRF-3-dependent pathway. The rotavirus E3 ubiquitin ligase nonstructural protein 1 (NSP1) also contains the pLxIS motif which binds to the same binding region in IRF-3 in an unphosphorylated manner preventing its activation and promoting its degradation. |
In STING, the Pro at position -1 is conserved in mamals and reptiles. Leu is present in birds, opossum has a Thr at position +5. In MAVS, the motif is only conserved in mammals. Birds and fish do not have it. Tasmania devil has RLLIS. Ornithorhynchus has RLDMS and a DLNIS at 280-284. Nestor notabilis (bird) has a DLYIS at 269-273. Dipodomys (kangaroo rat) has a small duplication in the motif: EDLAISPSSSLscsEDLAISPSSSL. In TRIF, the human instance is NLEIS, which is present in 29 species in the alignment, including four legged mammals, bats and wild ducks. 12 sequences have HL.IS including primates, panda, mus musculus and fish. Other mammals had Ser, Ala, Glu, Val and Lys. Ser at position +5 was conserved in Mammals, reptiles, birds and fish. The lizard Anolis has HLEIS at 344-348. Birds have a Phe at position +2. In IRF-3, the motif is conserved in Mammals, reptiles, fish. Common marmoset (new world monkey), ginea pig, bats and european polecat have RLQIS. Tetraodon nigroviridis (fish) has SLQIS. The common marmoset, ginea pig, bat and the european polecat have DLLIS at ~227-231. Tetrodon nigrovorans has DLEIS at 209-213. In NSP1, the phosphorylation is not necessary. Substitution of Ser at position +5 did not abolish the targeting of IRF-3, however it is conserved. L486A (position +2) abolished the activity of NSP1. I488A (position +4) partially impairs the activity of NSP1. |
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LIG_CRIB_1 | I[SG].P..{0,1}.[FA][EKRQ]H..[HT][VT][GSQ] | 7493928 First described the Cdc42/Rac interactive binding motif. 9601050 Fragments as short as 75 to 94 of PAK1 still bound to either Cdc42 or Rac. Fragments 75-105 showed binding to Q61L Rac.GTP with Kd=1.9 µM. 9660763 They calculated that the 37 aas long region of WASP (221-257) still bound to Cdc42 with a Kd of 470 nM as measured by titration. Secondary structure was only observed for the longer fragment (W13). 9774440 and 10551809 showed that the substitution of His83 (position +9) and His86 (position +12) for Leu strongly decreased binding of PAK1 with Cdc42. 9774440 PAK1 75 to 132 (which includes the CRIB motif (75-88)) did not bind Cdc42. 22653441 The binding of PAK4 and Cdc42 was demonstrated by anti-tag coimmunoprecipitation. 22362774 The beta-strand is only 5 aas long ("EIIVL"). The correct alignment starts at Ile49 in SopB (Ile12 in PAK6). The Ile in position +1 (the only one conserved) was mutated in SopB and the (22362774) and the binding to Cdc42 got disrupted. 9528787 The Ile present in all Cdc42 binders at position +1 has been mutated for Asn and the affinity decreased 3-fold. 11940652 Ser at position +2 reduces interaction with CDC42. His at position +10 reduces interaction with CDC42. 12586692 His at position +10 reduces interaction with CDC42. His at position +12 reduces interaction with CDC42. 11940652 Mutations in the CRIB motif allows Cdc42-independent kinase activity and signaling ability, indicating the CRIB motif also works in the autoinhibition of Ste20. 10802735 They obtained the NMR structure of rat Pak1 and Cdc42 with overall very low wwPDB validation scores. In general, it does not overlap with any of the other structures of Rho GTPases, for example its RMS distance to Rac3 (2QME) is 3.16. |
A linear motif of 14 to 15 residues long mediates the binding of different kinase and non-kinase proteins to the small Rho GTPases Cdc42 and Rac. The motif has been previously described as Cdc42 and Rac-interactive binding (CRIB) motif (7493928). The p21-activated kinase (PAK) proteins are serine/threonine kinases activated by Cdc42 and Rac. They play roles in cytoskeleton dynamics, cell adhesion, apoptosis and mitosis. They link integrin activation with JNK MAP kinase pathway, phosphorylate and activate MEK1. PAK orthologs have a well conserved N-terminal region. However, only the positions corresponding to the CRIB motif share conservation among paralogs. Other unrelated proteins like the actin polymerization regulator WASP and the tyrosine-protein kinase PR2 are also binders of Cdc42 and Ras (9660763; 7493928). In all these cases the presence of the CRIB motif is necessary for binding, but high affinity is only observed with additional molecular interactions that depend on an extended region C-terminal from the motif (9601050; 9660763). Several crytallographic and NMR structures have been solved of the interaction of the CRIB motif and either Cdc42 or Rac (1EES; 1E0A; 2OV2; 2ODB; 1CEE; 4MIT; 4JSO; 1NF3; 4DID; 2QME), the comprehensive analysis of these structures show that around 26 amino acids are suficient to keep a static complex structure. The CRIB motif forms a beta aumentation with the small Rho-GTPase. |
The bacterial protein SopB from Salmonella enterica binds to GDP-bound Cdc42 with a Kd=6uM +-2uM also creating a beta augmentation. However, the sequence is highly degenerated and is not covered by the current regular expression (22362774). The putative paralog of PAK in Entamoeba histolytica binds to RacC from E. histolytica. The structure (4MIT) compared to PAK6 bound to Cdc42 (2ODB) shows that the helix present at the C terminal of the crystalized region is irrelevant for the interaction with the Rho GTPase. |
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MOD_ARK/PRK/AAK1_1 | [LI]..Q.(T)G | 12956961, Zeng,1999, Zeng,2001, Huang,2003, Ricotta,2002 |
Optimal phosphorylation site motif for mammalian AAK1 and yeast PRK/ARK kinases that are involved in the regulation of endocytosis. A more relaxed version of the motif is [L/I/V/M]xx[Q/N/T/S]xTG |
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LIG_APP_AP2beta_1 | [FL]..G[FL].DF | Schmid,2006, 1E42 |
Motif binding to the side site of the C-terminal beta2-appendage domain of the large subunit beta2-adaptin. This interaction is part of the system for recruiting partners for assembly of clathrin-coated vesicles. |
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LIG_MHD_FCHO_1 | DPFxxxDPFxxDPF | 27237791 25061211 |
The motif binds to mu humology domain (MHD) of FCHO with an affinity of 2μm. |
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eIF2alpha_binding_motif | Rx[Gnl]x1-2Wxxx[Arlv]x[Dn][Rg]xRFxx[Rlvk][Ivc] | 26100893 |
The eIF2α-binding motif is characterized by the consensus sequence Rx[Gnl]x1-2Wxxx[Arlv]x[Dn][Rg]xRFxx[Rlvk][Ivc], where capital letters are preferred and x is any residue. This eIF2α-binding motif is found in the PP1 regulatory subunits GADD34, CReP, and several viral proteins including, ICP34.5, DP71L, and CNPV231. |
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LIG_PEX19_mPTS_1 | 15133130 | PEX19 is thought to be the receptor for importing peroxisomal membrane proteins by binding to a short mostly hydrophobic peptide, the mPTS. |
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TRG_Transportin_M9nls_1 | R..PY..P | 7730395, 15703190, 16901787, 22778397, 16179349, 4FDD, 4JLQ, 2OT8, 2Z5K, 2Z5O, 2Z5N |
Non-canonical NLS bound by transportin/karyopherin beta. Found in some RNA processing proteins, in T-box and ATF4/5 transcription factors. Always has a PY doublet, usually preceded by positively charged residues and also a weakly conserved second hydrophobic motif. Mutations in M9 class NLSes cause Di George syndrome (mutated in Tbx1) and ALS (mutated in FUS, EWS, TAF15). | Observed instances are quite variable and likely require several motif patterns to capture the range of possibilities. |
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Lig_IntegrinA4B1_MLD | MLD | 14769041 | Extracellular alpha4beta1, alpha9beta1 and alpha7beta4 Integrin-binding motif. Motif was first identified in snake venom disintegrins. | Not sure if a native protein with MLD has been identified. |
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LIG_RGD_High | RGDL..[LI] | Dong,2014 4UM8 4UM9 |
Integrin alphaVbeta6 binds with high affinity to a RGDLXXL/I motif within the prodomains of TGF-β1 and TGF-β3. |
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LIG_MSL3 | AFG..[LIV]..[LIMF].{4,10}F.LPW | 21217699, 2Y0N | Long extended peptide wrapping around the MRG domain of MSL3, with one part forming a short hairpin; highly conserved hydrophobic residues (mainly Phe) insert into different hydrophobic pockets on the MSL3 surface; found in MSL1 (subunit of the male-specific lethal complex involved in gene dosage compensation); (see also literature on WDR5-binding motifs in ELM). | 21217699 discusses other proteins using similar surfaces/sequences for binding, see references therein; model presented here only describes core, should be extended at the N-terminus |
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LIG_MOF | E.[LI].D[^P][^P][FY][^P][^P][^P]H[^P][KR] | 21217699, 2Y0M | Helical motif that binds the HAT domain of the histone acetyltransferase MOF; found in MSL1 (subunit of the male-specific lethal complex involved in gene dosage compensation) and NSL1 (subunit of the nonspecific lethal complex involved in transcription regulation and cell reprogramming) (see also literature on WDR5-binding motifs in ELM). |
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LIG_NRBOX_AR_2 | F..LF | 15178743 | LBD-binding motif in the N-terminal region of androgen receptor that binds to coactivator-binding groove on androgen receptor (AR), competing with coactivators. This groove is deeper on AR compared to for instance estrogen receptor, which does not bind this motif. |
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LIG_Munc18/Sec1 | D[RL].{3,4}[FL] | 23572542,20884800,21139055,11879635,12426383,1MQS | Conserved Munc18/Sec1-binding peptide present in N-terminal region of eukaryotic SNARE proteins, e.g. vertebrate syntaxin 5, yeast Sed5 and Ufe1, and arabidopsis SYP121. |
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LIG_KC1 | F.RF | 20884800,23572542 | Motif in arabidopsis SNARE protein SYP121 required for binding to K+ channel subunit KC1; overlaps with a Sec1/Munc18-binding motif. |
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LIG_AP_GAE_2 | W..[FW] | 14973137,17506864,2DWX | Motif in hinge region of GGA1, also in NECAP1 and amphiphysin II, that mediates interaction with the AP-1 gamma-ear domain; binds to same or overlapping site as LIG_AP_GAE_1 |
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LIG_OST | ([FVL].C)|(C.[FVL]) | 24685145,4M91,4M92 | peptide that binds to the N33/Tusc3 (and maybe paralogous IAP/MagT1) subunit of the oligosaccharyl transferase (OST) complex to improve glycosylation efficiency; found in OST substrates; peptides can be accommodated in opposite orientations; peptide is covalently anchored to N33/Tusc3 via the cysteine residue (disulfide link); prefers Leu, Val or Phe in the -/+2 position relative to Cys; also backbone interactions |
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LIG_CagA | 24474782, 4IRV | N-terminal domain of the Cytotoxin Associated Gene A (CagA) of Helicobacter pylori binds to a 20aa long helical motif in the Apoptosis-stimulation protein p53-2 (ASPP2). |
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MOD_N-GLC_2 | [DE].(N)[^P][ST].. | 16619027 21209858 20523900 20847188 20581208 |
similar regular expression to MOD_N-GLC_1 but also found within bacteria and archea. | bacterial N-glycosyltransferases exhibit a more stringent specificity for the acceptor site than the eukaryotic counterpart. This restricts glycosylation to a narrow set of polypeptides |
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CLV_MetAP1 | ^M[ACGPS][^P]... | Xiao,2010, 12665801, 18828628, 10574784, 16274222, 12475202 | Target site for cleavage of N-terminal methionine by methionine aminopeptidase MetAP1. | Overlapping substrate specificity with MetAP2 but MetAP1 cannot accommodate the larger side chains tolerated by MetAP2 (Thr and Val) in the P1' position due to its smaller active site. Disfavors acidic residues in positions P2' to P5'. His and Trp were underrepresented in P2' and P3' in the most active substrate peptides as determined by peptide library screening. Strong preference for Ala in P1'. |
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CLV_MetAP2 | ^M[ACGPSTV][^P]... | Xiao,2010, 12665801, 18828628, 10574784, 16274222, 12475202 | Target site for cleavage of N-terminal methionine by methionine aminopeptidase MetAP2. | Overlapping substrate specificity with MetAP1 but can accommodate larger side chains of Thr and Val in the P1' position due to its larger active site. Disfavors acidic residues in positions P2' to P5'. Disfavors Trp at P2' and P3'. |
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MOD_NatF | ^(M)[LFIWK]... | 21750686, 22405572, 21655309, 19660095, 20885971, 22718636, 19885390 | Target site for acetylation of N-terminal methionine by NatF/NAA60. See 19660095 for nomenclature. | Found only in higher eukaryotes, consequently MK termini are rarely found to be acetylated in yeast. |
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MOD_NatE | ^(M)[KLMA]... | 3TFY, 21900231, 21383206, 22405572, 21655309, 19660095, 20885971, 22718636, 19885390 | Target site for acetylation of N-terminal methionine by NatE/NAA50. See 19660095 for nomenclature. | Specificity partially overlaps with NatB and NatC. |
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MOD_NatD | 19332560, 22405572, 21655309, 19660095, 20885971, 22718636, 19885390 | Target site in histones H2A and H4 for N-terminal acetylation (SGRGK termini) by NatD/NAA40 after cleavage of initiator methionine. See 19660095 for nomenclature. | In vivo substrate specificity for NatD is determined by N-terminal 30-50 amino acid region in its histone substrates, instead of the first few residues (2-5) in case of the other N-acetyltransferases. |
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MOD_NatC | ^(M)[LFIW]... | 23613772, 10545125, 22405572, 21655309, 19660095, 20885971, 22718636, 19885390 | Target site for acetylation of N-terminal methionine by NatC/NAA30. See 19660095 for nomenclature. | Might also accept a Tyr residue in the second position. Specificity partially overlaps with NatB and NatE. |
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MOD_NatB | ^(M)[DENQ]... | 22814378, 12507466, 10545125, 22405572, 21655309, 19660095, 20885971, 22718636, 19885390 | Target site for acetylation of N-terminal methionine by NatB/NAA20. See 19660095 for nomenclature. | Specificity partially overlaps with NatC and NatE. |
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MOD_NatA | ^([SATVCG])[^P]... | 4KVM, 19420222, 10545125, 21383206, 23912279, 22405572, 21655309, 19660095, 20885971, 22718636, 19885390 | Target site for N-terminal acetylation by NatA/NAA10 after cleavage of initiator methionine. See 19660095 for nomenclature. | There might be subtle differences in specificity between yeast and human. NatA might also target N-terminal acidic residues, likely only in higher eukaryots and when acting independently from its auxiliary protein NAA15. |
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LIG_Talin | [WY].{4}NP.Y | 15362227, 20332112, 19903453, 19863457 | Composite motif in the C-termal region of integrin. It is regulated by tyrosine phosphorylation and PTB domain binding at NPxY. Unphosphorylated form binds talin by beta addition. |
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LIG_FDF | FDF|.DW | 19285948, 2WAX, 2WAY, 23851565, 4BRU, 4BRW | Motif in regulators of mRNA decapping like Pat1 and Edc3; mediates binding to the RecA2/Helicase_C (PF00271/IPR001650) domain of yeast Dhh1 and human Ddx6 RNA helicases. Edc3 contains the FDF variant, as well as yeast Pat1, while vertebrate Pat1 has the DW variant. Interactions mediated by this motif likely regulates binding of RNA to the helicase. | In Edc3 the motif has been described as part of the FDF domain (PF09532/IPR025762), an alpha-helical domain with the conserved FDF sequence at the N-terminal. Structures show that additional binding elements determine the interactions. A helical acidic motif N-terminal to the FDF/DW motif in Pat1 binds to a second pocket on Dhh1, while a helical segment (F[DN]K) located C-terminal of the FDf motif in Edc3 binds yet another pocket on Ddx6/Dhh1. |
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FUN_FG_nucleoporin | (FG)n | 18688269, 12065398, 12372823, 17161424, 16338415 | Motif present in nucleoporins that function as intramolecular cohesion elements imparting order to the FG domain and compacting its ensemble of structures into native premolten globular configurations. |
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LIG_Kln1_MELT_1 | ..M[ED][LIVMF]T.. | 24066227, 24361068, 4bl0 |
Repeated semi-conserved motifs with the consensus MELT are found in Kln1/Spc105 and bind to the BUB3 beta-propeller as part of the spindle assembly checkpoint. The motifs are phosphorylated on the Thr residue by Mps1. A structure of the motif in complex with the Bub3 domain has been solved in the yeast system. | By sequence alignment, the mammalian MELT repeats might be longer than the yeast ones. The core MELT should be similar though. Backbone interactions extend beyond the core MELT motif: Pro might be excluded from some adjacent positions. |
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Lig_CaM_1-5-10 | ...[FILVW]...[FILVW]....[FILVW] | Rhoads,1997 | Several helical motif variants can bind calmodulin, including the Ca++ independent IQ motif and the 1-8-15 and the 1-5-10 motifs. The 1-5-10 motif is defined by the hydrophobic residue spacing. Other key features are lack of proline and a preference for positive and against negative charge. | Additional info here http://calcium.uhnres.utoronto.ca/ctdb/ctdb/ http://structbio.vanderbilt.edu/cabp_database/index.html |
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Lig_CaM_1-8-15 | [FILVW]......[FILVW].....[FILVW] | Rhoads,1997 | Several helical motif variants can bind calmodulin, including the Ca++ independent IQ motif and the 1-8-15 and the 1-5-10 motifs. The 1-8-15 motif is defined by the hydrophobic residue spacing. Other key features are lack of proline and a preference for positive and against negative charge. | Additional info here http://calcium.uhnres.utoronto.ca/ctdb/ctdb/ http://structbio.vanderbilt.edu/cabp_database/index.html |
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LIG_SCF-TrCP1_2 | [EDST][ESTD][GAS].{1,3}[STD] | 19150432 14676825 Watanabe,2004 15845771 18354483 17387146 18378670 15917222 15767683 Zhao,2010 20858893 23948254 |
non-canonical variants of the LIG_SCF-TrCP1_1 |
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LIG_Menin_MBM_2 | Grembecka,2010, Huang,2012 |
Bipartite interaction interface recognised by Menin. MBM1 (90nM) and MBM2 (1,400 nM) bind with different affinities but together bind with a much stronger affinity (6.8 nM). Exact residues are unknown but fall between residues 23-40. | This entry may be fused with MBM_1 in light of the crystal structures of JunD and MLL1 complexes |
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LIG_Menin_MBM_1 | ...R{0,2)FP[GA].P | Grembecka,2010, Huang,2012, 3U85, 3U86 |
Part of Bipartite interaction interface recognised by Menin. MBM1 (90nM) and MBM2 (1,400 nM) bind with different affinities but together bind with a much stronger affinity (6.8 nM). MBM1 binds in an extended conformation. Crystal structures with MLL1 and JunD define this core part | Positive charged residues c-terminally are also critical for the motif and if possible should be added to the core motif. |
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MOD_Citrullination | ^M{0,1}[SGAT].R. | 16567635 23818587 |
Peptidylarginine deiminase 4 (PAD4) is a Ca2+-dependent enzyme that converts arginine and methylarginine residues to citrulline. Originally identified in Histones, more recently PAD4-mediated citrullination of GSK3β has been discovered | may not be only N-terminal |
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MOD_PKB_1 | R.R[^PRK].[ST][FY^P] | Yang,2002, 1O6L | Improved P-site motif for PKB. Position -2 cannot allow Pro due to backbone H-bond. Position -2 considered not to allow R on structural grounds: this would differentiate relative to some other basophilic kinases. Position -2 has a strong T preference too. Position +1 is probably not strong enough to demand hydrophobic residue, though clearly favouring one. GSK3beta p-site is close to optimal. |
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Mod_PIMK_1 | R.R[RKH^PDE].[ST][G^P] | 16227208,2BZK | PIM kinases of the CAMK-related group are mediators of cytokine signaling pathways in hematopoietic cells. Their P-sites are basophilic with a preference for R at the -5 and -3 positions like some other basophilic kinases. They have a weaker preference for positive charge at -2 (and cannot tolerate P). A weak G preference is found at +1 and P is rejected. |
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MOD_LRRK2_1 | [FY].(T).R | 21060682 | The Parkinson's kinase LRRK2 phosphosite motif derived by oriented peptide library. | Y is weaker than F at -3. K and R are generally favoured in the +1,+2,+3 positions of the motif. |
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LIG_Neur_NXXN | N..N..L | 19580805 | N-rich motifs such as N..N..L in bearded and QN..NA in Delta reported to bind to the Neuralized E3 ligase. Motifs seem to play a role in both inhibition and activation of Notch signalling. |
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LIG_PSI_ProlineMotif_1 | P.PPP | 15990112 | Proline-rich sequence binding to small double alpha-helical module known as PSI A,B box or PFAM DUF1897 found as two or three copies in a few RNA-binding proteins e.g. PSI, KHRP. Aromatic residues on one helical face make hydrophobic interactions with Pro residues in the peptide motif which is found in U1-70k protein of the U1 snRNP. In fly, involved in P-element transposase alternative splicing. Strong phylogenetic conservation suggests that there is a more general cellular function. | Not clear if this interaction is well enough described yet to make a motif pattern capturing the allowed Pro residue spacing and any possible additional residues. |
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TRG_NoDS | RR[IL].{1,10}[ILVF][ILVF][ILVF] | 22284675 | Nucleolus targeting signals that results in sequestration of proteins by ncRNA |
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MOD_SUMO_SCM | [PG].{0,4}[VILMAFP](K).E.{0,3}[PG] | 10913186, 22829593, 12429819, 20150575 | Synergy Control Motif (SCM) found in steroid receptors such as Androgen Receptor, Glucocorticoid Receptor transcription factors. SCM consists of a core 4 residue sumoylation site and within 3-4 residues N or C terminal of this site, a Pro or Gly residue is found. Mutations in these Pro or Gly residues are reported in various diseases including prostate and testicular cancer. |
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LIG_UBAN | DF..ER | 19185524, 18212736, 20428114 | di-ubiquitin recognition motif found in ABIN proteins, Optineurin, and NEMO. The motif is required for inhibition of NFkB activation. Missense mutations disrupting the motif have been shown to be causal in diseases including Diffuse Large B-Cell Lymphoma and Amyothrophic Lateral Sclerosis. |
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LIG_JAK_Box1 | P.[IV]P.P[EK] | 12374810, 7896787 |
Box1 motif conserved in the common gamma subunit of cytokine receptors including erithropoietin receptor, interleukin3/5/6 receptors, prolactin receptor, interferon-gammaR receptor, and growth hormone receptors. The motif is required for association with JAK kinases. |
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LIG_sHSP_IxI_1 | .I.[IV]. | 23188086, 23340341 |
Oligomerisation motif of alpha-crystallins and related small heat shock proteins. |
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MOD_Spalmitoyl_3 | (C)CIF | 19092927 | variant motif; instance does not match current RegEx | instance in switches.elm: SWTI000549 CDC42_HUMAN (P60953-1) 188 191 |
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MOD_CDK_3 | ([ST])P... | Byeon,2005 | variant motif; instance does not match current RegEx | instance in switches.elm: SWTI000284 MK67I_HUMAN (Q9BYG3) 235 241 |
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LIG_Dynein_DLC8_2 | [KR].TMT | 17029413;16981716 | variant | instance in switches.elm: SWTI000541 MYO5A_HUMAN (Q9Y4I1) 1286 1290 |
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CLV_CASPASE3_1 | D..D | 12637508 | relaxed Caspase3-1 cleavage site | instance in switches.elm: SWTI000550 CEAM1_MOUSE (P31809) 457 460 |
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LIG_S100A4_1 | 22460785,22483112,3ZWH,2LNK | Ca2+ dependent binding of myosin IIA peptide to S100A4 dimer, involved in filament disassembly. The peptide binds across the S100A4 dimer surface (1:2 stoichiometry). Hydrophobic side chains insert into hydrophobic pockets on the dimer. In addition, charged and polar peptide residues form hydrogen bonds and salt bridges with complementary S100A4 residues. | Composite binding site, will be added to switches.ELM. |
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LIG_S100A10_AnxA2_1 | .[^FLVIMAWP][GLVAI][^FLVIMAWP][FIL][PVA][KHR][MIFLV][KHR].[GP][KR][FILV][^FLVIMAWP] | 21949189, 23275167, 4DRW,4FTG | Several regions in C-terminal of membrane-repair protein AHNAK bind to AnnexinA2-S100A10 (2:2) heterotetramer often localised at plasma membrane. A single AHNAK peptide binds across the tetramer surface, making contacts with all 4 components of the S100A10-AnxA2 complex. Binding mainly governed by hydrophobic interactions between AHNAK side chains and pockets on S100A10 (some with additional residues of AnxA2) and hydrogen bonds with backbone atoms of AHNAK. | Composite binding site, will be added to switches.ELM. |
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TRG_NES | Mazanka,2008 | NES |
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LIG_BROMO_BET | (K)[GILVMF]{0,1}[^MFYLW].(K) | 2WP2 19794495 22464331 |
Diacetylation recgnition motif for bromodomain of BET family | first BRDs of the BET family |
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LIG_BROMO | 20502673,11080160 1E6I | The Bromodomain binds acetylated lysine residues in the flexible N- and C-terminal tails of histones. |
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TRG_NLS | Shin,2002 1594241 Duprez,1999 21092142 21182795 | non-canonical nuclear localisation signals |
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MOD_EZH2 | RKS | 23063525 | EZH2 can monomethylate the lysine on a RKS histone-like sequence on RORα leading to its subsequent ubiquitination through the chromo domain of DCAF1 | see LIG_CHROMO for DCAF1 recognition motif |
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LIG_MBT | 20502673 1OYX 12842041 | Malignant brain tumor (MBT) repeats have been implicated as methyl-lysine binding modules. |
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LIG_CHROMO | ARK[ST] | 20502673 1KNA 11859155 | Chromo domains promote binding to methylated lysines in Histone H3 tails. |
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MOD_SUMO_PHOS | [VILMAFP](K).[ST]. | Picard,2012 | Novel Sumoylation site found in Estrogen receptor beta connected to a GSK-beta phosphorylation site |
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LIG_KIX_CBP | [DEST][LMYI]..[LIF][LIV] | 22474372, 2KWF, 16253272, 2AGH, 9413984, 1KDX, 19220000, 17467953 | hydrophobic motif found in transcription factors (FOXO3a, CREB, c-Myb, p53, TCF4...) that interacts with the KIX domain of CBP/p300 to recruit this transcription coactivator. Promiscuous as they might also bind to TAZ1 and TAZ2 domains of CBP/p300. For FOXO3a, phosphorylation of overlapping serine increases affinity. |
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LIG_MO25alpha_WEF_1 | WEF | 14730349, 19892943, 1UPK | The WEF motif contributes to docking the STRADalpha pseudokinase to MOF25alpha in the LKB1-STRAD-MO25 complex | System of increasing interest as LKB1 (STE11) is a tumour suppressor kinase and has recently been is associated with primary cilia and WNT/HH signalling |
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LIG_SH2_IA | (Y)[DE][DE][AFILVWY] | Huang,2008 | Subgroup IA, which consists of members of the SRC, SYK/ZAP-70, and TEC kinase families as well as the adaptor proteins NCK1 and NCK2, selects for the common motif (Y)[DE][DE][AFILVWY] |
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LIG_SH2_III | (Y)..Q | Huang,2008 | Group III comprises the STAT family of SH2 domains. |
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LIG_SH2_IID | (Y)... | Huang,2008 | this is the generic motif for Group 2 SH2 domains. |
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LIG_SH2_IIC | (Y)... | Huang,2008 | this is the generic motif for Group 2 SH2 domains. |
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LIG_SH2_IIB | (Y)[ED].[AFILVWY] | Huang,2008 | Subgroup IIB selects for a hydrophobic residue at P+3 within the general consensus (Y)[ED].[AFILVWY]. The SHC and SHB families of adaptor proteins, BLNK, and SLNK all belong to this subgroup |
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LIG_SH2_IIA | (Y)[AFILVWY].[AFILVWY] | Huang,2008 | Subgroup IIA loosely selects for the degenerated motif (Y)[AFILVWY].[AFILVWY]. This subgroup is represented by the SH2 domains from several protein families that include VAV, phosphatidylinositol 3-kinase, PLCG1, PTPN, and SOCS. |
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LIG_SH2_IE | (Y)[DEKNPR][DEKNPR][AFILVWY] | Huang,2008 | this is the generic motif for Group 1 SH2 domains. |
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LIG_SH2_ID | (Y)[DEKNPR][DEKNPR][AFILVWY] | Huang,2008 | this is the generic motif for Group 1 SH2 domains. |
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LIG_SH2_IB | (Y)..[AFILVWY] | Huang,2008 | Subgroup IB, including SH2 domains from SH2D1A, SHIP1/2, and CRK/CRKL, are related to one another by a shared propensity for a hydropho- bic residue at P+3. Selectivity at P+1 or P+2 for this group of SH2 domains is wider than for subgroup IA |
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TRG_AP2beta_CARGO_2 | [FY]F.{6}W.[FY] | 19287005 | non-canonical AP2-beta2 binding found in isoform of PIPKIγ |
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TRG_NES_CRM1_2 | L.{2,3}L.L | 11074002 | very general NES |
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LIG_PTB_Talin | SPLH | 1Y19, 2G35 12422219 |
Non-canonical PTB binding motif found to bind to the Talin PTB domain | motif only found in PIP5K1C for far. Waiting for more instances before annotation |
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CLV_C14_Metacaspase | 17028019, 18005666, Sundstrom,2009, 21597462 |
Metacaspases are distantly related to caspases and are found in protozoa, fungi and plants. They are involved in regulation of different cell biological processes, like programmed cell death and development. Contrary to caspases which cleave specific after aspartate, metacaspases cleave specific after arginine and lysine. Depending on their prodomain metacaspases were distinguished into type I and II. | Less is known about metacaspases' cleavage motif. Only 3 metacaspases' substrates were described. |
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TRG_LysEnd_APsAcLL_2 | [DERQ].{2,4}L[LVI] | 18315530 Kirchhausen,1999 |
Slight variation of TRG_LysEnd_APsAcLL_1 |
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TRG_MLS | 22178138 10837244 16616497 |
The N-terminal Mitochondrial localisation signal recognised by Tom70. | Could not define regular expression |
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LIG_IQ_3 | [FILV]Q...[RK]G...[RK]..[FILVWYM] | Rhoads,1997 8805510 8127365 12351846 Bahler,2002 |
extended IQ motif |
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LIG_IQ_2 | [FILV]Q...[RK] | Rhoads,1997 8805510 8127365 12351846 Bahler,2002 |
IQ-like motif. |
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LIG_BIR_internal | A.[AP]. | 14523016 | Internal BIR-binding site. In this case, precursor mitochondrial localisation signal is removed exposing BIR site |
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LIG_PI(4,5)P2 | [KR].{3,4}K.[KR][KR] | 9891784,Kojima,2004 | lipid binding motif for PI(4,5)P2 |
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LIG_Filamin_2 | Y..A[VIL]...[VIL] | 16455489 2BRQ |
Based on integrin binding to filamin |
No mention of importance of threonines defined in LIG_Filamin |
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LIG_TPR_4 | [ST].[ST] | 21454478 3Q4A |
phosphorylated version of LIG_TPR found in Smad 1/5 |
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LIG_TPR_3 | K[IL].{0,2}Q | 18759457 17942943 |
internal TPR binding motif with similatities found in androgen receptor and vpu | unsure of veracity |
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TRG_multiple | 19482617 | Review of several motifs responsible for internalization and trafficking of cell-surface membrane receptors |
NP.Y is mentioned in LIG_PTB_Phospho_1 |
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LIG_MIU | [DE][LIVY].[LIV]A..[LIVY]..[DE]{DE] | 16499958 2C7N 2C7M 19217402 |
MIU (motif interacting with ubiquitin; also known as IUIM or inverted UIM) |
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LIG_TAZ2 | F.[DE]...L | 10196247,19217391,16319895, 2KJE, 2K8F | Binding motif for the TAZ2 domain in transcriptional adapter protein CBP/PCAF/p300 | First attempt to annotate failed. Needs more information. A better structure for the P53 instance would be useful. |
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LIG_DUIM | [DE].[LIVY]..A[LIVYM]A.S.[SA][DE] | 16462748 2D3G | double sided ubiquitin interacting motif |
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LIG_UIM | [DE][DE]..[ILVY]..A[ILVY].S.. | 16462748 12970172 1Q0V 2D3G 12750381 1O06 | Ubiquitin interacting motif |
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MOD_N-GLC_3 | NG. | 20510933 21978957 | Non-canonical N-glycosylations sites found in the mouse glycoproteome |
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MOD_N-GLC_4 | N.V | 20510933 21978957 | Non-canonical N-glycosylations sites found in the mouse glycoproteome |
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LIG_PCNA_PIP_2 | ...[LIM][DE].[FHY][FHY]. | Hishiki,2009, 2ZVM,Kim,2010,Shibutani,2008 | Non-canonical PIP box, missing the p1 glutamine. Mediates binding to PCNA. Found in Polη, Polκ. | The PIP boxes of Xic1 in X. laevis and E2F in D. melanogaster overlap the PIP degron LIG_CRL4_Cdt2_1 and LIG_CRL4_Cdt2_2, respectively. |
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CLV_C14_Caspase-1 | [WFYML][^P].D | 1221285 1236692 15296730 | Caspase-1 is involved in inflammation. | Motif suggestion is based on in vitro data. Optimal described sequence is WEHD. For protein substrate see MEROPS or CutDB |
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LIG_WW_Nedd4L | .(S)P.L(S)PN | Aragon,2011, 2LAJ | Motif in Smad3 that binds to the third WW domain of Nedd4L. Phosphorylation of Smad3 by CDK8/9 and GSK3 recruits ubiquitin ligase Nedd4-like via its third WW domain; second WW domain displaces Pin1 at WW motif upstream; leads to Smad3 destruction. |
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MOD_Geranyl_CAAXbox_1 | (C).[LIVM][ILMV]$ | 12702202 | Motif modified by Geranylgeranyltransferase I (GGT1). | Should replace current MOD_CAAXbox to define specificity. |
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MOD_Farnesyl_CAAXbox_1 | (C).[LIVM].$ | 12702202 | Motif modified by Farnesyltransferase. | Should replace current MOD_CAAXbox to define specificity. |
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LIG_DCUN1_1 | (M)[IL].L | Scott,2011 3TDZ | Acetylated N-terminal methionine motif that mediates binding to the DCUN domain of E3 ligase DCN1 found in E2 ligase Ubc12. |
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LIG_LCK_1 | C.CP | 14500983 1Q69 1Q68 | Found in CD4 and CD8. Beautiful mechanism where LCK contributes 2 cysteines and CD4/CD8 contribute 2 cysteines to bind zinc and form a "zinc clasp" binding site. 400nM affinity. Also buries a di-leucine sorting signal regulating trafficking. | May not be a short linear motif by some definitions. |
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LIG_TKB | (Y)[TS]..PT | 20877636, 18273061, 3OB1, 3OB2 | Recognition motif in EGFR and Sprouty2 for non-canonical SH2 domain (TKB domain) in E3 ubiquitin ligase c-Cbl |
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CLV_C14_Caspase4-5 | [LIVMWYF][EDQ][^RKGL]D | 1221285 1236692 | Caspase-4 and -5 are involved in inflammation. | Motif suggestion is based on in vitro data. Optimal described sequence is [WL]EHD. For protein substrate see MEROPS or CutDB |
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CLV_C14_Caspase-2 | [DEIL].[DEFY]D | 1221285 1236692 12920126 | Caspase-2 induces the intrinsic apoptotic pathway during cell stress signaling. | Motif suggestion is based on in vitro data. Optimal described sequence is DEHD. For protein substrate see MEROPS or CutDB |
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CLV_C14_Caspase-9 | [^RK][EDQ]HD | 1221285 1236692 11734640 | Caspase-9 is an initiator caspase in the intrinsic apoptotic pathway and cleaves executor caspases. | Motif suggestion is based on in vitro data. Optimal described sequence is LEHD. For protein substrate see MEROPS or CutDB |
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CLV_C14_Caspase-6 | VLIT][EDQ][^DENQRKAPGS]D | 1221285 1236692 19694615 21111746 | Caspase-6 is an effector caspase during apoptosis. Putative role in Huntington’s and Alzheimer’s disease | Motif suggestion is based on in vitro data. Optimal described sequence is VEHD For protein substrate see MEROPS or CutDB |
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LIG_TPR_2 | [ILMV][DE]{1,2}[ILMV][DE]$ | None | Extension of the current over-defined TPR binding motif based on sequence analysis. |
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LIG_RIP_CTP | SD[DE]DMGFGLFD$ | 19073700 2JDL | 11 residue long C terminal peptide motif of ribosomal stalk proteins which interact with ribosome inactivating proteins (RIP), which in turn leads to depurination of a specific Adenine residue of 28S rRNA and failure of the recruitment of elongation factors to the ribosomal GTPase-associated center, thus inhibition of the translation in the ribosome. |
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LIG_PUL_PLAA_1 | [DE][DE][DE][DE]LY[AGS]$ | 3EBB 19887378 | Motif in ATPase VCP/p97 that binds to the PUL domain of PLAA. C-termianl motif with acidic extension that fits into a highly positive grove on the PUL domain surface. Involved in the regualtion of Ubiquitination. |
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LIG_Glycolytic_Aldolase | W[DE]{2,3}W | 3LGE 20129922 | Motif that mediates binding to Aldolase A |
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LIG_SH3_9 | SAMP | 18786926 20509626 2RQU | a non-canonical SH3 binding motif associated binding to ASAP1 and colocalized at microtubule ends. |
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LIG_Alpha-synuclein | .DVF. | 19762560 | interaction with coiled coils of Synphilin-1 |
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LIG_Actin_DMD | LK..E[ST] | 9883911 | actin binding motif found in the Dp71 dystrophin isoform |
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LIG_ECD_CRF | LM..I$ | 18801728, 3EHT | Extracellular domain (ECD) of corticotropin-releasing factor (CRF) receptor 1 (CRFR1) binds to CRF via its C terminally amidated ligand motif. |
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LIG_BTB_SMRT | [GL][IV][AT]T[IV]KE[AM]GRSIHEIPR | 14690607, 1R2B | Motif mediating binding of BCL6 BTB domain to SMRT |
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LIG_EAR | 20935498 11487705 | EAR motif mediates transcriptional repression of plant genes via recruitment of a histone deacetylase complex, which leads to chromatin modification. |
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TRG_Golgi | 21283809 | potential Golgi-retention motif and a number of conserved motifs with unknown function |
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LIG_SH3_7 | [RK][RK].PXXPPXXP..[RK] | 17437541 | Motif in proline-rich domain of dynamin I that interacts with SH3 domain of endophilin I, consists of tandem core PxxP motif flanked by basic residues; bidirectional binding |
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LIG_SH3_6 | [RK][RK].{9}[RK][RK].PXXPXX[RK]...[RK] | 17437541 | Motif in proline-rich domain of dynamin I that interacts with SH3 domain of syndapin I, consists of core PxxP motif flanked by basic residues; syndapin I binding sensitive to introduction of negative charges; bidirectional binding |
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MOD_acetyl_E2ligase_1 | [KR]R[IL].KE | 21791702 | Motif found associated with the acetylation of ubiquitin E2 ligases |
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LIG_ARM | [DEG].EGGGE.D...[FY]....L | 20371349, 3L6Y | Motif in JMD domain in C-terminal tail of cadherins that interacts with Armadillo repeats in p120 catenin |
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LIG_BH1_BH3 | LA..GD | 16475813 | Motif of Bid-BH3 that binds to BH1 domain of Bcl-w. This interaction is lost upon Bcl-w lipid binding |
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LIG_Filamin | ..(T)TT.. | 20332112,Takala,2008, 2V7D | Motif recognized by Filamin. First threonine must not be phosphorylated. | Molecular switch. See LIG_Talin and LIG_14-3-3-3 (latter might need updating of regex as does not cover binding motif in integrins mentioned in 18550856) |
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LIG_Sin3_4 | [FLW]..[ILV][ILV]... | 21440557, 2L9S | PAH motif in Pf1 (Q96QT6) binds to Sin3 (Q60520). | Basically extends LIG_Sin3_3. (cave: pdb-structure features human motif but mouse sin3a) |
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LIG_TF2_FCP1_1 | [DE]...[ILMV][AGS]..L..[DE][ILMF] | 12732728,12591941, 1J2X | Motif in carboxy terminus of FCP1 interacts with carboxy terminus of "Transcription initiation factor IIF subunit alpha" (RAP74). Interaction relies extensively on van der Waals contacts between hydrophobic residues situated within alpha-helices in both domains. | Might not be linear |
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LIG_CAVB_AID | L.GY..WI | 15141227, 1T0J | Motif in Voltage-gated calcium channel beta-subunit (Cavb) binds to the conserved alpha-interaction domain (AID) of the same channel | Interaction happens between subunits of calcium channel. Motif resides in structured region; found in multiple Voltage-dependent calcium channel subunits. |
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LIG_FERM_2 | L...M..L..LM..L..IT | Hirano,2011,Wei,2011, 3PZD | Large cargo recognition helix in DCC, Ngn and Fz1A that binds to the FERM domain of Myosin-X. |
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LIG_20S | [ILMV]Y.$ | 21499243,20019667, 3IPM | Binding site on the 20S protesome that is used by both assembly factors such as Pba1-Pba2 and activators such as PAN, Blm10 and PA28. |
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LIG_CORNRBOX_2 | [IL]..[ILV][IL]..[ILVYF] | Phelan,2010,3N00 | An improved definition of the CoRNbox motif based on structural studies from SMRT and N-Cor. Should update current entry rather than make new entry as they are overlapping. |
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LIG_RCT | L..L[KR].[KR] | 21217703,3OWT | Helical motif that mediates the binding to the RCT domain of yeast telomeric protein RAP1. Found in TAZ1(1.97uM) and Sir3(2.3uM) overlaps the binding site of a larger higher affinity disordered interface found in TRF2 (16.5nM). |
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LIG_Caveolin | [WFY]....[WFY]..[WFY] | 9325253 | Motif mediating binding to Caveolin. Found in G-proteins, Src-like kinases, Ha-Ras, and eNOS. Also functions in a anti-parallel conformation. |
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MOD_phos_AURORA | R.([ST]) | 21712546,Alexander,2011 | Canonical motif phosphorylated by Aurora kinase A/B |
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LIG_APH1 | G...G | 18061918, 21507970 | conserved alpha helix binding motif; plays a role in maturation of the gamma-secretase complex, but may be involved in other recognitions (see ref2) | earns a closer look (Mk) |
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LIG_AcetylCoA | [QR]..G.[GA] | 19660096 | Conserved core motif responsible for acetyl coenzyme A binding as found in all members of the GNAT superfamily of N-acetyltransferases (GNAT, Pfam: PF00583 Acetyltransf_1) |
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MOD_HEME | CP[ILMVFY] | 7835342 | Short sequence that has been shown to bind heme and is repeated up to 6 times. |
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DCK_dephos_PP1_4 | F..[KR].[KR] | 12115603,20376316 | Docking motif for PP1 phosphatase found in several proteins involved in apoptosis such as Bcl-xL. |
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MOD_SPalmitoyl_X | 15189153 | Modification site by palmitoylation; may also mask other modifications or binding sites, e.g. by recognins | extention of entries class 2 and class 4 |
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LIG_FERM_ICAM2 | R...Y.V...W | 12554651, 1J19 | Cytosolic side motif in ICAM-2 binds to the PTB-like C domain of the FERM module. Important for membrane-associated cytoskeleton. | Peptides with low similarity to ICAM-2 from other proteins also bind in this region of FERM so it may be difficult to define ELM motifs. |
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LIG_cpSR43_ANK | DPLG | 18621669, 3DEP | The DPLG motif binds L18p to cpSRP43. Part of a chloroplast system inserting light harvesting proteins into thylakoid membranes |
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LIG_Cdc20_Spo13 | L.E...N | 17493939 | Degron in the yeast meiosis-specific protein SPO13 recognised by the cdc20 subunit of the APC. |
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MOD_SMAD | (S)[IVLM](S)$ | 9346908,18387785 | C-terminal phosphorylation motif found in receptor-activated Smads. Phosphorylated by TGF-beta1 kinase after its activation |
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LIG_DHB_DAXX | [DE]..[IL]..[WHFY][[WFHY] | 21134643 | Motifs in Rassf1C mediating binding to the DHB domain of the scaffold protein DAXX. | Has structure but not yet in pdb (see paper). |
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LIG_N_degron_Doa10_Ac | ^([MAVSTC]) | 20110468 | Acetylated N-terminal degron signal recognized by ubiquitin ligase Doa10. Promotes proteosomal degradation. |
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LIG_AGO_PIWI_1 | WG | 17891150 | Mediates interaction with the Argonaute PIWI domain. Found in Argonaute-interacting protein Tas3. | Difficult to annotate. Very variable other than conserved tryptophan. |
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LIG_BIR_Survivin | ^AX(PT) | 20705815 | Most BIR domain interacting peptides are unmodified but the Survivin BIR domain recognises an N-terminal peptide with phosphothreonine in the third position. |
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TRG_TAT | [ST]RR.FLK | 16987314 | Tat export consensus motif. |
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LIG_RNA_RGG | RGG | 8290338,12925994,12628254 | Motif potentially involved in RNA binding in RGG transcriptional regulators. SMN Tudor domain binds dimethyl-Arg of RGG. |
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MOD_LammerK | (RS)n | 11827553,1577277,8772383 | Many Lammer kinases (clk1-4, Doa, PK12) phosphorylate (RS)n motifs, regulating splicing. |
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TRG_VTS | R.L.[EQ] | Hiller,2004,Marti,2004 | Vacuolar protein export signal. |
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LIG_MIT_MIM2 | [ILMV]P[DE]VP[ST]..LP | Kieffer,2008, 2K3W | VPS4 MIT domain binding "MIM2? motif found in a subset of ESCRT-III subunits |
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LIG_MYPT1 | Y.Y | Terrak,2004 | Motif on PP1delta reciprocating the RV.F motif on the targeting subunit of MYPT1. MYPT1 also has an N-terminal helical motif interacting with PP1delta. |
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LIG_RHIM_1 | [IV]Q[ILV]G | 20346680 | RIP homotypic interaction motif found in several programmed necrotic cell injury related proteins. Probably the core of a longer disordered interface |
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LIG_Notch | DSL | 17006545 | Conserved N-terminal motif in Notch ligands. |
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LIG_PKC | [YF][SA][VI](Y)[QR].[YF]. | 15851033 | Phosphotyrosine motif in CDCP1 binding to the PKCd C2 domain. |
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MOD_MegPhos | PPPSP | 17555532 | Necessary for phosphorylation of Megalin, possibly by GSK3. |
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Lig_PAH1_SID | 16288918,18089292 | Helical motif binding the PAH1 domain of the Sin3 corepressor. There are four PAH domains in Sin3 that are likely to bind helical peptides with different specificities. Reversed orientation binding has been observed for PAH1-binding helices. |
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LIG_PAS_STAT6 | L..LL | 14757047,12138096 | Stat6 motif found in complex wit the PAS domain of NCoA, not the usual nuclear receptor. Indicates a more complex story. |
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MOD_acetylation | 10656693,10607594,9744860,9774110,9809067 | Acetylation targets in the nucleus beyond histone tails: p53, HMG I/Y, TCF, etc. |
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LIG_TAZ1 | LP.L / LPMSP | 14594809,12778114,11959977, 1L8C, 1L3E | Minimal region of a lager binding motif for the TAZ1 domain in transcriptional adapter protein CBP/PCAF/p300. Complicated binding read [19214187] for explanation. |
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LIG_TRADD | YYD$ | 9356494 | Tumor necrosis factor receptor-associated death domain protein (TRADD) binding motif in LMP1 |
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LIG_PHDfingers_H3 | ^...K | 16728977 | NURF and ING types of PHD finger bind histone H3 trimethylated lysine. |
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MOD_methylation | 8366133 | Modification sites in histone tails and nucleolin. |
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LIG_R3IM | [DE][DE][DE]EFE[DE] | 18775730 | Motif of the DSS1 protein required for proteasome interaction and p53 protein degradation. |
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MOD_Prk1p_1 | [LVIM]....(T)G | Huang,2003,11694597,19220811 | Motif modified by Prk1p, a yeast kinase localised at cortical actin patches and regulating endocytosis. Substrates include epsins and the Bni1p formin. |
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TRG_TGN | YW | 16978406 | Retrograde endosome to trans-Golgi network motif. |
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TRG_Paranodin | PGY | 17093057 | Paranodin trafficking repeat motif. |
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TRG_RS | (RS)n | 12215544,1577277,8772383 | C-terminal RS domain rich in arginine and serine residues (extensively phosphorylated) that promotes protein protein interactions and directs subcellular localization of SR splicing factors. |
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TRG_PEXEL_VTS | 16046186 | Export motif for RBC stage of the malaria parasite. Similar motif in potato blight. |
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TRG_Parasite_HT | R.L.[EDQ] | Dou,2008,19170882 | Core motif for N terminal host-targeting (HT) motif composed of 11 amino acids that is found in Plasmodium and other parasites. |
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TRG_nucleolus | 10469277,10050887,9731210 | Nucleolar targeting signals. |
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TRG_Mit | 11381593 | Mitochondrial targetting peptides. |
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TRG_ERM-PM | RGGKYSV | 17995939 | Motif responsible for the recruitment of ERM proteins to the plasma membrane in neurogenesis. |
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TRG_Dendritic | LLY..[FYW] | 16988049 | Dendritic targeting motif. |
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TRG_chloroplast | 10998602 | Chloroplast transit peptides. |
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LIG_Sap1_Bbox | F.L..L | 11406578 | SRF binding motif with beta-augmentation core. |
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LIG_IntA3B1 | NVR | 17034138 | Integrin a3b1 binding motif in thrombospondin. |
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LIG_LIM | [IVLMF]I[IVLMF]R[IVLMF] | 16616188 | Motif that binds some LIM domains. It is part of larger conserved induced fit module where there might be a second LM02-LIM-binding motif. |
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LIG_integrin_TGFbeta | DL..L | 14572313 | Integrin binding motif in TGFbeta. |
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FUN_Aurora | 14752279 | Double motif in TPX2 regulating Aurora kinase activity |
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LIG_Integrin_Cell_Adhesion | GRKRK | 19617625 | C-terminal motif of tropoelastin that can bind to cells in a divalent cation dependent manner. Might be an integrin binding motif required for cell adhesion. |
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LIG_ERCC1 | D[ST]G[AG]GF | 17948053 | Used by XPA to recruits ERCC1-XPF to nucleotide excision repair complexes |
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FUN_Pin1_Isomerisation | P[ST]P | 12571275 | Pin1 isomerization motif. |
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FUN_Synaptotagmin | KK...K | 16987956 | Motif required for efficient synaptic transmission. |
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FUN_UBX | QA | 16267091 | Motif is present in Drosophila Ubx family of HOX genes and with pleiotropic functions in development. |
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LIG_Abox | Littlepage,2002 | Another destruction box proposed in Aurora A kinases. |
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LIG_FERM | RSLE | 17045809 | A FERM domain binding motif in neurofascin. |
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LIG_Hsc70 | QLMLT | 17978091,7649995 | Motif in the Clathrin Heavy Chain Required for the Hsc70/Auxilin Uncoating Reaction. Sequence bound preferentially by the substrate groove of Hsc70 |
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LIG_COPII | YNNSNPF, L..LE, D.E | 12941276,15093828 | Motifs involved in vesicle budding interactions of SNARES with COPII (subunits sec23/24). |
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LIG_FF | 12381297,16253993 | Phosphorylated and possibly other motifs bind FF domains. Notably the RNA polII CTD. |
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LIG_Fn_binding | LIPAD | 19699715 | Fibronectin binding motif on the C-terminus of the Leptospira adhesin LigB (LigBCtv), residues 1708-1712 containing sequence LIPAD with an beta-strand and nascent helical structure. |
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LIG_MDAS_MEF2 | 12700764 | Motif found in the interaction between the MADS box of MEF2b and Cabin1. It aquires an amphipathic alpha-helix structure upon interaction. |
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FUN_Delta | [DE].{2,4}NN[IL] | 17006545 | Motif conserved between invertebrates and vertebrates in Delta interacting proteins (Serrate/Jagged). Involved in the interaction with the E3 ubiquitin ligases Mib1 and Neur. |
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LIG_integrin_extracell | LDV | Belkina,2009 | Another extracellular integrin binding motif. |
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LIG_alphaActin | FGPVVA | 1142354 | Actin binding motif in plaque protein zyxin. Said to require alpha-actinin dimerisation. |
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LIG_AnkyrinG | [VA]P[IL]A..E[SD]D | 12716895,12829783 | A conserved 9-amino acid motif required for ankyrinG binding. |
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LIG_AP2alpha_3 | W..[FW] | 14565955 | An AP-2 adaptor interaction motif initially identified in the long-splice isoform of Synaptojanin1. |
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LIG_betaCatenin_armadillo | 11136974,9774110 | Motif responsible for the induced fit of 3-segmented IUP regions with the central KEGE-motif. K is not sampled but is acetylated by CBP to regulate the interaction. E/C-Cadherins have similar motif without K so not AC-regulated. Found in TCF/pangolin. |
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LIG_Calnexin | KPKKKKK | 14988724 | Poly Lysine motif found in Erp57 and responsible for Calnexin binding. Highly conserved in orthologs and always located at the C-terminal end. Might determine the specificity of Calnexin binding versus the protein disulfide-isomerase (PDI). |
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LIG_chromoshadow_EMSY | [VILMF].[VILMF].[VILMF]..[VILMF] | 16615912 | Motif that binds to HP1 chromoshadow domains from EMSY. |
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LIG_CH_Parvin_Forwards | EL..L[LM]..L | 18940607, 2VZD | Motif mediating binding to the C-terminal calponin homology domain (CH(C)) of alpha-parvin. Possible molecular switch by binding the FAT domain targeting LD motifs of Paxillin. Can bind in an anti parallel orientation. |
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LIG_CH_Parvin_Backwards | L..L[LM]..LE | 18940607, 2VZD | Motif mediating binding to the C-terminal calponin homology domain (CH(C)) of alpha-parvin. Possible molecular switch by binding the FAT domain targeting LD motifs of Paxillin. Can bind in an anti parallel orientation. |
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LIG_CK1 | F...F | 15121840 | Motif in NFAT and Per reported to dock CK1 kinase. Reminiscent of the FXXF motif in the PIF pocket kinases. |
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LIG_clathr_ClatBox_Cter | L[IVLMF].[IVLMF]$ | 10449404 | Variant clathrin box in yeast found at carboxy termini of e.g. some epsins. |
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LG_CyclophinA | FGP.LP | 15845542 | Motif proposed to bind Cyclophin A. |
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FUN_GPIanchor | 11814051,11677780,7482705 | Glycosylphosphatidylinositol extracellular plasma membrane anchor. |
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LIG_Chromatin_H2A-H2B | M.LRSG | 18688256,16469929 | Only 2 instances so far and the motif is completely conserved like this in both. Looking at the structures the SG (both small) is probably just there to allow the angles necessary for a hairpin Chromatin binding peptide, interacts with an acidic pocket formed by a H2A-H2B dimer. |
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LIG_CKB_1 | M.E.L.LC(ST)G.F | 15707391,12545175 | Triple phosphorylated docking motif in Claspin that binds checkpoint kinase CHK1 |
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LIG_epitope | MYPPPY | 11418697 | Epitope recognition motif present in CDC28 and conserved accross species. It is involved in the regulation of the immune response of T cells. |
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LIG_CtBP_2 | RRT..PPAL | Nardini,2003 | Another motif that binds to CtBP. |
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CLV_GxGD | G.GD | 20021564 | Motif that could be evolutionary conserved to allow cleavage of all possible gamma-secretase substrates. |
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FAM_apoptotic | XX...DD....D | Motif found in apoptosis induction proteins: GPP synthases, Nox-a, Bad, Bid, Bik, yt-ppy-a, s81f. |
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LIG_RCD1_1 | [DE].{1,2)}[YF].{1,4}[DE]L | 27881680 25348421 |
Motif in plant transcription factors binding to stress-associated plant protein Radical-induced Cell Death 1 (RCD1) |
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LIG_SH3_8 | [RK]..[RK] | Berry,2002 1H3H Kojima,2004 |
non canonical SH3 binding motif | confers specificity for the interaction between Gads and SLP-76 in T cell signaling. Berry,2002 analyses the binding using short peptides. SLP-76 contains two R..K motifs, but only the first (PSIDRSTK) binds, the second (TFPSRSTK) does not (or wasn't done) |
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LIG_PUB_PIM_1 | DDDLY. | Elliott,2014 Schaeffer,2014 4OYK 4P0A 4P0B |
Motif in OTULIN/Fam105B binding to the PUB domain of the HOIP protein, part of the LUBAC complex, a generator of Met1-linked ubiquitin chains. Similar motif in P97 binds more weakly and also binds to PLAA PUL domain (see LIG_PUL_PLAA_1 candidate) |
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LIG_PLK_PoloBox_1 | #.S([ST]).. | Elia,2003,Elia,2003 | Phosphoserine site recognised by the Polo-like-kinase via the Polo Boxes. The pSer-peptide binds along the groove between the two Polo boxes |
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LIG_PH_Tfb1 | [ILVF]..W[ILVF].[DE] | 16793543,2GS0 | Amphipathic helix motif in P53 that is recognised by the PH domain of the p62 subunit of TFIIH. 3uM and phosphorheostatic binding (pS46 518nM, pT55 457nM and pS46pT55 97nM). |
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LIG_Rrp6Rrp47_Mtr4_1 | [DE]LFx[VC]F[ED]{1,2} | Schuch,2014 4WFD |
Exosome associated Rrp6 and Rrp47 modules associate by mutual induced fit into a six-helical intertwined heterodimeric folded domain. The N-terminal helical motif of TRAMP complex factor Mtr4 binds in a surface groove of the preassembled Rrp6-Rrp47 fold. In this way, the TRAMP complex can dock to the exosome as part of its RNA processing function. |
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LIG_FAT_Reverse | L..L[LM] | 18078954,3B71 | Motif in CD4 used to bind FAT domain of Focal Adhesion Kinase. Binds the same binding surface as the similarly hydrophobic helical LD motifs of Paxillin but has an anti parallel orientation. |
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LIG_CDC20_ABBA_1 | [FIVL].[ILMVP][FHY].[DE].{0,3}[DEST] | Di Fiore,2015, He,2013, 4bh6 |
The ABBA motif binds the CDC20/CDH1 coactivator subunit of the anaphase promoting complex. It is found in a number of key cell cycle proteins. In yeast ACM1, ABBA acts cooperatively with KEN and D-Box motifs to inhibit the APC. It is likely to function similarly in metazoan BubR1. In metazoan cyclin A, the ABBA acts as a degron enabling the cyclin’s destruction in prometaphase, while the APC is otherwise not yet active. |
undergoing annotation |
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LIG_BART_Arl2_1 | LL[^p][^p]L[^p][^p]LK | Zhang,2009, 3DOE |
In the GTP bound form, the small GTPase Arl2 expels its N-terminal helix which becomes available to bind the BART domain of BART protein. The Arl2 molecular switching system regulates transport of farnesylated proteins. |
undergoing annotation |
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LIG_CaM_NSCaTE_1 | W[^P][^P][^P][IL][^P][AGS][AT] | Taiakina,2013, Liu,2012, Dick,2008, Liu,2012, 2LQC |
Helical motif binding to Calmodulin. Found in N-termini of some calcium channels (CaV1.2/CaV1.3). Presence in long isoforms dependent on alternative translation start. Involved in channel function. Different from the classical Lig_IQ Calmodulin-binding motif. |
undergoing annotation |
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LIG_LSD1_SNAG_1 | ^mPRsFLv[KR]k | Lin,2010, Baron,2011, 2Y48 |
The SNAG domain is a conserved N-terminal motif in some zinc finger and homeobox TFs such as SNAIL, Scratch, GFI1, Gsx1. Inhibits LSD1 demethylation of H3K4 by competitive inhibition of the active site. Has repressive effect. |
undergoing annotation |
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MOD_Chk_1 | L.R..[ST]. or L.P..[ST]F | 12711320, 11821419, 15279791 | Several basophilic kinases are reported to have additional hydrophobic residue preferences, including CHK1,2, MK2, PKD. LxRXX(ST) is one such variant p-site motif. Also the +1 position is often hydrophobic. In the case of CHK2, the R can be replaced by P (as in BRCA-1) but then the other positions must be optimal as in LxPxxSF. Therefore it appears that some flexibility in the 3 specificity residues is possible, where, if one position is poor, the others must be optimal. |
undergoing annotation |
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DCK_phos_PKA_1 | [ILMVFA][ILMVFA]..[ILMVFA]...[ILMVFA][ILMVFA]..[ILMVFA] | 20159461, 3IM4 | Large amphipathic hydrophobic docking motif for RI and RII regulatory subunits of cyclic AMP dependent protein kinase (PKA). Binds to the D/D dimerisation/docking domain. Found in most AKAP proteins. |
undergoing annotation |
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Mod_CDK_Long_2 | ...[SP]..K | Alexander,2011 | Longer version of the cyclin/CDK phosphosite recognised by e.g. CDK1. Lysine is specific in the charge position. |
undergoing annotation |
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MOD_HedgehogLipid | Pepinsky,1998,Chamoun,2001,11493554 | Keeps Hedgehog attached to plasma membrane for short range extracellular signalling. Probably needs its own functional site and different ELM entries. |
undergoing annotation |
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LIG_WW_Itch | PP.Y....[ST][ILV] | 20855944 | Extended WW domain binding motif necessary for binding to the 2nd WW domain of Itch. Mutations in the final hydrophobic position have been shown to reduce binding and have been implicated in both Hays-Wells syndrome and Rapp Hodgkin syndrome. |
undergoing annotation |
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LIG_WW_Fe65 | PPLA | 18547980 | Putative motif claimed for GSK3beta for binding to Fe65. This interaction is posited to regulate apoptosis and phosphorylation of Tyr 216 of GSK3beta. | The sequence region is post-kinase domain but is structured. The PPLA sequence is very poorly conserved too... |
undergoing annotation |
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LIG_Centrin_XPC | W..L...[IL] | 15964821 | Motif responsible for the binding of XPC repair protein to Centrin 2. PDB structures available. |
undergoing annotation |
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DOC_CYCLIN_LxRrev_6 | [EDST].{0,3}[FL].{0,1}[IL][^D][KR][^D][^EDWNSG]((.{0,3}[KRH])|.) | Kelso,2021, 7LUO |
In yeast SKP2, the Cyclin A L/IxR docking motif binds in the reverse orientation to the more commonly found RxL motif. |
fully annotated |
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DEG_CRBN_cyclicCter_1 | [NQ]$ | Heim,2022 Ichikawa,2022 8BC6 8BC7 |
Cereblon is the E3 ligase adapter inhibited by the teratogenic drug thalidomide. It binds a C-terminal degron comprising the cyclic imides aspartimide and aminoglutarimide. These arise spontaneously by sidechain:peptide bond reaction and cleave the protein chain. Therefore the role of cereblon is to remove gthe damaged proteins. Cereblon is also found in prokaryotes where it presumably plays a similar role. |
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LIG_CTBP_RRT_2 | [Rg]RT[^P].PP | Quinlan,2006 2HU2 |
Motif that binds to the nBD (nucleotide-binding domain) of the NAD regulated CtBP transcriptional repressor protein. PxDLS binds the second domain in CtBP. Some proteins like ZNF217 have both PxDLS and RRT motifs. |
fully annotated |
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LIG_AIR1_Trf4 | IWRxY | Fasken,2011, Holub,2012, 3NYB | The Air1-Trf4 interaction motif is important for TRAMP formation, which plays a major role in RNA surveillance and polyadenylation of RNA targets, marking them for exosomal degradation. The motif was found in yeast and presumably is conserved in an human orthologue of Air1. | Motif in linker region between zinc knuckle 4 and 5 of Air1. |
fully annotated |
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MOD_LOK | [KR][Yf].[ST][LIVMF][RKH] | Belkina,2009 Johnson,2023 |
LOK kinase optimal phosphorylation site. LOK is a basophilic kinase with unusual Y preference at position -2. |
fully annotated |
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lig_p97N__SHPbox_1 | .((W)|(F.))G.G.[RKv]L. | Lim,2016 25078495 Sato,2006 27684549 Hanzelmann,2016 5GLF 5C1B 5B6C |
The SHP box (also known as BS1) binds to the N-terminal domain of the p97/VCP/Segregase/Ter AAA ATPase by beta augmentation. The SHP box occurs in proteins involved in ERAD translocation and destruction of ubiquitylated ER proteins. Proteins with SHP boxes include Ufd1, Derlin-1 and ITA10. |
The helical VBM motif binds elsewhere to the same p97N domain. |
fully annotated |
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LIG_ARC_Nlobe | [^P][RP][^P][YFH][^P] | Zhang,2015; Hallin,2021; Nielsen,2019; 4X3I; 4X3H; 6TQ0; 6TNQ |
Binding motif ([^P][RP][^P][YFH][^P]) for Arc N-lobe, the N-lobe domain has structural homology with HIV virus capsid. Arc is a hub protein for many postsynaptic and nuclear proteins. |
fully annotated |
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LIG_ARS2_EDGEI_1 | [ED][ED]GE[ILVM] | Dobrev,2021 Foucher,2022 7QY5 |
This motif with consensus EDGEI is found in several nuclear RNA transcript decay proteins, such as Red1, which bind to Ars2 in the S. pombe MTREC complex. The equivalent complex in human is PAXT. The motif is present either singly or repeated up to 3 times. A useful mnemonic maybe to pronounce this as the “Edgy” motif. |
fully annotated |
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LIG_WIRS | [FMYL].[TS]F.. | 4N78 Chia,2014 Chen,2014 |
Motif binds to a conserved WAVE regulatory complex surface formed by Sra and Abi subunits. Motif therefore directly links diverse membrane proteins to the WRC and actin cytoskeleton |
fully annotated |
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LIG_CYCLIN_2 | L..P[ILVMF].[ILVMF] or LLPP | Bhaduri,2011, Koivomagi,2011, Koivomagi,2013 | These non-canonical cyclin boxes bind preferentially to the yeast cyclin Cln2 and enhance phosphorylation of Cdk substrates in a cyclin-specific manner. | found in yeast. |
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LIG_MIT_MIM1 | [DE]..L..RL..L[KR] | Obita,2007, 2V6Y | VPS4 MIT domain binding "MIM1? motif found in a subset of ESCRT-III subunits |
fully annotated |
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LIG_CP | L.H.T..R[AP]K | Takeda,2010, 3AA6, 3AA1, 3AA0 | Motif found in the CARMIL proteins (CARMIL, CD2AP and CKIP-1) that regulate actin capping protein (CP) by removing them from the actin filaments. 10nM affinity. |
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TRG_Pyrenoid_Rubisco_1 | [DN]W[RK]..[ILAV] | Meyer,2020,He,2020, 7JSX, 7JN4, 7JFO | The Rubisco-binding motif, present in Chlamydomonas, targets proteins to the Pyrenoid. It helps in the organelle assembly as it's present in the proteins that connect Its different compartments. |
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LIG_p75_IBD_2 | Tesina,2015 | Conserved consensus binding motif in JPO2, PogZ, MLL1,2, MED1, ASK and IWS1 allows interaction with LEDGF/p75 integrate binding domain (IBD). |
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LIG_p75_IBD_1 | Tesina,2015 | Binding motif in MLL1 allows interaction with LEDGF/p75 integrate binding domain (IBD). |
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MOD_CAAXbox_2 | (C)[^DEQ][LIVMF].$ | Ivanov,2010, Reinicke,2005, 17411337 | Two bacterial instances (SifA from Salmonella and Lpg1976 from Legionella) are experimentally validated Prenylation motifs. However, they slightly differ from the canonical ELM MOD_CAAXbox. | The in silico predictor PrePS recognizes this extended regular expression. |
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LIG_ALIX_SIVld_1 | [PA]Y..[AV][^P][^P][^P]L[^P][^P][YLF] | Zhai,2011 2XS1PDB:2XS8 |
Late domain of SIV helical motif binding ESCRT Alix. Tyr residue is in same location as more common LYPxL motif. |
fully annotated |
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LIG_KLC1_Yacidic_2 | D[#]Y[#][DE] | Pernigo,2018, 6FUZ 6FV0 |
A second Kinesin cargo motif binding to KLC1 in addition to WD. Binds the TPR domain. Found in JIP1 and TorsinA. Interacts much more weakly with KLC2. |
fully annotated |
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LIG_Cdc14_PxL_1 | [FLM]...P.[LIM].[FYPLM] | Kataria,2018 6G85 6G86 |
The PxL motif is found in substrates and inhibitors of the major yeast cell cycle phosphatase Cdc14. The motif interaction is especially important during mitotic exit. |
fully annotated |
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LIG_Cyclin_yLxF | P[NEQ][KR]LXF | Ord,2019 | A linear motif present in the yeast mitotic cyclins (clb1 and clb2) substrates or inhibitors used for efficient Cdk phosphorylation. There could be a different docking site mediated mechanism in other higher eukaryotes. |
fully annotated |
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LIG_SH3KBP1_nSH3_x | P.[PA].PR | Kowanetz,2003 Jozic,2005 Huber,2018 2BZ8 |
Non-canonical SH3-binding motif. The Cbl-b motif simultaneously binds sandwiched between the N-terminal SH3 domain of the SH3KBP1 (CD2BP3/CIN85) and the SH3 domain of ARHGEF7. SH3KBP1 is an adaptor protein involved in endocytosis, Lysosomal degradation and signal transduction and ARHGEF7 is a RHO exchange factor. The motif is used by the Apicomplexan parasite Theileria as part of a set of effector protein motifs used to gain entry into the cell. |
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DEG_SCF_FBX31_1 | D...[VI][^P][IL]$ | Li,2018 | C-terminal degron motif in metazoan Cyclin D1,2,3 that targets the cyclin for destruction by the proteasome via the E3 ligase FBX31. FBX31 can be reduced abundance in cancer. Cyclin Ds are essential components of the Rb checkpoint and target CDK4/6 to phosphorylate Rb. | Insect motif is different with F at the C-terminus. |
fully annotated |
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LIG_Vh1_VBS_1 | ([IL][VILY].[^P]A[^P].[VIL][^P].[^P][VLMT][^P][^P][VL][VIL])|(DD[IL][VILY].[^P]A[^P].[VL][^P].[^P][VLM][^P]P[VL][VIL]) | Izard,2004 Crystal structure of the VBS-N in Talin 1 with Vh1 from Vinculin. 22334306 The second alpha-helix in Talin 1 (VBS-C) binds to Vh1 in Vinculin. Izard,2004 Talin 1 from Gallus gallus opens/activates human Vinculin. Gingras,2006 Spot-peptide arrays to determine which positions that are or are not allowed in the binding VBS. Structures different helices in Talin in complex with Vh1 from Gallus gallus. Gingras,2005 Crystal structure of Talin 1 from Gallus gallus with Vh1 from Gallus gallus. Izard,2006 IpaA from Shigella flexneri contains two VBS motifs that bind in a mutually exclusive fashion to human Vinculin. Hamiaux,2006 IpaA from Shigella flexneri contains two VBS motifs that bind simultaneously to two Vh1 domains from Vinculin. Park,2011 VBS N and C terminal in sca4 from Rickettsia rickettsii. |
Vinculin works as a linker that strengthens the association of Talin and F-Actin at sites of integrin activation allowing stronger actin binding and major stability of the sites of focal adhesion (23719537). Talin contains a small globular head and a long tail containing 63 predicted alpha helices. Apparently, some of these helices can form a tertiary structure when not activated, as shown by NMR experiments (Gingras,2006). After a substantial change in this tertiary structure, 11 out of the 63 helices are able to bind to Vh1 head domain of Vinculin, forming a helix bundle, as demonstrated by SPOT peptide analysis and crystallographic structures (Gingras,2006), the helical motif that allows the binding is referred as Vinculin Binding Site (VBS). Interestingly, bacterial pathogens like Shigella flexneri and Rickettsia have developed mimic structures that resemble the architecture of the VBSs in Talin with the same biological function and co-localization with Talin that can induce actin polymerization without the need of integrin activation (Izard,2006; Hamiaux,2006; Park,2011). |
The current regular expression matches some but not all the peptides that were confirmed as binders in a SPOT peptide analysis (Gingras,2005). In particular, it matches the one helix that has a crystal structure (1ZW2) demonstrating the binding but that it is unexpected to be a real one since it covers the binding site for the F-actin. A crystal structure (1ZVZ) showed that helix having a Met at the +1 position can bind Vh1 from Vinculin but after major changes in the side chains and the orientation of one alpha helix in Vh1. This Met in the +1 position was shown to impair the binding of VBS1 on a SPOT-peptide substitution array. Therefore, the current regular expression do not allows a Met in the +1 position. Positions +4, +6, +9, +11 and +13 do not allow a Pro based on the SPOT-peptide substitution array. Position +14 allows a Pro when two Asp are present at position -2 and -1. |
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LIG_GBD_Chelix_1 | [ILV][VA][^P][^P][LI][^P][^P][^P][LM] | Kim,2000 NMR structure of autoinhibited human WASP (1EJ5). Peterson,2004 NMR structure of human WASP with a small molecule inhibitor (1T84). Alto,2007 EspF from EPEC can bind to N-WASP as proved by coimmunoprecipitation assays and in vitro Arp2/3 activation. They measured the Kd for EspF and mini-N-WASP/Arp2/3 =11.8 nM. Cheng,2008 EspFU activates WASP (NMR structure 2K42). Sallee,2008 Alanine scan in rat N-WASP and human WASP and defined the main contacting residues. Effect on multiple binding of the repeats in EspFU. Aitio,2012 NMR structure of the 3-proteins complex: human N-WASP, the SH3 domain of human IRTKS (aka BAIAP2L1) and one repeat of EspFU (2LNH). Okrut,2015 Nck1 contains the C-helix that competes with the C-helix in the VCA segment when WASP is in its autoinhibited state. |
WASP and N-WASP proteins are required to initiate actin nucleation by activating actin-related protein (ARP)2/3 complex. WASP/N-WASP contains a GTPase-binding domain (GBD) at the N-terminus and a verprolin-homology, connector-helix, acidic motif (VCA) (also referred to as WCA as the V region is also called WH2) segment at the C-terminus. Under basal conditions the C-helix motif fits in the GBD domain closing the protein and preventing its nucleation promoting function (Kim,2000). Three factors participate in coordination to activate N-WASP in the membrane, a GTPase like CDC42 that binds the GBD domain, an acidic phospholipid like PtdIns(4,5)P2 and a SH3-domain-containing protein (like Nck) that binds to the PxxP motifs located between the GBD and the VCA segments (Abdul-Manan,1999; Rohatgi,2001; Okrut,2015). Nck can get a membrane localization by using its SH2 domain to bind to phosphorylated tyrosine-containing proteins like Nephrin that is a transmembranal protein. The co-localization of Nck and N-WASP allows the C-helix motif located in the linker space of the first and the second SH3 domains to bind to the GBD domain, out competing with the intramolecular C-helix in N-WASP. Additional bindings between N-WASP and Nck can occur due to interactions between the PxxP motifs in N-WASP and the second and third SH3 domains in Nck Okrut,2015. Interestingly, the effector proteins EspF and EspFU from the human pathogens Enterohaemorrhagic and Enteropathogenic Escherichia coli are able to activate WASP/N-WASP by using a mimic of the C-helix motif that is present in multiple copies, three in the case of EspF and between five and seven for EspFU (Alto,2007; Cheng,2008; Sallee,2008). The motif is conserved in homologous proteins from Citrobacter rodentium, a mouse enteric bacterium. The actin polymerization activating potency is higher in the pathogenic proteins due to a multiple binding of the repeats, increasing the density of activated N-WASP molecules (Sallee,2008). |
Position +1: Ile in WASP, WASL, NCK and EspF; Leu in WASP, NCK and EspF; Val in EspFU Position +2: Val in WASP, WASL and NCK; Ala in EspF and EspFU Position +3: Gly in WASP and WASL; Lys in NCK; Gln in EspF and EspFU Position +4: Ala in WASP, WASL and EspF; Asn in NCK; Arg in EspFU Position +5: Leu in all except in some fish (Iso) Position +6: Met in WASP and WASL; Lys in NCK and EspF; Iso, Met and Val in any repeat in EspFU (7 Iso; 76 Met; 54 Val) Position +7: Different in WASP and EspF; Glu in WASL; Asp in NCK; Gln in EspFU Position +8: Val in WASP and WASL; Thr in NCK; His in EspFU Position +9: Met in WASP and WASL; Leu in NCK, EspF and EspFU A regular expression based on occurrence of instances would be the following: [ILV][VA][^P][^P][LI][IMVK][^P][HTV][LM] |
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LIG_IBAR_NPY_1 | NPY | Campellone,2006 The binding site in Tir to induce EspFU-dependent actin assembly was mapped to a 12 aas region which is necessary and sufficient to recruit EspFU and initiate actin pedestal formation. Brady,2007 Defined the motif NPY as responsible for pedestal formation when present in a Tir protein (either EHEC or EPEC). Its function is EspFU-dependent. Weiss,2009 IRSp53 links the enterohemorrhagic E. coli effectors Tir and EspFU for actin pedestal formation. Vingadassalom,2009 IRTKS links the EHEC actin assembly effectors Tir and EspF(U) during pedestal formation. WASP, EspFU and IRTKS-SH3 domain forms a complex. de Groot,2011 Got the structure of EHEC Tir and the I-BAR domains of IRSp53 (2YKT). All residues contacting the NPY motif are conserved in IRSp53 and IRTKS. |
Some pathogens have developed infection mechanisms that hijack host cell signalling so that they can extend their survival and satisfy their metabolic needs. Enterohemorrhagic Escherichia coli (EHEC) and Enteropathogenic E. coli (EPEC) interfere with the regulation of actin polymerization to ultimately form an actin pedestal that probably increases the contact area between the infected cell and the bacteria. To do so, two slightly different mechanisms are used by EHEC and EPEC. Initially, the translocated intimin receptor (Tir) is traslocated by the type III secretrion system (T3SS). The Tir protein contains one globular cytoplasmic N-terminal domain that is dispensable for the pedestal formation but regulates its length (Campellone,2006), one central and extracellular domain that mediates binding to the bacterial intimin protein and a C-terminal domain that differs in the different pathovars. EPEC Tir contains a short insertion around Tyr 474 that is phosphorylated by host cell kinases and works as a binding motif (LIG_SH2_SRC) for the SH2 domain in Nck proteins. Nck, recruited to the plasma membrane and in particular close to the bacterial attachment site, activates N-WASP by using its LIG_GBD_Chelix_1 motif to bind to the GBD domain of N-WASP. The VCA regions can, then, activate Arp2/3 and initiate actin polimerization leading to pestestal formation. EHEC Tir lacks the Nck binding property, instead, it sequesters and activates N-WASP by a ternary complex that includes a second effector protein, EspFU, and the host proteins IRSp53 or IRTKS. EHEC Tir uses the NPY motif located at the C-terminal domain to bind to the I-BAR domain of IRSp53/IRTKS (Campellone,2006; Brady,2007; Weiss,2009; Vingadassalom,2009; de Groot,2011). IRSp53/IRTKS has an SH3 domain that interacts with the multiple LIG_SH3_3 motif in EspFU. EspFU, in addition, has a LIG_GBD_Chelix_1 that mimics the same motif in Nck then converging in the activation of actin polymerization and pedestal formation with EPEC. |
Based on the alignment of EHEC Tir proteins, the Ala at position +4 is conserved in EHEC Tir and EPEC Tir homologs as well as in putative intimin receptors in Edwarsiella and not in Lactobacilus aquaticus that has a Val at +4. The Ala at position +4 faces opposite to the I-BAR domain in the 2YKT structure. Position -1 is not conserved and varies in homologs (Val EHEC, D/E EPEC). Position -2 has a conserved Val in all Escherichia spp. homologs and a Leu in Edwardsiella homologs. The Val fits in a non-hydrophobic pocket. Mutation of this Val to Ala did not affect pedestal formation (Brady,2007). The pocket is made by Arg114 and Tyr115. Supplementary Table 3 from de Groot (de Groot,2011) contains possible NPY-containing interactors of I-BAR: Only LIMK1 and LIMK2 had Val in position -2. Only MYO15 had Ala in position +4. These proteins matched with the MEME logo generated with the EHEC and EPEC Tir homologs and putative intimin receptors: ITSN1, ITSN2 and SHAN2 (SHANK2). |
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LIG_MLH1_MIPbox_1 | ..S[rk][FY][F] | Gueneau,2013, Boehm,2016, Dherin,2009, 4FMO, 4FMN |
The MIP Box is found in repair and meiotic proteins including BLM, Ntg2, and Sgs1 that bind to the MLH1 component of MutL. The motif is recognised by the C-terminal domain of MLH1. |
The MIP Box has a core aromatic doublet and also has a preference for basic residues. These features are shared with RIR and PIP Box motifs: Some of the MIP motifs might also superpose on those motifs enabling switching between motif interaction partners. Backbone peptides and the conserved Ser make several H-bonds to orient the motif. |
fully annotated |
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LIG_integrinA1B1_KTS | [RK]TS | wh0cd7749203 Order Propecia | wh0cd7749203 <a href=http://buypropecia2017.com/>Order Propecia</a> | wh0cd7749203 <a href=http://buypropecia2017.com/>Order Propecia</a> |
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LIG_ANKRIN_ANKRA2_1 | PxLPx[IL] | Xu,2012,3SO8,3V2O,3V2X,3V31,3V30,3UXG,3UZD | Sequence-Specific Recognition of a PxLPxL Motif by an Ankyrin Repeatin ANKRA2. Motif is found in HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5). | Annotated as LIG_ANK_PxLPxL_1 |
fully annotated |
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DOC_MAPK_RevD_# | Garai,2012, 2Y9Q, 3TEI |
RevD is the reverse orientation of the MapK docking motif or D motif. It has an amphipathic helical component positioning three hydrophobic residues, a variable spacer and then at least two positively charged residues. Variants of the motif may have preferences for different MapKs such as ERK or p38. (DOC_MAPK_1) |
Annotated as DOC_MAPK_RevD_3 |
fully annotated |
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LIG_G3BP_FGDF_1 | ##FG[DE]F[DEST] | Panas,2015 | Motif in USP10 that binds to G3BP as part of stress granule regulation. The system is hijacked by some viral proteins e.g. Semliki Forest virus nsP3 and HSV ICP8 | Annotated as LIG_G3BP_FGDF_1 |
fully annotated |
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LIG_KLC1_TPR_1 | [ILMV].W[ED][DN][ES] | Konecna,2006 Morgan,2010 Rosa-Ferreira,2011 Pernigo,2013 3ZFW |
Motif in calsyntenin binding to TPR (tetratricopeptide repeat) domains of Kinesin Light Chain1 (KLC1. Also used by Vaccinia Virus. Probably general cargo binding motif, often found paired in cargo proteins. | Probably only the W is absolutely conserved, followed by the +1 DE position. Elsewhere charge complementarity may involve multiple alternative positions. Annotated as LIG_KLC1_TPR_1 |
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LIG_CSL | [VILMF]W[VILMF]P | 15297877, Wilson,2006, 2FO1 | N-terminal motif in Notch, responsible for its interaction with the CSL transcription factor in the nucleus to activate the pathway. | Annotated as LIG_CSL_BTD_1. |
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LIG_PALB2_BRCA2_1 | WF..L | Oliver,2009, 3EU7 |
Motif in the BRCA2 N-terminus that binds to PALB2. The interaction is required to bring BRCA2 to nuclear foci and is important for DNA double strand break repair. The helical motif core WF..L enters a hydrophobic pocket on the beta-propeller. Additional residues preceding the core also interact on a shallower part of the surface. | The N-terminal region of BRCA2 is highly conserved, implying additional interactions are made. This complicates conservation-based estimation of the motif pattern. Annoteted as LIG_PALB2_WD40_1 |
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LIG__UBA3_E1E2_1 | [MLI][ILMF].[VILM].{0,4}K | Huang,2004 1TT5 |
Motif in UBC12 (Neddylation E2) N-terminus that binds in a groove of UBA3 in the E1 complex, determining a neddylation specific interaction. The N-terminal region has an overlapping motif that binds the DCNL co-E3 ligase so this peptide segment must be part of a switching mechanism during neddylation. | Spacing of the terminal basic residue needs to be assessed from alignments. Also whether arginine at different spacing will replace lysine. annotated as LIG_UBA3_1 |
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LIG_PONY_DCNL_1 | ^M[ILMF].[IL] | Monda,2013 Scott,2011 Huang,2009 4GAO 4GBA 3TDU |
N-terminally acetylated motif used during neddylation. When acetylated, NEDD8 E2 ligase N-termini bind the PONY domain of paralogous DCNL1,2,3 NEDD8 co-E3 ligases. Structures of the bound motif available for the NEDD8 E2s UBC12 and UBE2F. The N-terminal region has an overlapping motif that binds the E1 UBA3 so this peptide segment must be part of a switching mechanism during neddylation. | Binds in helical conformation so may be possible to extend the motif e.g. to include lysines that make electrostatic interactions but might not be positionally fixed. annotated as LIG_DCNL_PONY_1 |
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LIG_LRP6_inhibitor | NX[VI] | Cheng,2011 Ahn,2011 22589387 Bourhis,2011 3SOV 3SOQ 3SOB 1NPE 2JTK |
LRP5/6 are the crucial membrane receptor proteins for Wnt Signalling. These proteins form complex with frizzled receptors and allow binding of Wnt which mediates the canonical Wnt Signalling. Antagonists such as Dickkopf (DKK) and sclerostin (SOST) compete with Wnt protein for binding with LRP5 and LRP6. Binding of antagonists halts the canonical Wnt signaling and presents these antagonists as an important therapeutic target. | DKK1 can bind independently on two different sites (2:1). Constructs with mutations in “NXI” motif (N40A, I42E) show decreased binding. annotated as LIG_LRP6_Inhibitor_1 |
fully annotated |
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LIG_GSK3_LRPinhibit_1 | PPP[ST]P.[ST] | Stamos,2014, 4NM5, 4NM7 |
The protein kinase GSK3 is active by default. Repeating phosphorylated motifs in the LRP5/6 wnt receptors bind as pseudosubstrates, inhibiting the kinase. As a result, the beta-catenin phosphodegron is no longer phosphorylated, stabilising the transcription factor and allowing its transfer into the nucleus. | GSK3 also has an auto-inhibitory N-terminal phosphopeptide which is phosphorylated in different regulatory contexts (e.g. insulin signalling) with a somewhat different, less Pro-rich, sequence preference. annotated as LIG_GSK3_LRP6_1 |
fully annotated |
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LIG_Fzd_KTXXXW | KTXXXW | 22411803 PMC:3657389 Wong,2003 Punchihewa,2009 Umbhauer,2000 4JKV |
The motif is present in C-terminal domain of frizzleds. This motif interacts with PDZ domains of Dishevelled proteins with a low binding affinity. The affinity is affected by the extended regions around motif (N-ter and C-ter both directions). It is known that mutations in this motif lead to disruption of Wnt signalling. This is justified as both Frizzled and Dishevelled are crucial for canonical and non-canonical Wnt signalling pathway. Further this motif is also present in smoothened (SMO) receptors which are having sequence similarity with FZDs. | Among the different frizzled types Fz1, Fz2, Fz3, Fz4, and Fz7 have been shown to bind directly with PDZ domain of Dishevelled. The binding of Dishevelled with Fz5 is via a discontinued motif which is spread over C-terminal region of latter. The interaction involves cooperative action of conserved motifs present in third intracellular loop alongwith KTXXXW motif. annotated as LIG_FZD_DVL_PDZ |
fully annotated |
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LIG_GBD_WASP_1 | [ILV][ILVA]..LM..[ILMV] | Sallee,2008, Cheng,2008,2K42 | Auto inhibitory motif in WASP and N-WASP that binds the autoinhibitory GTPase binding domain (GBD). E. coli EspF(U) also use the motif to deregulate actin assembly. |
fully annotated |
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LIG_SUMO_Rev_2 | [ED].{0,4}[DE].(K)[FLMVI] | Impens,2014 Tammsalu,2014 Hendriks,2014 |
The reverse sumoylation site is less common (about 20% of SUMO sites) than the canonical site. The requirement for a hydrophobic residue adjacent to the modified K may be weaker. | MOD_SUMO_rev_2 |
fully annotated |
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LIG_SUFU_Gli_1 | [CY]GH[LF} | Dunaeva,2003 ZeRuth,2011 |
responsible for Gli proteins interactions with Sufu. | Found in Gli1,2,3 but probably not Gli4. Also found in Glis3 but probably not in Glis1,2. In fly Y is replaced by C. Have not checked animals at higher divergence. LIG_SUFU_1 |
fully annotated |
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LIG_RPA_C_ 1 | R[QN][RK].[AL] | Mer,2000 Ciccia,2009 1DPU |
RPA recognition motif found in DNA repair proteins SMARCAL1, Tipin, UNG2, XPA and AD52 | LIG_RPA_C_Fungi, LIG_RPA_C_Insects, LIG_RPA_C_Plants, LIG_RPA_C_Vert |
fully annotated |
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LIG_SPRY_SPSB | [DE][IL]NNN | Filippakopoulos,2010, 2V24 | Motif found in PAR-4/VASA mediating binding to the SPRY domain of the SPSB family of E3 ubiquitin ligases and their orthologue GUSTAVUS | LIG_SPRY_1 |
fully annotated |
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Doc_Pex_5 | LVAEF | Neuhaus,2014 4BXU |
LVAEF is a Pex14-binding motif located at the N-terminal domain of the human PTS1 (Peroxisomal targeting signal 1) receptor Pex5. It has been suggested that the motif represents a docking site for cargo loaded receptor. Mutating motif to alanines affects the import of proteins into peroxisomes. Evolutionary conserved consensus sequence of the motif is LVXEF. The motif is not found in plant and yeast Pex5 but is present in Pex5 from a number of filamentous fungi. | Binding kinetics of LVAEF motif are faster than the canonical diaromatic pentapeptide motif (WXXX[FY]) present in Pex5. This suggests that site might assist in establishing the first contact of Pex14 with PTS1 receptor. LIG_Pex14_3 |
fully annotated |
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LIG_LIR | WxxL or [WYF]xx[LIV] | Rozenknop,2011 | LC3-interacting region (LIR) might link ubiquitinated substrates that should be degraded to the autophagy modifiers in the autophagosome membrane | LIG_LIR_Gen_1; LIG_LIR_Apic_2, LIG_LIR_LC3C_4, LIG_LIR_Nem_3 |
fully annotated |
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LIG_CID_NIM_1 | DDDEDgyNPYTl | Tudek,2014 2MOW |
Motif in Trf4 that binds to the CID domain of Nrd1. Links the TRAMP complex to the NNS complex involved in sn/snoRNA production. NIM acts as a molecular switch, competing for binding with the RNA Pol CTD phosphomotif YSPTSPS. | Interaction defined in yeast. Alignment needed to derive the motif conservation in fungi, metazoa etc. Not to be confused with the CNOT1 binding NIM motif. LIG_CID_NIM_1 |
fully annotated |
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DEG_Kelch_KLHL2_1 | E.EE.E[AV]DQH | Takahashi,2013 | WNK kinases are involved in osmotic regulation and may be mutated in certain diseases that show a hypertension phenotype. An Acidic degron motif is highly conserved in vertebrate WNKs and is reported to target them for destruction by the cullin/KLHL2,3 kelch proteins, the latter designated as E3 ligases. WNK kinases disregulated for proper destruction can cause hypertensive disease. |
Motif very strongly conserved in 4 vertebrate paralogues. Should look deeper into metazoa for motif definition. DEG_Kelch_KLHL3_1 |
fully annotated |
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DEG_Kelch_KEAP1_1 | D.ETGE | Padmanabhan,2006, Lo,2006, Lo,2006, 2FLU | Oxidative stress response degron motif in the Nrf2 TF binding to the Kelch beta propeller domain in E3 ligase Keap1. A second Nrf2 motif LxxQDxDLG may bind the same Kelch domain with lower affinity. PGAM5 has an NxESGE and is also a Keap1 substrate. | DEG_Kelch_Keap1_1 |
fully annotated |
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LIG_APCC_Dbox_3 | .R.{2,3}L.{1,3}[LIVM] | Hames,2001 11285280 |
Extended Dbox also tends to have further residues upstream that are required for recognition | DEG_APCC_DBOX_1 |
fully annotated |
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Mtr4-binding motif in Air2 | GRYFG | Falk,2014 4U4C |
One of several peptide motifs used in assembly of the TRAMP complex in yeast. Docks the zinc knuckle protein Air1/2 onto the helicase Mtr4. TRAMP is involved in nuclear surveillance of ncRNAs. |
fully annotated |
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DEG_SPOP_SBC_1 | [AVP].S[ST][ST] | Zhuang,2009 Zhang,2009 3IVQ |
The SPOP Cullin E3 ligase recognizes an unusual ST-rich peptide motif in substrate proteins. The phosphorylated site does not bind SPOP, offering possibilities for PTM regulation. Substrates include GLI3 and MacroH2A. |
fully annotated |
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DOC_Cks1_1 | [PLFWY][^P](T)P. | McGrath,2013, Koivomagi,2013, 4LPA | Cks1 co-regulates CDK activity. A subset of pTP sites can be bound in CDK substrates or other regulators. CDK site targeting becomes more precise than with cyclin docking alone. | Only described so far in the yeast experimental system but Cks1 homologues are found in e.g. vertebrates too. |
fully annotated |
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Doc_PP2A_KARD_1 | LS.I[IML]E.S....T | Suijkerbuijk,2012,Kruse,2013,Xu,2013 | The card motif in BUBR1 recruits the phosphatase PP2A during cell cycle. This is important for mitotic progression. The motif is considered to be triply phosphorylated to bind PP2A. |
fully annotated |
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Doc_GSK3_Axin_1 | P[^P][^P]Fa[^P][^P]Li[^P][^P]L[^P][^P][VIL] | Dajani,2003 1O9U |
Helical motif in Axin protein docks GSK3beta into the Axin-scaffolded complexes. Docked GSK3beta can mark beta-catenin for destruction. The FRAT helical motif binds the same surface but the details are different. |
fully annotated |
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LIG_MTR4_Trf4_1 | NxDFIx[FL] | Falk,2014 Losh,2015 4U4C |
One of several peptide motifs used in assembly of the TRAMP complex in yeast. Docks the poly(A)polymerase Trf4/5 by beta augmentation onto the helicase Mtr4. TRAMP is involved in nuclear surveillance of ncRNAs. |
Motif pattern should be possible to define for metazoan equivalent with core EQxDF[IL]P |
fully annotated |
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LIG_ALG2 | PPYP.{1,4}YP | Suzuki,2008, 2ZNE | motif in Alix that binds to ALG-2 in a calcium-dependent manner (allosteric opening of hydrophobic pocket on ALG-2); similar sequence present in annexin A7 and A11, and in TSG101 |
fully annotated |
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LIG_AIM | [WY]..[ILV] | Noda,2010,3dow,2zzp,2zjd,2zpn | Atg8-family interacting motif (AIM) found in Atg19, p62, Atg4B and Calreticulin, involved in autophagy related processes |
fully annotated |
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LIG_GABARAP | W.FL | Thielmann,2009 Mohrluder,2007 17916189 3DOW |
GABAA receptor binding to clathrin and calreticulin. possibly linked to trafficking |
fully annotated |
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DCK_dephos_PP1_2 | R..Q[VIL][KR].[YW] | Terrak,2004,Hendrickx,2009, 1S70 | Docking motif, referred to as the MyPhoNe motif, for PP1 phosphatase found in Myosin phosphatase-targeting subunit 1. |
fully annotated |
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LIG_CNOT1_NIM_1 | F..W.DY..L | Bhandari,2014, 4CQO | The NIM motif (Not1 Interacting Motif) is conserved in the vertebrate RNA-binding paralogues, Nanos1, -2, -3. It binds the SHD domain of CNOT1, thereby recruiting the CCR4-NOT deadenylase complex. | Nanos is a classical developmental regulator affecting posterior pattern formation in Drosophila. It is an RNA-binding protein affecting post-transcriptional mRNA regulation. The CCR4-NOT deadenylase complex catalyses the removal of poly(A) tails. The Nanos/CCR4-NOT interaction therefore modulates translational repression. |
fully annotated |
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LIG_PP2B_2 | .L.VP | Rodriguez,2009, Roy,2009, Liu,2001, 10202017, Martinez-Martinez,2006, Park,2000, Dougherty,2009, Mehta,2009, Blumenthal,1986, Grigoriu,2013, 4F0Z |
Secondary, lower affinity(?), docking motif for the calcium-activated phosphatase Calcineurin/PP2B. Found in NFATc1-4, KSR2, PRKAR2A and yeast RCN1. ("PVIVIT") is the other Calcineurin binding motif. High affinity motifs may have a large hydrophobic residue preceding the L. The solved motif structure has lysine replacing proline. | Binds activated form of Calcineurin; requires both catalytic CNA and regulatory CNB subunits for binding (binding site was identified in silico as hydrophobic cleft formed at interface of preassembled CNA and CNB and confirmed with the solved structure). |
fully annotated |
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FUN_N-end_rule_pathway | Tasaki,2007 | N-terminal ubiquitin mediated destruction system. May be ancient. Might not be a single motif but a combination of post translational modifications. |
fully annotated |
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TRG_ER_diArg_2 | .RR. | 14527949 | Generic di-arginine ER retention motif |
fully annotated |
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LIG_TRAF2_3 | P.Q.[ST] | 12917691 Ye,1999 Ye,1999 1CZY 1QSC 1CZZ |
Slight variant of LIG_TRAF motifs already in ELM. |
fully annotated |
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FUN_RANK | P[VILF]QE | 16260781 | Motif in cytosolic part of RANK (TNFR11A) reported to mediate osteoclast formation, survival and function. Also found in TNFR5. Specific subset of LIG_TRAF2 with improved motif definition. | PVQE is absolutely conserved twice in RANK and once in TNFR5. The reported PFQE is unconserved. Therefore the motif is probably an exact match to PVQE Ligand domain is not known yet? |
fully annotated |
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LIG_WD40_WDR5win_1 | G[GASC]AR....[FLYM] | Dharmarajan,2012, 18829457, 18829459, 16829960, 3UVN, 3UVL |
The Win motif has a turn of helix with an Arg residue that binds deep into the wD40 domain axis. Found in WDR5-interacting proteins including SET1A and MLL2 | Small sidechains precede the R. Pro should be disfavoured at several positions of the motif due to backbone H-bonding requirements. A preference for a hydrophobic residue is found +5 of the R. |
fully annotated |
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LIG_WD40_WDR5_2 | .VDV[TV] | Odho,2010 2XL2 |
The VDV motif is found in RbBP5 and interacts with an edge cleft of the WD40 domain in WDR5. This interaction surface is different from the canonical axial site (in this case bound by the Win motif). RbBP5 is found in a number of chromatin complexes including SET1 and MLL. |
Core motif may be preceded by several negatively charged residues. The core D does not directly bind WDR5 but makes an internal charged interaction that is probably important for the peptide geometry. |
fully annotated |
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DCK_dephos_PP1_3 | [GS]IL[RK] | Wakula,2003 | Docking motif, referred to as the SILK motif, for PP1 phosphatase found in NIPP1 |
fully annotated |
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LIG_CASK_CID_1 | E.[IV]W[IV].R | Stafford,2011 | Docking motif in Caskin1, Mint1 and TIAM1 that binds to the CASK hub protein involved in brain, synapse, cell polarity. |
fully annotated |
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LIG_N_degron_UBR_type1 | ^[RKH][^P] | Matta-Camacho,2010,Choi,2010, 3NY1, 3NIT | Primary N-terminal basic degron. Likes hydrophobics in second position. Lysine binds with the highest affinity (~20uM). N-degrons are N-terminal proteosomal degradation targeting motifs recognised by UBR domains of the Ubiquitin recognin (UBR) family. Several N-degrons are known, defined as primary (type 1 & type 2), secondary and tertiary. |
fully annotated |
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LIG_N_degron_UBR_type2 | ^[FLWYI] | Tasaki,2007 | Primary N-terminal bulky hydrophobic degron. N-degrons are N-terminal proteosomal degradation targeting motifs recognised by UBR domains of the Ubiquitin recognin (UBR) family. Several N-degrons are known, defined as primary (type 1 & type 2), secondary and tertiary. |
fully annotated |
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LIG_N_degron_UBR_secondary | ^[DEC] | Tasaki,2007 | Secondary N-degron, arginylated (addition of an N-terminal arginine) by Arg-tRNA-tranferase. Cysteine must first be oxidised into Cys-sulfinic acid before arginylation. Once arginylated the motif is recognised as a type1 N-degron. N-degrons are N-terminal proteosomal degradation targeting motifs recognised by UBR domains of the Ubiquitin recognin (UBR) family. Several N-degrons are known, defined as primary (type 1 & type 2), secondary and tertiary |
fully annotated |
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LIG_N_degron_UBR_tertiary | ^[NQ] | Tasaki,2007 | Tertiary N-degron, deamidated by N-terminal amidohydrolase. Deamidation creates the secondary destabilising N-terminal residues Asp and Glu, which in turn are arginylated (addition of an N-terminal arginine) by Arg-tRNA-tranferase to create a primary N-degron. N-degrons are N-terminal proteosomal degradation targeting motifs recognised by UBR domains of the Ubiquitin recognin (UBR) family. Several N-degrons are known, defined as primary (type 1 & type 2), secondary and tertiary. |
fully annotated |
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LIG_TNK_1 | R..PDG | 22153076,Guettler,2011 | Tankyrase 1 & 2 (TNKS, TNKS2) bind to a common set of proteins including IRAP, TAB182 and FBP17, all of whom share this common motif. | Annotated as LIG_TNKBM_1 |
fully annotated |
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LIG_APCC_Cbox | DR[YF]IP.R | Schwab,2001 | motif required for association with APC/C, conserved in Cdc20-related proteins | annotated as LIG_APCC_Cbox_1 / LIG_APCC_Cbox_2 |
fully annotated |
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LIG_APCC_#R_1 | .[LM]R$ | Sedgwick,2013, Hayes,2006 | Some proteins interact with APC/C via C-terminal LR or MR motifs. These include Nek2A and Kif18A. The MR motif in Nek2A allows it to be destroyed by APC/C in a checkpoint independent manner | annotated as LIG_APCC_TPR_1 |
fully annotated |
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LIG_APCC_IR_1 | .IR$ | Burton,2005,Passmore,2003,Vodermaier,2003 | The C-terminal IR motif anchors CDC20 and CDH1 D/KEN box adaptors as well as APC10 to the main APC/C complex. Recognised by a groove in TPR repeats. | annotated as LIG_APCC_TPR_1 |
fully annotated |
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LIG_SCF_TIR1 | GWPPV | 15295098 Ramos,2001 Parry,2006 Tan,2007 2P1Q |
A degron motif found in plants responsible for the degradation of members of the Aux/IAA family of transcriptional repressors |
fully annotated |
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LIG_PAM2_2 | W..EF.PG..W.... | Jinek,2010,Kozlov,2010, 2X04, 3KTP | binding motif in GW182 family proteins for binding with PABC domain of PABP1, essential for microRNA-mediated translation repression and deadenylation |
fully annotated |
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LIG_PAM2 | [FPLV][^P][IPVTA].A..F.P | Kozlov,2004,Albrecht,2004,Kozlov,2010 | PABC/MLLE2-binding motifs involved in translational regulation. |
fully annotated |
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LIG_SCF_COI1 | RR..L..FL | Chini,2007 Sheard,2010 3OGM Thines,2007 Katsir,2008 Gfeller,2010 |
a degron found in plants associated with the Jasmonate family of transcription repressors. |
fully annotated |
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LIG_NBox_RRM_1 | Cukier,2010 | Ala-rich amphipathic helical motif in FBP and homologues binding to the helical side of FIR RRM2 which has a shallow hydrophobic face. Part of FIR mediated c-myc transcriptional control. |
fully annotated |
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LIG_MYND_2 | PPPLI | Liu,2007, 2ODD | Motif that mediates the interaction between MYND domain of AML1/ETO and co-repressors SMRT and N-CoR. |
fully annotated |
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LIG_MYND_PHD2_1 | P.LE | Song,2013 | Variant MYND binding motif found in the HSP90 co-chaperones p23 and FKBP38 interacting with PHD2 MYND domain | Interaction is part of HIF1-alpha hydroxyproline oxygene sensing system |
fully annotated |
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MOD_phos_NEK2 | [FLM][^P][^P]([ST])[^DEP][HR] | Alexander,2011 | Canonical motif phosphorylated by NEK2 | MOD_NEK2_1, MOD_NEK2_2 |
fully annotated |
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LIG_CEP55 | GPP...Y | Lee,2008, 3E1R | motif in Alix and TSG101 that interacts with coiled coil in CEP55; motif overlaps with motif for binding to ALG-2 |
fully annotated |
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TRG_ER_diArg_1 | R.{0, 1}R | Michelsen,2005 | ER retention/retrieving signal found in ER membrane proteins (cytoplasmic side) | should replace current TRG_ER_diArg_1 |
fully annotated |
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LIG_SCF_SKP2 | Hao,2005 | Complex phosphopeptide motif binding to the assembled dimer of Skp2 and Cks1 (SCF components), in the ubiquitin degradation process. | annotated as LIG_SCF_Skp2-Cks1_1 |
fully annotated |
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LIG_PIKK_1 | [DEN][DEN].{2,3}[ILMVA][DEN][DEN]L.{0,20}$ | Falck,2005 | Docking motif for PIKK kinases family found in DNA damage proteins Nbs1, ATRIP and XRCC5. | alias DCK_phos_PIKK_1 |
fully annotated |
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LIG_eIF4E_1 | Y....L[VILMF] | Fierro-Monti,2006 | Motif present in some interacting partners of eIF4E. | annotated as LIG_eIF4E_1 |
fully annotated |
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LIG_eIF4E_2 | Y.PP.[ILMV]R | Shih,2008 | Mediates binding to the dorsal surface of eIF4E. Found in DDX3, eIF-3G and eIF-2A | annotated as LIG_eIF4E_2 |
fully annotated |
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MOD_LATS_1 | H.R..[ST] | Zhao,2007 | Mammalian tumour suppressors LATS1 and 2 are AGC group kinases involved in the Hippo pathway. Similar kinases are conserved in other Eukaryotes. Known substrates YAP1 and WWTR1 (TAZ) have multiple HxRxxS motifs that are phosphorylated by the LATS kinases. Thus these kinases appear to have a target specificity that is distinct from other AGC group kinases. | annotated as MOD_LATS_1 |
fully annotated |
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LIG_SUMO_SBM | V.[VI][VI] | Song,2004, Hecker,2006, Berndt,2009 | Motif reported to bind SUMO present in RanBP2, PML, among cothers. | annotated as LIG_SUMO_SBM_1 and LIG_SUMO_SBM_2 |
fully annotated |
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CLV_Separin | S[HILMV][DE].GR[RKS] | Sullivan,2001 | Recognition site for cleavage by Caspase-like protease Separin. | annotated as CLV_Separin_Metazoa and CLV_Separin_Fungi |
fully annotated |
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LIG_RhoGAP_OCRL_1 | F...H..[ILVFY] | PDB:Pirruccello,2011,3QIS | F&H motif mediates binding to the RhoGAP domain of OCRL. Found in Ses1, Ses2 and APPL1. | annotated as LIG_OCRL_FandH_1 |
fully annotated |
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LIG_Pex3P_1 | L..LL...L..F | Sato,2010 | Large induced hydrophobic helix mediating binding to the Pex3p protein, found in Pex19p. | annotated as TRG_PEX_3 |
fully annotated |
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Lig_CAP-Gly_2 | W[KR][ED]GCY$ | van der Vaart,2011,3RDV | C-terminal Tyr-based motif in SLAIN2 that binds the CAP-Gly motif of CLIP-170 as part of MT regulation by +TIP interaction networks. | Lig_CAP-Gly_CLIP170_2 |
fully annotated |
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CLV_Caspase3-7 | D..D[AGS] | 12107159 | Caspase-3/Caspase-7 cleavage motif. |
fully annotated |
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LIG_SCF_Cks1_1 | .E.(T)P. | Hao,2005, 2AST | Phosphodegron in P27kip1 which must be targeted for destruction by SCF ubiquitination to allow the cell cycle progression |
fully annotated |
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LIG_HCF-1 | [ED]H.Y | Luciano,2003 | HCF-binding motif, to bind to a six-bladed β-propeller domain at the N terminus of HCF-1 |
fully annotated |
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LIG_RB_pocket | [IL]..L[YF] | Liu,2007,Xiao,2003 | Binding to the E2f binding pocket between the Rb-A and Rb-B domains |
fully annotated |
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LIG_SPAK-OSR1 | RF.V | Villa,2007 | Docking motif in substrates of OSR1 and SPAK kinases that binds to the CCT domain. |
fully annotated |
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LIG_Integrin_isoDGR | NGR | Spitaleri,2008 | Integrin aVB3 binding motif in the 5th type I repeat of fibronectin. Aspargine deamidation at an NGR peptide generates the functional isoDGR binding motifs. Binds with comparable affinity to the canonical RGD peptide that binds the same site. |
fully annotated |
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LIG_Actin_WH2_1 | [ILMV][ILMV]..I.{4,7}L[KR][KR][ILMVT] | Paunola,2002,2A3Z,2A40,2A41,2D1K,2VCP,3MN5,3MN7 | Long actin binding motif, probably too large to be defined as an ELM but if we put LIG_Actin_RPEL_1 in then this will also be entered. |
fully annotated |
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LIG_Actin_RPEL_1 | L..[KR][IL]..R[PQ]...[ED]L..[RK].[ILMV][ILMV] | Mouilleron,2008,2V52 | Bipartite helical motif mediating binding to the subdomain 1-3 hydrophobic cleft and a ledge on subdomain 3 of G-actin. Probably to large to be defined as an ELM but may be seen as a bipartite motif with possible unknown monopartite motif-containing binding partners binding one of the two interfaces. |
fully annotated |
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LIG_PIF | F..F or F..F([ST]) | Biondi,2004 | Binding motif in PDK1, PKA, PKG, PKC etc. AGC kinase pockets, usually in cis, except in PDK1 where there it is a trans docking motif. |
fully annotated |
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TRG_ER-exit | LLV | 19535327 | A highly conserved motif near the C-terminus that dictates ER exit and cell-surface expression of NKCC2. | Although very conserved, the motif seems to be quite specific for NKCC2 and not very general: several reports show that deletion/mutation of this motif in other receptors do not retain the protein in the ER. (see student's report) |
not annotatable |
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FAM_TypeIII | W...E | 16413475 | Motif present in signalling effectors used by pathogens to mimic activated Ras-like cellular GTPases. | no linear motif: Motif resides (in all checked instances) in a globular region (helix). |
not annotatable |
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LIG_PCNA_2 | [ILVM][^ILVM][DHFM][ILVM] | 11682605 | slight variation on original PCNA motif |
deleted |
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Mod_PLK_1 | (.[DEN][^GP]([ST])[FILMVW]..) or (.[DEN][^GP]([ST])[^P][FILMVW].) | Alexander,2011 |
Revised PLK1 phosphosite based on peptide data. | Better description than the current ELM model. |
deleted |
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LIG_14-3-3_4 | [RHK][STALV].([ST]).[PESRDIFTQL] | 17166838 | Slightly modifified LIG_14-3-3_3 motif, allowing for Leucine in last position to match instance. | instance in switches.elm: SWTI000583 HAP1_RAT (P54256-2) 594 598 |
deleted |
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LIG_Sliding_Clamp | QL.L.[FL] | 14729336 | bacterial siding clamp |
deleted |
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Lig_MHD_deltaCOP_1 | W.{1,6}[WF] | Suckling,2015, 5FJZ |
The delta-COP subunit of the Coatomer complex binds a Wx(1-6)[WF] motif in interacting proteins like Dsl1 tether (yeast) and ArfGAP1 (mammal). The motif binds to the mu homology domain of delta-COP |
deleted |
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LIG_FXI_DFP_1 | [FYWHIL].DFP | Wong,2016, 5EOK, 5EOD, 5I25, |
The DFP motif is found in proteins, including laminins, collagen V and kininogen, that bind to an apple domain of coagulation factor XI. Depending on other properties of the DFP-containing proteins, the motif is likely to be important for localisation and/or activation of FXI |
deleted |
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Mod_DYRK_RxxSP_1 | Rp.[ST]P[^DEWY].. | Soppa,2015, Campbell,2002 |
Dual specificity tyrosine phosphorylated and regulated kinases (DYRKs) phosphorylate motifs like RpxSP. These sites cannot be recognised by other basophilic kinases due to the Pro at +1 |
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LIG_REV1_RIR_1 | ..FF[^P]{0,2}[KR][^P]{0,4}[KR?] | Ohashi,2009, Pozhidaeva,2012, 28821613, 2N1G, 2LSI, 2LSK, 2LSJ, 4GK5 |
The RIR motif is found in DNA repair proteins including XRCC1, Pol-Eta, -Iota, -Kappa and -Zeta. The motif binds the C-terminal domain of the modular protein REV1 which catalyses deoxycytidyl transfer to the 3’ end of a DNA primer. |
The motif has two core phenylalanine residues which initiate an alpha-helix: Their backbone peptide groups make electrostatic interactions to an Asp residue in Rev1. The remainder of the helix has one or more semi-conserved basic residues interacting with acidic residues on the Rev1 surface. The aromatic residue pair and basic amino acid preference is similar to PIP Box and MIP box and some motifs might overlap. |
deleted |
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DOC_PP2B_PxIxI_2 | .P.LP[IL]. | xx | xx |
deleted |
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LIG_VCP_VBM_2 | [MILVAK][RK][^P][^P]R[LFWE][^P][^P][FLI][^P] |
Lim,2016 18208387 5EPP |
Helical motif binding a groove in the N-terminal domain of the VCP/P97/Segregase ATPase involved in transitional ER formation and other processes including ubiquitin-proteasome targeting. The VIM motif binds the same pocket in reverse orientation. |
deleted |
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LIG_SH2_SRC11 | P[KR] | 123123 | hello | hello |
deleted |
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LIG_SH2_SRC1 | TTT | 123123 | 123safd | sadfsafd |
deleted |
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LIG_SH2_SRC3 | P..P[KR]T | 123123 | lkjss | lkjsdf |
deleted |
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LIG_KLC1 | [ILMV].WD.. | Konecna,2006 | motif mediating binding to the tetratricopeptide repeats of KLC1 | duplicate of LIG_KLC1_TPR_1 |
deleted |
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LIG_Wnt | LT...W | Umbhauer,2000 | Motif found in Frizzled (Receptor of Wnt) and involved in the activation of the Wnt/beta-catenin signaling pathway. Mutations in the fixed positions induce the expression of the Wnt target gene siamois. | see LIG_Fzd_KTXXXW |
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LIG_APCC_KILR | KILR | Izawa,2012 | Motif in Cdc20 that mediates binding to APC/C subunits. The main determinants are the I and L residues; mutation of the basic residues decreases but not abrogates binding to both APC/C and Mad2. This same sequence also mediates binding of Cdc20 to Mad2 (see LIG_MAD2); preventing the motif to bind APC/C by hiding by Mad2 would be one of several mechanisms involved in regulation of APC/C activity and substrate specificity by the spindle assembly checkpoint. | Possible interactor is Cdc23 TPR region, see Matyskiela,2009. |
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LIG_VHS | D..LL | 20502673 1ELK 10985773 | The VHS domain of GGA proteins binds to an acidic di-leucine motif in the cytoplasmic domain of sorting receptors including the mannose 6-phosphate receptor. | duplicate of TRG_LysEnd_GGAAcLL_1 |
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LIG_BCL2 | L..I[AG]D.[ILV] | 20502673 1BXL Sattler,1997 |
Bcl2 motif |
deleted |
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LIG_HIV1-GP41 | H..NPF | 16904109 | HIV-1 gp41 core-binding motif. |
deleted |
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CLV_C14_Caspase-8-10 | [^RK][EDQ].D | 1221285 1236692 19694615 10964557 10508785 | Caspase-8 and -10 are the initiator caspase in the extrinsic apoptotic pathway and cleaves executor caspases. | Motif suggestion is based on in vitro data. Optimal described sequence is LETD. For protein substrate see MEROPS or CutDB No in vitro data for caspase-10 but cleavage motif LEXD in literature is described. |
deleted |
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LIG_CD40 | EQLKKSKTL | 21998326 | Linear peptide in an exposed loop mediates interaction between CD40L and Mac-1 | might be too specific paper not freely accessible |
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LIG_PTB_splicing | [SG][IL]LG..P | Rideau,2006 | Motif essential for splicing repressor activity found in cofactors of the PTB regulatory splicing repressor (Polypyrimidine tract-binding protein). |
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LIG_CENPC_LxxLFL_1 | F..[LM][FLY]LE[^P][VAIL] | 35420891,29280735 | Helical LxxLFL motif in CENP-C binding to the CENP-HIKM interface as part of the inner kinetochore. A second motif in CENP-C DEFxIDE binds to CENP-LN. |
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LIG_MOB1_1 | [YF].([ST])[AV][AV] | 23579499 4JIZ |
Interaction in the mitotic exit network (MEN) or HIPPO pathway. Cell cycle motif modified by Cdc15 kinase and then bound by Mob1 | Should be possible to derive motif by alignment due to deep conservation in eukaryotes. But should check if yeast and metazoan motifs can be represented together. |
annotatable |
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Please cite:
ELM-the Eukaryotic Linear Motif resource-2024 update.
(PMID:37962385)
ELM data can be downloaded & distributed for non-commercial use according to the ELM Software License Agreement
ELM data can be downloaded & distributed for non-commercial use according to the ELM Software License Agreement