The Eukaryote Linear Motif resource for Functional Sites in Proteins
LIG_CtBP_PxDLS_1 98
 
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Functional site class: CtBP ligand motif
Functional site description: The PxDLS motif is present in a number of nuclear proteins, including certain transcription factors and HDACs, that recruit CtBP (C-terminal binding protein) into nuclear complexes. CtBP has a generally repressive effect on transcription and must be removed to active CtBP regulated genes.
ELMs: LIG_CtBP_PxDLS_1
Description: The PxDLS motif pattern is based on the conservation of reported sequence instances together with the structure of the CtBP domain in complex with a PxDLS peptide (1HL3 ). Beta-augmentation at the sheet edge places the peptide sidechains in specific places on the CtBP surface. Pro at position 1 makes an H-bond to strand edge backbone and fits in a hydrophobic pocket that will not accommodate other residues (Gly with no side chain may be the least disruptive). Position 2 contributes to beta augmentation so that the semiconserved sidechain is placed in a shallow hydrophobic pocket which also allows Glu due to proximity of surface positive charge. Position 3 is most often Asp, probably due to facourable charged residue proximity but is surface accessible and accepts some changes. Position 4 contributes to beta augmentation so that the sidechain enters a deep hydrophobic groove that fits to Leu and would probably allow Met but reject most other residues. Position 5 has a Ser-Thr preference but appears to accept R (as in HDACs) and some other mostly small residues. Following the core peptide there are clear preferences for Lys or Arg but these are not a strict requirement. However the conserved GLDLSKK motif in Hic1 is reported to bind CtBP but lacks Pro: Therefore for Gly at position 1 which must weaken the interaction, the motif in ELM requires C-terminal positive charge compensation.
Pattern: ([P][LVIPME][DENS][LM][VASTRG])|([G][LVIPME][DENS][LM][VASTRG]((K)|(.[KR])))
Present in taxons: Metazoa
Interaction Domain:

2-Hacid_dh (PF00389)
D-isomer specific 2-hydroxyacid dehydrogenase, catalytic domain
(Stochiometry: 1 : 1)

o See 32 Instances for LIG_CtBP_PxDLS_1


o Abstract

The CtBP (C-terminal binding protein) protein was first identified by Boyd at al. 1993 8440238, where a short region in adenovirus E1A was found essential in its interaction with CtBP. Deletion of this region in E1A resulted in increased transcriptional activity, suggesting that CtBP might be a co-repressor for E1A. Several eukaryotic proteins such as Hairy, Knirps, Ikaros, Polycomb and several zinc finger proteins interact with CtBP through a short motif with the consensus PxDLS (see review 11864595). CtBP is structurally related to dehydrogenases and is indeed a NAD-dependent dehydrogenase (12419229). CtBP interacts with the PxDLS motif through its dehydrogenase domain, in a NAD+ dependent manner. CtBP proteins dimerise (vertebrate CtBP1 and CtBP2 can homo or heterodimerise) and can simultaneously interact with two PxDLS containing proteins, e.g. with a DNA binding protein and a repressor. Binding to NAD+/NADPH aids dimerisation and therefore CtBP is sensitive to nutritional status (21281737). A second role for CtBP in Golgi membrane fission may not involve PxDLS motifs (16483777).

o 7 selected references:

o 8 GO-Terms:

o 32 Instances for LIG_CtBP_PxDLS_1
(click table headers for sorting)
SequenceStartEndSubsequence
Instance LogicPDB Organism
HDAC7_MOUSE 22 26 TPGSQPQPMDLRVGQRPTVE true positive --- Mus musculus (House mouse)
FOG2_HUMAN 829 833 SCLEMDVPIDLSKKCLSQSE true positive --- Homo sapiens (Human)
HDAC5_HUMAN 56 60 GGGGSPSPVELRGALVGSVD true positive --- Homo sapiens (Human)
HDAC4_HUMAN 48 52 QVAPSAVPMDLRLDHQFSLP true positive --- Homo sapiens (Human)
TTKB_DROME 593 597 SGASTPPPPDLSGQNSNQSL true positive --- Drosophila melanogaster (Fruit fly)
HIC1_HUMAN 241 246 RRCSPLCGLDLSKKSPPGSA true positive --- Homo sapiens (Human)
KLF8_HUMAN 86 90 FSLPQVEPVDLSFHKPKAPL true positive --- Homo sapiens (Human)
COM1_HUMAN 490 494 GDCVMDKPLDLSDRFSAIQR true positive --- Homo sapiens (Human)
ZEB1_HUMAN 734 738 QEEPQVEPLDLSLPKQQGEL true positive --- Homo sapiens (Human)
KLF3_HUMAN 61 65 SHGIQMEPVDLTVNKRSSPP true positive --- Homo sapiens (Human)
KNIR_DROME 331 335 TVSAQEGPMDLSMKTSRSSV true positive --- Drosophila melanogaster (Fruit fly)
NRIP1_HUMAN 440 444 SSYSNCVPIDLSCKHRTEKS true positive --- Homo sapiens (Human)
HDAC9_MOUSE 23 27 MGLEPISPLDLRTDLRMMMP true positive --- Mus musculus (House mouse)
SOX6_HUMAN 424 428 KDEAAAQPLNLSSRPKTAEP true positive --- Homo sapiens (Human)
TGIF1_HUMAN 153 157 DEDSMDIPLDLSSSAGSGKR true positive --- Homo sapiens (Human)
FOG1_HUMAN 794 798 PGPAADGPIDLSKKPRRPLP true positive --- Homo sapiens (Human)
Q91647_XENLA 455 459 LDSDLDEPIDLRCVKSRCDS true positive --- Xenopus laevis (African clawed frog)
LCOR_HUMAN 64 68 LMADQDSPLDLTVRKSQSEP true positive --- Homo sapiens (Human)
CBX4_HUMAN 472 476 LDSDLDEPIDLRCVKTRSEA true positive --- Homo sapiens (Human)
TRPS1_HUMAN 1163 1167 VGSDNDIPLDLAIKHSRPGP true positive --- Homo sapiens (Human)
T7L1A_XENLA 469 473 THSEQAQPLSLTTKPEARAQ true positive --- Xenopus laevis (African clawed frog)
T7L1A_XENLA 545 549 LQALPLLQAQPLSLVTKSSD true positive --- Xenopus laevis (African clawed frog)
ZEB2_HUMAN 815 819 SEELQAEPLDLSLPKQMKEP true positive --- Homo sapiens (Human)
ZEB2_HUMAN 785 789 SRSNTPSPLNLSSTSSKNSH true positive --- Homo sapiens (Human)
ZEB2_HUMAN 859 863 SSENSDEPLNLTFIKKEFSN true positive --- Homo sapiens (Human)
IKZF4_HUMAN 425 429 SREAGEGPEDLADGGPLLYR true positive --- Homo sapiens (Human)
EVI1_HUMAN 584 588 PATSQDQPLDLSMGSRSRAS true positive --- Homo sapiens (Human)
ZFH1_DROME 786 790 SLTREDQPLDLSVKRDPLTP true positive --- Drosophila melanogaster (Fruit fly)
HAIR_DROME 318 322 RVPMEQQPLSLVIKKQIKEE true positive --- Drosophila melanogaster (Fruit fly)
ELK3_HUMAN 273 277 HDSDSLEPLNLSSGSKTKSP true positive --- Homo sapiens (Human)
IKZF1_HUMAN 34 38 GDEPMPIPEDLSTTSGGQQS true positive --- Homo sapiens (Human)
E1A_ADE02 279 283 EDLLNESGQPLDLSCKRPRP true positive --- Human adenovirus 2

Please cite: ELM - the database of eukaryotic linear motifs (PMID:22110040)

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