The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
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.
ELM 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 semi-conserved 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 favourable 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 Probability: 0.0001173
Present in taxon: 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,1993, 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 Chinnadurai,2002). CtBP is structurally related to dehydrogenases and is indeed a NAD-dependent dehydrogenase (Kumar,2002). 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 (Jack,2011). A second role for CtBP in Golgi membrane fission may not involve PxDLS motifs (Corda,2006).
o 8 selected references:

o 8 GO-Terms:

o 32 Instances for LIG_CtBP_PxDLS_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
P03254 Early E1A 32
279 283 EDLLNESGQPLDLSCKRPRP TP 4 Human adenovirus 2
56 60 GGGGSPSPVELRGALVGSVD TP 1 Homo sapiens (Human)
Q14526 HIC1
241 246 RRCSPLCGLDLSKKSPPGSA TP 1 Homo sapiens (Human)
O60315 ZEB2
859 863 SSENSDEPLNLTFIKKEFSN TP 1 Homo sapiens (Human)
O60315 ZEB2
815 819 SEELQAEPLDLSLPKQMKEP TP 1 Homo sapiens (Human)
O60315 ZEB2
785 789 SRSNTPSPLNLSSTSSKNSH TP 1 Homo sapiens (Human)
P70062 tcf7l1-a
545 549 LQALPLLQAQPLSLVTKSSD TP 1 Xenopus laevis (African clawed frog)
P70062 tcf7l1-a
469 473 THSEQAQPLSLTTKPEARAQ TP 1 Xenopus laevis (African clawed frog)
1163 1167 VGSDNDIPLDLAIKHSRPGP TP 1 Homo sapiens (Human)
425 429 SREAGEGPEDLADGGPLLYR TP 1 Homo sapiens (Human)
O00257 CBX4
472 476 LDSDLDEPIDLRCVKTRSEA TP 1 Homo sapiens (Human)
Q91647 cbx4
455 459 LDSDLDEPIDLRCVKSRCDS TP 1 Xenopus laevis (African clawed frog)
794 798 PGPAADGPIDLSKKPRRPLP TP 1 Homo sapiens (Human)
64 68 LMADQDSPLDLTVRKSQSEP TP 1 Homo sapiens (Human)
Q15583 TGIF1
153 157 DEDSMDIPLDLSSSAGSGKR TP 1 Homo sapiens (Human)
P35712 SOX6
424 428 KDEAAAQPLNLSSRPKTAEP TP 1 Homo sapiens (Human)
P17789 ttk
593 597 SGASTPPPPDLSGQNSNQSL TP 1 Drosophila melanogaster (Fruit fly)
P56524 HDAC4
48 52 QVAPSAVPMDLRLDHQFSLP TP 1 Homo sapiens (Human)
Q8C2B3 Hdac7
22 26 TPGSQPQPMDLRVGQRPTVE TP 1 Mus musculus (House mouse)
Q99N13 Hdac9
23 27 MGLEPISPLDLRTDLRMMMP TP 1 Mus musculus (House mouse)
P28166 zfh1
786 790 SLTREDQPLDLSVKRDPLTP TP 1 Drosophila melanogaster (Fruit fly)
P14003 h
318 322 RVPMEQQPLSLVIKKQIKEE TP 1 Drosophila melanogaster (Fruit fly)
P41970 ELK3
273 277 HDSDSLEPLNLSSGSKTKSP TP 1 Homo sapiens (Human)
Q13422 IKZF1
34 38 GDEPMPIPEDLSTTSGGQQS TP 1 Homo sapiens (Human)
829 833 SCLEMDVPIDLSKKCLSQSE TP 1 Homo sapiens (Human)
P48552 NRIP1
440 444 SSYSNCVPIDLSCKHRTEKS TP 1 Homo sapiens (Human)
P10734 kni
331 335 TVSAQEGPMDLSMKTSRSSV TP 1 Drosophila melanogaster (Fruit fly)
P57682 KLF3
61 65 SHGIQMEPVDLTVNKRSSPP TP 1 Homo sapiens (Human)
P37275 ZEB1
734 738 QEEPQVEPLDLSLPKQQGEL TP 1 Homo sapiens (Human)
Q99708 RBBP8
490 494 GDCVMDKPLDLSDRFSAIQR TP 1 Homo sapiens (Human)
O95600 KLF8
86 90 FSLPQVEPVDLSFHKPKAPL TP 1 Homo sapiens (Human)
Q03112 MECOM
584 588 PATSQDQPLDLSMGSRSRAS TP 1 Homo sapiens (Human)
Please cite: ELM 2016-data update and new functionality of the eukaryotic linear motif resource. (PMID:26615199)

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