Accession: | |
---|---|
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: | (P[LVIPME][DENS][LM][VASTRG])|(G[LVIPME][DENS][LM][VASTRG]((K)|(.[KR]))) |
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)
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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). |



(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Please cite:
The Eukaryotic Linear Motif resource: 2022 release.
(PMID:34718738)
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