The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
Functional site class:
EVH1 ligands
Functional site description:
Proline-rich sequences that bind to the signal transduction modules EVH1.
ELMs with same func. site: LIG_EVH1_1  LIG_EVH1_2  LIG_EVH1_3 
ELM Description:
Proline-rich motif binding to signal transduction class II EVH1 domains.
Pattern: PP..F
Pattern Probability: 0.0001632
Present in taxons: Bos taurus Caenorhabditis elegans Drosophila melanogaster Eumetazoa Homo sapiens Mus musculus Oryctolagus cuniculus Rattus norvegicus Sus scrofa Xenopus laevis
Interaction Domain:
WH1 (PF00568) WH1 domain (Stochiometry: 1 : 1)
PDB Structure: 1DDV
o See 8 Instances for LIG_EVH1_2
o Abstract
Enabled/vasodilator-stimulated phosphoprotein homology 1 (EVH1) domains are 115 residue protein-protein interaction modules which provide essential links for their host proteins to various signal transduction pathways. Many EVH1-containing proteins are associated closely with actin-based structures and are involved in re-organization of the actin cytoskeleton. EVH1 domains are also present in proteins enriched in neuronal tissue, thus implicating them as potential mediators of synaptic plasticity, linking them to memory formation and learning. EVH1 domains recognize and bind specific proline-rich sequences (PRSs). In general, a small (3-6 residue) core PRS in the target protein binds a 'recognition pocket' on the domain surface. Further affinity- and specificity-increasing interactions are then formed between additional domain epitopes and peptide 'core-flanking' residues. The protein-protein interactions mediated by EVH1 domains are clearly highly important for the regulation of signal transduction events, re-organization of the actin cytoskeleton, and modulation of actin dynamics and actin-based motility.
EVH1 domains can be divided into three classes based on the consensus sequences of their target PRS ligands. Single residue peptide substitution experiments have shown the consensus binding motif for class I EVH1 domains to be F-P-X-(hydrophobic)-P. Such sequences are found in a number of mammalian proteins, including the focal adhesion proteins zyxin and vinculin, as well as in the ActA protein of the intracellular pathogen Listeria monocytogenes. Class II EVH1 domains are found in the Homer-Vesl protein family of postsynaptic receptor associated proteins. These recognize a consensus PRS, with a core motif comprising PPxxF, found in the group I mGluRs, IP3Rs, RyRs and the Shank family proteins. The EVH1 domains exclusive for WASP and N-WASP proteins are also called WH1/ WASP-homology 1 domains. The EVH1 class III motifs are found in the verprolin family of proteins. They are known to play a role in WASP/N-WASP- mediated processes (e.g. regulation actin filament dynamics by WIP and WIRE), yet their exact functions remain to be elucidated. The recognition motif of EVH1 class III includes a polyproline region, which is a common feature of all EVH1 motifs, yet in class III it comprises an additional region which contains two highly conserved phenylalanines.
o 6 selected references:

o 10 GO-Terms:

o 8 Instances for LIG_EVH1_2
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
Q9JLU4 Shank3
908 912 EVGDVPRPAPAATPPERPKR TP 2 Rattus norvegicus (Norway rat)
Q9JLU4 Shank3
1385 1389 STVSSMSTLSSESGELTDTH TP 4 Rattus norvegicus (Norway rat)
P21817 RYR1
1773 1777 GVTTSLRPPHHFSPPCFVAA TP 4 Homo sapiens (Human)
P31424 Grm5
1156 1160 EELVALTPPSPFRDSVDSGS TP 5 Rattus norvegicus (Norway rat)
Q13255 GRM1
1147 1151 DDSPALTPPSPFRDSVASGS TP 1 Homo sapiens (Human)
P23385 Grm1
1152 1156 EDSPALTPPSPFRDSVASGS TP 5 Rattus norvegicus (Norway rat)
Q14643 ITPR1
49 53 ETGDLNNPPKKFRDCLFKLC TP 1 Homo sapiens (Human)
Q08877 Dnm3
809 813 PGPHSGAPPVPFRPGPLPPF TP 1 Rattus norvegicus (Norway rat)
Please cite: The Eukaryotic Linear Motif resource: 2022 release. (PMID:34718738)

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