WASP family, EVH1 domain (IPR033927)
Short name: WASPfam_EVH1
Overlapping homologous superfamilies
- PH-like domain superfamily (IPR011993)
- WH1/EVH1 domain (IPR000697)
- WASP family, EVH1 domain (IPR033927)
The entry refers to the EVH1 domain found in WASP family proteins.
The EVH1 (WH1, RanBP1-WASP) domain is found in multi-domain proteins implicated in a diverse range of signalling, nuclear transport and cytoskeletal events. This domain of around 115 amino acids is present in species ranging from yeast to mammals. Many EVH1-containing proteins associate with actin-based structures and play a role in cytoskeletal organisation. EVH1 domains recognise and bind the proline-rich motif FPPPP with low-affinity, further interactions then form between flanking residues [PMID: 11911879, PMID: 9312002].
WASP family proteins contain an EVH1 (WH1) in their N-terminals which bind proline-rich sequences in the WASP interacting protein. Proteins of the RanBP1 family contain a WH1 domain in their N-terminal region, which seems to bind a different sequence motif present in the C-terminal part of RanGTP protein [PMID: 9883880,PMID: 7724562].
Tertiary structure of the WH1 domain of the Mena protein revealed structure similarities with the pleckstrin homology (PH) domain. The overall fold consists of a compact parallel beta-sandwich, closed along one edge by a long alpha-helix. A highly conserved cluster of three surface-exposed aromatic side-chains forms the recognition site for the molecules target ligands. [PMID: 10338211].
The Wiskott-Aldrich Syndrome Protein (WASP; also called Bee1p) and its homologue N (neuronal)-WASP are signal transduction proteins that promote actin polymerization in response to upstream intracellular signals [PMID: 17229736]. Wiskott-Aldrich Syndrome (WAS) is an X-linked recessive disease, characterized by eczema, immunodeficiency, and thrombocytopenia [PMID: 9618767]. The majority of patients with WAS, or a milder version of the disorder, X-linked thrombocytopenia (XLT), have point mutations in the EVH1 domain of WASP [PMID: 11140379]. WASP is an actin regulatory protein consisting of an N-terminal EVH1 domain, a basic region (B), a GTP binding domain (GBP), a proline rich region, a WH2 domain, and a verprolin-cofilin-acidic motif (VCA) which activates the actin-related protein (Arp)2/3 actin nucleating complex [PMID: 12437929]. The B, GBD, and the proline-rich region are involved in autoinhibitory interactions that repress or block the activity of the VCA. Yeast members lack the GTP binding domain. The EVH1 domains are part of the PH domain superfamily [PMID: 9883880].
- cd01205 (EVH1_WASP-like)