WH1 domain#EVH1

WH1 domains are important for all cellular processes involving actin, this includes cell motility, cell trafficking, cell division and cytokinesis, cell signalling, and the establishment and maintenance of cell junctions and cell shape.{{cite journal|vauthors=Veltman DM, Insall RH | title=WASP family proteins: their evolution and its physiological implications. | journal=Mol Biol Cell | year= 2010 | volume= 21 | issue= 16 | pages= 2880–93 | pmid=20573979 | doi=10.1091/mbc.E10-04-0372 | pmc=2921111 }}

Tertiary structure of the WH1 domain of the Mena protein revealed structure similarities with the pleckstrin (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 molecule's target ligands.{{cite journal |vauthors=Prehoda KE, Lee DJ, Lim WA | title = Structure of the enabled/VASP homology 1 domain-peptide complex: a key component in the spatial control of actin assembly | journal = Cell | volume = 97 | issue = 4 | pages = 471–80 |date=May 1999 | pmid = 10338211 | doi = 10.1016/S0092-8674(00)80757-6 | s2cid = 17078939 | doi-access = free }}

The WASP protein family control actin polymerization by activating the Arp2/3 complex.

WASP is defective in Wiskott–Aldrich syndrome (WAS) whereby in most patient cases, the majority of point mutations occur within the N-terminal WH1 domain. The metabotropic glutamate receptors mGluR1alpha and mGluR5 bind a protein called homer, which is a WH1 domain homologue.{{cite journal |vauthors=Ponting CP, Phillips C | title = Identification of homer as a homologue of the Wiskott-Aldrich syndrome protein suggests a receptor-binding function for WH1 domains | journal = J. Mol. Med. | volume = 75 | issue = 11–12 | pages = 769–71 | year = 1997 | pmid = 9428607 | doi = 10.1007/s001090050166 | s2cid = 39958754 }}{{cite journal |vauthors=Niebuhr K, Ebel F, Frank R, Reinhard M, Domann E, Carl UD, Walter U, Gertler FB, Wehland J, Chakraborty T | title = A novel proline-rich motif present in ActA of Listeria monocytogenes and cytoskeletal proteins is the ligand for the EVH1 domain, a protein module present in the Ena/VASP family | journal = EMBO J. | volume = 16 | issue = 17 | pages = 5433–44 |date=September 1997 | pmid = 9312002 | pmc = 1170174 | doi = 10.1093/emboj/16.17.5433 }}

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.{{cite journal |vauthors=Callebaut I, Cossart P, Dehoux P | title = EVH1/WH1 domains of VASP and WASP proteins belong to a large family including Ran-binding domains of the RanBP1 family | journal = FEBS Lett. | volume = 441 | issue = 2 | pages = 181–5 |date=December 1998 | pmid = 9883880 | doi = 10.1016/S0014-5793(98)01541-5| s2cid = 8527080 | doi-access = }}{{cite journal |vauthors=Beddow AL, Richards SA, Orem NR, Macara IG | title = The Ran/TC4 GTPase-binding domain: identification by expression cloning and characterization of a conserved sequence motif | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 92 | issue = 8 | pages = 3328–32 |date=April 1995 | pmid = 7724562 | pmc = 42159 | doi = 10.1073/pnas.92.8.3328| doi-access = free }}

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.

{{Infobox protein family

| Symbol = EVH1

| Name = EVH1

| image = PDB 1mke EBI.jpg

| width =

| caption = structure of the n-wasp evh1 domain-wip complex

| Pfam = PF00568

| Pfam_clan = CL0266

| InterPro = IPR000697

| SMART = WH1

| PROSITE =

| MEROPS =

| SCOP = 1evh

| TCDB =

| OPM family =

| OPM protein =

| CAZy =

| CDD = cd00837

}}

A subset of WH1 domains has been termed the EVH1 domain bind a polyproline motif. The EVH1 domain (also known as the WH1, RanBP1-WASP, or enabled/VASP homology 1 domain) is also an evolutionary conserved protein domain. EVH1 domains recognise and bind the proline-rich motif FPPPP with low-affinity, further interactions then form between flanking residues.{{cite journal |vauthors=Ball LJ, Jarchau T, Oschkinat H, Walter U | title = EVH1 domains: structure, function and interactions | journal = FEBS Lett. | volume = 513 | issue = 1 | pages = 45–52 |date=February 2002 | pmid = 11911879 | doi = 10.1016/S0014-5793(01)03291-4| s2cid = 10368115 | doi-access = free }}

The EVH1 domain is found in multi-domain Ena/Vasp homology 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.{{cite web | url = http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=217 | title = EVH1 Domain | author = Pawson T | publisher = The Pawson Lab | access-date = 2011-06-09 }}{{PDB|1QC6}}; {{cite journal |vauthors=Fedorov AA, Fedorov E, Gertler F, Almo SC | title = Structure of EVH1, a novel proline-rich ligand-binding module involved in cytoskeletal dynamics and neural function | journal = Nat. Struct. Biol. | volume = 6 | issue = 7 | pages = 661–5 |date=July 1999 | pmid = 10404224 | doi = 10.1038/10717 | s2cid = 22881412 }}

Human genes encoding proteins containing the WH1 (EVH1) domain include:

• ENAH, EVL
• HOMER1, HOMER2, HOMER3
• SPRED1, SPRED2, SPRED3
• VASP, WAS, WASL

{{Reflist}}

• {{ELM|LIG_EVH1_1}}
• {{ELM|LIG_EVH1_2}}
• {{ELM|LIG_WH1}}

{{InterPro content|IPR000697}}

{{InterPro content|IPR007875}}

Category:Protein domains