Summary: WH2 motif
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WH2 motif Edit Wikipedia article
The WH2 motif or WH2 domain is an evolutionarily conserved sequence motif contained in proteins. It is found in WASP proteins which control actin polymerisation, therefore, WH2 is important in cellular processes such as cell contractility, cell motility, cell trafficking and cell signalling.
The WH2 (WASP-Homology 2, or Wiskott-Aldrich homology 2) domain is an ~18 amino acids actin-binding motif. This domain was first recognized as an essential element for the regulation of the cytoskeleton by the mammalian Wiskott-Aldrich syndrome protein (WASP) family. WH2 proteins occur in eukaryotes from yeast to mammals, in insect viruses, and in some bacteria. The WH2 domain is found as a modular part of larger proteins; it can be associated with the WH1 or EVH1 domain and with the CRIB domain, and the WH2 domain can occur as a tandem repeat. The WH2 domain binds to actin monomers and can facilitate the assembly of actin monomers into actin filaments.
Human genes encoding proteins containing the WH2 motif include:
- COBL, COBLL1, ESPN, INF2, JMY
- LMOD1, LMOD2, LMOD3
- MTSS1, PXK
- WAS, WASF1, WASF2, WASF3, WASF4, WASL, WASPIP, WHDC1, WIPF1, WIPF2
- "Structural basis for the actin-binding function of missing-in-metastasis". Structure. 15 (2): 145–55. doi:10.1016/j.str.2006.12.005. PMC . PMID 17292833.; Lee SH, Kerff F, Chereau D, Ferron F, Klug A, Dominguez R (February 2007).
- Machesky LM, Insall RH (1998). "Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex". Curr. Biol. 8 (25): 1347–56. doi:10.1016/S0960-9822(98)00015-3. PMID 9889097.
- Veltman DM, Insall RH (2010). "WASP family proteins: their evolution and its physiological implications.". Mol Biol Cell. 21 (16): 2880–93. doi:10.1091/mbc.E10-04-0372. PMC . PMID 20573979.
- Machesky LM, Insall RH, Volkman LE (2001). "WASP homology sequences in baculoviruses". Trends Cell Biol. 11 (7): 286–287. doi:10.1016/S0962-8924(01)02009-8. PMID 11434350.
- Lappalainen P, Paunola E, Mattila PK (2002). "WH2 domain: a small, versatile adapter for actin monomers". FEBS Lett. 513 (1): 92–97. doi:10.1016/S0014-5793(01)03242-2. PMID 11911886.
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The WH2 motif (for Wiskott Aldrich syndrome homology region 2) has been shown in WASP P42768 and Scar1 (mammalian homologue) to be the region that interacts with actin.
Machesky LM, Insall RH; , Curr Biol 1998;8:1347-1356.: Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex. PUBMED:9889097 EPMC:9889097
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR003124
The WH2 (WASP-Homology 2, or Wiskott-Aldrich homology 2) domain is an ~18 amino acids actin-binding motif. This domain was first recognised as an essential element for the regulation of the cytoskeleton by the mammalian Wiskott-Aldrich syndrome protein (WASP) family. WH2 proteins occur in eukaryotes from yeast to mammals, in insect viruses, and in some bacteria. The WH2 domain is found as a modular part of larger proteins; it can be associated with the WH1 or EVH1 domain INTERPRO and with the CRIB domain INTERPRO , and the WH2 domain can occur as a tandem repeat. The WH2 domain binds actin monomers and can facilitate the assembly of actin monomers into newly forming actin filaments [ PUBMED:11434350 , PUBMED:11911886 ].
Some proteins known to contain a WH2 domain:
- Mammalian Wiskott-Aldrich syndrome protein (WASP), a possible regulator of lymphocyte and platelet function. Defects in WASP are the cause of Wiskott- Aldrich syndrome (WAS), an X-linked recessive disease characterised by immune dysregulation and microthrombocytopenia. WASP proteins bind the actin nucleating protein complex Arp2/3.
- Mammalian N-WASP/WASL and WASF/SCAR/WAVE1-3, and yeast LAS17, which are also proteins from the WASP family that participate in the transduction of signals from the cell surface to the actin cytoskeleton.
- WAS protein family homologue 1 (WASH1), acts as a nucleation-promoting factor at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerisation.
- Baker's yeast Verprolin, a protein involved in cytoskeletal organisation and cellular growth.
- Human WASP interacting protein (WASPIP/WIP), a WASP-, profilin- and actin-binding protein which induces actin polymerisation and redistribution.
- Nuclear polyhedrosis virus (NPV) P61/78/83 capsid protein, which may be important for the persistence and survival of the virus.
- Fruit fly Spir(e) protein, an actin nucleation factor involved in the development of oocytes and embryos. Spir is conserved among metazoans.
- Mammalian metastasis suppressor 1 or Missing in Metastasis (MIM) protein, an actin-binding protein that may be related to cancer progression or tumor metastasis.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||actin binding (GO:0003779)|
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|Seed source:||Alignment kindly provided by SMART|
|Number in seed:||43|
|Number in full:||8824|
|Average length of the domain:||26.70 aa|
|Average identity of full alignment:||38 %|
|Average coverage of the sequence by the domain:||4.76 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||23|
|Download:||download the raw HMM for this family|
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the WH2 domain has been found. There are 28 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.