WASF1

Wiskott–Aldrich syndrome protein family member 1, also known as WASP-family verprolin homologous protein 1 (WAVE1), is a protein that in humans is encoded by the WASF1 gene.[5][6][7]

WASF1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3P8C, 4N78
Identifiers
Aliases	WASF1, SCAR1, WAVE, WAVE1, WAS protein family member 1, WASP family member 1, NEDALVS
External IDs	OMIM: 605035 MGI: 1890563 HomoloGene: 2920 GeneCards: WASF1
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6q21 Start 110,099,819 bp[1] End 110,180,004 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10 B1|10 22.07 cM Start 40,883,475 bp[2] End 40,938,570 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • actin binding • Rac GTPase binding • GO:0001948 protein binding • protein kinase A binding • GO:0032403 macromolecular complex binding Cellular component • cytoplasm • mitochondrial outer membrane • cell junction • synapse • cytoskeleton • mitochondrion • SCAR complex • lamellipodium • focal adhesion • actin cytoskeleton • macromolecular complex • dendrite cytoplasm • postsynapse Biological process • actin filament polymerization • Rac protein signal transduction • positive regulation of Arp2/3 complex-mediated actin nucleation • lamellipodium morphogenesis • actin cytoskeleton organization • neuron projection development • positive regulation of neurotrophin TRK receptor signaling pathway • dendrite extension • receptor-mediated endocytosis • cellular response to brain-derived neurotrophic factor stimulus • macromolecular complex assembly • modification of postsynaptic actin cytoskeleton • dendritic transport of mitochondrion Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	8936	83767
Ensembl	ENSG00000112290	ENSMUSG00000019831
UniProt	Q92558	Q8R5H6
RefSeq (mRNA)	NM_001024934 NM_001024935 NM_001024936 NM_003931	NM_031877 NM_001379453 NM_001379454
RefSeq (protein)	NP_001020105 NP_001020106 NP_001020107 NP_003922	NP_114083 NP_001366382 NP_001366383
Location (UCSC)	Chr 6: 110.1 – 110.18 Mb	Chr 10: 40.88 – 40.94 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The protein encoded by this gene, a member of the Wiskott–Aldrich syndrome protein (WASP) family, plays a critical role downstream of Rac, a Rho-family small GTPase, through its involvement in the WAVE regulatory complex in regulating the actin cytoskeleton required for membrane ruffling. It has been shown to associate with an actin nucleation core Arp2/3 complex while enhancing actin polymerization in vitro.

Clinical significance

Wiskott–Aldrich syndrome is a disease of the immune system, likely due to defects in regulation of actin cytoskeleton.[7]

Interactions

WASF1 has been shown to interact with BAIAP2[8] and Profilin 1.[5]

References

1. GRCh38: Ensembl release 89: ENSG00000112290 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000019831 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Miki H, Suetsugu S, Takenawa T (February 1999). "WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac". EMBO J. 17 (23): 6932–41. doi:10.1093/emboj/17.23.6932. PMC 1171041. PMID 9843499.
6. Machesky LM, Insall RH (March 1999). "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. S2CID 16661755.
7. "Entrez Gene: WASF1 WAS protein family, member 1".
8. Miki H, Yamaguchi H, Suetsugu S, Takenawa T (December 2000). "IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling". Nature. 408 (6813): 732–5. Bibcode:2000Natur.408..732M. doi:10.1038/35047107. PMID 11130076. S2CID 4426046.

Further reading

• Sloane JA, Vartanian TK (2007). "WAVE1 and regulation of actin nucleation in myelination". The Neuroscientist : A Review Journal Bringing Neurobiology, Neurology and Psychiatry. 13 (5): 486–91. doi:10.1177/1073858407299423. PMID 17901257. S2CID 295778.
• Whitebread S, Mele M, Kamber B, de Gasparo M (1989). "Preliminary biochemical characterization of two angiotensin II receptor subtypes". Biochem. Biophys. Res. Commun. 163 (1): 284–91. doi:10.1016/0006-291X(89)92133-5. PMID 2775266.
• Kitamura T, Kitamura Y, Yonezawa K, et al. (1996). "Molecular cloning of p125Nap1, a protein that associates with an SH3 domain of Nck". Biochem. Biophys. Res. Commun. 219 (2): 509–14. doi:10.1006/bbrc.1996.0264. PMID 8605018.
• Nagase T, Seki N, Ishikawa K, et al. (1997). "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain". DNA Res. 3 (5): 321–9, 341–54. doi:10.1093/dnares/3.5.321. PMID 9039502.
• She HY, Rockow S, Tang J, et al. (1997). "Wiskott–Aldrich syndrome protein is associated with the adapter protein Grb2 and the epidermal growth factor receptor in living cells". Mol. Biol. Cell. 8 (9): 1709–21. doi:10.1091/mbc.8.9.1709. PMC 305731. PMID 9307968.
• Witke W, Podtelejnikov AV, Di Nardo A, et al. (1998). "In mouse brain profilin I and profilin II associate with regulators of the endocytic pathway and actin assembly". EMBO J. 17 (4): 967–76. doi:10.1093/emboj/17.4.967. PMC 1170446. PMID 9463375.
• Bear JE, Rawls JF, Saxe CL (1998). "SCAR, a WASP-related protein, isolated as a suppressor of receptor defects in late Dictyostelium development". J. Cell Biol. 142 (5): 1325–35. doi:10.1083/jcb.142.5.1325. PMC 2149354. PMID 9732292.
• Wu Y, Dowbenko D, Lasky LA (1998). "PSTPIP 2, a second tyrosine phosphorylated, cytoskeletal-associated protein that binds a PEST-type protein-tyrosine phosphatase". J. Biol. Chem. 273 (46): 30487–96. doi:10.1074/jbc.273.46.30487. PMID 9804817.
• Suetsugu S, Miki H, Takenawa T (1999). "Identification of two human WAVE/SCAR homologues as general actin regulatory molecules which associate with the Arp2/3 complex". Biochem. Biophys. Res. Commun. 260 (1): 296–302. doi:10.1006/bbrc.1999.0894. PMID 10381382.
• Banin S, Gout I, Brickell P (1999). "Interaction between Wiskott–Aldrich Syndrome protein (WASP) and the Fyn protein-tyrosine kinase". Mol. Biol. Rep. 26 (3): 173–7. doi:10.1023/A:1006954206151. PMID 10532312. S2CID 36018089.
• Higgs HN, Blanchoin L, Pollard TD (1999). "Influence of the C terminus of Wiskott–Aldrich syndrome protein (WASp) and the Arp2/3 complex on actin polymerization". Biochemistry. 38 (46): 15212–22. doi:10.1021/bi991843. PMID 10563804.
• Westphal RS, Soderling SH, Alto NM, et al. (2000). "Scar/WAVE-1, a Wiskott–Aldrich syndrome protein, assembles an actin-associated multi-kinase scaffold". EMBO J. 19 (17): 4589–600. doi:10.1093/emboj/19.17.4589. PMC 302050. PMID 10970852.
• Prehoda KE, Scott JA, Mullins RD, Lim WA (2000). "Integration of multiple signals through cooperative regulation of the N-WASP-Arp2/3 complex". Science. 290 (5492): 801–6. Bibcode:2000Sci...290..801P. doi:10.1126/science.290.5492.801. PMID 11052943.
• Miki H, Yamaguchi H, Suetsugu S, Takenawa T (2001). "IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling". Nature. 408 (6813): 732–5. doi:10.1038/35047107. PMID 11130076. S2CID 4426046.
• Marchand JB, Kaiser DA, Pollard TD, Higgs HN (2001). "Interaction of WASP/Scar proteins with actin and vertebrate Arp2/3 complex". Nat. Cell Biol. 3 (1): 76–82. doi:10.1038/35050590. PMID 11146629. S2CID 30437883.
• Eden S, Rohatgi R, Podtelejnikov AV, et al. (2002). "Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck". Nature. 418 (6899): 790–3. Bibcode:2002Natur.418..790E. doi:10.1038/nature00859. PMID 12181570. S2CID 4350733.
• Yarar D, D'Alessio JA, Jeng RL, Welch MD (2003). "Motility determinants in WASP family proteins". Mol. Biol. Cell. 13 (11): 4045–59. doi:10.1091/mbc.E02-05-0294. PMC 133613. PMID 12429845.
• Soderling SH, Binns KL, Wayman GA, et al. (2003). "The WRP component of the WAVE-1 complex attenuates Rac-mediated signalling". Nat. Cell Biol. 4 (12): 970–5. doi:10.1038/ncb886. PMID 12447388. S2CID 1423222.