WASL (gene)

Neural Wiskott–Aldrich syndrome protein is a protein that in humans is encoded by the WASL gene.

WASL
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2FF3, 2LNH, 2VCP, 4CC2, 4CC7
Identifiers
Aliases	WASL, N-WASP, NWASP, WASPB, WASL (gene), Wiskott-Aldrich syndrome like, WASP like actin nucleation promoting factor
External IDs	OMIM: 605056; MGI: 1920428; HomoloGene: 136779; GeneCards: WASL; OMA:WASL - orthologs
Gene location (Human) Chr. Chromosome 7 (human) Band 7q31.32 Start 123,681,943 bp End 123,749,003 bp
Gene location (Mouse) Chr. Chromosome 6 (mouse) Band 6|6 A3.1 Start 24,613,804 bp End 24,665,008 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in middle temporal gyrus lateral nuclear group of thalamus jejunal mucosa Brodmann area 23 skin of thigh mucosa of colon mucosa of sigmoid colon renal medulla trigeminal ganglion postcentral gyrus Top expressed in medullary collecting duct Region I of hippocampus proper renal corpuscle ciliary body retinal pigment epithelium conjunctival fornix vestibular membrane of cochlear duct facial motor nucleus Paneth cell Epithelium of choroid plexus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function GTPase regulator activity protein binding actin binding Cellular component cytoplasm endocytic vesicle membrane cytosol plasma membrane actin cytoskeleton actin cap extracellular exosome cytoskeleton nucleus lamellipodium cytoplasmic vesicle Biological process negative regulation of membrane tubulation regulation of transcription, DNA-templated response to bacterium Fc-gamma receptor signaling pathway involved in phagocytosis vesicle organization actin filament organization ephrin receptor signaling pathway regulation of nitric-oxide synthase activity positive regulation of Arp2/3 complex-mediated actin nucleation transcription, DNA-templated regulation of protein localization cell division vesicle budding from membrane positive regulation of clathrin-dependent endocytosis vesicle transport along actin filament cell cycle actin polymerization or depolymerization spindle localization negative regulation of lymphocyte migration positive regulation of filopodium assembly actin cytoskeleton organization membrane organization dendritic spine morphogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8976 73178 Ensembl ENSG00000106299 ENSMUSG00000029684 UniProt O00401 Q91YD9 RefSeq (mRNA) NM_003941 NM_001167745 NM_028459 RefSeq (protein) NP_003932 NP_001161217 NP_082735 Location (UCSC) Chr 7: 123.68 – 123.75 Mb Chr 6: 24.61 – 24.67 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

The Wiskott–Aldrich syndrome (WAS) family of proteins share similar domain structure, and are involved in transduction of signals from receptors on the cell surface to the actin cytoskeleton. The presence of a number of different motifs suggests that they are regulated by a number of different stimuli, and interact with multiple proteins. Recent studies have demonstrated that these proteins, directly or indirectly, associate with the small GTPase, Cdc42, known to regulate formation of actin filaments, and the cytoskeletal organizing complex, Arp2/3. The WASL gene product is a homolog of WAS protein, however, unlike the latter, it is ubiquitously expressed and shows highest expression in neural tissues. It has been shown to bind Cdc42 directly, and induce formation of long actin microspikes.

According to one study, mouse DAB1 regulates actin cytoskeleton through N-WASP.

Diseases associated with WASL include Wiskottt-Aldrich Syndrome and Vaccinia.

Interactions

WASL (gene) has been shown to interact with:

• CDC42,
• Cortactin
• NCK1,
• Profilin 1, and
• RHOQ.

Further reading

• Ramesh N, Antón IM, Martínez-Quiles N, Geha RS (Jan 1999). "Waltzing with WASP". Trends in Cell Biology. 9 (1): 15–9. doi:10.1016/S0962-8924(98)01411-1. PMID 10087612.
• Carlier MF, Ducruix A, Pantaloni D (Sep 1999). "Signalling to actin: the Cdc42-N-WASP-Arp2/3 connection". Chemistry & Biology. 6 (9): R235–40. doi:10.1016/S1074-5521(99)80107-0. PMID 10467124.
• Suzuki T, Miki H, Takenawa T, Sasakawa C (May 1998). "Neural Wiskott–Aldrich syndrome protein is implicated in the actin-based motility of Shigella flexneri". The EMBO Journal. 17 (10): 2767–76. doi:10.1093/emboj/17.10.2767. PMC 1170617. PMID 9582270.
• Suetsugu S, Miki H, Takenawa T (Nov 1998). "The essential role of profilin in the assembly of actin for microspike formation". The EMBO Journal. 17 (22): 6516–26. doi:10.1093/emboj/17.22.6516. PMC 1170999. PMID 9822597.
• Qualmann B, Roos J, DiGregorio PJ, Kelly RB (Feb 1999). "Syndapin I, a synaptic dynamin-binding protein that associates with the neural Wiskott–Aldrich syndrome protein". Molecular Biology of the Cell. 10 (2): 501–13. doi:10.1091/mbc.10.2.501. PMC 25183. PMID 9950691.
• Suetsugu S, Miki H, Takenawa T (Jun 1999). "Identification of two human WAVE/SCAR homologues as general actin regulatory molecules which associate with the Arp2/3 complex". Biochemical and Biophysical Research Communications. 260 (1): 296–302. doi:10.1006/bbrc.1999.0894. PMID 10381382.
• Egile C, Loisel TP, Laurent V, Li R, Pantaloni D, Sansonetti PJ, Carlier MF (Sep 1999). "Activation of the CDC42 effector N-WASP by the Shigella flexneri IcsA protein promotes actin nucleation by Arp2/3 complex and bacterial actin-based motility". The Journal of Cell Biology. 146 (6): 1319–32. doi:10.1083/jcb.146.6.1319. PMC 2156126. PMID 10491394.
• Higgs HN, Blanchoin L, Pollard TD (Nov 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.
• Qualmann B, Kelly RB (Mar 2000). "Syndapin isoforms participate in receptor-mediated endocytosis and actin organization". The Journal of Cell Biology. 148 (5): 1047–62. doi:10.1083/jcb.148.5.1047. PMC 2174535. PMID 10704453.
• Kim AS, Kakalis LT, Abdul-Manan N, Liu GA, Rosen MK (Mar 2000). "Autoinhibition and activation mechanisms of the Wiskott–Aldrich syndrome protein". Nature. 404 (6774): 151–8. Bibcode:2000Natur.404..151K. doi:10.1038/35004513. PMID 10724160. S2CID 4416185.
• Carlier MF, Nioche P, Broutin-L'Hermite I, Boujemaa R, Le Clainche C, Egile C, Garbay C, Ducruix A, Sansonetti P, Pantaloni D (Jul 2000). "GRB2 links signaling to actin assembly by enhancing interaction of neural Wiskott–Aldrich syndrome protein (N-WASp) with actin-related protein (ARP2/3) complex". The Journal of Biological Chemistry. 275 (29): 21946–52. doi:10.1074/jbc.M000687200. PMID 10781580.
• Mimuro H, Suzuki T, Suetsugu S, Miki H, Takenawa T, Sasakawa C (Sep 2000). "Profilin is required for sustaining efficient intra- and intercellular spreading of Shigella flexneri". The Journal of Biological Chemistry. 275 (37): 28893–901. doi:10.1074/jbc.M003882200. PMID 10867004.
• Prehoda KE, Scott JA, Mullins RD, Lim WA (Oct 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.
• Modregger J, Ritter B, Witter B, Paulsson M, Plomann M (Dec 2000). "All three PACSIN isoforms bind to endocytic proteins and inhibit endocytosis". Journal of Cell Science. 113 (24): 4511–21. doi:10.1242/jcs.113.24.4511. PMID 11082044.
• Marchand JB, Kaiser DA, Pollard TD, Higgs HN (Jan 2001). "Interaction of WASP/Scar proteins with actin and vertebrate Arp2/3 complex". Nature Cell Biology. 3 (1): 76–82. doi:10.1038/35050590. PMID 11146629. S2CID 30437883.
• Fukuoka M, Suetsugu S, Miki H, Fukami K, Endo T, Takenawa T (Feb 2001). "A novel neural Wiskott–Aldrich syndrome protein (N-WASP) binding protein, WISH, induces Arp2/3 complex activation independent of Cdc42". The Journal of Cell Biology. 152 (3): 471–82. doi:10.1083/jcb.152.3.471. PMC 2196001. PMID 11157975.