WASL (gene)

Wiskott-Aldrich syndrome-like
Rendering of WASL from PDB 2FF3​
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2FF3​, 2LNH​, 2VCP​, 4CC2​, 4CC7​
Identifiers
Symbols	WASL ; N-WASP; NWASP; WASPB
External IDs	OMIM: 605056 MGI: 1920428 HomoloGene: 136779 GeneCards: WASL Gene
Gene ontology Molecular function • actin binding • protein binding • GTPase regulator activity Cellular component • Golgi membrane • nucleus • cytosol • plasma membrane • actin cytoskeleton • cytoplasmic membrane-bounded vesicle • lamellipodium • actin cap • endocytic vesicle membrane • extracellular exosome Biological process • transcription, DNA-templated • regulation of transcription, DNA-templated • protein complex assembly • membrane budding • movement of cell or subcellular component • mitotic nuclear division • small GTPase mediated signal transduction • axon guidance • actin polymerization or depolymerization • response to bacterium • vesicle organization • vesicle transport along actin filament • regulation of protein localization • cellular protein complex localization • Fc-gamma receptor signaling pathway involved in phagocytosis • small molecule metabolic process • innate immune response • nitric oxide metabolic process • ephrin receptor signaling pathway • regulation of nitric-oxide synthase activity • cell division • positive regulation of filopodium assembly • spindle localization • negative regulation of membrane tubulation • positive regulation of clathrin-mediated endocytosis • negative regulation of lymphocyte migration • positive regulation of Arp2/3 complex-mediated actin nucleation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8976	73178
Ensembl	ENSG00000106299	ENSMUSG00000029684
UniProt	O00401	Q91YD9
RefSeq (mRNA)	NM_003941	NM_001167745
RefSeq (protein)	NP_003932	NP_001161217
Location (UCSC)	Chr 7: 123.68 – 123.75 Mb	Chr 6: 24.61 – 24.67 Mb
PubMed search

Neural Wiskott-Aldrich syndrome protein is a protein that in humans is encoded by the WASL gene.^[1][2][3]

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.^[3]

According to one study, mouse DAB1 regulates actin cytoskeleton through N-WASP.^[4]

Interactions

WASL (gene) has been shown to interact with:

• CDC42,^[1][5]
• Cortactin^[6]
• NCK1,^[7]
• Profilin 1,^[8][9] and
• RHOQ.^[10]

References

1. Miki H, Sasaki T, Takai Y, Takenawa T (Jan 1998). "Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP". Nature 391 (6662): 93–6. doi:10.1038/34208. PMID 9422512.
2. Fukuoka M, Miki H, Takenawa T (Sep 1997). "Identification of N-WASP homologs in human and rat brain". Gene 196 (1-2): 43–8. doi:10.1016/S0378-1119(97)00184-4. PMID 9322739.
3. "Entrez Gene: WASL Wiskott-Aldrich syndrome-like".
4. Suetsugu S, Tezuka T, Morimura T, Hattori M, Mikoshiba K, Yamamoto T, Takenawa T (Nov 2004). "Regulation of actin cytoskeleton by mDab1 through N-WASP and ubiquitination of mDab1". The Biochemical Journal 384 (Pt 1): 1–8. doi:10.1042/BJ20041103. PMC 1134082. PMID 15361067.
5. 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.
6. Mizutani K, Miki H, He H, Maruta H, Takenawa T (Feb 2002). "Essential role of neural Wiskott-Aldrich syndrome protein in podosome formation and degradation of extracellular matrix in src-transformed fibroblasts". Cancer Research 62 (3): 669–74. PMID 11830518.
7. Rohatgi R, Nollau P, Ho HY, Kirschner MW, Mayer BJ (Jul 2001). "Nck and phosphatidylinositol 4,5-bisphosphate synergistically activate actin polymerization through the N-WASP-Arp2/3 pathway". The Journal of Biological Chemistry 276 (28): 26448–52. doi:10.1074/jbc.M103856200. PMID 11340081.
8. 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.
9. 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.
10. Abe T, Kato M, Miki H, Takenawa T, Endo T (Jan 2003). "Small GTPase Tc10 and its homologue RhoT induce N-WASP-mediated long process formation and neurite outgrowth". Journal of Cell Science 116 (Pt 1): 155–68. doi:10.1242/jcs.00208. PMID 12456725.

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. doi:10.1038/35004513. PMID 10724160.
• 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. 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. 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.
• 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.