ID WASL_MOUSE Reviewed; 501 AA. AC Q91YD9; DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 27-MAR-2024, entry version 184. DE RecName: Full=Actin nucleation-promoting factor WASL {ECO:0000305}; DE AltName: Full=Neural Wiskott-Aldrich syndrome protein; DE Short=N-WASP; GN Name=Wasl; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=C57BL/6J; TISSUE=Brain; RX PubMed=11559594; DOI=10.1093/embo-reports/kve197; RA Lommel S., Benesch S., Rottner K., Franz T., Wehland J., Kuehn R.; RT "Actin pedestal formation by enteropathogenic Escherichia coli and RT intracellular motility of Shigella flexneri are abolished in N-WASP- RT defective cells."; RL EMBO Rep. 2:850-857(2001). RN [2] RP INTERACTION WITH PACSIN1; PACSIN2 AND PACSIN3. RX PubMed=11082044; DOI=10.1242/jcs.113.24.4511; RA Modregger J., Ritter B., Witter B., Paulsson M., Plomann M.; RT "All three PACSIN isoforms bind to endocytic proteins and inhibit RT endocytosis."; RL J. Cell Sci. 113:4511-4521(2000). RN [3] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-253. RX PubMed=12871950; DOI=10.1074/jbc.m302177200; RA Suetsugu S., Takenawa T.; RT "Translocation of N-WASP by nuclear localization and export signals into RT the nucleus modulates expression of HSP90."; RL J. Biol. Chem. 278:42515-42523(2003). RN [4] RP INTERACTION WITH DNMBP. RX PubMed=14506234; DOI=10.1074/jbc.m308104200; RA Salazar M.A., Kwiatkowski A.V., Pellegrini L., Cestra G., Butler M.H., RA Rossman K.L., Serna D.M., Sondek J., Gertler F.B., De Camilli P.; RT "Tuba, a novel protein containing bin/amphiphysin/Rvs and Dbl homology RT domains, links dynamin to regulation of the actin cytoskeleton."; RL J. Biol. Chem. 278:49031-49043(2003). RN [5] RP INTERACTION WITH PRPF40A. RX PubMed=14697212; DOI=10.1016/j.bbrc.2003.11.139; RA Mizutani K., Suetsugu S., Takenawa T.; RT "FBP11 regulates nuclear localization of N-WASP and inhibits N-WASP- RT dependent microspike formation."; RL Biochem. Biophys. Res. Commun. 313:468-474(2004). RN [6] RP INTERACTION WITH PTK2/FAK1, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT RP TYR-253. RX PubMed=14676198; DOI=10.1074/jbc.m310739200; RA Wu X., Suetsugu S., Cooper L.A., Takenawa T., Guan J.L.; RT "Focal adhesion kinase regulation of N-WASP subcellular localization and RT function."; RL J. Biol. Chem. 279:9565-9576(2004). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-253, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=18034455; DOI=10.1021/pr0701254; RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.; RT "Large-scale identification and evolution indexing of tyrosine RT phosphorylation sites from murine brain."; RL J. Proteome Res. 7:311-318(2008). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-253, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006; RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M., RA Thibault P.; RT "The phagosomal proteome in interferon-gamma-activated macrophages."; RL Immunity 30:143-154(2009). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-253, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200; RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.; RT "Large scale localization of protein phosphorylation by use of electron RT capture dissociation mass spectrometry."; RL Mol. Cell. Proteomics 8:904-912(2009). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-253 AND SER-480, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Kidney, Liver, Lung, Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [11] RP INTERACTION WITH FCHSD2. RX PubMed=23437151; DOI=10.1371/journal.pone.0056516; RA Cao H., Yin X., Cao Y., Jin Y., Wang S., Kong Y., Chen Y., Gao J., RA Heller S., Xu Z.; RT "FCHSD1 and FCHSD2 are expressed in hair cell stereocilia and cuticular RT plate and regulate actin polymerization in vitro."; RL PLoS ONE 8:E56516-E56516(2013). RN [12] RP FUNCTION. RX PubMed=25851601; DOI=10.1091/mbc.e14-08-1310; RA Jaudon F., Raynaud F., Wehrle R., Bellanger J.M., Doulazmi M., Vodjdani G., RA Gasman S., Fagni L., Dusart I., Debant A., Schmidt S.; RT "The RhoGEF DOCK10 is essential for dendritic spine morphogenesis."; RL Mol. Biol. Cell 26:2112-2127(2015). RN [13] RP INTERACTION WITH FCHSD2 AND FCHSD1. RX PubMed=29887380; DOI=10.1016/j.cell.2018.05.020; RA Almeida-Souza L., Frank R.A.W., Garcia-Nafria J., Colussi A., RA Gunawardana N., Johnson C.M., Yu M., Howard G., Andrews B., Vallis Y., RA McMahon H.T.; RT "A Flat BAR Protein Promotes Actin Polymerization at the Base of Clathrin- RT Coated Pits."; RL Cell 174:325-337(2018). CC -!- FUNCTION: Regulates actin polymerization by stimulating the actin- CC nucleating activity of the Arp2/3 complex. Involved in various CC processes, such as mitosis and cytokinesis, via its role in the CC regulation of actin polymerization. Together with CDC42, involved in CC the extension and maintenance of the formation of thin, actin-rich CC surface projections called filopodia. In addition to its role in the CC cytoplasm, also plays a role in the nucleus by regulating gene CC transcription, probably by promoting nuclear actin polymerization (By CC similarity). Binds to HSF1/HSTF1 and forms a complex on heat shock CC promoter elements (HSE) that negatively regulates HSP90 expression CC (PubMed:12871950). Plays a role in dendrite spine morphogenesis CC (PubMed:25851601). {ECO:0000250|UniProtKB:O00401, CC ECO:0000269|PubMed:12871950, ECO:0000269|PubMed:25851601}. CC -!- SUBUNIT: Binds actin and the Arp2/3 complex. Interacts with CDC42 (By CC similarity). Interacts with FCHSD1 (PubMed:29887380). Interacts with CC FCHSD2 (PubMed:23437151, PubMed:29887380). Binds to SH3 domains of CC GRB2. Interacts with the C-terminal SH3 domain of DNMBP CC (PubMed:14506234). Interacts with SNX9 (By similarity). Interacts with CC the WW domains of PRPF40A/FBP11 (PubMed:14697212). Interacts with CC PTK2/FAK1 (PubMed:14676198). Interacts with PACSIN1, PACSIN2 and CC PACSIN3 (PubMed:11082044). Interacts with NOSTRIN. Binds to TNK2. CC Interacts with SNX33. Interacts with NONO (via second RRM domain); the CC interaction is direct. Component of a multiprotein complex with NONO CC and SFPQ; associates with the complex via direct interaction with NONO CC (By similarity). {ECO:0000250|UniProtKB:O00401, CC ECO:0000250|UniProtKB:Q95107, ECO:0000269|PubMed:11082044, CC ECO:0000269|PubMed:14506234, ECO:0000269|PubMed:14676198, CC ECO:0000269|PubMed:14697212, ECO:0000269|PubMed:23437151, CC ECO:0000269|PubMed:29887380}. CC -!- INTERACTION: CC Q91YD9; Q60598: Cttn; NbExp=4; IntAct=EBI-642417, EBI-397955; CC Q91YD9; P09055: Itgb1; NbExp=2; IntAct=EBI-642417, EBI-644224; CC Q91YD9; P05622: Pdgfrb; NbExp=2; IntAct=EBI-642417, EBI-1554855; CC Q91YD9; P68135: ACTA1; Xeno; NbExp=5; IntAct=EBI-642417, EBI-367540; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton CC {ECO:0000250|UniProtKB:O08816}. Nucleus {ECO:0000269|PubMed:12871950, CC ECO:0000269|PubMed:14676198}. Cytoplasm {ECO:0000269|PubMed:12871950, CC ECO:0000269|PubMed:14676198}. Note=Preferentially localized in the CC cytoplasm when phosphorylated and in the nucleus when unphosphorylated CC (PubMed:12871950, PubMed:14676198). Exported from the nucleus by an CC nuclear export signal (NES)-dependent mechanism to the cytoplasm CC (PubMed:12871950). {ECO:0000269|PubMed:12871950, CC ECO:0000269|PubMed:14676198}. CC -!- PTM: Phosphorylation at Ser-239, Tyr-253, Ser-480 and Ser-481 enhances CC actin polymerization activity. {ECO:0000250|UniProtKB:O00401}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ318416; CAC69994.1; -; mRNA. DR CCDS; CCDS19945.1; -. DR RefSeq; NP_082735.2; NM_028459.2. DR PDB; 3M3N; X-ray; 7.00 A; W=397-474. DR PDB; 6UHC; EM; 3.90 A; H/I=1-501. DR PDBsum; 3M3N; -. DR PDBsum; 6UHC; -. DR AlphaFoldDB; Q91YD9; -. DR BMRB; Q91YD9; -. DR EMDB; EMD-20770; -. DR EMDB; EMD-25707; -. DR SMR; Q91YD9; -. DR BioGRID; 215819; 7. DR CORUM; Q91YD9; -. DR DIP; DIP-29788N; -. DR IntAct; Q91YD9; 11. DR MINT; Q91YD9; -. DR STRING; 10090.ENSMUSP00000031695; -. DR iPTMnet; Q91YD9; -. DR PhosphoSitePlus; Q91YD9; -. DR SwissPalm; Q91YD9; -. DR jPOST; Q91YD9; -. DR MaxQB; Q91YD9; -. DR PaxDb; 10090-ENSMUSP00000031695; -. DR ProteomicsDB; 297624; -. DR Pumba; Q91YD9; -. DR Antibodypedia; 1487; 298 antibodies from 37 providers. DR DNASU; 73178; -. DR Ensembl; ENSMUST00000031695.15; ENSMUSP00000031695.9; ENSMUSG00000029684.15. DR GeneID; 73178; -. DR KEGG; mmu:73178; -. DR UCSC; uc009bbv.2; mouse. DR AGR; MGI:1920428; -. DR CTD; 8976; -. DR MGI; MGI:1920428; Wasl. DR VEuPathDB; HostDB:ENSMUSG00000029684; -. DR eggNOG; KOG3671; Eukaryota. DR GeneTree; ENSGT00730000110895; -. DR HOGENOM; CLU_015385_3_1_1; -. DR InParanoid; Q91YD9; -. DR OMA; LGRKCQT; -. DR OrthoDB; 3837860at2759; -. DR PhylomeDB; Q91YD9; -. DR TreeFam; TF316736; -. DR BioGRID-ORCS; 73178; 3 hits in 79 CRISPR screens. DR ChiTaRS; Wasl; mouse. DR EvolutionaryTrace; Q91YD9; -. DR PRO; PR:Q91YD9; -. DR Proteomes; UP000000589; Chromosome 6. DR RNAct; Q91YD9; Protein. DR Bgee; ENSMUSG00000029684; Expressed in renal medulla collecting duct and 249 other cell types or tissues. DR ExpressionAtlas; Q91YD9; baseline and differential. DR GO; GO:0030478; C:actin cap; IDA:MGI. DR GO; GO:0031252; C:cell leading edge; ISO:MGI. DR GO; GO:0005737; C:cytoplasm; IC:MGI. DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:BHF-UCL. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0000139; C:Golgi membrane; ISO:MGI. DR GO; GO:0030027; C:lamellipodium; IDA:MGI. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0098794; C:postsynapse; ISO:MGI. DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW. DR GO; GO:0008092; F:cytoskeletal protein binding; ISO:MGI. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0030036; P:actin cytoskeleton organization; IMP:MGI. DR GO; GO:0030041; P:actin filament polymerization; ISS:UniProtKB. DR GO; GO:0045010; P:actin nucleation; TAS:MGI. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0060997; P:dendritic spine morphogenesis; IMP:UniProtKB. DR GO; GO:0010324; P:membrane invagination; ISO:MGI. DR GO; GO:2000402; P:negative regulation of lymphocyte migration; ISO:MGI. DR GO; GO:1903526; P:negative regulation of membrane tubulation; ISO:MGI. DR GO; GO:0097320; P:plasma membrane tubulation; ISO:MGI. DR GO; GO:0050921; P:positive regulation of chemotaxis; ISO:MGI. DR GO; GO:2000370; P:positive regulation of clathrin-dependent endocytosis; ISS:BHF-UCL. DR GO; GO:0051491; P:positive regulation of filopodium assembly; ISS:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0099173; P:postsynapse organization; ISO:MGI. DR GO; GO:0098974; P:postsynaptic actin cytoskeleton organization; ISO:MGI. DR GO; GO:0031503; P:protein-containing complex localization; IMP:MGI. DR GO; GO:0060491; P:regulation of cell projection assembly; ISO:MGI. DR GO; GO:0099175; P:regulation of postsynapse organization; IDA:SynGO. DR GO; GO:0032880; P:regulation of protein localization; IMP:MGI. DR GO; GO:0009617; P:response to bacterium; IMP:MGI. DR GO; GO:0051653; P:spindle localization; IMP:MGI. DR GO; GO:0006900; P:vesicle budding from membrane; ISS:BHF-UCL. DR GO; GO:0016050; P:vesicle organization; ISS:BHF-UCL. DR GO; GO:0030050; P:vesicle transport along actin filament; ISS:BHF-UCL. DR CDD; cd00132; CRIB; 1. DR CDD; cd01205; EVH1_WASP-like; 1. DR CDD; cd22075; WH2_hN-WASP_r2_like; 1. DR CDD; cd22074; WH2_N-WASP_r1; 1. DR DisProt; DP02830; -. DR Gene3D; 3.90.810.10; CRIB domain; 2. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR InterPro; IPR000095; CRIB_dom. DR InterPro; IPR036936; CRIB_dom_sf. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR011026; WAS_C. DR InterPro; IPR033927; WASPfam_EVH1. DR InterPro; IPR000697; WH1/EVH1_dom. DR InterPro; IPR003124; WH2_dom. DR PANTHER; PTHR11202:SF36; NEURAL WISKOTT-ALDRICH SYNDROME PROTEIN; 1. DR PANTHER; PTHR11202; SPROUTY-RELATED, EVH1 DOMAIN-CONTAINING PROTEIN FAMILY MEMBER; 1. DR Pfam; PF00786; PBD; 1. DR Pfam; PF00568; WH1; 1. DR Pfam; PF02205; WH2; 2. DR SMART; SM00285; PBD; 1. DR SMART; SM00461; WH1; 1. DR SMART; SM00246; WH2; 2. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF47912; Wiscott-Aldrich syndrome protein, WASP, C-terminal domain; 2. DR PROSITE; PS50108; CRIB; 1. DR PROSITE; PS50229; WH1; 1. DR PROSITE; PS51082; WH2; 2. DR Genevisible; Q91YD9; MM. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Actin-binding; Cell cycle; Cell division; KW Cytoplasm; Cytoskeleton; Methylation; Mitosis; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; Transcription; Transcription regulation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:O00401" FT CHAIN 2..501 FT /note="Actin nucleation-promoting factor WASL" FT /id="PRO_0000189001" FT DOMAIN 31..138 FT /note="WH1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00410" FT DOMAIN 200..213 FT /note="CRIB" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057" FT DOMAIN 401..418 FT /note="WH2 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00406" FT DOMAIN 429..446 FT /note="WH2 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00406" FT REGION 135..159 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 263..403 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 442..501 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 271..391 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 442..459 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 482..501 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000250|UniProtKB:O00401" FT MOD_RES 239 FT /note="Phosphoserine; by TNK2" FT /evidence="ECO:0000250|UniProtKB:O00401" FT MOD_RES 253 FT /note="Phosphotyrosine; by FAK1 and TNK2" FT /evidence="ECO:0000269|PubMed:14676198, FT ECO:0007744|PubMed:18034455, ECO:0007744|PubMed:19131326, FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079" FT MOD_RES 304 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:O00401" FT MOD_RES 480 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 481 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O00401" FT MUTAGEN 253 FT /note="Y->E: No effect on phosphorylation. Protein FT preferentially localized in cytoplasm." FT /evidence="ECO:0000269|PubMed:12871950" FT MUTAGEN 253 FT /note="Y->F: Abolishes phosphorylation. Protein FT preferentially localized in nucleus." FT /evidence="ECO:0000269|PubMed:12871950" SQ SEQUENCE 501 AA; 54274 MW; F5ABF44DF9A9F716 CRC64; MSSGQQPPRR VTNVGSLLLT PQENESLFSF LGKKCVTMSS AVVQLYAADR NCMWAKKCSG VACLVKDNPQ RSYFLRIFDI KDGKLLWEQE LYNNFVYNSP RGYFHTFAGD TCQVALNFAN EEEAKKFRKA VTDLLGRRQR KSEKRRDAPN GPNLPMATVD IKNPEITTNR FYGSQVNNIS HTKEKKKGKA KKKRLTKADI GTPSNFQHIG HVGWDPNTGF DLNNLDPELK NLFDMCGISE AQLKDRETSK VIYDFIEKTG GVEAVKNELR RQAPPPPPPS RGGPPPPPPP PHSSGPPPPP ARGRGAPPPP PSRAPTAAPP PPPPSRPGVV VPPPPPNRMY PPPPPALPSS APSGPPPPPP PSMAGSTAPP PPPPPPPPPG PPPPPGLPSD GDHQVPAPSG NKAALLDQIR EGAQLKKVEQ NSRPVSCSGR DALLDQIRQG IQLKSVSDGQ ESTPPTPAPT SGIVGALMEV MQKRSKAIHS SDEDEDDDDE EDFEDDDEWE D //