WASL_MOUSE
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 03-AUG-2022, entry version 175.
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}.
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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 SMR; Q91YD9; -.
DR BioGRID; 215819; 6.
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 jPOST; Q91YD9; -.
DR MaxQB; Q91YD9; -.
DR PaxDb; Q91YD9; -.
DR PRIDE; Q91YD9; -.
DR ProteomicsDB; 297624; -.
DR Antibodypedia; 1487; 243 antibodies from 37 providers.
DR DNASU; 73178; -.
DR Ensembl; ENSMUST00000031695; ENSMUSP00000031695; ENSMUSG00000029684.
DR GeneID; 73178; -.
DR KEGG; mmu:73178; -.
DR UCSC; uc009bbv.2; mouse.
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; 60972at2759; -.
DR PhylomeDB; Q91YD9; -.
DR TreeFam; TF316736; -.
DR Reactome; R-MMU-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-MMU-203641; NOSTRIN mediated eNOS trafficking.
DR Reactome; R-MMU-373753; Nephrin family interactions.
DR Reactome; R-MMU-3928662; EPHB-mediated forward signaling.
DR Reactome; R-MMU-418885; DCC mediated attractive signaling.
DR Reactome; R-MMU-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013406; RHOQ GTPase cycle.
DR Reactome; R-MMU-9013409; RHOJ GTPase cycle.
DR Reactome; R-MMU-9013424; RHOV GTPase cycle.
DR BioGRID-ORCS; 73178; 3 hits in 74 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 246 other tissues.
DR ExpressionAtlas; Q91YD9; baseline and differential.
DR Genevisible; Q91YD9; MM.
DR GO; GO:0030478; C:actin cap; IDA:MGI.
DR GO; GO:0005884; C:actin filament; IBA:GO_Central.
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; ISO:MGI.
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:0030048; P:actin filament-based movement; IBA:GO_Central.
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:2000601; P:positive regulation of Arp2/3 complex-mediated actin nucleation; IEA:InterPro.
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: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: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; cd01205; EVH1_WASP-like; 1.
DR DisProt; DP02830; -.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.90.810.10; -; 2.
DR InterPro; IPR000095; CRIB_dom.
DR InterPro; IPR036936; CRIB_dom_sf.
DR InterPro; IPR030214; N-WASP.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR011026; WASP_C.
DR InterPro; IPR033927; WASPfam_EVH1.
DR InterPro; IPR000697; WH1/EVH1_dom.
DR InterPro; IPR003124; WH2_dom.
DR PANTHER; PTHR23202:SF39; PTHR23202:SF39; 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; SSF47912; SSF47912; 2.
DR PROSITE; PS50108; CRIB; 1.
DR PROSITE; PS50229; WH1; 1.
DR PROSITE; PS51082; WH2; 2.
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
