WASP_MOUSE
ID WASP_MOUSE Reviewed; 520 AA.
AC P70315;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Actin nucleation-promoting factor WAS {ECO:0000305};
DE AltName: Full=Wiskott-Aldrich syndrome protein homolog;
DE Short=WASp;
GN Name=Was; Synonyms=Wasp;
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=BALB/cJ;
RX PubMed=8666397; DOI=10.1006/geno.1995.9979;
RA Derry J.M.J., Wiedemann P., Blair P., Wang Y., Kerns J.A., Lemahieu V.,
RA Godfrey V.L., Wilkinson J.E., Francke U.;
RT "The mouse homolog of the Wiskott-Aldrich syndrome protein (WASP) gene is
RT highly conserved and maps near the scurfy (sf) mutation on the X
RT chromosome.";
RL Genomics 29:471-477(1995).
RN [2]
RP INTERACTION WITH NCK1.
RX PubMed=8910519; DOI=10.1074/jbc.271.46.28772;
RA Quilliam L.A., Lambert Q.T., Mickelson-Young L.A., Westwick J.K.,
RA Sparks A.B., Kay B.K., Jenkins N.A., Gilbert D.J., Copeland N.G., Der C.J.;
RT "Isolation of a NCK-associated kinase, PRK2, an SH3-binding protein and
RT potential effector of Rho protein signaling.";
RL J. Biol. Chem. 271:28772-28776(1996).
RN [3]
RP INTERACTION WITH PSTPIP1.
RX PubMed=9488710; DOI=10.1074/jbc.273.10.5765;
RA Wu Y., Spencer S.D., Lasky L.A.;
RT "Tyrosine phosphorylation regulates the SH3-mediated binding of the
RT Wiskott-Aldrich syndrome protein to PSTPIP, a cytoskeletal-associated
RT protein.";
RL J. Biol. Chem. 273:5765-5770(1998).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-293, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-293; SER-501 AND SER-502, AND
RP IDENTIFICATION BY 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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-293; SER-501 AND SER-502, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver, Lung, and Spleen;
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 [7]
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).
CC -!- FUNCTION: Effector protein for Rho-type GTPases that regulates actin
CC filament reorganization via its interaction with the Arp2/3 complex.
CC Important for efficient actin polymerization. Possible regulator of
CC lymphocyte and platelet function. Mediates actin filament
CC reorganization and the formation of actin pedestals upon infection by
CC pathogenic bacteria. In addition to its role in the cytoplasmic
CC cytoskeleton, also promotes actin polymerization in the nucleus,
CC thereby regulating gene transcription and repair of damaged DNA.
CC Promotes homologous recombination (HR) repair in response to DNA damage
CC by promoting nuclear actin polymerization, leading to drive motility of
CC double-strand breaks (DSBs). {ECO:0000250|UniProtKB:P42768}.
CC -!- SUBUNIT: Binds the Arp2/3 complex (By similarity). Interacts with
CC CDC42, RAC, NCK, HCK, FYN, SRC kinase FGR, BTK, ABL1, PSTPIP1, WIP, and
CC to the p85 subunit of PLC-gamma (PubMed:9488710). Interacts (via C-
CC terminus) with ALDOA (By similarity). Interacts with NCK1 (via SH3
CC domains) (PubMed:8910519). Interacts with FCHSD2 (PubMed:23437151).
CC {ECO:0000250|UniProtKB:P42768, ECO:0000269|PubMed:23437151,
CC ECO:0000269|PubMed:8910519, ECO:0000269|PubMed:9488710}.
CC -!- INTERACTION:
CC P70315; Q8BKC5: Ipo5; NbExp=8; IntAct=EBI-644195, EBI-643605;
CC P70315; P05480: Src; NbExp=2; IntAct=EBI-644195, EBI-298680;
CC P70315; Q8K1I7: Wipf1; NbExp=3; IntAct=EBI-644195, EBI-644216;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:P42768}. Nucleus {ECO:0000250|UniProtKB:P42768}.
CC -!- DOMAIN: The WH1 (Wasp homology 1) domain may bind a Pro-rich ligand.
CC -!- DOMAIN: The CRIB (Cdc42/Rac-interactive-binding) region binds to the C-
CC terminal WH2 domain in the autoinhibited state of the protein. Binding
CC of Rho-type GTPases to the CRIB induces a conformation change and leads
CC to activation.
CC -!- PTM: Phosphorylated at Tyr-293 by FYN and HCK, inducing WAS effector
CC activity after TCR engagement. Phosphorylation at Tyr-293 enhances WAS
CC activity in promoting actin polymerization and filopodia formation.
CC {ECO:0000250|UniProtKB:P42768}.
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DR EMBL; U54788; AAC52556.1; -; mRNA.
DR CCDS; CCDS29984.1; -.
DR RefSeq; NP_033541.1; NM_009515.2.
DR AlphaFoldDB; P70315; -.
DR BMRB; P70315; -.
DR SMR; P70315; -.
DR BioGRID; 204544; 10.
DR CORUM; P70315; -.
DR DIP; DIP-36426N; -.
DR IntAct; P70315; 29.
DR MINT; P70315; -.
DR STRING; 10090.ENSMUSP00000033505; -.
DR iPTMnet; P70315; -.
DR PhosphoSitePlus; P70315; -.
DR EPD; P70315; -.
DR jPOST; P70315; -.
DR PaxDb; P70315; -.
DR PeptideAtlas; P70315; -.
DR PRIDE; P70315; -.
DR ProteomicsDB; 297625; -.
DR Antibodypedia; 701; 517 antibodies from 43 providers.
DR DNASU; 22376; -.
DR Ensembl; ENSMUST00000033505; ENSMUSP00000033505; ENSMUSG00000031165.
DR GeneID; 22376; -.
DR KEGG; mmu:22376; -.
DR UCSC; uc009sns.2; mouse.
DR CTD; 7454; -.
DR MGI; MGI:105059; Was.
DR VEuPathDB; HostDB:ENSMUSG00000031165; -.
DR eggNOG; KOG3671; Eukaryota.
DR GeneTree; ENSGT00730000110895; -.
DR HOGENOM; CLU_015385_3_2_1; -.
DR InParanoid; P70315; -.
DR OMA; VGNTYWI; -.
DR OrthoDB; 1407277at2759; -.
DR PhylomeDB; P70315; -.
DR TreeFam; TF316736; -.
DR Reactome; R-MMU-202433; Generation of second messenger molecules.
DR Reactome; R-MMU-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-MMU-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013409; RHOJ GTPase cycle.
DR BioGRID-ORCS; 22376; 2 hits in 73 CRISPR screens.
DR PRO; PR:P70315; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; P70315; protein.
DR Bgee; ENSMUSG00000031165; Expressed in granulocyte and 97 other tissues.
DR ExpressionAtlas; P70315; baseline and differential.
DR Genevisible; P70315; MM.
DR GO; GO:0005884; C:actin filament; ISO:MGI.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0045335; C:phagocytic vesicle; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB.
DR GO; GO:0012506; C:vesicle membrane; IDA:MGI.
DR GO; GO:0003779; F:actin binding; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; IDA:MGI.
DR GO; GO:0043274; F:phospholipase binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0017124; F:SH3 domain binding; ISO:MGI.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0030041; P:actin filament polymerization; IDA:MGI.
DR GO; GO:0030048; P:actin filament-based movement; IDA:MGI.
DR GO; GO:0008154; P:actin polymerization or depolymerization; IDA:MGI.
DR GO; GO:0032488; P:Cdc42 protein signal transduction; ISO:MGI.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IDA:MGI.
DR GO; GO:0016197; P:endosomal transport; IDA:MGI.
DR GO; GO:0006955; P:immune response; ISO:MGI.
DR GO; GO:2000146; P:negative regulation of cell motility; ISO:MGI.
DR GO; GO:0051497; P:negative regulation of stress fiber assembly; ISO:MGI.
DR GO; GO:2000601; P:positive regulation of Arp2/3 complex-mediated actin nucleation; IEA:InterPro.
DR GO; GO:1905168; P:positive regulation of double-strand break repair via homologous recombination; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0008064; P:regulation of actin polymerization or depolymerization; ISO:MGI.
DR GO; GO:0010591; P:regulation of lamellipodium assembly; ISO:MGI.
DR GO; GO:0051492; P:regulation of stress fiber assembly; ISO:MGI.
DR GO; GO:0002625; P:regulation of T cell antigen processing and presentation; ISO:MGI.
DR GO; GO:0042110; P:T cell activation; IMP:MGI.
DR CDD; cd01205; EVH1_WASP-like; 1.
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; IPR011993; PH-like_dom_sf.
DR InterPro; IPR027641; WASP.
DR InterPro; IPR011026; WASP_C.
DR InterPro; IPR033927; WASPfam_EVH1.
DR InterPro; IPR000697; WH1/EVH1_dom.
DR InterPro; IPR003124; WH2_dom.
DR PANTHER; PTHR23202:SF79; PTHR23202:SF79; 2.
DR Pfam; PF00786; PBD; 1.
DR Pfam; PF00568; WH1; 1.
DR Pfam; PF02205; WH2; 1.
DR SMART; SM00285; PBD; 1.
DR SMART; SM00461; WH1; 1.
DR SMART; SM00246; WH2; 1.
DR SUPFAM; SSF47912; SSF47912; 2.
DR PROSITE; PS50108; CRIB; 1.
DR PROSITE; PS50229; WH1; 1.
DR PROSITE; PS51082; WH2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Cytoskeleton; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat.
FT CHAIN 1..520
FT /note="Actin nucleation-promoting factor WAS"
FT /id="PRO_0000188991"
FT DOMAIN 41..150
FT /note="WH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00410"
FT DOMAIN 240..253
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT REPEAT 354..363
FT /note="GRSGPLPPXP motif 1"
FT REPEAT 393..402
FT /note="GRSGPLPPXP motif 2"
FT DOMAIN 448..465
FT /note="WH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00406"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 148..247
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 307..520
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 160..187
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 361..441
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 458..481
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 506..520
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 293
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660,
FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT MOD_RES 501
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 502
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
SQ SEQUENCE 520 AA; 54192 MW; 9C223733C59F0C8A CRC64;
MNSGPGPVGG RPGGRGGPAV QQNIPSNLLQ DHENQRLFEL LGRKCWTLAT TVVQLYLALP
PGAEHWTMEH CGAVCFVKDN PQKSYFIRLY GLQAGRLLWE QELYSQLVYL TPTPFFHTFA
GDDCQVGLNF ADESEAQAFR ALVQEKIQKR NQRQSGERRQ LPPPPAPINE ERRGGLPPVP
PHPGGDHGGP SGGPLSLGLV TVDIQNPDIT SSRYRGLPAP GPGPTDKKRS GKKKISKADI
GAPSGFKHVS HVGWDPQNGF DVNNLDPDLR SLFSRAGISE AQLTDAETSK LIYDFIEDQG
GLEAVRQEMR RQEPLPPPPP PCRGGGGGGG GGGGGGGGGG GQPLRPPVVG SNKGRSGPLP
PVPMGGAPPP PTPRGPPPPG RGGPPPPPPP ATGRSGPPPP PLPGAGGPPA PPPPPPPPPP
PPCPGSGPAP PPLPPTPVSG GSPAPGGGRG ALLDQIRQGI QLNKTPGALE NSVQQPPAQQ
SEGLVGALMH VMQKRSRVIH SSDEGEDQTG EDEEDDEWDD
