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   27-MAR-2024, entry version 190.
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; 10090-ENSMUSP00000033505; -.
DR   PeptideAtlas; P70315; -.
DR   ProteomicsDB; 297625; -.
DR   Antibodypedia; 701; 565 antibodies from 43 providers.
DR   DNASU; 22376; -.
DR   Ensembl; ENSMUST00000033505.7; ENSMUSP00000033505.7; ENSMUSG00000031165.7.
DR   GeneID; 22376; -.
DR   KEGG; mmu:22376; -.
DR   UCSC; uc009sns.2; mouse.
DR   AGR; MGI:105059; -.
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; WIKMVDI; -.
DR   OrthoDB; 3837860at2759; -.
DR   PhylomeDB; P70315; -.
DR   TreeFam; TF316736; -.
DR   BioGRID-ORCS; 22376; 2 hits in 78 CRISPR screens.
DR   PRO; PR:P70315; -.
DR   Proteomes; UP000000589; Chromosome X.
DR   RNAct; P70315; Protein.
DR   Bgee; ENSMUSG00000031165; Expressed in granulocyte and 99 other cell types or tissues.
DR   ExpressionAtlas; P70315; baseline and differential.
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 type II interferon; 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: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; cd00132; CRIB; 1.
DR   CDD; cd01205; EVH1_WASP-like; 1.
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   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; 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; 1.
DR   Genevisible; P70315; MM.
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
//