WASH3_HUMAN
ID WASH3_HUMAN Reviewed; 463 AA.
AC C4AMC7;
DT 19-JAN-2010, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 2.
DT 25-MAY-2022, entry version 72.
DE RecName: Full=Putative WAS protein family homolog 3;
DE AltName: Full=Protein FAM39DP;
GN Name=WASH3P; Synonyms=FAM39DP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP GENE DUPLICATION, FUNCTION, DOMAIN, AND SUBCELLULAR LOCATION.
RX PubMed=10655549; DOI=10.1093/hmg/9.3.395;
RA Ciccodicola A., D'Esposito M., Esposito T., Gianfrancesco F.,
RA Migliaccio C., Miano M.G., Matarazzo M.R., Vacca M., Franze A.,
RA Cuccurese M., Cocchia M., Curci A., Terracciano A., Torino A., Cocchia S.,
RA Mercadante G., Pannone E., Archidiacono N., Rocchi M., Schlessinger D.,
RA D'Urso M.;
RT "Differentially regulated and evolved genes in the fully sequenced Xq/Yq
RT pseudoautosomal region.";
RL Hum. Mol. Genet. 9:395-401(2000).
RN [4]
RP GENE DUPLICATION.
RX PubMed=18159949; DOI=10.1371/journal.pgen.0030237;
RA Linardopoulou E.V., Parghi S.S., Friedman C., Osborn G.E., Parkhurst S.M.,
RA Trask B.J.;
RT "Human subtelomeric WASH genes encode a new subclass of the WASP family.";
RL PLoS Genet. 3:E237-E237(2007).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20175130; DOI=10.1002/cm.20437;
RA Duleh S.N., Welch M.D.;
RT "WASH and the Arp2/3 complex regulate endosome shape and trafficking.";
RL Cytoskeleton 67:193-206(2010).
RN [6]
RP SUBUNIT, FUNCTION OF THE WASH CORE COMPLEX, MUTAGENESIS OF TRP-461, AND
RP SUBCELLULAR LOCATION.
RX PubMed=20498093; DOI=10.1073/pnas.0913293107;
RA Jia D., Gomez T.S., Metlagel Z., Umetani J., Otwinowski Z., Rosen M.K.,
RA Billadeau D.D.;
RT "WASH and WAVE actin regulators of the Wiskott-Aldrich syndrome protein
RT (WASP) family are controlled by analogous structurally related complexes.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:10442-10447(2010).
CC -!- FUNCTION: Acts as a nucleation-promoting factor at the surface of
CC endosomes, where it recruits and activates the Arp2/3 complex to induce
CC actin polymerization, playing a key role in the fission of tubules that
CC serve as transport intermediates during endosome sorting
CC (PubMed:18159949, PubMed:20175130). Involved in endocytic trafficking
CC of EGF (PubMed:20175130). Involved in transferrin receptor recycling.
CC Regulates the trafficking of endosomal alpha5beta1 integrin to the
CC plasma membrane and involved in invasive cell migration (By
CC similarity). In T-cells involved in endosome-to-membrane recycling of
CC receptors including T-cell receptor (TCR), CD28 and ITGAL; proposed to
CC be implicated in T cell proliferation and effector function. In
CC dendritic cells involved in endosome-to-membrane recycling of major
CC histocompatibility complex (MHC) class II probably involving retromer
CC and subsequently allowing antigen sampling, loading and presentation
CC during T-cell activation. Involved in Arp2/3 complex-dependent actin
CC assembly driving Salmonella typhimurium invasion independent of
CC ruffling (By similarity). Involved in the exocytosis of MMP14 leading
CC to matrix remodeling during invasive migration and implicating late
CC endosome-to-plasma membrane tubular connections and cooperation with
CC the exocyst complex (By similarity). Involved in negative regulation of
CC autophagy independently from its role in endosomal sorting by
CC inhibiting BECN1 ubiquitination to inactivate PIK3C3/Vps34 activity (By
CC similarity). {ECO:0000250|UniProtKB:A8K0Z3,
CC ECO:0000250|UniProtKB:Q8VDD8, ECO:0000269|PubMed:18159949,
CC ECO:0000269|PubMed:20175130}.
CC -!- SUBUNIT: Component of the WASH core complex also described as WASH
CC regulatory complex (SHRC) composed of WASH (WASHC1, WASH2P or WASH3P),
CC WASHC2 (WASHC2A or WASHC2C), WASHC3, WASHC4 and WASHC5. The WASH core
CC complex associates with the F-actin-capping protein dimer (formed by
CC CAPZA1, CAPZA2 or CAPZA3 and CAPZB) in a transient or substoichiometric
CC manner which was initially described as WASH complex (PubMed:20498093).
CC Interacts (via WHD1 region) with WASHC2C; the interaction is direct (By
CC similarity). Interacts with alpha-tubulin. Interacts with BECN1; WASHC1
CC and AMBRA1 can competitively interact with BECN1. Interacts with
CC BLOC1S2; may associate with the BLOC-1 complex. Interacts with tubulin
CC gamma chain (TUBG1 or TUBG2). Interacts with EXOC1, EXOC4, EXOC8; in
CC MMP14-positive endosomes in breast tumor cells; indicative for an
CC association with the exocyst complex (By similarity).
CC {ECO:0000250|UniProtKB:A8K0Z3, ECO:0000250|UniProtKB:Q8VDD8}.
CC -!- SUBCELLULAR LOCATION: Early endosome {ECO:0000269|PubMed:20175130,
CC ECO:0000269|PubMed:20498093}. Early endosome membrane
CC {ECO:0000250|UniProtKB:A8K0Z3}. Recycling endosome membrane
CC {ECO:0000250|UniProtKB:Q8VDD8}. Cell projection, lamellipodium
CC {ECO:0000269|PubMed:18159949}. Cell projection, filopodium
CC {ECO:0000269|PubMed:18159949}. Cytoplasmic vesicle, autophagosome
CC {ECO:0000250|UniProtKB:Q8VDD8}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome, centriole
CC {ECO:0000250|UniProtKB:Q8VDD8}. Note=Localization to the endosome
CC membrane is mediated via its interaction with WASHC2. Localizes to
CC MMP14-positive late endosomes and transiently to invadipodia (By
CC similarity). Localized to Salmonella typhimurium entry sites (By
CC similarity). {ECO:0000250|UniProtKB:A8K0Z3,
CC ECO:0000250|UniProtKB:Q8VDD8}.
CC -!- DOMAIN: The VCA (verprolin, cofilin, acidic) domain promotes actin
CC polymerization by the Arp2/3 complex in vitro.
CC {ECO:0000269|PubMed:18159949, ECO:0000269|PubMed:20175130}.
CC -!- MISCELLANEOUS: WASH genes duplicated to multiple chromosomal ends
CC during primate evolution, with highest copy number reached in humans,
CC whose WASH repertoires probably vary extensively among individuals
CC (PubMed:18159949). It is therefore difficult to determine which gene is
CC functional or not. The telomeric region of chromosome 9p is paralogous
CC to the pericentromeric regions of chromosome 9 as well as to 2q.
CC Paralogous regions contain 7 transcriptional units. Duplicated WASH
CC genes are also present in the Xq/Yq pseudoautosomal region, as well as
CC on chromosome 1 and 15. The chromosome 16 copy seems to be a
CC pseudogene. {ECO:0000305|PubMed:18159949}.
CC -!- SIMILARITY: Belongs to the WASH1 family. {ECO:0000305}.
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DR EMBL; AC140725; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC048328; -; NOT_ANNOTATED_CDS; mRNA.
DR AlphaFoldDB; C4AMC7; -.
DR SMR; C4AMC7; -.
DR ComplexPortal; CPX-1169; WASH complex, variant WASH3P/WASHC2C.
DR ComplexPortal; CPX-1174; WASH complex, variant WASH3P/WASHC2A.
DR IntAct; C4AMC7; 7.
DR BioMuta; HGNC:24362; -.
DR EPD; C4AMC7; -.
DR jPOST; C4AMC7; -.
DR MassIVE; C4AMC7; -.
DR MaxQB; C4AMC7; -.
DR PeptideAtlas; C4AMC7; -.
DR PRIDE; C4AMC7; -.
DR ProteomicsDB; 7594; -.
DR GeneCards; WASH3P; -.
DR HGNC; HGNC:24362; WASH3P.
DR neXtProt; NX_C4AMC7; -.
DR InParanoid; C4AMC7; -.
DR PathwayCommons; C4AMC7; -.
DR SignaLink; C4AMC7; -.
DR ChiTaRS; WASH3P; human.
DR Pharos; C4AMC7; Tbio.
DR PRO; PR:C4AMC7; -.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; C4AMC7; protein.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005814; C:centriole; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IC:ComplexPortal.
DR GO; GO:0030175; C:filopodium; IDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0071203; C:WASH complex; ISS:UniProtKB.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0043014; F:alpha-tubulin binding; ISS:UniProtKB.
DR GO; GO:0043015; F:gamma-tubulin binding; IBA:GO_Central.
DR GO; GO:0034314; P:Arp2/3 complex-mediated actin nucleation; IDA:UniProtKB.
DR GO; GO:0045022; P:early endosome to late endosome transport; IMP:UniProtKB.
DR GO; GO:0032456; P:endocytic recycling; IBA:GO_Central.
DR GO; GO:0016197; P:endosomal transport; ISS:UniProtKB.
DR GO; GO:0007032; P:endosome organization; IMP:UniProtKB.
DR GO; GO:0006887; P:exocytosis; IBA:GO_Central.
DR GO; GO:0006622; P:protein targeting to lysosome; IMP:UniProtKB.
DR GO; GO:0034315; P:regulation of Arp2/3 complex-mediated actin nucleation; IC:ComplexPortal.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; ISS:UniProtKB.
DR InterPro; IPR028290; WASH1.
DR InterPro; IPR021854; WASH1_WAHD.
DR InterPro; IPR003124; WH2_dom.
DR PANTHER; PTHR23331; PTHR23331; 1.
DR Pfam; PF11945; WASH_WAHD; 1.
DR PROSITE; PS51082; WH2; 1.
PE 1: Evidence at protein level;
KW Actin-binding; Cell projection; Cytoplasm; Cytoplasmic vesicle;
KW Cytoskeleton; Endosome; Isopeptide bond; Membrane; Reference proteome;
KW Transport; Ubl conjugation.
FT CHAIN 1..463
FT /note="Putative WAS protein family homolog 3"
FT /id="PRO_0000390962"
FT DOMAIN 359..381
FT /note="WH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00406"
FT REGION 1..165
FT /note="WHD1"
FT REGION 1..54
FT /note="Required for WASH complex assembly"
FT /evidence="ECO:0000269|PubMed:20498093"
FT REGION 295..463
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 347..463
FT /note="VCA"
FT /evidence="ECO:0000269|PubMed:20498093"
FT COMPBIAS 298..326
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 331..347
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 377..395
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 218
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:A8K0Z3"
FT MUTAGEN 461
FT /note="W->A: No effect on WASH complex assembly."
FT /evidence="ECO:0000269|PubMed:20498093"
FT CONFLICT 54
FT /note="Q -> R (in Ref. 2; BC048328)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="P -> S (in Ref. 2; BC048328)"
FT /evidence="ECO:0000305"
FT CONFLICT 139
FT /note="D -> LKY (in Ref. 2; BC048328)"
FT /evidence="ECO:0000305"
FT CONFLICT 181
FT /note="G -> Y (in Ref. 2; BC048328)"
FT /evidence="ECO:0000305"
FT CONFLICT 255
FT /note="T -> A (in Ref. 2; BC048328)"
FT /evidence="ECO:0000305"
FT CONFLICT 261
FT /note="I -> S (in Ref. 2; BC048328)"
FT /evidence="ECO:0000305"
FT CONFLICT 292
FT /note="V -> A (in Ref. 2; BC048328)"
FT /evidence="ECO:0000305"
FT CONFLICT 300
FT /note="T -> TAPP (in Ref. 2; BC048328)"
FT /evidence="ECO:0000305"
FT CONFLICT 319
FT /note="P -> S (in Ref. 2; BC048328)"
FT /evidence="ECO:0000305"
FT CONFLICT 381
FT /note="M -> V (in Ref. 2; BC048328)"
FT /evidence="ECO:0000305"
FT CONFLICT 390
FT /note="Q -> K (in Ref. 2; BC048328)"
FT /evidence="ECO:0000305"
FT CONFLICT 405
FT /note="H -> D (in Ref. 2; BC048328)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 463 AA; 49995 MW; FD6B57565AFDAB82 CRC64;
MTPVRMQHSL AGQTYAVPLI QPDLRREEAV QQMADALQYL QKVSGDIFSR ISQQVEQSRS
QVQAIGEKVS LAQAKIEKIK GSKKAIKVFS SAKYPAPERL QEYGSIFTGA QDPGLQRRPR
HRIQSKHRPL DERALQEKDF PVCVSTKPEP EDDAEEGLGG LPSNISSVSS LLLFNTTENL
GKKYVFLDPL AGAVTKTHVM LGAETEEKLF DAPLSISKRE QLEQQVPENY FYVPDLGQVP
EIDVPSYLPD LPGITNDLMY IADLGPGIAP SAPGTIPELP TFHTEVAEPL KVDLQDGVLT
PPPPPPPPPP APEVLASAPP LPPSTAAPVG QGARQDDSSS SASPSVQGAP REVVDPSGGR
ATLLESIRQA GGIGKAKLRS MKERKLEKKQ QKEQEQVRAT SQGGHLMSDL FNKLVMRRKG
ISGKGPGAGE GPGGAFARVS DSIPPLPPPQ QPQAEEDEDD WES
