{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"C4AMC7","uniProtkbId":"WASH3_HUMAN","entryAudit":{"firstPublicDate":"2010-01-19","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2009-11-03","entryVersion":85,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Putative WAS protein family homolog 3"}},"alternativeNames":[{"fullName":{"value":"Protein FAM39DP"}}]},"genes":[{"geneName":{"value":"WASH3P"},"synonyms":[{"value":"FAM39DP"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"A8K0Z3"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8VDD8"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18159949"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20175130"}],"value":"Acts as a nucleation-promoting factor at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerization, playing a key role in the fission of tubules that serve as transport intermediates during endosome sorting (PubMed:18159949, PubMed:20175130). Involved in endocytic trafficking of EGF (PubMed:20175130). Involved in transferrin receptor recycling. Regulates the trafficking of endosomal alpha5beta1 integrin to the plasma membrane and involved in invasive cell migration (By similarity). In T-cells involved in endosome-to-membrane recycling of receptors including T-cell receptor (TCR), CD28 and ITGAL; proposed to be implicated in T cell proliferation and effector function. In dendritic cells involved in endosome-to-membrane recycling of major histocompatibility complex (MHC) class II probably involving retromer and subsequently allowing antigen sampling, loading and presentation during T-cell activation. Involved in Arp2/3 complex-dependent actin assembly driving Salmonella typhimurium invasion independent of ruffling (By similarity). Involved in the exocytosis of MMP14 leading to matrix remodeling during invasive migration and implicating late endosome-to-plasma membrane tubular connections and cooperation with the exocyst complex (By similarity). Involved in negative regulation of autophagy independently from its role in endosomal sorting by inhibiting BECN1 ubiquitination to inactivate PIK3C3/Vps34 activity (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"A8K0Z3"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8VDD8"}],"value":"Component of the WASH core complex also described as WASH regulatory complex (SHRC) composed of WASH (WASHC1, WASH2P or WASH3P), WASHC2 (WASHC2A or WASHC2C), WASHC3, WASHC4 and WASHC5. The WASH core complex associates with the F-actin-capping protein dimer (formed by CAPZA1, CAPZA2 or CAPZA3 and CAPZB) in a transient or substoichiometric manner which was initially described as WASH complex (PubMed:20498093). Interacts (via WHD1 region) with WASHC2C; the interaction is direct (By similarity). Interacts with alpha-tubulin. Interacts with BECN1; WASHC1 and AMBRA1 can competitively interact with BECN1. Interacts with BLOC1S2; may associate with the BLOC-1 complex. Interacts with tubulin gamma chain (TUBG1 or TUBG2). Interacts with EXOC1, EXOC4, EXOC8; in MMP14-positive endosomes in breast tumor cells; indicative for an association with the exocyst complex (By similarity)"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"A8K0Z3"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8VDD8"}],"value":"Localization to the endosome membrane is mediated via its interaction with WASHC2. Localizes to MMP14-positive late endosomes and transiently to invadipodia (By similarity). Localized to Salmonella typhimurium entry sites (By similarity)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20175130"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20498093"}],"value":"Early endosome","id":"SL-0094"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"A8K0Z3"}],"value":"Early endosome membrane","id":"SL-0093"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8VDD8"}],"value":"Recycling endosome membrane","id":"SL-0231"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18159949"}],"value":"Cell projection, lamellipodium","id":"SL-0291"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18159949"}],"value":"Cell projection, filopodium","id":"SL-0286"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8VDD8"}],"value":"Cytoplasmic vesicle, autophagosome","id":"SL-0023"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8VDD8"}],"value":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole","id":"SL-0046"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18159949"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20175130"}],"value":"The VCA (verprolin, cofilin, acidic) domain promotes actin polymerization by the Arp2/3 complex in vitro"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"18159949"}],"value":"WASH genes duplicated to multiple chromosomal ends during primate evolution, with highest copy number reached in humans, whose WASH repertoires probably vary extensively among individuals (PubMed:18159949). It is therefore difficult to determine which gene is functional or not. The telomeric region of chromosome 9p is paralogous to the pericentromeric regions of chromosome 9 as well as to 2q. Paralogous regions contain 7 transcriptional units. Duplicated WASH genes are also present in the Xq/Yq pseudoautosomal region, as well as on chromosome 1 and 15. The chromosome 16 copy seems to be a pseudogene"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the WASH1 family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":463,"modifier":"EXACT"}},"description":"Putative WAS protein family homolog 3","featureId":"PRO_0000390962"},{"type":"Domain","location":{"start":{"value":359,"modifier":"EXACT"},"end":{"value":381,"modifier":"EXACT"}},"description":"WH2","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00406"}]},{"type":"Region","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":165,"modifier":"EXACT"}},"description":"WHD1"},{"type":"Region","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":54,"modifier":"EXACT"}},"description":"Required for WASH complex assembly","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20498093"}]},{"type":"Region","location":{"start":{"value":295,"modifier":"EXACT"},"end":{"value":463,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":347,"modifier":"EXACT"},"end":{"value":463,"modifier":"EXACT"}},"description":"VCA","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20498093"}]},{"type":"Compositional bias","location":{"start":{"value":300,"modifier":"EXACT"},"end":{"value":312,"modifier":"EXACT"}},"description":"Pro residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":380,"modifier":"EXACT"},"end":{"value":396,"modifier":"EXACT"}},"description":"Basic and acidic residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":422,"modifier":"EXACT"},"end":{"value":434,"modifier":"EXACT"}},"description":"Gly residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":454,"modifier":"EXACT"},"end":{"value":463,"modifier":"EXACT"}},"description":"Acidic residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Cross-link","location":{"start":{"value":218,"modifier":"EXACT"},"end":{"value":218,"modifier":"EXACT"}},"description":"Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"A8K0Z3"}]},{"type":"Mutagenesis","location":{"start":{"value":461,"modifier":"EXACT"},"end":{"value":461,"modifier":"EXACT"}},"description":"No effect on WASH complex assembly.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20498093"}],"alternativeSequence":{"originalSequence":"W","alternativeSequences":["A"]}},{"type":"Sequence conflict","location":{"start":{"value":54,"modifier":"EXACT"},"end":{"value":54,"modifier":"EXACT"}},"description":"in Ref. 2; 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