WASH2_HUMAN
ID WASH2_HUMAN Reviewed; 465 AA.
AC Q6VEQ5;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 19-JAN-2010, sequence version 2.
DT 25-MAY-2022, entry version 108.
DE RecName: Full=WAS protein family homolog 2;
DE AltName: Full=CXYorf1-like protein on chromosome 2;
DE AltName: Full=Protein FAM39B;
GN Name=WASH2P; Synonyms=FAM39B;
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=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 202-465, AND GENE DUPLICATION.
RX PubMed=15233989; DOI=10.1016/j.ygeno.2004.03.001;
RA Wong A., Vallender E.J., Heretis K., Ilkin Y., Lahn B.T., Lese Martin C.,
RA Ledbetter D.H.;
RT "Diverse fates of paralogs following segmental duplication of telomeric
RT genes.";
RL Genomics 84:239-247(2004).
RN [3]
RP GENE DUPLICATION.
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).
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. Involved in
CC endocytic trafficking of EGF. Involved in transferrin receptor
CC recycling. Regulates the trafficking of endosomal alpha5beta1 integrin
CC to the plasma membrane and involved in invasive cell migration. In T-
CC cells involved in endosome-to-membrane recycling of receptors including
CC T-cell receptor (TCR), CD28 and ITGAL; proposed to be implicated in T-
CC cell proliferation and effector function. In dendritic cells involved
CC in endosome-to-membrane recycling of major histocompatibility complex
CC (MHC) class II probably involving retromer and subsequently allowing
CC antigen sampling, loading and presentation during T-cell activation.
CC Involved in Arp2/3 complex-dependent actin assembly driving Salmonella
CC typhimurium invasion independent of ruffling. Involved in the
CC exocytosis of MMP14 leading to matrix remodeling during invasive
CC migration and implicating late endosome-to-plasma membrane tubular
CC connections and cooperation with the exocyst complex. Involved in
CC negative regulation of autophagy independently from its role in
CC endosomal sorting by inhibiting BECN1 ubiquitination to inactivate
CC PIK3C3/Vps34 activity (By similarity). {ECO:0000250|UniProtKB:A8K0Z3,
CC ECO:0000250|UniProtKB:C4AMC7, ECO:0000250|UniProtKB:Q8VDD8}.
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. Interacts (via
CC WHD1 region) with WASHC2C; the interaction is direct. Interacts with
CC alpha-tubulin. Interacts with BECN1; WASHC1 and AMBRA1 can
CC competitively interact with BECN1. Interacts with BLOC1S2; may
CC associate with the BLOC-1 complex. Interacts with tubulin gamma chain
CC (TUBG1 or TUBG2). Interacts with EXOC1, EXOC4, EXOC8; in MMP14-positive
CC endosomes in breast tumor cells; indicative for an association with the
CC exocyst complex (By similarity). {ECO:0000250|UniProtKB:A8K0Z3,
CC ECO:0000250|UniProtKB:C4AMC7, ECO:0000250|UniProtKB:Q8VDD8}.
CC -!- SUBCELLULAR LOCATION: Early endosome membrane
CC {ECO:0000250|UniProtKB:A8K0Z3}. Recycling endosome membrane
CC {ECO:0000250|UniProtKB:Q8VDD8}. Late endosome
CC {ECO:0000250|UniProtKB:A8K0Z3}. 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.
CC {ECO:0000250|UniProtKB:A8K0Z3}.
CC -!- DOMAIN: The VCA (verprolin, cofilin, acidic) domain promotes actin
CC polymerization by the Arp2/3 complex in vitro.
CC {ECO:0000250|UniProtKB:C4AMC7}.
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AL078621; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; AL078621; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AY341936; AAQ76875.1; -; mRNA.
DR AlphaFoldDB; Q6VEQ5; -.
DR SMR; Q6VEQ5; -.
DR ComplexPortal; CPX-1168; WASH complex, variant WASH2P/WASHC2C.
DR ComplexPortal; CPX-1173; WASH complex, variant WASH2P/WASHC2A.
DR IntAct; Q6VEQ5; 8.
DR MINT; Q6VEQ5; -.
DR STRING; 9606.ENSP00000485442; -.
DR iPTMnet; Q6VEQ5; -.
DR PhosphoSitePlus; Q6VEQ5; -.
DR BioMuta; HGNC:33145; -.
DR DMDM; 284018148; -.
DR EPD; Q6VEQ5; -.
DR jPOST; Q6VEQ5; -.
DR MassIVE; Q6VEQ5; -.
DR MaxQB; Q6VEQ5; -.
DR PaxDb; Q6VEQ5; -.
DR PeptideAtlas; Q6VEQ5; -.
DR PRIDE; Q6VEQ5; -.
DR GeneCards; WASH2P; -.
DR HGNC; HGNC:33145; WASH2P.
DR neXtProt; NX_Q6VEQ5; -.
DR eggNOG; KOG1366; Eukaryota.
DR InParanoid; Q6VEQ5; -.
DR PhylomeDB; Q6VEQ5; -.
DR PathwayCommons; Q6VEQ5; -.
DR SignaLink; Q6VEQ5; -.
DR ChiTaRS; WASH2P; human.
DR Pharos; Q6VEQ5; Tdark.
DR PRO; PR:Q6VEQ5; -.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; Q6VEQ5; 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; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IC:ComplexPortal.
DR GO; GO:0005770; C:late endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0055037; C:recycling endosome; ISS: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; ISS:UniProtKB.
DR GO; GO:0032456; P:endocytic recycling; IBA:GO_Central.
DR GO; GO:0016197; P:endosomal transport; ISS:UniProtKB.
DR GO; GO:0006887; P:exocytosis; IBA:GO_Central.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
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 2: Evidence at transcript level;
KW Actin-binding; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton; Endosome;
KW Isopeptide bond; Membrane; Protein transport; Reference proteome;
KW Transport; Ubl conjugation.
FT CHAIN 1..465
FT /note="WAS protein family homolog 2"
FT /id="PRO_0000257971"
FT DOMAIN 361..383
FT /note="WH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00406"
FT REGION 1..167
FT /note="WHD1"
FT REGION 1..54
FT /note="Required for WASH complex assembly"
FT /evidence="ECO:0000250|UniProtKB:C4AMC7"
FT REGION 297..407
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 349..465
FT /note="VCA"
FT /evidence="ECO:0000250|UniProtKB:C4AMC7"
FT REGION 422..465
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 300..328
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 333..349
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 379..398
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 220
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:A8K0Z3"
SQ SEQUENCE 465 AA; 50312 MW; 54FD1BB405E391DF CRC64;
MTPVRMQHSL AGQTYAVPLI QPDLRREEAV QQMADALQYL QKVSGDIFSR ISQQVEQSRS
QVQAIGEKVS LAQAKIEKIK GSKKAIKVFS SAKYPAPERL QEYGSIFTGA QDPGLQRRPR
HRIQSKHRPL DERALQEKLK DFPVCVSTKP EPEDDAEEGL GGLPSNISSV SSLLLFNTTE
NLYKKYVFLD PLAGAVTKTH VMLGAETEEK LFDAPLSISK REQLEQQVPE NYFYVPDLGQ
VPEIDVPSYL PDLPGIANDL MYIADLGPGI APSAPGTIPE LPTFHTEVAE PLKVDLQDGV
LTPPPPPPPP PPAPEVLASA PPLPPSTAAP VGQGARQDDS SSSASPSVQG APREVVDPSG
GRATLLESIR QAGGIGKAKL RSMKERKLEK KKQKEQEQVR ATSQGGHLMS DLFNKLVMRR
KGISGKGPGA GEGPGGAFAR VSDSIPPLPP PQQPQAEEDE DDWES
