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   24-JAN-2024, entry version 113.
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; 7.
DR   MINT; Q6VEQ5; -.
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; 9606-ENSP00000485442; -.
DR   PeptideAtlas; Q6VEQ5; -.
DR   Pumba; Q6VEQ5; -.
DR   AGR; HGNC:33145; -.
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; NAS: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; NAS: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; CXYORF1; 1.
DR   PANTHER; PTHR23331:SF5; WAS PROTEIN FAMILY HOMOLOG 2-RELATED; 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
//