ID WAC2C_HUMAN Reviewed; 1341 AA. AC Q9Y4E1; A0A096LPC5; B4DZQ6; B9EK53; F5H0J6; F5H871; Q5SQU4; Q5SQU5; Q7L521; AC Q9UG79; DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot. DT 03-MAY-2023, sequence version 5. DT 27-MAR-2024, entry version 164. DE RecName: Full=WASH complex subunit 2C {ECO:0000312|HGNC:HGNC:23414}; DE AltName: Full=Vaccinia virus penetration factor {ECO:0000303|PubMed:18550675}; DE Short=VPEF {ECO:0000303|PubMed:18550675}; GN Name=WASHC2C {ECO:0000312|HGNC:HGNC:23414}; GN Synonyms=FAM21C, KIAA0592, VPEF {ECO:0000303|PubMed:18550675}; 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 MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=9628581; DOI=10.1093/dnares/5.1.31; RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., RA Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. IX. The RT complete sequences of 100 new cDNA clones from brain which can code for RT large proteins in vitro."; RL DNA Res. 5:31-39(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6). RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 1007-1341. RC TISSUE=Lung, and Testis; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1037-1341. RC TISSUE=Kidney; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] RP SUBCELLULAR LOCATION, AND FUNCTION (MICROBIAL INFECTION). RX PubMed=18550675; DOI=10.1128/jvi.00894-08; RA Huang C.Y., Lu T.Y., Bair C.H., Chang Y.S., Jwo J.K., Chang W.; RT "A novel cellular protein, VPEF, facilitates vaccinia virus penetration RT into HeLa cells through fluid phase endocytosis."; RL J. Virol. 82:7988-7999(2008). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-539, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [8] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH WASHC1, AND MISCELLANEOUS. RX PubMed=19922874; DOI=10.1016/j.devcel.2009.09.009; RA Gomez T.S., Billadeau D.D.; RT "A FAM21-containing WASH complex regulates retromer-dependent sorting."; RL Dev. Cell 17:699-711(2009). RN [9] RP FUNCTION OF THE WASH COMPLEX, AND IDENTIFICATION IN THE WASH COMPLEX. RX PubMed=19922875; DOI=10.1016/j.devcel.2009.09.010; RA Derivery E., Sousa C., Gautier J.J., Lombard B., Loew D., Gautreau A.; RT "The Arp2/3 activator WASH controls the fission of endosomes through a RT large multiprotein complex."; RL Dev. Cell 17:712-723(2009). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-539, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [11] RP FUNCTION, IDENTIFICATION IN THE WASH CORE COMPLEX, SUBUNIT, FUNCTION OF THE RP WASH CORE COMPLEX, MUTAGENESIS OF ARG-1031, PHOSPHOLIPID-BINDING, 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). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-539, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-539 AND SER-909, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [15] RP INTERACTION WITH VPS35 AND FKBP15. RX PubMed=22070227; DOI=10.1042/bj20111761; RA Harbour M.E., Breusegem S.Y., Seaman M.N.; RT "Recruitment of the endosomal WASH complex is mediated by the extended RT 'tail' of Fam21 binding to the retromer protein Vps35."; RL Biochem. J. 442:209-220(2012). RN [16] RP FUNCTION, AND DOMAIN. RX PubMed=22513087; DOI=10.1091/mbc.e11-12-1059; RA Jia D., Gomez T.S., Billadeau D.D., Rosen M.K.; RT "Multiple repeat elements within the FAM21 tail link the WASH actin RT regulatory complex to the retromer."; RL Mol. Biol. Cell 23:2352-2361(2012). RN [17] RP FUNCTION, INTERACTION WITH VPS35, AND MUTAGENESIS OF PHE-1299; PHE-1331 AND RP ASP-1333. RX PubMed=23331060; DOI=10.1111/boc.201200038; RA Helfer E., Harbour M.E., Henriot V., Lakisic G., Sousa-Blin C., RA Volceanov L., Seaman M.N., Gautreau A.; RT "Endosomal recruitment of the WASH complex: active sequences and mutations RT impairing interaction with the retromer."; RL Biol. Cell 105:191-207(2013). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-539, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [19] RP FUNCTION, AND INTERACTION WITH VPS35. RX PubMed=24980502; DOI=10.1016/j.cub.2014.06.024; RA McGough I.J., Steinberg F., Jia D., Barbuti P.A., McMillan K.J., RA Heesom K.J., Whone A.L., Caldwell M.A., Billadeau D.D., Rosen M.K., RA Cullen P.J.; RT "Retromer binding to FAM21 and the WASH complex is perturbed by the RT Parkinson disease-linked VPS35(D620N) mutation."; RL Curr. Biol. 24:1670-1676(2014). RN [20] RP FUNCTION, AND INTERACTION WITH VPS35. RX PubMed=25278552; DOI=10.1242/jcs.156299; RA McGough I.J., Steinberg F., Gallon M., Yatsu A., Ohbayashi N., Heesom K.J., RA Fukuda M., Cullen P.J.; RT "Identification of molecular heterogeneity in SNX27-retromer-mediated RT endosome-to-plasma-membrane recycling."; RL J. Cell Sci. 127:4940-4953(2014). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-550, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [22] RP FUNCTION, AND INTERACTION WITH CCDC93; CCDC22 AND VPS35L. RX PubMed=25355947; DOI=10.1091/mbc.e14-06-1073; RA Phillips-Krawczak C.A., Singla A., Starokadomskyy P., Deng Z., RA Osborne D.G., Li H., Dick C.J., Gomez T.S., Koenecke M., Zhang J.S., RA Dai H., Sifuentes-Dominguez L.F., Geng L.N., Kaufmann S.H., Hein M.Y., RA Wallis M., McGaughran J., Gecz J., van de Sluis B., Billadeau D.D., RA Burstein E.; RT "COMMD1 is linked to the WASH complex and regulates endosomal trafficking RT of the copper transporter ATP7A."; RL Mol. Biol. Cell 26:91-103(2015). RN [23] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=28892079; DOI=10.1038/ncb3610; RA McNally K.E., Faulkner R., Steinberg F., Gallon M., Ghai R., Pim D., RA Langton P., Pearson N., Danson C.M., Naegele H., Morris L.L., Singla A., RA Overlee B.L., Heesom K.J., Sessions R., Banks L., Collins B.M., Berger I., RA Billadeau D.D., Burstein E., Cullen P.J.; RT "Retriever is a multiprotein complex for retromer-independent endosomal RT cargo recycling."; RL Nat. Cell Biol. 19:1214-1225(2017). RN [24] RP PROBABLE INTERACTION WITH TBC1D23. RX PubMed=29084197; DOI=10.1038/ncb3627; RA Shin J.J.H., Gillingham A.K., Begum F., Chadwick J., Munro S.; RT "TBC1D23 is a bridging factor for endosomal vesicle capture by golgins at RT the trans-Golgi."; RL Nat. Cell Biol. 19:1424-1432(2017). CC -!- FUNCTION: Acts as a component of the WASH core complex that functions CC as a nucleation-promoting factor (NPF) at the surface of endosomes, CC where it recruits and activates the Arp2/3 complex to induce actin CC polymerization, playing a key role in the fission of tubules that serve CC as transport intermediates during endosome sorting. Mediates the CC recruitment of the WASH core complex to endosome membranes via binding CC to phospholipids and VPS35 of the retromer CSC. Mediates the CC recruitment of the F-actin-capping protein dimer to the WASH core CC complex probably promoting localized F-actin polymerization needed for CC vesicle scission (PubMed:19922874, PubMed:20498093, PubMed:22513087, CC PubMed:23331060). Via its C-terminus binds various phospholipids, most CC strongly phosphatidylinositol 4-phosphate (PtdIns-(4)P), CC phosphatidylinositol 5-phosphate (PtdIns-(5)P) and phosphatidylinositol CC 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma CC membrane trafficking and recycling of SNX27-retromer-dependent cargo CC proteins, such as GLUT1 (PubMed:25278552). Required for the association CC of DNAJC13, ENTR1, ANKRD50 with retromer CSC subunit VPS35 CC (PubMed:24980502). Required for the endosomal recruitment of CCC and CC retriever complexes subunits COMMD1 and CCDC93 as well as the CC retrievere complex subunit VPS35L (PubMed:25355947, PubMed:28892079). CC {ECO:0000269|PubMed:19922874, ECO:0000269|PubMed:20498093, CC ECO:0000269|PubMed:22513087, ECO:0000269|PubMed:23331060, CC ECO:0000269|PubMed:24980502, ECO:0000269|PubMed:25278552, CC ECO:0000269|PubMed:25355947, ECO:0000269|PubMed:28892079}. CC -!- FUNCTION: (Microbial infection) Plays a role in fluid-phase CC endocytosis, a process exploited by vaccinia intracellular mature virus CC (IMV) to enter cells. As a result, may facilitate the penetration of CC IMV into cells. {ECO:0000269|PubMed:18550675}. 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; in the complex CC interacts (via N-terminus) directly with WASHC1. The WASH core complex CC associates via WASHC2 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:19922875, CC PubMed:20498093). Interacts with VPS35; mediates the association with CC the retromer CSC complex. Interacts with FKBP15. Interacts with CCDC93, CC CCDC22, VPS35L; indicative for an association of the WASH core complex CC with the CCC and retriever complexes. May directly interact with CC TBC1D23 (Probable). {ECO:0000269|PubMed:19922874, CC ECO:0000269|PubMed:19922875, ECO:0000269|PubMed:20498093, CC ECO:0000269|PubMed:22070227, ECO:0000269|PubMed:23331060, CC ECO:0000269|PubMed:24980502, ECO:0000269|PubMed:25278552, CC ECO:0000269|PubMed:25355947, ECO:0000305|PubMed:29084197}. CC -!- INTERACTION: CC Q9Y4E1; Q96QK1: VPS35; NbExp=7; IntAct=EBI-948957, EBI-1054634; CC -!- SUBCELLULAR LOCATION: Early endosome membrane CC {ECO:0000269|PubMed:20498093}. Cell membrane. Note=Partially CC colocalizes with RAB11A, a recycling endosome marker. Associates with CC lipid raft microdomains on the plasma membrane. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Name=1; CC IsoId=Q9Y4E1-7; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y4E1-4; Sequence=VSP_061817; CC Name=5; CC IsoId=Q9Y4E1-1; Sequence=VSP_061814, VSP_061817; CC Name=3; CC IsoId=Q9Y4E1-2; Sequence=VSP_061812, VSP_061814, VSP_061817; CC Name=4; CC IsoId=Q9Y4E1-3; Sequence=VSP_061811, VSP_061814, VSP_061817; CC Name=6; CC IsoId=Q9Y4E1-5; Sequence=VSP_061813, VSP_061815, VSP_061817; CC Name=7; CC IsoId=Q9Y4E1-6; Sequence=VSP_061816; CC -!- DOMAIN: The LFa (leucine-phenylalanine-acidic) motif bind directly to CC VPS35 of retromer CSC; adjacent motifs can act cooperatively to bind CC multiple CSCs, although there is significant variability in the CC affinities of different motifs for retromer. CC {ECO:0000269|PubMed:22513087}. CC -!- MISCELLANEOUS: In human, WASHC2 has undergone evolutionary duplication, CC with 2 highly homologous family members WASHC2A and WASHC2C. CC {ECO:0000305|PubMed:19922874}. CC -!- SIMILARITY: Belongs to the FAM21 family. {ECO:0000305}. CC -!- CAUTION: One study reported a nucleation-promoting factor (NPF) CC activity towards the Arp2/3 complex using partially purified samples of CC the WASH complex (PubMed:19922875). In another study, the in vitro CC reconstituted and purified recombinant WASH core complex, consisting of CC WASHC3, WASHC4, WASHC5, WASHC1 and the N-terminal residues 1-356 of CC WASHC2, did not show activity toward Arp2/3 complex (PubMed:20498093). CC {ECO:0000269|PubMed:19922875, ECO:0000269|PubMed:20498093}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH06456.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAA25518.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB011164; BAA25518.1; ALT_INIT; mRNA. DR EMBL; AK303048; BAG64168.1; -; mRNA. DR EMBL; AC012044; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL645998; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL731535; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC006456; AAH06456.1; ALT_INIT; mRNA. DR EMBL; BC150611; AAI50612.1; -; mRNA. DR EMBL; AL050279; CAB43380.2; -; mRNA. DR CCDS; CCDS44374.2; -. [Q9Y4E1-4] DR CCDS; CCDS53528.1; -. [Q9Y4E1-6] DR CCDS; CCDS53529.1; -. [Q9Y4E1-5] DR CCDS; CCDS81453.1; -. [Q9Y4E1-7] DR PIR; T00347; T00347. DR PIR; T08735; T08735. DR RefSeq; NP_001162577.1; NM_001169106.1. [Q9Y4E1-6] DR RefSeq; NP_001162578.1; NM_001169107.1. [Q9Y4E1-5] DR RefSeq; NP_001317003.1; NM_001330074.1. [Q9Y4E1-7] DR RefSeq; NP_056077.2; NM_015262.2. [Q9Y4E1-4] DR AlphaFoldDB; Q9Y4E1; -. DR SMR; Q9Y4E1; -. DR BioGRID; 128984; 65. DR ComplexPortal; CPX-1163; WASH complex, variant WASHC1/WASHC2C. DR ComplexPortal; CPX-1168; WASH complex, variant WASH2P/WASHC2C. DR ComplexPortal; CPX-1169; WASH complex, variant WASH3P/WASHC2C. DR ComplexPortal; CPX-1170; WASH complex, variant WASH4P/WASHC2C. DR ComplexPortal; CPX-1171; WASH complex, variant WASH6P/WASHC2C. DR CORUM; Q9Y4E1; -. DR IntAct; Q9Y4E1; 19. DR MINT; Q9Y4E1; -. DR STRING; 9606.ENSP00000485513; -. DR TCDB; 9.A.3.1.2; the sorting nexin27 (snx27)-retromer assembly apparatus (retromeraa) family. DR GlyGen; Q9Y4E1; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9Y4E1; -. DR PhosphoSitePlus; Q9Y4E1; -. DR BioMuta; WASHC2C; -. DR DMDM; 284018172; -. DR EPD; Q9Y4E1; -. DR jPOST; Q9Y4E1; -. DR MassIVE; Q9Y4E1; -. DR MaxQB; Q9Y4E1; -. DR PaxDb; 9606-ENSP00000363482; -. DR PeptideAtlas; Q9Y4E1; -. DR ProteomicsDB; 25361; -. DR ProteomicsDB; 27701; -. DR ProteomicsDB; 86174; -. [Q9Y4E1-1] DR ProteomicsDB; 86175; -. [Q9Y4E1-2] DR ProteomicsDB; 86176; -. [Q9Y4E1-3] DR ProteomicsDB; 86177; -. [Q9Y4E1-4] DR Pumba; Q9Y4E1; -. DR Antibodypedia; 27042; 68 antibodies from 12 providers. DR DNASU; 253725; -. DR Ensembl; ENST00000374362.6; ENSP00000363482.2; ENSG00000172661.20. [Q9Y4E1-4] DR Ensembl; ENST00000537517.6; ENSP00000442128.1; ENSG00000172661.20. [Q9Y4E1-5] DR Ensembl; ENST00000540872.6; ENSP00000439811.1; ENSG00000172661.20. [Q9Y4E1-6] DR Ensembl; ENST00000623400.4; ENSP00000485513.1; ENSG00000172661.20. [Q9Y4E1-7] DR GeneID; 253725; -. DR KEGG; hsa:253725; -. DR MANE-Select; ENST00000623400.4; ENSP00000485513.1; NM_001330074.2; NP_001317003.1. DR UCSC; uc001jcu.4; human. [Q9Y4E1-7] DR AGR; HGNC:23414; -. DR CTD; 253725; -. DR GeneCards; WASHC2C; -. DR HGNC; HGNC:23414; WASHC2C. DR HPA; ENSG00000172661; Low tissue specificity. DR MIM; 613631; gene. DR neXtProt; NX_Q9Y4E1; -. DR OpenTargets; ENSG00000172661; -. DR VEuPathDB; HostDB:ENSG00000172661; -. DR eggNOG; ENOG502QTIY; Eukaryota. DR GeneTree; ENSGT00940000153997; -. DR HOGENOM; CLU_267715_0_0_1; -. DR InParanoid; Q9Y4E1; -. DR OMA; RFRIFHD; -. DR OrthoDB; 131637at2759; -. DR PhylomeDB; Q9Y4E1; -. DR TreeFam; TF329309; -. DR PathwayCommons; Q9Y4E1; -. DR SignaLink; Q9Y4E1; -. DR SIGNOR; Q9Y4E1; -. DR BioGRID-ORCS; 253725; 54 hits in 1055 CRISPR screens. DR ChiTaRS; FAM21C; human. DR GeneWiki; FAM21C; -. DR GenomeRNAi; 253725; -. DR Pharos; Q9Y4E1; Tbio. DR PRO; PR:Q9Y4E1; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; Q9Y4E1; Protein. DR Bgee; ENSG00000172661; Expressed in sural nerve and 96 other cell types or tissues. DR ExpressionAtlas; Q9Y4E1; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005769; C:early endosome; IDA:UniProtKB. DR GO; GO:0031901; C:early endosome membrane; NAS:ComplexPortal. DR GO; GO:0005768; C:endosome; IDA:MGI. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0071203; C:WASH complex; IDA:UniProtKB. DR GO; GO:1901981; F:phosphatidylinositol phosphate binding; IBA:GO_Central. DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:UniProtKB. DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; IDA:UniProtKB. DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; IDA:UniProtKB. DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IDA:UniProtKB. DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB. DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IDA:UniProtKB. DR GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; IDA:UniProtKB. DR GO; GO:1905394; F:retromer complex binding; IDA:UniProtKB. DR GO; GO:0032456; P:endocytic recycling; IMP:UniProtKB. DR GO; GO:0016197; P:endosomal transport; NAS:ComplexPortal. DR GO; GO:2000813; P:negative regulation of barbed-end actin filament capping; IDA:UniProtKB. DR GO; GO:0036010; P:protein localization to endosome; IMP:UniProtKB. 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:1900024; P:regulation of substrate adhesion-dependent cell spreading; IDA:UniProtKB. DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; IMP:UniProtKB. DR InterPro; IPR029341; FAM21/CAPZIP. DR PANTHER; PTHR21669; CAPZ-INTERACTING PROTEIN AND RELATED PROTEINS; 1. DR PANTHER; PTHR21669:SF38; WASH COMPLEX SUBUNIT 2A-RELATED; 1. DR Pfam; PF15255; CAP-ZIP_m; 1. DR Genevisible; Q9Y4E1; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Endosome; Lipid-binding; Membrane; KW Phosphoprotein; Protein transport; Reference proteome; Transport. FT CHAIN 1..1341 FT /note="WASH complex subunit 2C" FT /id="PRO_0000186714" FT REGION 1..220 FT /note="Sufficient for interaction with WASHC3, WASHC4 and FT WASHC5; required for interaction with WASHC1" FT /evidence="ECO:0000269|PubMed:19922874, FT ECO:0000269|PubMed:20498093" FT REGION 202..405 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 356..600 FT /note="Sufficient for interaction with CCDC93" FT /evidence="ECO:0000269|PubMed:25355947" FT REGION 357..1339 FT /note="Interaction with VPS35" FT /evidence="ECO:0000269|PubMed:22513087" FT REGION 422..609 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 621..662 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 696..734 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 751..796 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 820..840 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 886..951 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 937..1339 FT /note="Interaction with phospholipids" FT /evidence="ECO:0000269|PubMed:20498093" FT REGION 988..1205 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1029..1047 FT /note="Required for interaction with F-actin-capping FT protein subunit alpha (CAPZA1 or CAPZA2 or CAPZA3)" FT /evidence="ECO:0000269|PubMed:20498093" FT REGION 1302..1326 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 367..378 FT /note="LFa 1" FT /evidence="ECO:0000305" FT MOTIF 411..419 FT /note="LFa 2" FT /evidence="ECO:0000305" FT MOTIF 450..463 FT /note="LFa 3" FT /evidence="ECO:0000305" FT MOTIF 482..491 FT /note="LFa 4" FT /evidence="ECO:0000305" FT MOTIF 537..548 FT /note="LFa 5" FT /evidence="ECO:0000305" FT MOTIF 572..583 FT /note="LFa 6" FT /evidence="ECO:0000305" FT MOTIF 617..627 FT /note="LFa 7" FT /evidence="ECO:0000305" FT MOTIF 664..674 FT /note="LFa 8" FT /evidence="ECO:0000305" FT MOTIF 690..702 FT /note="LFa 9" FT /evidence="ECO:0000305" FT MOTIF 726..738 FT /note="LFa 10" FT /evidence="ECO:0000305" FT MOTIF 803..817 FT /note="LFa 11" FT /evidence="ECO:0000305" FT MOTIF 839..847 FT /note="LFa 12" FT /evidence="ECO:0000305" FT MOTIF 856..862 FT /note="LFa 13" FT /evidence="ECO:0000305" FT MOTIF 878..888 FT /note="LFa 14" FT /evidence="ECO:0000305" FT MOTIF 1129..1136 FT /note="LFa 15" FT /evidence="ECO:0000305" FT MOTIF 1171..1185 FT /note="LFa 16" FT /evidence="ECO:0000305" FT MOTIF 1201..1209 FT /note="LFa 17" FT /evidence="ECO:0000305" FT MOTIF 1234..1240 FT /note="LFa 18" FT /evidence="ECO:0000305" FT MOTIF 1262..1270 FT /note="LFa 19" FT /evidence="ECO:0000305" FT MOTIF 1290..1299 FT /note="LFa 20" FT /evidence="ECO:0000305" FT MOTIF 1330..1338 FT /note="LFa 21" FT /evidence="ECO:0000305" FT COMPBIAS 250..275 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 297..344 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 381..395 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 479..494 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 595..609 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 621..638 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 751..772 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 773..793 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 898..933 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1030..1044 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 539 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 550 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 909 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT VAR_SEQ 43..97 FT /note="Missing (in isoform 4)" FT /id="VSP_061811" FT VAR_SEQ 43..50 FT /note="Missing (in isoform 3)" FT /id="VSP_061812" FT VAR_SEQ 311..335 FT /note="TLPSGEAKPRKTLKEKKERRTPSDD -> N (in isoform 6)" FT /id="VSP_061813" FT VAR_SEQ 624..625 FT /note="Missing (in isoform 3, isoform 4 and isoform 5)" FT /id="VSP_061814" FT VAR_SEQ 714..764 FT /note="Missing (in isoform 6)" FT /id="VSP_061815" FT VAR_SEQ 897..958 FT /note="Missing (in isoform 7)" FT /id="VSP_061816" FT VAR_SEQ 937..957 FT /note="Missing (in isoform 2, isoform 3, isoform 4, isoform FT 5 and isoform 6)" FT /id="VSP_061817" FT MUTAGEN 1031 FT /note="R->A: Disrupts interaction with F-actin-capping FT protein subunit alpha (CAPZA1 or CAPZA2 or CAPZA3)." FT /evidence="ECO:0000269|PubMed:20498093" FT MUTAGEN 1299 FT /note="F->A: Impairs interaction with VPS35." FT /evidence="ECO:0000269|PubMed:23331060" FT MUTAGEN 1331 FT /note="F->A: Impairs interaction with VPS35." FT /evidence="ECO:0000269|PubMed:23331060" FT MUTAGEN 1333 FT /note="D->A: Disrupts interaction with VPS35." FT /evidence="ECO:0000269|PubMed:23331060" FT CONFLICT 244 FT /note="Q -> R (in Ref. 4; AAI50612)" FT /evidence="ECO:0000305" FT CONFLICT 302 FT /note="M -> V (in Ref. 4; AAI50612)" FT /evidence="ECO:0000305" FT CONFLICT 342 FT /note="A -> T (in Ref. 4; AAI50612)" FT /evidence="ECO:0000305" FT CONFLICT 382 FT /note="S -> P (in Ref. 4; AAI50612)" FT /evidence="ECO:0000305" FT CONFLICT 427 FT /note="L -> M (in Ref. 4; AAI50612)" FT /evidence="ECO:0000305" FT CONFLICT 474 FT /note="R -> G (in Ref. 4; AAI50612)" FT /evidence="ECO:0000305" FT CONFLICT 521 FT /note="Y -> S (in Ref. 1; BAA25518 and 2; BAG64168)" FT /evidence="ECO:0000305" FT CONFLICT 1061 FT /note="V -> I (in Ref. 1; BAA25518)" FT /evidence="ECO:0000305" FT CONFLICT 1301 FT /note="T -> S (in Ref. 1; BAA25518)" FT /evidence="ECO:0000305" SQ SEQUENCE 1341 AA; 147154 MW; C90F2B628505ADD0 CRC64; MMNRTTPDQE LVPASEPVWE RPWSVEEIRR SSQSWSLAAD AGLLQFLQEF SQQTISRTHE IKKQVDGLIR ETKATDCRLH NVFNDFLMLS NTQFIENRVY DEEVEEPVLK AEAEKTEQEK TREQKEVDLI PKVQEAVNYG LQVLDSAFEQ LDIKAGNSDS EEDDANGRVE LILEPKDLYI DRPLPYLIGS KLFMEQEDVG LGELSSEEGS VGSDRGSIVD TEEEKEEEES DEDFAHHSDN EQNQHTTQMS DEEEDDDGCD LFADSEKEEE DIEDIEENTR PKRSRPTSFA DELAARIKGD AMGRVDEEPT TLPSGEAKPR KTLKEKKERR TPSDDEEDNL FAPPKLTDED FSPFGSGGGL FSGGKGLFDD EDEESDLFTE ASQDRQAGAS VKEESSSSKP GKKIPAGAVS VFLGDTDVFG AASVPSLKEP QKPEQPTPRK SPYGPPPTGL FDDDDGDDDD DFFSAPHSKP SKTRKVQSTA DIFGDEEGDL FKEKAVASPE ATVSQTDENK ARAEKKVTLS YSKNLKPSSE TKTQKGLFSD EEDSEDLFSS QSASNLKGAS LLPGKLPTSV SLFDDEDEED NLFGGTAAKK QTLSLQAQRE EKAKASELSK KKASALLFSS DEEDQWNIPA SQTHLASDSR SKGEPRDSGT LQSQEAKAVK KTSLFEEDKE DDLFAIAKDS QKKTQRVSLL FEDDVDSGGS LFGSPPTSVP PATKKKETVS EAPPLLFSDE EEKEAQLGVK SVDKKVESAK ESLKFGRTDV AESEKEGLLT RSAQETVKHS DLFSSSSPWD KGTKPRTKTV LSLFDEEEDK MEDQNIIQAP QKEVGKGCDP DAHPKSTGVF QDEELLFSHK LQKDNDPDVD LFAGTKKTKL LEPSVGSLFG DDEDDDLFSS AKSQPLVQEK KRVVKKDHSV NSFKNQKHPE SIQGSKEKGI WKPETPQDSS GLAPFKTKEP STRIGKIQAN LAINPAALLP TAASQISEVK PVLPELAFPS SEHRRSHGLE SVPVLPGSGE AGVSFDLPAQ ADTLHSANKS RVKMRGKRRP QTRAARRLAA QESSEAEDMS VPRGPIAQWA DGAISPNGHR PQLRAASGED STEEALAAAA APWEGGPVPG VDTSPFAKSL GHSRGEADLF DSGDIFSTGT GSQSVERTKP KAKIAENPAN PPVGGKAKSP MFPALGEASS DDDLFQSAKP KPAKKTNPFP LLEDEDDLFT DQKVKKNETK SSSQQDVILT TQDIFEDDIF ATEAIKPSQK TREKEKTLES NLFDDNIDIF ADLTVKPKEK SKKKVEAKSI FDDDMDDIFS TGIQAKTTKP KSRSAQAAPE PRFEHKVSNI FDDPLNAFGG Q //