WAC2C_HUMAN
ID WAC2C_HUMAN Reviewed; 1320 AA.
AC Q9Y4E1; B4DZQ6; B9EK53; F5H0J6; F5H871; Q5SQU4; Q5SQU5; Q7L521; Q9UG79;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 4.
DT 03-AUG-2022, entry version 155.
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 1).
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 5).
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 6), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 986-1320.
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 1016-1320.
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-1010, 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-1278; PHE-1310 AND
RP ASP-1312.
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=6;
CC Name=1;
CC IsoId=Q9Y4E1-4; Sequence=Displayed;
CC Name=4;
CC IsoId=Q9Y4E1-1; Sequence=VSP_059789;
CC Name=2;
CC IsoId=Q9Y4E1-2; Sequence=VSP_059787, VSP_059789;
CC Name=3;
CC IsoId=Q9Y4E1-3; Sequence=VSP_059786, VSP_059789;
CC Name=5;
CC IsoId=Q9Y4E1-5; Sequence=VSP_059788, VSP_059790;
CC Name=6;
CC IsoId=Q9Y4E1-6; Sequence=VSP_059791;
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: A WASHC2C construct with WASHC2A-specific sequence insertions
CC of 2 aa and 21 aa resulting in a construct length of 1341 aa similar to
CC WASHC2A length has been used for a number of experiments; a part of
CC this construct covering the WASHC2A-specific 21 aa insert has been used
CC to produce an anti-WASHC2 antibody (PubMed:19922874, PubMed:22513087,
CC PubMed:20498093).
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};
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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 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_056077.2; NM_015262.2. [Q9Y4E1-4]
DR AlphaFoldDB; Q9Y4E1; -.
DR SMR; Q9Y4E1; -.
DR BioGRID; 128984; 51.
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.ENSP00000363482; -.
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; Q9Y4E1; -.
DR PeptideAtlas; Q9Y4E1; -.
DR PRIDE; 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 Antibodypedia; 27042; 54 antibodies from 10 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 GeneID; 253725; -.
DR KEGG; hsa:253725; -.
DR UCSC; uc001jcu.4; human. [Q9Y4E1-4]
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 PhylomeDB; Q9Y4E1; -.
DR TreeFam; TF329309; -.
DR PathwayCommons; Q9Y4E1; -.
DR SignaLink; Q9Y4E1; -.
DR SIGNOR; Q9Y4E1; -.
DR BioGRID-ORCS; 253725; 52 hits in 1002 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 95 other tissues.
DR ExpressionAtlas; Q9Y4E1; baseline and differential.
DR Genevisible; Q9Y4E1; HS.
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; IC: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; IC: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; IC: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 Pfam; PF15255; CAP-ZIP_m; 1.
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..1320
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..1318
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..841
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 886..930
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 937..1318
FT /note="Interaction with phospholipids"
FT /evidence="ECO:0000269|PubMed:20498093"
FT REGION 967..1184
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1008..1026
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 1281..1304
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 1108..1115
FT /note="LFa 15"
FT /evidence="ECO:0000305"
FT MOTIF 1150..1164
FT /note="LFa 16"
FT /evidence="ECO:0000305"
FT MOTIF 1180..1188
FT /note="LFa 17"
FT /evidence="ECO:0000305"
FT MOTIF 1213..1219
FT /note="LFa 18"
FT /evidence="ECO:0000305"
FT MOTIF 1241..1249
FT /note="LFa 19"
FT /evidence="ECO:0000305"
FT MOTIF 1269..1278
FT /note="LFa 20"
FT /evidence="ECO:0000305"
FT MOTIF 1309..1317
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..927
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1009..1023
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 3)"
FT /id="VSP_059786"
FT VAR_SEQ 43..50
FT /note="Missing (in isoform 2)"
FT /id="VSP_059787"
FT VAR_SEQ 311..335
FT /note="TLPSGEAKPRKTLKEKKERRTPSDD -> N (in isoform 5)"
FT /id="VSP_059788"
FT VAR_SEQ 624..625
FT /note="Missing (in isoform 4, isoform 2 and isoform 3)"
FT /id="VSP_059789"
FT VAR_SEQ 715..765
FT /note="Missing (in isoform 5)"
FT /id="VSP_059790"
FT VAR_SEQ 895..937
FT /note="PLVQEKKRVVKKDHSVNSFKNQKHPESIQGSKEKGIWKPETPQ -> PL
FT (in isoform 6)"
FT /id="VSP_059791"
FT MUTAGEN 1010
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 1278
FT /note="F->A: Impairs interaction with VPS35."
FT /evidence="ECO:0000269|PubMed:23331060"
FT MUTAGEN 1310
FT /note="F->A: Impairs interaction with VPS35."
FT /evidence="ECO:0000269|PubMed:23331060"
FT MUTAGEN 1312
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 1040
FT /note="V -> I (in Ref. 1; BAA25518)"
FT /evidence="ECO:0000305"
FT CONFLICT 1280
FT /note="T -> S (in Ref. 1; BAA25518)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1320 AA; 144911 MW; 156651EE158BE32F 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 WKPETPQANL AINPAALLPT AASQISEVKP
VLPELAFPSS EHRRSHGLES VPVLPGSGEA GVSFDLPAQA DTLHSANKSR VKMRGKRRPQ
TRAARRLAAQ ESSEAEDMSV PRGPIAQWAD GAISPNGHRP QLRAASGEDS TEEALAAAAA
PWEGGPVPGV DTSPFAKSLG HSRGEADLFD SGDIFSTGTG SQSVERTKPK AKIAENPANP
PVGGKAKSPM FPALGEASSD DDLFQSAKPK PAKKTNPFPL LEDEDDLFTD QKVKKNETKS
SSQQDVILTT QDIFEDDIFA TEAIKPSQKT REKEKTLESN LFDDNIDIFA DLTVKPKEKS
KKKVEAKSIF DDDMDDIFST GIQAKTTKPK SRSAQAAPEP RFEHKVSNIF DDPLNAFGGQ
