ID CHIP_HUMAN Reviewed; 303 AA. AC Q9UNE7; A2IDB9; O60526; Q969U2; Q9HBT1; DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot. DT 25-OCT-2005, sequence version 2. DT 28-JAN-2026, entry version 217. DE RecName: Full=E3 ubiquitin-protein ligase CHIP {ECO:0000305}; DE EC=2.3.2.27 {ECO:0000269|PubMed:11557750, ECO:0000269|PubMed:15466472, ECO:0000269|PubMed:24043303}; DE AltName: Full=Antigen NY-CO-7 {ECO:0000303|PubMed:9610721}; DE AltName: Full=CLL-associated antigen KW-8 {ECO:0000303|PubMed:12200376}; DE AltName: Full=Carboxy terminus of Hsp70-interacting protein {ECO:0000303|PubMed:10330192}; DE AltName: Full=RING-type E3 ubiquitin transferase CHIP {ECO:0000305}; DE AltName: Full=STIP1 homology and U box-containing protein 1 {ECO:0000312|HGNC:HGNC:11427}; GN Name=STUB1 {ECO:0000303|PubMed:23973223, ECO:0000312|HGNC:HGNC:11427}; GN Synonyms=CHIP {ECO:0000303|PubMed:10330192, GN ECO:0000303|PubMed:20724525}; GN ORFNames=PP1131 {ECO:0000312|EMBL:AAG17211.1}; 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 [MRNA] (ISOFORM 1), AND IDENTIFICATION AS RP TUMOR-ASSOCIATED ANTIGEN. RC TISSUE=Colon carcinoma; RX PubMed=9610721; RX DOI=10.1002/(sici)1097-0215(19980529)76:5<652::aid-ijc7>3.0.co;2-p; RA Scanlan M.J., Chen Y.-T., Williamson B., Gure A.O., Stockert E., RA Gordan J.D., Tuereci O., Sahin U., Pfreundschuh M., Old L.J.; RT "Characterization of human colon cancer antigens recognized by autologous RT antibodies."; RL Int. J. Cancer 76:652-658(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH HSPA8 RP AND HSPA1A, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RC TISSUE=Heart; RX PubMed=10330192; DOI=10.1128/mcb.19.6.4535; RA Ballinger C.A., Connell P., Wu Y., Hu Z., Thompson L.J., Yin L.-Y., RA Patterson C.; RT "Identification of CHIP, a novel tetratricopeptide repeat-containing RT protein that interacts with heat shock proteins and negatively regulates RT chaperone functions."; RL Mol. Cell. Biol. 19:4535-4545(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND IDENTIFICATION AS RP TUMOR-ASSOCIATED ANTIGEN. RX PubMed=12200376; DOI=10.1182/blood-2002-02-0513; RA Krackhardt A.M., Witzens M., Harig S., Hodi F.S., Zauls A.J., Chessia M., RA Barrett P., Gribben J.G.; RT "Identification of tumor-associated antigens in chronic lymphocytic RT leukemia by SEREX."; RL Blood 100:2123-2131(2002). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=11157797; DOI=10.1093/hmg/10.4.339; RA Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., Tufarelli C., RA Kearney L., Buckle V.J., Doggett N.A., Flint J., Higgs D.R.; RT "Sequence, structure and pathology of the fully annotated terminal 2 Mb of RT the short arm of human chromosome 16."; RL Hum. Mol. Genet. 10:339-352(2001). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=15498874; DOI=10.1073/pnas.0404089101; RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X., RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.; RT "Large-scale cDNA transfection screening for genes related to cancer RT development and progression."; RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon, and Skin; 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 [9] RP PROTEIN SEQUENCE OF 13-30; 56-66; 86-119; 129-140; 155-167; 235-241; RP 256-263 AND 273-287, PHOSPHORYLATION AT SER-19, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Embryonic kidney; RA Bienvenut W.V., Waridel P., Quadroni M.; RL Submitted (MAR-2009) to UniProtKB. RN [10] RP TISSUE SPECIFICITY. RX PubMed=11435423; DOI=10.1074/jbc.m102755200; RA Hatakeyama S., Yada M., Matsumoto M., Ishida N., Nakayama K.I.; RT "U box proteins as a new family of ubiquitin-protein ligases."; RL J. Biol. Chem. 276:33111-33120(2001). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND INTERACTION WITH HSPA8; UBE2D1; RP UBE2D2 AND UBE2D3. RX PubMed=11557750; DOI=10.1074/jbc.m101968200; RA Jiang J., Ballinger C.A., Wu Y., Dai Q., Cyr D.M., Hoehfeld J., RA Patterson C.; RT "CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as RT a target for ubiquitylation."; RL J. Biol. Chem. 276:42938-42944(2001). RN [12] RP FUNCTION, AND INTERACTION WITH HSP90. RX PubMed=11146632; DOI=10.1038/35050618; RA Connell P., Ballinger C.A., Jiang J., Wu Y., Thompson L.J., Hoehfeld J., RA Patterson C.; RT "The co-chaperone CHIP regulates protein triage decisions mediated by heat- RT shock proteins."; RL Nat. Cell Biol. 3:93-96(2001). RN [13] RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY. RX PubMed=15466472; DOI=10.1074/jbc.m406926200; RA Peng H.M., Morishima Y., Jenkins G.J., Dunbar A.Y., Lau M., Patterson C., RA Pratt W.B., Osawa Y.; RT "Ubiquitylation of neuronal nitric-oxide synthase by CHIP, a chaperone- RT dependent E3 ligase."; RL J. Biol. Chem. 279:52970-52977(2004). RN [14] RP INTERACTION WITH HSPA1A AND HSPBP1. RX PubMed=15215316; DOI=10.1091/mbc.e04-04-0293; RA Alberti S., Boehse K., Arndt V., Schmitz A., Hoehfeld J.; RT "The cochaperone HspBP1 inhibits the CHIP ubiquitin ligase and stimulates RT the maturation of the cystic fibrosis transmembrane conductance RT regulator."; RL Mol. Biol. Cell 15:4003-4010(2004). RN [15] RP INTERACTION WITH BAG2. RX PubMed=16169850; DOI=10.1074/jbc.m507986200; RA Dai Q., Qian S.B., Li H.-H., McDonough H., Borchers C., Huang D., RA Takayama S., Younger J.M., Ren H.Y., Cyr D.M., Patterson C.; RT "Regulation of the cytoplasmic quality control protein degradation pathway RT by BAG2."; RL J. Biol. Chem. 280:38673-38681(2005). RN [16] RP INTERACTION WITH UBE2N AND UBE2V1. RX PubMed=16307917; DOI=10.1016/j.molcel.2005.09.023; RA Zhang M., Windheim M., Roe S.M., Peggie M., Cohen P., Prodromou C., RA Pearl L.H.; RT "Chaperoned ubiquitylation -- crystal structures of the CHIP U box E3 RT ubiquitin ligase and a CHIP-Ubc13-Uev1a complex."; RL Mol. Cell 20:525-538(2005). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [18] RP FUNCTION, INTERACTION WITH UBE4B, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=17369820; DOI=10.1038/ncb1554; RA Janiesch P.C., Kim J., Mouysset J., Barikbin R., Lochmueller H., RA Cassata G., Krause S., Hoppe T.; RT "The ubiquitin-selective chaperone CDC-48/p97 links myosin assembly to RT human myopathy."; RL Nat. Cell Biol. 9:379-390(2007). RN [19] RP POLYUBIQUITINATION AT LYS-22; LYS-221 AND LYS-255, AND DOMAIN TPR. RX PubMed=18042044; DOI=10.1042/bj20071338; RA Windheim M., Peggie M., Cohen P.; RT "Two different classes of E2 ubiquitin-conjugating enzymes are required for RT the mono-ubiquitination of proteins and elongation by polyubiquitin chains RT with a specific topology."; RL Biochem. J. 409:723-729(2008). RN [20] RP INTERACTION WITH MKKS. RX PubMed=18094050; DOI=10.1091/mbc.e07-07-0631; RA Hirayama S., Yamazaki Y., Kitamura A., Oda Y., Morito D., Okawa K., RA Kimura H., Cyr D.M., Kubota H., Nagata K.; RT "MKKS is a centrosome-shuttling protein degraded by disease-causing RT mutations via CHIP-mediated ubiquitination."; RL Mol. Biol. Cell 19:899-911(2008). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19; SER-23 AND SER-273, AND RP IDENTIFICATION BY 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 [23] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [24] RP FUNCTION. RX PubMed=19103148; DOI=10.1016/j.abb.2008.12.001; RA Pabarcus M.K., Hoe N., Sadeghi S., Patterson C., Wiertz E., Correia M.A.; RT "CYP3A4 ubiquitination by gp78 (the tumor autocrine motility factor RT receptor, AMFR) and CHIP E3 ligases."; RL Arch. Biochem. Biophys. 483:66-74(2009). RN [25] RP FUNCTION, AND INTERACTION WITH POLB. RX PubMed=19713937; DOI=10.1038/emboj.2009.243; RA Parsons J.L., Tait P.S., Finch D., Dianova I.I., Edelmann M.J., RA Khoronenkova S.V., Kessler B.M., Sharma R.A., McKenna W.G., Dianov G.L.; RT "Ubiquitin ligase ARF-BP1/Mule modulates base excision repair."; RL EMBO J. 28:3207-3215(2009). RN [26] RP INTERACTION WITH DNAAF4. RX PubMed=19423554; DOI=10.1093/hmg/ddp215; RA Massinen S., Tammimies K., Tapia-Paez I., Matsson H., Hokkanen M.E., RA Soederberg O., Landegren U., Castren E., Gustafsson J.A., Treuter E., RA Kere J.; RT "Functional interaction of DYX1C1 with estrogen receptors suggests RT involvement of hormonal pathways in dyslexia."; RL Hum. Mol. Genet. 18:2802-2812(2009). RN [27] RP FUNCTION, AND INTERACTION WITH FOXO1. RX PubMed=19483080; DOI=10.1074/jbc.m109.017046; RA Li F., Xie P., Fan Y., Zhang H., Zheng L., Gu D., Patterson C., Li H.; RT "C terminus of Hsc70-interacting protein promotes smooth muscle cell RT proliferation and survival through ubiquitin-mediated degradation of RT FoxO1."; RL J. Biol. Chem. 284:20090-20098(2009). RN [28] RP FUNCTION. RX PubMed=19567782; DOI=10.1158/1541-7786.mcr-08-0582; RA Annamalai B., Liu X., Gopal U., Isaacs J.S.; RT "Hsp90 is an essential regulator of EphA2 receptor stability and signaling: RT implications for cancer cell migration and metastasis."; RL Mol. Cancer Res. 7:1021-1032(2009). RN [29] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, 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 [31] RP FUNCTION, INTERACTION WITH MAPK7, UBIQUITINATION, AND MUTAGENESIS OF RP HIS-260. RX PubMed=20724525; DOI=10.1096/fj.10-162636; RA Woo C.H., Le N.T., Shishido T., Chang E., Lee H., Heo K.S., Mickelsen D.M., RA Lu Y., McClain C., Spangenberg T., Yan C., Molina C.A., Yang J., RA Patterson C., Abe J.; RT "Novel role of C terminus of Hsc70-interacting protein (CHIP) ubiquitin RT ligase on inhibiting cardiac apoptosis and dysfunction via regulating ERK5- RT mediated degradation of inducible cAMP early repressor."; RL FASEB J. 24:4917-4928(2010). RN [32] RP INTERACTION WITH BAG3; HSPA8 AND HSPB8 IN CASA COMPLEX. RX PubMed=20060297; DOI=10.1016/j.cub.2009.11.022; RA Arndt V., Dick N., Tawo R., Dreiseidler M., Wenzel D., Hesse M., RA Fuerst D.O., Saftig P., Saint R., Fleischmann B.K., Hoch M., Hoehfeld J.; RT "Chaperone-assisted selective autophagy is essential for muscle RT maintenance."; RL Curr. Biol. 20:143-148(2010). RN [33] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19 AND SER-273, AND RP IDENTIFICATION BY 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 [34] 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 [35] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19 AND SER-23, 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 [36] RP INTERACTION WITH DNAJB6. RX PubMed=22366786; DOI=10.1038/ng.1103; RA Sarparanta J., Jonson P.H., Golzio C., Sandell S., Luque H., Screen M., RA McDonald K., Stajich J.M., Mahjneh I., Vihola A., Raheem O., Penttila S., RA Lehtinen S., Huovinen S., Palmio J., Tasca G., Ricci E., Hackman P., RA Hauser M., Katsanis N., Udd B.; RT "Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 RT cause limb-girdle muscular dystrophy."; RL Nat. Genet. 44:450-455(2012). RN [37] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [38] RP UBIQUITINATION AT LYS-2. RX PubMed=23560854; DOI=10.1042/bj20130244; RA Tatham M.H., Plechanovova A., Jaffray E.G., Salmen H., Hay R.T.; RT "Ube2W conjugates ubiquitin to alpha-amino groups of protein N-termini."; RL Biochem. J. 453:137-145(2013). RN [39] RP FUNCTION, INDUCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-30 AND RP HIS-260. RX PubMed=23973223; DOI=10.1016/j.immuni.2013.08.006; RA Chen Z., Barbi J., Bu S., Yang H.Y., Li Z., Gao Y., Jinasena D., Fu J., RA Lin F., Chen C., Zhang J., Yu N., Li X., Shan Z., Nie J., Gao Z., Tian H., RA Li Y., Yao Z., Zheng Y., Park B.V., Pan Z., Zhang J., Dang E., Li Z., RA Wang H., Luo W., Li L., Semenza G.L., Zheng S.G., Loser K., Tsun A., RA Greene M.I., Pardoll D.M., Pan F., Li B.; RT "The ubiquitin ligase Stub1 negatively modulates regulatory T cell RT suppressive activity by promoting degradation of the transcription factor RT Foxp3."; RL Immunity 39:272-285(2013). RN [40] RP FUNCTION, INTERACTION WITH HSPA8, AND MUTAGENESIS OF PRO-269. RX PubMed=23990462; DOI=10.1074/jbc.m113.479345; RA Matsumura Y., Sakai J., Skach W.R.; RT "Endoplasmic reticulum protein quality control is determined by cooperative RT interactions between Hsp/c70 protein and the CHIP E3 ligase."; RL J. Biol. Chem. 288:31069-31079(2013). RN [41] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19; SER-23; SER-25 AND RP SER-149, AND IDENTIFICATION BY 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 [42] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-260. RX PubMed=24043303; DOI=10.1128/mcb.00480-13; RA Ronnebaum S.M., Wu Y., McDonough H., Patterson C.; RT "The ubiquitin ligase CHIP prevents SirT6 degradation through noncanonical RT ubiquitination."; RL Mol. Cell. Biol. 33:4461-4472(2013). RN [43] RP FUNCTION, AND INTERACTION WITH SMAD3; HSPA1A; HSPA1B; HSP90AA1 AND RP HSP90AB1. RX PubMed=24613385; DOI=10.1016/j.bbrc.2014.02.124; RA Shang Y., Xu X., Duan X., Guo J., Wang Y., Ren F., He D., Chang Z.; RT "Hsp70 and Hsp90 oppositely regulate TGF-beta signaling through RT CHIP/Stub1."; RL Biochem. Biophys. Res. Commun. 446:387-392(2014). RN [44] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, 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 [45] RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH UBXN2A; VCP AND CHRNA3, AND RP MUTAGENESIS OF HIS-260. RX PubMed=26265139; DOI=10.1016/j.bcp.2015.08.084; RA Teng Y., Rezvani K., De Biasi M.; RT "UBXN2A regulates nicotinic receptor degradation by modulating the E3 RT ligase activity of CHIP."; RL Biochem. Pharmacol. 97:518-530(2015). RN [46] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [47] RP FUNCTION. RX PubMed=26634371; DOI=10.1007/s12192-015-0661-5; RA Sane S., Abdullah A., Nelson M.E., Wang H., Chauhan S.C., Newton S.S., RA Rezvani K.; RT "Structural studies of UBXN2A and mortalin interaction and the putative RT role of silenced UBXN2A in preventing response to chemotherapy."; RL Cell Stress Chaperones 21:313-326(2016). RN [48] RP INTERACTION WITH FLCN AND HSP90AA1. RX PubMed=27353360; DOI=10.1038/ncomms12037; RA Woodford M.R., Dunn D.M., Blanden A.R., Capriotti D., Loiselle D., RA Prodromou C., Panaretou B., Hughes P.F., Smith A., Ackerman W., RA Haystead T.A., Loh S.N., Bourboulia D., Schmidt L.S., Marston Linehan W., RA Bratslavsky G., Mollapour M.; RT "The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance RT drug binding."; RL Nat. Commun. 7:12037-12037(2016). RN [49] RP FUNCTION, AND INTERACTION WITH HSPA1A; HSPA1B AND HSPA8. RX PubMed=27708256; DOI=10.1038/ncomms12882; RA Seo J.H., Park J.H., Lee E.J., Vo T.T., Choi H., Kim J.Y., Jang J.K., RA Wee H.J., Lee H.S., Jang S.H., Park Z.Y., Jeong J., Lee K.J., Seok S.H., RA Park J.Y., Lee B.J., Lee M.N., Oh G.T., Kim K.W.; RT "ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding RT and degradation."; RL Nat. Commun. 7:12882-12882(2016). RN [50] RP FUNCTION. RX PubMed=28813410; DOI=10.1038/nature23669; RA Mezzadra R., Sun C., Jae L.T., Gomez-Eerland R., de Vries E., Wu W., RA Logtenberg M.E.W., Slagter M., Rozeman E.A., Hofland I., Broeks A., RA Horlings H.M., Wessels L.F.A., Blank C.U., Xiao Y., Heck A.J.R., Borst J., RA Brummelkamp T.R., Schumacher T.N.M.; RT "Identification of CMTM6 and CMTM4 as PD-L1 protein regulators."; RL Nature 549:106-110(2017). RN [51] RP MUTAGENESIS OF LYS-30 AND HIS-260. RX PubMed=29934347; DOI=10.1523/jneurosci.0699-18.2018; RA Lizama B.N., Palubinsky A.M., Raveendran V.A., Moore A.M., Federspiel J.D., RA Codreanu S.G., Liebler D.C., McLaughlin B.; RT "Neuronal Preconditioning Requires the Mitophagic Activity of C-terminus of RT HSC70-Interacting Protein."; RL J. Neurosci. 38:6825-6840(2018). RN [52] RP FUNCTION. RX PubMed=29883609; DOI=10.1016/j.molcel.2018.05.016; RA Choi S.W., Park H.H., Kim S., Chung J.M., Noh H.J., Kim S.K., Song H.K., RA Lee C.W., Morgan M.J., Kang H.C., Kim Y.S.; RT "PELI1 selectively targets kinase-active RIP3 for ubiquitylation-dependent RT proteasomal degradation."; RL Mol. Cell 70:920-935(2018). RN [53] RP INVOLVEMENT IN SCA48. RX PubMed=30381368; DOI=10.1212/wnl.0000000000006550; RA Genis D., Ortega-Cubero S., San Nicolas H., Corral J., Gardenyes J., RA de Jorge L., Lopez E., Campos B., Lorenzo E., Tonda R., Beltran S., RA Negre M., Obon M., Beltran B., Fabregas L., Alemany B., Marquez F., RA Ramio-Torrenta L., Gich J., Volpini V., Pastor P.; RT "Heterozygous STUB1 mutation causes familial ataxia with cognitive RT affective syndrome (SCA48)."; RL Neurology 91:E1988-E1998(2018). RN [54] RP FUNCTION, INTERACTION WITH NFATC3, AND MUTAGENESIS OF LYS-30 AND HIS-260. RX PubMed=30980393; DOI=10.1002/jcp.28614; RA Chao C.N., Lai C.H., Badrealam K.F., Lo J.F., Shen C.Y., Chen C.H., RA Chen R.J., Viswanadha V.P., Kuo W.W., Huang C.Y.; RT "CHIP attenuates lipopolysaccharide-induced cardiac hypertrophy and RT apoptosis by promoting NFATc3 proteasomal degradation."; RL J. Cell. Physiol. 234:20128-20138(2019). RN [55] RP INTERACTION WITH PRMT5. RX PubMed=33376131; DOI=10.26508/lsa.202000699; RA Chakrapani B., Khan M.I.K., Kadumuri R.V., Gupta S., Verma M., Awasthi S., RA Govindaraju G., Mahesh A., Rajavelu A., Chavali S., Dhayalan A.; RT "The uncharacterized protein FAM47E interacts with PRMT5 and regulates its RT functions."; RL Life. Sci Alliance 4:e202000699-e202000699(2021). RN [56] RP VARIANTS SCAR16 ILE-130; CYS-147; PHE-165 AND THR-236, AND INVOLVEMENT IN RP SCAR16. RX PubMed=24312598; DOI=10.1371/journal.pone.0081884; RA Shi Y., Wang J., Li J.D., Ren H., Guan W., He M., Yan W., Zhou Y., Hu Z., RA Zhang J., Xiao J., Su Z., Dai M., Wang J., Jiang H., Guo J., Zhou Y., RA Zhang F., Li N., Du J., Xu Q., Hu Y., Pan Q., Shen L., Wang G., Xia K., RA Zhang Z., Tang B.; RT "Identification of CHIP as a novel causative gene for autosomal recessive RT cerebellar ataxia."; RL PLoS ONE 8:E81884-E81884(2013). RN [57] RP VARIANT SCAR16 MET-246. RX PubMed=24113144; DOI=10.1093/hmg/ddt497; RA Shi C.H., Schisler J.C., Rubel C.E., Tan S., Song B., McDonough H., Xu L., RA Portbury A.L., Mao C.Y., True C., Wang R.H., Wang Q.Z., Sun S.L., RA Seminara S.B., Patterson C., Xu Y.M.; RT "Ataxia and hypogonadism caused by the loss of ubiquitin ligase activity of RT the U box protein CHIP."; RL Hum. Mol. Genet. 23:1013-1024(2014). RN [58] RP VARIANTS SCAR16 ASP-79; THR-79; VAL-123 AND THR-240. RX PubMed=24742043; DOI=10.1186/1750-1172-9-57; RA Synofzik M., Schuele R., Schulze M., Gburek-Augustat J., Schweizer R., RA Schirmacher A., Kraegeloh-Mann I., Gonzalez M., Young P., Zuechner S., RA Schoels L., Bauer P.; RT "Phenotype and frequency of STUB1 mutations: next-generation screenings in RT Caucasian ataxia and spastic paraplegia cohorts."; RL Orphanet J. Rare Dis. 9:57-64(2014). RN [59] RP VARIANT SCAR16 GLN-145. RX PubMed=24719489; DOI=10.1212/wnl.0000000000000416; RA Depondt C., Donatello S., Simonis N., Rai M., van Heurck R., Abramowicz M., RA D'Hooghe M., Pandolfo M.; RT "Autosomal recessive cerebellar ataxia of adult onset due to STUB1 RT mutations."; RL Neurology 82:1749-1750(2014). RN [60] RP VARIANTS SCAR16 LYS-28; SER-65 AND MET-246, AND CHARACTERIZATION OF RP VARIANTS SCAR16 LYS-28; SER-65 AND MET-246. RX PubMed=25258038; DOI=10.1186/s13023-014-0146-0; RA Heimdal K., Sanchez-Guixe M., Aukrust I., Bollerslev J., Bruland O., RA Jablonski G.E., Erichsen A.K., Gude E., Koht J.A., Erdal S., RA Fiskerstrand T., Haukanes B.I., Boman H., Bjoerkhaug L., Tallaksen C.M., RA Knappskog P.M., Johansson S.; RT "STUB1 mutations in autosomal recessive ataxias - evidence for mutation- RT specific clinical heterogeneity."; RL Orphanet J. Rare Dis. 9:146-146(2014). RN [61] RP VARIANT SER-57. RX PubMed=33798445; DOI=10.1016/j.ajhg.2021.03.013; RA Courage C., Oliver K.L., Park E.J., Cameron J.M., Grabinska K.A., Muona M., RA Canafoglia L., Gambardella A., Said E., Afawi Z., Baykan B., Brandt C., RA di Bonaventura C., Chew H.B., Criscuolo C., Dibbens L.M., Castellotti B., RA Riguzzi P., Labate A., Filla A., Giallonardo A.T., Berecki G., RA Jackson C.B., Joensuu T., Damiano J.A., Kivity S., Korczyn A., Palotie A., RA Striano P., Uccellini D., Giuliano L., Andermann E., Scheffer I.E., RA Michelucci R., Bahlo M., Franceschetti S., Sessa W.C., Berkovic S.F., RA Lehesjoki A.E.; RT "Progressive myoclonus epilepsies-Residual unsolved cases have marked RT genetic heterogeneity including dolichol-dependent protein glycosylation RT pathway genes."; RL Am. J. Hum. Genet. 108:722-738(2021). CC -!- FUNCTION: E3 ubiquitin-protein ligase which targets misfolded chaperone CC substrates towards proteasomal degradation (PubMed:10330192, CC PubMed:11146632, PubMed:11557750, PubMed:23990462, PubMed:26265139). CC Plays a role in the maintenance of mitochondrial morphology and CC promotes mitophagic removal of dysfunctional mitochondria; thereby acts CC as a protector against apoptosis in response to cellular stress (By CC similarity). Negatively regulates vascular smooth muscle contraction, CC via degradation of the transcriptional activator MYOCD and subsequent CC loss of transcription of genes involved in vascular smooth muscle CC contraction (By similarity). Promotes survival and proliferation of CC cardiac smooth muscle cells via ubiquitination and degradation of CC FOXO1, resulting in subsequent repression of FOXO1-mediated CC transcription of pro-apoptotic genes (PubMed:19483080). Ubiquitinates CC ICER-type isoforms of CREM and targets them for proteasomal CC degradation, thereby acts as a positive effector of MAPK/ERK-mediated CC inhibition of apoptosis in cardiomyocytes (PubMed:20724525). Inhibits CC lipopolysaccharide-induced apoptosis and hypertrophy in cardiomyocytes, CC via ubiquitination and subsequent proteasomal degradation of NFATC3 CC (PubMed:30980393). Collaborates with ATXN3 in the degradation of CC misfolded chaperone substrates: ATXN3 restricting the length of CC ubiquitin chain attached to STUB1/CHIP substrates and preventing CC further chain extension (PubMed:10330192, PubMed:11146632, CC PubMed:11557750, PubMed:23990462). Ubiquitinates NOS1 in concert with CC Hsp70 and Hsp40 (PubMed:15466472). Modulates the activity of several CC chaperone complexes, including Hsp70, Hsc70 and Hsp90 (PubMed:10330192, CC PubMed:11146632, PubMed:15466472). Ubiquitinates CHRNA3 targeting it CC for endoplasmic reticulum-associated degradation in cortical neurons, CC as part of the STUB1-VCP-UBXN2A complex (PubMed:26265139). CC Ubiquitinates and promotes ESR1 proteasomal degradation in response to CC age-related circulating estradiol (17-beta-estradiol/E2) decline, CC thereby promotes neuronal apoptosis in response to ischemic reperfusion CC injury (By similarity). Mediates transfer of non-canonical short CC ubiquitin chains to HSPA8 that have no effect on HSPA8 degradation CC (PubMed:11557750, PubMed:23990462). Mediates polyubiquitination of DNA CC polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby CC playing a role in base-excision repair: catalyzes polyubiquitination by CC amplifying the HUWE1/ARF-BP1-dependent monoubiquitination and leading CC to POLB-degradation by the proteasome (PubMed:19713937). Mediates CC polyubiquitination of CYP3A4 (PubMed:19103148). Ubiquitinates EPHA2 and CC may regulate the receptor stability and activity through proteasomal CC degradation (PubMed:19567782). Acts as a co-chaperone for HSPA1A and CC HSPA1B chaperone proteins and promotes ubiquitin-mediated protein CC degradation (PubMed:27708256). Negatively regulates the suppressive CC function of regulatory T-cells (Treg) during inflammation by mediating CC the ubiquitination and degradation of FOXP3 in a HSPA1A/B-dependent CC manner (PubMed:23973223). Catalyzes monoubiquitination of SIRT6, CC preventing its degradation by the proteasome (PubMed:24043303). Likely CC mediates polyubiquitination and down-regulates plasma membrane CC expression of PD-L1/CD274, an immune inhibitory ligand critical for CC immune tolerance to self and antitumor immunity (PubMed:28813410). CC Negatively regulates TGF-beta signaling by modulating the basal level CC of SMAD3 via ubiquitin-mediated degradation (PubMed:24613385). Plays a CC role in the degradation of TP53 (PubMed:26634371). Mediates CC ubiquitination of RIPK3 leading to its subsequent proteasome-dependent CC degradation (PubMed:29883609). May regulate myosin assembly in striated CC muscles together with UBE4B and VCP/p97 by targeting myosin chaperone CC UNC45B for proteasomal degradation (PubMed:17369820). Ubiquitinates CC PPARG in macrophages playing a role in M2 macrophages polarization and CC angiogenesis (By similarity). {ECO:0000250|UniProtKB:A6HD62, CC ECO:0000250|UniProtKB:Q9WUD1, ECO:0000269|PubMed:10330192, CC ECO:0000269|PubMed:11146632, ECO:0000269|PubMed:11557750, CC ECO:0000269|PubMed:15466472, ECO:0000269|PubMed:17369820, CC ECO:0000269|PubMed:19103148, ECO:0000269|PubMed:19483080, CC ECO:0000269|PubMed:19567782, ECO:0000269|PubMed:19713937, CC ECO:0000269|PubMed:20724525, ECO:0000269|PubMed:23973223, CC ECO:0000269|PubMed:23990462, ECO:0000269|PubMed:24043303, CC ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:26265139, CC ECO:0000269|PubMed:26634371, ECO:0000269|PubMed:27708256, CC ECO:0000269|PubMed:28813410, ECO:0000269|PubMed:29883609, CC ECO:0000269|PubMed:30980393}. CC -!- CATALYTIC ACTIVITY: CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:11557750, CC ECO:0000269|PubMed:15466472, ECO:0000269|PubMed:24043303}; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:11557750, ECO:0000269|PubMed:15466472}. CC -!- SUBUNIT: Homodimer (By similarity). Interacts with BAG2 CC (PubMed:16169850). Interacts with E2 ubiquitin conjugating enzymes CC UBE2D1, UBE2D2 and UBE2D3 (PubMed:11557750). Detected in a ternary CC complex containing STUB1, HSPA1A and HSPBP1 (PubMed:15215316). Part of CC a complex composed of STUB1/CHIP, VCP/p97, CHRNA3, and UBXN2A that CC modulates the ubiquitination and endoplasmic reticulum-associated CC degradation (ERAD) of CHRNA3 (PubMed:26265139). Within the complex CC UBXN2A acts as a scaffold protein required for the interaction of CC CHRNA3 with VCP/p97, this interaction also inhibits CHRNA3 CC ubiquitination by STUB1/CHIP and subsequently ERAD (PubMed:26265139). CC Interacts with MKKS (PubMed:18094050). Interacts with DNAAF4 CC (PubMed:19423554). Interacts (when monoubiquitinated) with ATXN3. CC Interacts with UBE2W. Interacts (via the U-box domain) with the UBE2V2- CC UBE2N heterodimer; the complex has a specific 'Lys-63'-linked CC polyubiquitination activity (By similarity). Interacts with DNAJB6 CC (PubMed:22366786). Interacts with FLCN (PubMed:27353360). Interacts CC with HSP90AA1 (PubMed:24613385, PubMed:27353360). Interacts with HSP90 CC (PubMed:11146632). Interacts with UBE2N and UBE2V1 (PubMed:16307917). CC Interacts (via TPR repeats) with HSPA8 (via C-terminus) CC (PubMed:10330192, PubMed:11557750, PubMed:23990462, PubMed:27708256). CC Interacts (via TPR repeats) with HSPA1A (via C-terminus) CC (PubMed:10330192). Interacts with the non-acetylated form of HSPA1A and CC HSPA1B (PubMed:27708256). Interacts with SMAD3 and HSP90AB1 CC (PubMed:24613385). Interacts with UBE4B (PubMed:17369820). Interacts CC with PRMT5 (PubMed:33376131). Interacts with MYOCD (via C-terminus) (By CC similarity). Interacts with FOXO1 (when phosphorylated on 'Ser-256') CC (PubMed:19483080). Interacts with MAPK7/ERK5; the interaction is CC enhanced in the presence of IGF1 or MAP2K5 and promotes STUB1/CHIP E3 CC ligase activity (PubMed:20724525). Interacts with and ubiquitinates CC ESR1; the interaction is promoted in the absence of estradiol (17-beta- CC estradiol/E2) (By similarity). Interacts with ESR2 (By similarity). CC Interacts with and ubiquitinates NFATC3; HSPA1A/HSP70 is required as a CC co-chaperone (PubMed:30980393). In macrophages, interacts with PAQR3; CC the interaction promotes PPARG poylubiquitination and STUB1-mediated CC degradation (By similarity). Component of the chaperone-assisted CC selective autophagy (CASA) complex consisting of BAG3, HSPA8/HSC70, CC HSPB8 and STUB1/CHIP (PubMed:20060297). {ECO:0000250|UniProtKB:A6HD62, CC ECO:0000250|UniProtKB:Q9WUD1, ECO:0000269|PubMed:10330192, CC ECO:0000269|PubMed:11146632, ECO:0000269|PubMed:11557750, CC ECO:0000269|PubMed:15215316, ECO:0000269|PubMed:16169850, CC ECO:0000269|PubMed:16307917, ECO:0000269|PubMed:17369820, CC ECO:0000269|PubMed:18094050, ECO:0000269|PubMed:19423554, CC ECO:0000269|PubMed:19483080, ECO:0000269|PubMed:19713937, CC ECO:0000269|PubMed:20060297, ECO:0000269|PubMed:20724525, CC ECO:0000269|PubMed:22366786, ECO:0000269|PubMed:23990462, CC ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:26265139, CC ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:27708256, CC ECO:0000269|PubMed:30980393}. CC -!- INTERACTION: CC Q9UNE7; P01023: A2M; NbExp=3; IntAct=EBI-357085, EBI-640741; CC Q9UNE7; Q96AP0: ACD; NbExp=2; IntAct=EBI-357085, EBI-717666; CC Q9UNE7; P61158: ACTR3; NbExp=3; IntAct=EBI-357085, EBI-351428; CC Q9UNE7; A0A0S2Z5Q7: ALS2; NbExp=3; IntAct=EBI-357085, EBI-25928834; CC Q9UNE7; Q86WG3: ATCAY; NbExp=4; IntAct=EBI-357085, EBI-1783328; CC Q9UNE7; Q99933: BAG1; NbExp=2; IntAct=EBI-357085, EBI-1030678; CC Q9UNE7; O95816: BAG2; NbExp=6; IntAct=EBI-357085, EBI-355275; CC Q9UNE7; O95817: BAG3; NbExp=3; IntAct=EBI-357085, EBI-747185; CC Q9UNE7; J3KQ12: BSCL2; NbExp=3; IntAct=EBI-357085, EBI-11532900; CC Q9UNE7; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-357085, EBI-1383687; CC Q9UNE7; Q9NRJ3: CCL28; NbExp=3; IntAct=EBI-357085, EBI-7783254; CC Q9UNE7; Q8N5K1: CISD2; NbExp=3; IntAct=EBI-357085, EBI-1045797; CC Q9UNE7; Q8NE08: COL25A1; NbExp=3; IntAct=EBI-357085, EBI-25836642; CC Q9UNE7; P21964-2: COMT; NbExp=3; IntAct=EBI-357085, EBI-10200977; CC Q9UNE7; Q15438: CYTH1; NbExp=3; IntAct=EBI-357085, EBI-997830; CC Q9UNE7; P53355: DAPK1; NbExp=2; IntAct=EBI-357085, EBI-358616; CC Q9UNE7; G5E9A7: DMWD; NbExp=3; IntAct=EBI-357085, EBI-10976677; CC Q9UNE7; Q8WXU2-2: DNAAF4; NbExp=3; IntAct=EBI-357085, EBI-9381887; CC Q9UNE7; A0AVK6: E2F8; NbExp=3; IntAct=EBI-357085, EBI-7779316; CC Q9UNE7; P00533: EGFR; NbExp=4; IntAct=EBI-357085, EBI-297353; CC Q9UNE7; O00471: EXOC5; NbExp=3; IntAct=EBI-357085, EBI-949824; CC Q9UNE7; O75344: FKBP6; NbExp=3; IntAct=EBI-357085, EBI-744771; CC Q9UNE7; Q9BZS1: FOXP3; NbExp=7; IntAct=EBI-357085, EBI-983719; CC Q9UNE7; P06241: FYN; NbExp=3; IntAct=EBI-357085, EBI-515315; CC Q9UNE7; P22466: GAL; NbExp=3; IntAct=EBI-357085, EBI-6624768; CC Q9UNE7; Q53GS7: GLE1; NbExp=3; IntAct=EBI-357085, EBI-1955541; CC Q9UNE7; P28799: GRN; NbExp=3; IntAct=EBI-357085, EBI-747754; CC Q9UNE7; P07900: HSP90AA1; NbExp=9; IntAct=EBI-357085, EBI-296047; CC Q9UNE7; P08238: HSP90AB1; NbExp=5; IntAct=EBI-357085, EBI-352572; CC Q9UNE7; P08107: HSPA1B; NbExp=5; IntAct=EBI-357085, EBI-629985; CC Q9UNE7; P11142: HSPA8; NbExp=9; IntAct=EBI-357085, EBI-351896; CC Q9UNE7; P04792: HSPB1; NbExp=4; IntAct=EBI-357085, EBI-352682; CC Q9UNE7; P42858: HTT; NbExp=12; IntAct=EBI-357085, EBI-466029; CC Q9UNE7; P02545: LMNA; NbExp=3; IntAct=EBI-357085, EBI-351935; CC Q9UNE7; Q07954-2: LRP1; NbExp=3; IntAct=EBI-357085, EBI-25833471; CC Q9UNE7; Q5S007: LRRK2; NbExp=4; IntAct=EBI-357085, EBI-5323863; CC Q9UNE7; Q9Y2U5: MAP3K2; NbExp=9; IntAct=EBI-357085, EBI-357393; CC Q9UNE7; P10636: MAPT; NbExp=2; IntAct=EBI-357085, EBI-366182; CC Q9UNE7; P58340: MLF1; NbExp=2; IntAct=EBI-357085, EBI-721328; CC Q9UNE7; Q15773: MLF2; NbExp=4; IntAct=EBI-357085, EBI-1051875; CC Q9UNE7; P00540: MOS; NbExp=2; IntAct=EBI-357085, EBI-1757866; CC Q9UNE7; P05164: MPO; NbExp=3; IntAct=EBI-357085, EBI-2556173; CC Q9UNE7; P13591: NCAM1; NbExp=3; IntAct=EBI-357085, EBI-2846607; CC Q9UNE7; P35240: NF2; NbExp=3; IntAct=EBI-357085, EBI-1014472; CC Q9UNE7; P08138: NGFR; NbExp=3; IntAct=EBI-357085, EBI-1387782; CC Q9UNE7; Q96PB7: OLFM3; NbExp=4; IntAct=EBI-357085, EBI-10292253; CC Q9UNE7; Q96PB7-3: OLFM3; NbExp=3; IntAct=EBI-357085, EBI-12005356; CC Q9UNE7; Q9BZ23-2: PANK2; NbExp=3; IntAct=EBI-357085, EBI-25929070; CC Q9UNE7; O00628-2: PEX7; NbExp=3; IntAct=EBI-357085, EBI-25882083; CC Q9UNE7; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-357085, EBI-9090282; CC Q9UNE7; P17612: PRKACA; NbExp=3; IntAct=EBI-357085, EBI-476586; CC Q9UNE7; O60260-5: PRKN; NbExp=6; IntAct=EBI-357085, EBI-21251460; CC Q9UNE7; P51149: RAB7A; NbExp=3; IntAct=EBI-357085, EBI-1056089; CC Q9UNE7; P04049: RAF1; NbExp=8; IntAct=EBI-357085, EBI-365996; CC Q9UNE7; Q14257: RCN2; NbExp=3; IntAct=EBI-357085, EBI-356710; CC Q9UNE7; O95072: REC8; NbExp=2; IntAct=EBI-357085, EBI-9361206; CC Q9UNE7; Q9UGC6: RGS17; NbExp=3; IntAct=EBI-357085, EBI-3918154; CC Q9UNE7; Q9BVN2: RUSC1; NbExp=3; IntAct=EBI-357085, EBI-6257312; CC Q9UNE7; Q15019-2: SEPTIN2; NbExp=3; IntAct=EBI-357085, EBI-10983222; CC Q9UNE7; P01011: SERPINA3; NbExp=3; IntAct=EBI-357085, EBI-296557; CC Q9UNE7; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-357085, EBI-5235340; CC Q9UNE7; O15269-2: SPTLC1; NbExp=3; IntAct=EBI-357085, EBI-25912901; CC Q9UNE7; Q13501: SQSTM1; NbExp=3; IntAct=EBI-357085, EBI-307104; CC Q9UNE7; Q86WV8: TSC1; NbExp=3; IntAct=EBI-357085, EBI-12806590; CC Q9UNE7; Q99757: TXN2; NbExp=3; IntAct=EBI-357085, EBI-2932492; CC Q9UNE7; P68036: UBE2L3; NbExp=3; IntAct=EBI-357085, EBI-711173; CC Q9UNE7; P61088: UBE2N; NbExp=5; IntAct=EBI-357085, EBI-1052908; CC Q9UNE7; Q7Z7E8: UBE2Q1; NbExp=3; IntAct=EBI-357085, EBI-1783287; CC Q9UNE7; Q9UBQ0-2: VPS29; NbExp=3; IntAct=EBI-357085, EBI-11141397; CC Q9UNE7; O76024: WFS1; NbExp=3; IntAct=EBI-357085, EBI-720609; CC Q9UNE7; Q5QJC9: Bag5; Xeno; NbExp=5; IntAct=EBI-357085, EBI-1374246; CC Q9UNE7; P32502: GCD7; Xeno; NbExp=3; IntAct=EBI-357085, EBI-6260; CC Q9UNE7; P38247: SLM4; Xeno; NbExp=3; IntAct=EBI-357085, EBI-21507; CC Q9UNE7; P12504: vif; Xeno; NbExp=2; IntAct=EBI-357085, EBI-779991; CC Q9UNE7-1; P31749: AKT1; NbExp=5; IntAct=EBI-15687717, EBI-296087; CC Q9UNE7-1; P11142-1: HSPA8; NbExp=4; IntAct=EBI-15687717, EBI-351908; CC Q9UNE7-1; Q5S007: LRRK2; NbExp=2; IntAct=EBI-15687717, EBI-5323863; CC Q9UNE7-1; P10636: MAPT; NbExp=5; IntAct=EBI-15687717, EBI-366182; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10330192, CC ECO:0000269|PubMed:17369820, ECO:0000269|PubMed:23973223}. Nucleus CC {ECO:0000269|PubMed:23973223}. Mitochondrion CC {ECO:0000250|UniProtKB:A6HD62}. Note=Translocates to the nucleus in CC response to inflammatory signals in regulatory T-cells (Treg). CC Localizes to mitochondria following oxygen and glucose deprivation- CC induced cellular stress (By similarity). {ECO:0000250|UniProtKB:A6HD62, CC ECO:0000269|PubMed:23973223}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9UNE7-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UNE7-2; Sequence=VSP_015947; CC -!- TISSUE SPECIFICITY: Expressed in differentiated myotubes (at protein CC level) (PubMed:17369820). Highly expressed in skeletal muscle, heart, CC pancreas, brain and placenta (PubMed:10330192, PubMed:11435423). CC Detected in kidney, liver and lung (PubMed:10330192, PubMed:11435423). CC {ECO:0000269|PubMed:10330192, ECO:0000269|PubMed:11435423, CC ECO:0000269|PubMed:17369820}. CC -!- INDUCTION: Up-regulated by inflammatory signals in regulatory T-cells CC (Treg). {ECO:0000269|PubMed:23973223}. CC -!- DOMAIN: The U-box domain is required for the ubiquitin protein ligase CC activity. {ECO:0000250|UniProtKB:Q9WUD1}. CC -!- DOMAIN: The TPR domain is essential for ubiquitination mediated by CC UBE2D1. {ECO:0000269|PubMed:18042044}. CC -!- PTM: Monoubiquitinated at Lys-2 following cell stress by UBE2W, CC promoting the interaction with ATXN3 (By similarity). Auto- CC ubiquitinated; mediated by UBE2D1 and UBE2D2 and enhanced in the CC presence of MAP2K5 (PubMed:20724525). {ECO:0000250, CC ECO:0000250|UniProtKB:Q9WUD1, ECO:0000269|PubMed:18042044, CC ECO:0000269|PubMed:20724525, ECO:0000269|PubMed:23560854}. CC -!- DISEASE: Spinocerebellar ataxia, autosomal recessive, 16 (SCAR16) CC [MIM:615768]: A form of spinocerebellar ataxia, a clinically and CC genetically heterogeneous group of cerebellar disorders. Patients show CC progressive incoordination of gait and often poor coordination of CC hands, speech and eye movements, due to degeneration of the cerebellum CC with variable involvement of the brainstem and spinal cord. SCAR16 is CC characterized by truncal and limb ataxia resulting in gait instability. CC Additionally, patients may show dysarthria, nystagmus, spasticity of CC the lower limbs, and mild peripheral sensory neuropathy. CC {ECO:0000269|PubMed:24113144, ECO:0000269|PubMed:24312598, CC ECO:0000269|PubMed:24719489, ECO:0000269|PubMed:24742043, CC ECO:0000269|PubMed:25258038}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Spinocerebellar ataxia 48 (SCA48) [MIM:618093]: A form of CC spinocerebellar ataxia, a clinically and genetically heterogeneous CC group of cerebellar disorders. Patients show progressive incoordination CC of gait and often poor coordination of hands, speech and eye movements, CC due to degeneration of the cerebellum with variable involvement of the CC brainstem and spinal cord. SCA48 is an autosomal dominant CC neurodegenerative disease characterized by onset in mid-adulthood of CC progressive cognitive decline and gait ataxia, and vermian and CC hemispheric cerebellar atrophy. {ECO:0000269|PubMed:30381368}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: Antibodies against STUB1 are found in patients with CC chronic lymphocytic leukemia (CLL) and in colorectal cancer patients. 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; AF039689; AAC18038.1; -; mRNA. DR EMBL; AF129085; AAD33400.1; -; mRNA. DR EMBL; AF432221; AAL99927.1; -; mRNA. DR EMBL; AF217968; AAG17211.1; -; mRNA. DR EMBL; AE006464; AAK61242.1; -; Genomic_DNA. DR EMBL; Z92544; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471112; EAW85758.1; -; Genomic_DNA. DR EMBL; BC007545; AAH07545.1; -; mRNA. DR EMBL; BC017178; AAH17178.1; -; mRNA. DR EMBL; BC022788; AAH22788.1; -; mRNA. DR EMBL; BC063617; AAH63617.1; -; mRNA. DR CCDS; CCDS10419.1; -. [Q9UNE7-1] DR CCDS; CCDS76797.1; -. [Q9UNE7-2] DR RefSeq; NP_001280126.1; NM_001293197.2. [Q9UNE7-2] DR RefSeq; NP_005852.2; NM_005861.4. [Q9UNE7-1] DR PDB; 4KBQ; X-ray; 2.91 A; A/B=21-154. DR PDB; 6EFK; X-ray; 1.50 A; A/B=23-154. DR PDB; 6NSV; X-ray; 1.30 A; A/B=23-152. DR PDB; 7TB1; X-ray; 1.78 A; A/B=16-153. DR PDB; 8EHZ; X-ray; 2.06 A; A/B=21-154. DR PDB; 8EI0; X-ray; 1.47 A; A=23-154. DR PDB; 8F14; X-ray; 1.69 A; A=23-154. DR PDB; 8F15; X-ray; 1.73 A; A/B/C=23-154. DR PDB; 8F16; X-ray; 1.56 A; A/B=23-154. DR PDB; 8F17; X-ray; 2.21 A; A/B=23-154. DR PDB; 8FYU; X-ray; 1.85 A; A/B=22-149. DR PDB; 8GCK; X-ray; 1.37 A; A/B=22-149. DR PDB; 8SUV; X-ray; 1.63 A; A/B/C/D=21-154. DR PDB; 9DRY; EM; 7.02 A; A/B=226-300. DR PDB; 9DYA; X-ray; 1.89 A; A=21-154. DR PDB; 9DYB; X-ray; 1.60 A; A=21-154. DR PDBsum; 4KBQ; -. DR PDBsum; 6EFK; -. DR PDBsum; 6NSV; -. DR PDBsum; 7TB1; -. DR PDBsum; 8EHZ; -. DR PDBsum; 8EI0; -. DR PDBsum; 8F14; -. DR PDBsum; 8F15; -. DR PDBsum; 8F16; -. DR PDBsum; 8F17; -. DR PDBsum; 8FYU; -. DR PDBsum; 8GCK; -. DR PDBsum; 8SUV; -. DR PDBsum; 9DRY; -. DR PDBsum; 9DYA; -. DR PDBsum; 9DYB; -. DR AlphaFoldDB; Q9UNE7; -. DR BMRB; Q9UNE7; -. DR EMDB; EMD-47134; -. DR SMR; Q9UNE7; -. DR BioGRID; 115563; 791. DR CORUM; Q9UNE7; -. DR DIP; DIP-29752N; -. DR FunCoup; Q9UNE7; 3456. DR IntAct; Q9UNE7; 350. DR MINT; Q9UNE7; -. DR STRING; 9606.ENSP00000219548; -. DR ChEMBL; CHEMBL5465258; -. DR GuidetoPHARMACOLOGY; 3202; -. DR MoonDB; Q9UNE7; Predicted. DR GlyGen; Q9UNE7; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9UNE7; -. DR PhosphoSitePlus; Q9UNE7; -. DR SwissPalm; Q9UNE7; -. DR BioMuta; STUB1; -. DR DMDM; 78099173; -. DR jPOST; Q9UNE7; -. DR MassIVE; Q9UNE7; -. DR PaxDb; 9606-ENSP00000219548; -. DR PeptideAtlas; Q9UNE7; -. DR ProteomicsDB; 85282; -. [Q9UNE7-1] DR ProteomicsDB; 85283; -. [Q9UNE7-2] DR Pumba; Q9UNE7; -. DR Antibodypedia; 22808; 479 antibodies from 46 providers. DR DNASU; 10273; -. DR Ensembl; ENST00000219548.9; ENSP00000219548.4; ENSG00000103266.12. [Q9UNE7-1] DR Ensembl; ENST00000564370.5; ENSP00000456875.1; ENSG00000103266.12. [Q9UNE7-2] DR Ensembl; ENST00000565677.5; ENSP00000457228.1; ENSG00000103266.12. [Q9UNE7-2] DR GeneID; 10273; -. DR KEGG; hsa:10273; -. DR MANE-Select; ENST00000219548.9; ENSP00000219548.4; NM_005861.4; NP_005852.2. DR UCSC; uc002cit.4; human. [Q9UNE7-1] DR AGR; HGNC:11427; -. DR ClinPGx; PA36227; -. DR CTD; 10273; -. DR DisGeNET; 10273; -. DR GeneCards; STUB1; -. DR HGNC; HGNC:11427; STUB1. DR HPA; ENSG00000103266; Low tissue specificity. DR MalaCards; STUB1; -. DR MIM; 607207; gene. DR MIM; 615768; phenotype. DR MIM; 618093; phenotype. DR OpenTargets; ENSG00000103266; -. DR Orphanet; 412057; Autosomal recessive cerebellar ataxia due to STUB1 deficiency. DR Orphanet; 631103; Spinocerebellar ataxia type 48. DR VEuPathDB; HostDB:ENSG00000103266; -. DR eggNOG; KOG4642; Eukaryota. DR GeneTree; ENSGT00930000151045; -. DR HOGENOM; CLU_056455_1_0_1; -. DR InParanoid; Q9UNE7; -. DR OMA; WAGVEHD; -. DR OrthoDB; 629492at2759; -. DR PAN-GO; Q9UNE7; 9 GO annotations based on evolutionary models. DR PhylomeDB; Q9UNE7; -. DR BRENDA; 2.3.2.27; 2681. DR PathwayCommons; Q9UNE7; -. DR Reactome; R-HSA-2173788; Downregulation of TGF-beta receptor signaling. DR Reactome; R-HSA-5213460; RIPK1-mediated regulated necrosis. DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling. DR Reactome; R-HSA-5675482; Regulation of necroptotic cell death. DR Reactome; R-HSA-8863795; Downregulation of ERBB2 signaling. DR Reactome; R-HSA-8939902; Regulation of RUNX2 expression and activity. DR Reactome; R-HSA-8948751; Regulation of PTEN stability and activity. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q9UNE7; -. DR SIGNOR; Q9UNE7; -. DR UniPathway; UPA00143; -. DR Agora; ENSG00000103266; -. DR BioGRID-ORCS; 10273; 123 hits in 1208 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; STUB1; human. DR EvolutionaryTrace; Q9UNE7; -. DR GeneWiki; STUB1; -. DR GenomeRNAi; 10273; -. DR Pharos; Q9UNE7; Tbio. DR PRO; PR:Q9UNE7; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q9UNE7; protein. DR Bgee; ENSG00000103266; Expressed in lateral nuclear group of thalamus and 202 other cell types or tissues. DR ExpressionAtlas; Q9UNE7; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:HGNC-UCL. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ParkinsonsUK-UCL. DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB. DR GO; GO:0042405; C:nuclear inclusion body; IDA:BHF-UCL. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProt. DR GO; GO:0101031; C:protein folding chaperone complex; IPI:ARUK-UCL. DR GO; GO:0031371; C:ubiquitin conjugating enzyme complex; TAS:HGNC-UCL. DR GO; GO:0000151; C:ubiquitin ligase complex; IDA:UniProtKB. DR GO; GO:0030018; C:Z disc; IBA:GO_Central. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0001664; F:G protein-coupled receptor binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0031072; F:heat shock protein binding; IPI:ARUK-UCL. DR GO; GO:0030544; F:Hsp70 protein binding; IDA:HGNC-UCL. DR GO; GO:0051879; F:Hsp90 protein binding; IDA:BHF-UCL. DR GO; GO:0019900; F:kinase binding; IPI:BHF-UCL. DR GO; GO:0051787; F:misfolded protein binding; IDA:BHF-UCL. DR GO; GO:0042803; F:protein homodimerization activity; IPI:ParkinsonsUK-UCL. DR GO; GO:0051087; F:protein-folding chaperone binding; IPI:ARUK-UCL. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; TAS:HGNC-UCL. DR GO; GO:0070412; F:R-SMAD binding; IPI:HGNC-UCL. DR GO; GO:0046332; F:SMAD binding; IPI:UniProtKB. DR GO; GO:0048156; F:tau protein binding; NAS:ARUK-UCL. DR GO; GO:0030911; F:TPR domain binding; IDA:HGNC-UCL. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB. DR GO; GO:0034450; F:ubiquitin-ubiquitin ligase activity; ISS:UniProtKB. DR GO; GO:0034605; P:cellular response to heat; ISS:ARUK-UCL. DR GO; GO:0071456; P:cellular response to hypoxia; ISS:ARUK-UCL. DR GO; GO:0071218; P:cellular response to misfolded protein; IDA:BHF-UCL. DR GO; GO:0061684; P:chaperone-mediated autophagy; IEA:Ensembl. DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW. DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IEA:Ensembl. DR GO; GO:0036503; P:ERAD pathway; IMP:ParkinsonsUK-UCL. DR GO; GO:0038128; P:ERBB2 signaling pathway; TAS:Reactome. DR GO; GO:0000165; P:MAPK cascade; ISS:UniProtKB. DR GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; IEA:Ensembl. DR GO; GO:0035359; P:negative regulation of peroxisome proliferator activated receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0034392; P:negative regulation of smooth muscle cell apoptotic process; IMP:UniProtKB. DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IMP:UniProtKB. DR GO; GO:1904694; P:negative regulation of vascular associated smooth muscle contraction; IEA:Ensembl. DR GO; GO:0090035; P:positive regulation of chaperone-mediated protein complex assembly; IDA:BHF-UCL. DR GO; GO:1904294; P:positive regulation of ERAD pathway; IMP:UniProtKB. DR GO; GO:1901526; P:positive regulation of mitophagy; ISS:UniProtKB. DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:HGNC-UCL. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:HGNC-UCL. DR GO; GO:0045862; P:positive regulation of proteolysis; IMP:UniProtKB. DR GO; GO:0034393; P:positive regulation of smooth muscle cell apoptotic process; ISS:UniProtKB. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProtKB. DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB. DR GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB. DR GO; GO:0006513; P:protein monoubiquitination; IDA:UniProt. DR GO; GO:0000209; P:protein polyubiquitination; IDA:HGNC-UCL. DR GO; GO:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; IDA:BHF-UCL. DR GO; GO:0050821; P:protein stabilization; IDA:UniProt. DR GO; GO:0016567; P:protein ubiquitination; IDA:FlyBase. DR GO; GO:0031943; P:regulation of glucocorticoid metabolic process; IDA:HGNC-UCL. DR GO; GO:0031647; P:regulation of protein stability; IDA:BHF-UCL. DR GO; GO:0002931; P:response to ischemia; ISS:ARUK-UCL. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR CDD; cd16654; RING-Ubox_CHIP; 1. DR FunFam; 1.25.40.10:FF:000198; E3 ubiquitin-protein ligase CHIP isoform X2; 1. DR FunFam; 3.30.40.10:FF:000124; STIP1 homology and U box-containing protein 1; 1. DR Gene3D; 6.10.140.2020; -; 1. DR Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR045202; CHIP_RING-Ubox. DR InterPro; IPR041312; CHIP_TPR_N. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR019734; TPR_rpt. DR InterPro; IPR003613; Ubox_domain. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR46803; E3 UBIQUITIN-PROTEIN LIGASE CHIP; 1. DR PANTHER; PTHR46803:SF2; E3 UBIQUITIN-PROTEIN LIGASE CHIP; 1. DR Pfam; PF12895; ANAPC3; 1. DR Pfam; PF18391; CHIP_TPR_N; 1. DR Pfam; PF04564; U-box; 1. DR SMART; SM00028; TPR; 3. DR SMART; SM00504; Ubox; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR SUPFAM; SSF48452; TPR-like; 1. DR PROSITE; PS50005; TPR; 3. DR PROSITE; PS50293; TPR_REGION; 1. DR PROSITE; PS51698; U_BOX; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Direct protein sequencing; KW Disease variant; DNA damage; DNA repair; Isopeptide bond; Mitochondrion; KW Neurodegeneration; Nucleus; Phosphoprotein; Proteomics identification; KW Reference proteome; Repeat; Spinocerebellar ataxia; TPR repeat; KW Transferase; Ubl conjugation; Ubl conjugation pathway. FT CHAIN 1..303 FT /note="E3 ubiquitin-protein ligase CHIP" FT /id="PRO_0000106329" FT REPEAT 26..59 FT /note="TPR 1" FT REPEAT 60..93 FT /note="TPR 2" FT REPEAT 95..127 FT /note="TPR 3" FT DOMAIN 226..300 FT /note="U-box" FT REGION 1..30 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 101..200 FT /note="Required for interaction with MAPK7" FT /evidence="ECO:0000269|PubMed:20724525" FT REGION 142..196 FT /note="Required for interaction with and ubiquitination of FT MYOCD" FT /evidence="ECO:0000250|UniProtKB:A6HD62" FT REGION 143..303 FT /note="Required for ubiquitination of FOXO1" FT /evidence="ECO:0000269|PubMed:19483080" FT REGION 143..197 FT /note="Required for interaction with FOXO1" FT /evidence="ECO:0000269|PubMed:19483080" FT COMPBIAS 1..10 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 19 FT /note="Phosphoserine" FT /evidence="ECO:0000269|Ref.9, ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 23 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 25 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 149 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 273 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231" FT CROSSLNK 2 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:23560854" FT CROSSLNK 22 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:18042044" FT CROSSLNK 221 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:18042044" FT CROSSLNK 255 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:18042044" FT VAR_SEQ 1..72 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15498874" FT /id="VSP_015947" FT VARIANT 28 FT /note="E -> K (in SCAR16; reduces protein level; does not FT reduce ubiquitin ligase activity and autoubiquitination)" FT /evidence="ECO:0000269|PubMed:25258038" FT /id="VAR_072348" FT VARIANT 57 FT /note="P -> S (found in a patient with progressive FT myoclonus epilepsy; uncertain significance)" FT /evidence="ECO:0000269|PubMed:33798445" FT /id="VAR_085041" FT VARIANT 65 FT /note="N -> S (in SCAR16; reduces protein level; reduces FT ubiquitin ligase activity; does not change FT autoubiquitination; dbSNP:rs690016544)" FT /evidence="ECO:0000269|PubMed:25258038" FT /id="VAR_072349" FT VARIANT 79 FT /note="A -> D (in SCAR16; dbSNP:rs587777347)" FT /evidence="ECO:0000269|PubMed:24742043" FT /id="VAR_071293" FT VARIANT 79 FT /note="A -> T (in SCAR16; dbSNP:rs587777346)" FT /evidence="ECO:0000269|PubMed:24742043" FT /id="VAR_071294" FT VARIANT 123 FT /note="L -> V (in SCAR16; dbSNP:rs587777344)" FT /evidence="ECO:0000269|PubMed:24742043" FT /id="VAR_071295" FT VARIANT 130 FT /note="N -> I (in SCAR16; dbSNP:rs587777341)" FT /evidence="ECO:0000269|PubMed:24312598" FT /id="VAR_071296" FT VARIANT 145 FT /note="K -> Q (in SCAR16; dbSNP:rs146251364)" FT /evidence="ECO:0000269|PubMed:24719489" FT /id="VAR_072350" FT VARIANT 147 FT /note="W -> C (in SCAR16; dbSNP:rs587777342)" FT /evidence="ECO:0000269|PubMed:24312598" FT /id="VAR_071297" FT VARIANT 165 FT /note="L -> F (in SCAR16; dbSNP:rs587777340)" FT /evidence="ECO:0000269|PubMed:24312598" FT /id="VAR_071298" FT VARIANT 236 FT /note="S -> T (in SCAR16; dbSNP:rs2039692794)" FT /evidence="ECO:0000269|PubMed:24312598" FT /id="VAR_071299" FT VARIANT 240 FT /note="M -> T (in SCAR16; dbSNP:rs587777345)" FT /evidence="ECO:0000269|PubMed:24742043" FT /id="VAR_071300" FT VARIANT 246 FT /note="T -> M (in SCAR16; inhibits ubiquitin ligase FT activity and autoubiquitination; dbSNP:rs587777343)" FT /evidence="ECO:0000269|PubMed:24113144, FT ECO:0000269|PubMed:25258038" FT /id="VAR_071301" FT MUTAGEN 30 FT /note="K->A: Loss of interaction with FOXP3 and its ability FT to ubiquitinate FOXP3. Loss of interaction with SMAD3, FT HSPA8, HSP90AA1 and HSP90AB1. Reduces interaction, FT ubiquitination and proteasomal degradation of NFATC3. No FT effect on localization to the mitochondria following oxygen FT and glucose deprivation-induced cellular stress." FT /evidence="ECO:0000269|PubMed:23973223, FT ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:29934347, FT ECO:0000269|PubMed:30980393" FT MUTAGEN 260 FT /note="H->Q: Loss of ability to ubiquitinate FOXP3 and FT SIRT6. Abolishes STUB1-mediated degradation of CHRNA3. FT Abolishes autoubiquitination and ubiquitination of FT ICER-type isoforms of CREM. Reduces interaction, FT ubiquitination and proteasomal degradation of NFATC3. No FT effect on localization to the mitochondria following oxygen FT and glucose deprivation-induced cellular stress." FT /evidence="ECO:0000269|PubMed:20724525, FT ECO:0000269|PubMed:23973223, ECO:0000269|PubMed:24043303, FT ECO:0000269|PubMed:26265139, ECO:0000269|PubMed:29934347, FT ECO:0000269|PubMed:30980393" FT MUTAGEN 269 FT /note="P->A: Abolishes E3 ligase activity." FT /evidence="ECO:0000269|PubMed:23990462" FT CONFLICT 52 FT /note="A -> V (in Ref. 2; AAD33400)" FT /evidence="ECO:0000305" FT CONFLICT 272 FT /note="R -> G (in Ref. 1; AAC18038)" FT /evidence="ECO:0000305" FT CONFLICT 280 FT /note="L -> F (in Ref. 1; AAC18038)" FT /evidence="ECO:0000305" FT HELIX 26..38 FT /evidence="ECO:0007829|PDB:6NSV" FT HELIX 42..55 FT /evidence="ECO:0007829|PDB:6NSV" FT HELIX 60..72 FT /evidence="ECO:0007829|PDB:6NSV" FT HELIX 76..89 FT /evidence="ECO:0007829|PDB:6NSV" FT HELIX 94..106 FT /evidence="ECO:0007829|PDB:6NSV" FT HELIX 110..126 FT /evidence="ECO:0007829|PDB:6NSV" FT HELIX 134..149 FT /evidence="ECO:0007829|PDB:6NSV" SQ SEQUENCE 303 AA; 34856 MW; 7E7D6568B17070BF CRC64; MKGKEEKEGG ARLGAGGGSP EKSPSAQELK EQGNRLFVGR KYPEAAACYG RAITRNPLVA VYYTNRALCY LKMQQHEQAL ADCRRALELD GQSVKAHFFL GQCQLEMESY DEAIANLQRA YSLAKEQRLN FGDDIPSALR IAKKKRWNSI EERRIHQESE LHSYLSRLIA AERERELEEC QRNHEGDEDD SHVRAQQACI EAKHDKYMAD MDELFSQVDE KRKKRDIPDY LCGKISFELM REPCITPSGI TYDRKDIEEH LQRVGHFDPV TRSPLTQEQL IPNLAMKEVI DAFISENGWV EDY //