STUB1

The CHIP protein encoded by this gene binds to and inhibits the ATPase activity of the chaperone proteins HSC70 and HSP70 and blocks the forward reaction of the HSC70-HSP70 substrate-binding cycle. In addition, CHIP possesses E3 ubiquitin ligase activity and promotes ubiquitylation,{{cite journal | vauthors = Jiang J, Ballinger CA, Wu Y, Dai Q, Cyr DM, Höhfeld J, Patterson C | title = CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation | journal = The Journal of Biological Chemistry | volume = 276 | issue = 46 | pages = 42938–44 | date = Nov 2001 | pmid = 11557750 | doi = 10.1074/jbc.M101968200 | doi-access = free }} mainly of chaperone-bound misfolded proteins.

CHIP enhances HSP70 induction during acute stress and also mediates its turnover during the stress recovery process. Hence CHIP appears to maintain protein homeostasis by controlling chaperone levels during stress and recovery.{{cite journal | vauthors = Qian SB, McDonough H, Boellmann F, Cyr DM, Patterson C | title = CHIP-mediated stress recovery by sequential ubiquitination of substrates and Hsp70 | journal = Nature | volume = 440 | issue = 7083 | pages = 551–5 | date = Mar 2006 | pmid = 16554822 | doi = 10.1038/nature04600 | pmc = 4112096| bibcode = 2006Natur.440..551Q }}

Mutations in STUB1 cause spinocerebellar ataxia type 16.{{cite journal | vauthors = Synofzik M, Schüle R, Schulze M, Gburek-Augustat J, Schweizer R, Schirmacher A, Krägeloh-Mann I, Gonzalez M, Young P, Züchner S, Schöls L, Bauer P | title = Phenotype and frequency of STUB1 mutations: next-generation screenings in Caucasian ataxia and spastic paraplegia cohorts | journal = Orphanet Journal of Rare Diseases | volume = 9 | issue = 1 | pages = 57 | year = 2014 | pmid = 24742043 | pmc = 4021831 | doi = 10.1186/1750-1172-9-57 | doi-access = free }}{{failed verification|date=January 2025}}

STUB1 has been shown to interact with:

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• C-Raf,{{cite journal | vauthors = Dogan T, Harms GS, Hekman M, Karreman C, Oberoi TK, Alnemri ES, Rapp UR, Rajalingam K | title = X-linked and cellular IAPs modulate the stability of C-RAF kinase and cell motility | journal = Nature Cell Biology | volume = 10 | issue = 12 | pages = 1447–55 | date = Dec 2008 | pmid = 19011619 | doi = 10.1038/ncb1804 | s2cid = 6553549}}
• DNAJB1,
• HSPA1A,
• HSPA4,
• HSPA8,
• Parkin (ligase),{{cite journal | vauthors = Imai Y, Soda M, Hatakeyama S, Akagi T, Hashikawa T, Nakayama KI, Takahashi R | title = CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity | journal = Molecular Cell | volume = 10 | issue = 1 | pages = 55–67 | date = Jul 2002 | pmid = 12150907 | doi = 10.1016/s1097-2765(02)00583-x| doi-access = free }} and
• RUNX2.{{cite journal | vauthors = Li X, Huang M, Zheng H, Wang Y, Ren F, Shang Y, Zhai Y, Irwin DM, Shi Y, Chen D, Chang Z | title = CHIP promotes Runx2 degradation and negatively regulates osteoblast differentiation | journal = The Journal of Cell Biology | volume = 181 | issue = 6 | pages = 959–72 | date = Jun 2008 | pmid = 18541707 | pmc = 2426947 | doi = 10.1083/jcb.200711044}}

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{{Reflist|2}}

{{Refbegin | 2}}

• {{cite journal | vauthors = Patterson C | title = A new gun in town: the U box is a ubiquitin ligase domain | journal = Science's STKE | volume = 2002 | issue = 116 | pages = pe4 | date = Jan 2002 | pmid = 11805346 | doi = 10.1126/stke.2002.116.pe4 | s2cid = 31977936 }}
• {{cite journal | vauthors = Scanlan MJ, Chen YT, Williamson B, Gure AO, Stockert E, Gordan JD, Türeci O, Sahin U, Pfreundschuh M, Old LJ | title = Characterization of human colon cancer antigens recognized by autologous antibodies | journal = International Journal of Cancer | volume = 76 | issue = 5 | pages = 652–8 | date = May 1998 | pmid = 9610721 | doi = 10.1002/(SICI)1097-0215(19980529)76:5<652::AID-IJC7>3.0.CO;2-P | doi-access = free }}
• {{cite journal | vauthors = Ballinger CA, Connell P, Wu Y, Hu Z, Thompson LJ, Yin LY, Patterson C | title = Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions | journal = Molecular and Cellular Biology | volume = 19 | issue = 6 | pages = 4535–45 | date = Jun 1999 | pmid = 10330192 | pmc = 104411 | doi = 10.1128/mcb.19.6.4535}}
• {{cite journal | vauthors = Connell P, Ballinger CA, Jiang J, Wu Y, Thompson LJ, Höhfeld J, Patterson C | title = The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins | journal = Nature Cell Biology | volume = 3 | issue = 1 | pages = 93–6 | date = Jan 2001 | pmid = 11146632 | doi = 10.1038/35050618 | s2cid = 19161960 }}
• {{cite journal | vauthors = Daniels RJ, Peden JF, Lloyd C, Horsley SW, Clark K, Tufarelli C, Kearney L, Buckle VJ, Doggett NA, Flint J, Higgs DR | title = Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16 | journal = Human Molecular Genetics | volume = 10 | issue = 4 | pages = 339–52 | date = Feb 2001 | pmid = 11157797 | doi = 10.1093/hmg/10.4.339 | doi-access = free }}
• {{cite journal | vauthors = Jiang J, Ballinger CA, Wu Y, Dai Q, Cyr DM, Höhfeld J, Patterson C | title = CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation | journal = The Journal of Biological Chemistry | volume = 276 | issue = 46 | pages = 42938–44 | date = Nov 2001 | pmid = 11557750 | doi = 10.1074/jbc.M101968200 | doi-access = free }}
• {{cite journal | vauthors = Demand J, Alberti S, Patterson C, Höhfeld J | title = Cooperation of a ubiquitin domain protein and an E3 ubiquitin ligase during chaperone/proteasome coupling | journal = Current Biology | volume = 11 | issue = 20 | pages = 1569–77 | date = Oct 2001 | pmid = 11676916 | doi = 10.1016/S0960-9822(01)00487-0 | s2cid = 2021754 | doi-access = free | bibcode = 2001CBio...11.1569D }}
• {{cite journal | vauthors = Imai Y, Soda M, Hatakeyama S, Akagi T, Hashikawa T, Nakayama KI, Takahashi R | title = CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity | journal = Molecular Cell | volume = 10 | issue = 1 | pages = 55–67 | date = Jul 2002 | pmid = 12150907 | doi = 10.1016/S1097-2765(02)00583-X | doi-access = free }}
• {{cite journal | vauthors = Krackhardt AM, Witzens M, Harig S, Hodi FS, Zauls AJ, Chessia M, Barrett P, Gribben JG | title = Identification of tumor-associated antigens in chronic lymphocytic leukemia by SEREX | journal = Blood | volume = 100 | issue = 6 | pages = 2123–31 | date = Sep 2002 | pmid = 12200376 | doi = 10.1182/blood-2002-02-0513 | doi-access = free }}
• {{cite journal | vauthors = Cardozo CP, Michaud C, Ost MC, Fliss AE, Yang E, Patterson C, Hall SJ, Caplan AJ | title = C-terminal Hsp-interacting protein slows androgen receptor synthesis and reduces its rate of degradation | journal = Archives of Biochemistry and Biophysics | volume = 410 | issue = 1 | pages = 134–40 | date = Feb 2003 | pmid = 12559985 | doi = 10.1016/S0003-9861(02)00680-X }}
• {{cite journal | vauthors = Zhou P, Fernandes N, Dodge IL, Reddi AL, Rao N, Safran H, DiPetrillo TA, Wazer DE, Band V, Band H | title = ErbB2 degradation mediated by the co-chaperone protein CHIP | journal = The Journal of Biological Chemistry | volume = 278 | issue = 16 | pages = 13829–37 | date = Apr 2003 | pmid = 12574167 | doi = 10.1074/jbc.M209640200 | doi-access = free }}
• {{cite journal | vauthors = Shimura H, Schwartz D, Gygi SP, Kosik KS | title = CHIP-Hsc70 complex ubiquitinates phosphorylated tau and enhances cell survival | journal = The Journal of Biological Chemistry | volume = 279 | issue = 6 | pages = 4869–76 | date = Feb 2004 | pmid = 14612456 | doi = 10.1074/jbc.M305838200 | doi-access = free }}
• {{cite journal | vauthors = Li L, Xin H, Xu X, Huang M, Zhang X, Chen Y, Zhang S, Fu XY, Chang Z | title = CHIP mediates degradation of Smad proteins and potentially regulates Smad-induced transcription | journal = Molecular and Cellular Biology | volume = 24 | issue = 2 | pages = 856–64 | date = Jan 2004 | pmid = 14701756 | pmc = 343794 | doi = 10.1128/MCB.24.2.856-864.2004 }}
• {{cite journal | vauthors = Petrucelli L, Dickson D, Kehoe K, Taylor J, Snyder H, Grover A, De Lucia M, McGowan E, Lewis J, Prihar G, Kim J, Dillmann WH, Browne SE, Hall A, Voellmy R, Tsuboi Y, Dawson TM, Wolozin B, Hardy J, Hutton M | author18-link=Benjamin Wolozin | title = CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation | journal = Human Molecular Genetics | volume = 13 | issue = 7 | pages = 703–14 | date = Apr 2004 | pmid = 14962978 | doi = 10.1093/hmg/ddh083 | doi-access = free }}
• {{cite journal | vauthors = Galigniana MD, Harrell JM, Housley PR, Patterson C, Fisher SK, Pratt WB | title = Retrograde transport of the glucocorticoid receptor in neurites requires dynamic assembly of complexes with the protein chaperone hsp90 and is linked to the CHIP component of the machinery for proteasomal degradation | journal = Brain Research. Molecular Brain Research | volume = 123 | issue = 1–2 | pages = 27–36 | date = Apr 2004 | pmid = 15046863 | doi = 10.1016/j.molbrainres.2003.12.015 | hdl = 11336/29101 | hdl-access = free }}
• {{cite journal | vauthors = He B, Bai S, Hnat AT, Kalman RI, Minges JT, Patterson C, Wilson EM | title = An androgen receptor NH2-terminal conserved motif interacts with the COOH terminus of the Hsp70-interacting protein (CHIP) | journal = The Journal of Biological Chemistry | volume = 279 | issue = 29 | pages = 30643–53 | date = Jul 2004 | pmid = 15107424 | doi = 10.1074/jbc.M403117200 | doi-access = free }}
• {{cite journal | vauthors = Alberti S, Böhse K, Arndt V, Schmitz A, Höhfeld J | title = The cochaperone HspBP1 inhibits the CHIP ubiquitin ligase and stimulates the maturation of the cystic fibrosis transmembrane conductance regulator | journal = Molecular Biology of the Cell | volume = 15 | issue = 9 | pages = 4003–10 | date = Sep 2004 | pmid = 15215316 | pmc = 515335 | doi = 10.1091/mbc.E04-04-0293 }}
• {{cite journal | vauthors = Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP | title = Large-scale characterization of HeLa cell nuclear phosphoproteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 33 | pages = 12130–5 | date = Aug 2004 | pmid = 15302935 | pmc = 514446 | doi = 10.1073/pnas.0404720101 | bibcode = 2004PNAS..10112130B | doi-access = free }}

{{Refend}}

• {{UCSC genome browser|STUB1}}
• {{UCSC gene details|STUB1}}

{{PDB Gallery|geneid=10273}}