STUB1
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Template:Short description An Error has occurred retrieving Wikidata item for infobox STUB1 (STIP1 homology and U-Box containing protein 1) is a human gene that codes for the protein CHIP (C terminus of HSC70-Interacting Protein).[1][2]
Function
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.[2] In addition, CHIP possesses E3 ubiquitin ligase activity and promotes ubiquitylation,[3] 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.[4]
Mutations in STUB1 cause spinocerebellar ataxia type 16.[5][failed verification]
STUB1 regulates cytokine receptors in T cells and myeloid cells.[6][7]
Interactions
STUB1 has been shown to interact with:
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References
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- ^ Page Module:Citation/CS1/styles.css has no content."Entrez Gene: STUB1 STIP1 homology and U-box containing protein 1".
- ^ a b c d e f Page Module:Citation/CS1/styles.css has no content.Ballinger CA, Connell P, Wu Y, Hu Z, Thompson LJ, Yin LY, Patterson C (Jun 1999). "Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions". Molecular and Cellular Biology. 19 (6): 4535–45. doi:10.1128/mcb.19.6.4535. PMC 104411. PMID 10330192.
- ^ Page Module:Citation/CS1/styles.css has no content.Jiang J, Ballinger CA, Wu Y, Dai Q, Cyr DM, Höhfeld J, Patterson C (Nov 2001). "CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation". The Journal of Biological Chemistry. 276 (46): 42938–44. doi:10.1074/jbc.M101968200. PMID 11557750.
- ^ Page Module:Citation/CS1/styles.css has no content.Qian SB, McDonough H, Boellmann F, Cyr DM, Patterson C (Mar 2006). "CHIP-mediated stress recovery by sequential ubiquitination of substrates and Hsp70". Nature. 440 (7083): 551–5. Bibcode:2006Natur.440..551Q. doi:10.1038/nature04600. PMC 4112096. PMID 16554822.
- ^ Page Module:Citation/CS1/styles.css has no content.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 (2014). "Phenotype and frequency of STUB1 mutations: next-generation screenings in Caucasian ataxia and spastic paraplegia cohorts". Orphanet Journal of Rare Diseases. 9 (1): 57. doi:10.1186/1750-1172-9-57. PMC 4021831. PMID 24742043.
- ^ LaFleur, M.W., Milling, L.E., Prathima, P. et al. A STUB1–CHIC2 complex inhibits CD8+ T cells to restrain tumor immunity. Nat Immunol (2025). https://doi.org/10.1038/s41590-025-02231-6
- ^ A STUB1 ubiquitin ligase/CHIC2 protein complex negatively regulates the IL-3, IL-5, and GM-CSF cytokine receptor common β chain (CSF2RB) protein stability. Koochaki, Sebastian H.J. et al. Journal of Biological Chemistry, Volume 298, Issue 10, 102484https://www.jbc.org/article/S0021-9258(22)00927-9/fulltext
- ^ Page Module:Citation/CS1/styles.css has no content.Dogan T, Harms GS, Hekman M, Karreman C, Oberoi TK, Alnemri ES, Rapp UR, Rajalingam K (Dec 2008). "X-linked and cellular IAPs modulate the stability of C-RAF kinase and cell motility". Nature Cell Biology. 10 (12): 1447–55. doi:10.1038/ncb1804. PMID 19011619. S2CID 6553549.
- ^ a b Page Module:Citation/CS1/styles.css has no content.Imai Y, Soda M, Hatakeyama S, Akagi T, Hashikawa T, Nakayama KI, Takahashi R (Jul 2002). "CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity". Molecular Cell. 10 (1): 55–67. doi:10.1016/s1097-2765(02)00583-x. PMID 12150907.
- ^ Page Module:Citation/CS1/styles.css has no content.Li X, Huang M, Zheng H, Wang Y, Ren F, Shang Y, Zhai Y, Irwin DM, Shi Y, Chen D, Chang Z (Jun 2008). "CHIP promotes Runx2 degradation and negatively regulates osteoblast differentiation". The Journal of Cell Biology. 181 (6): 959–72. doi:10.1083/jcb.200711044. PMC 2426947. PMID 18541707.
Further reading
Page Template:Refbegin/styles.css has no content.
- Page Module:Citation/CS1/styles.css has no content.LaFleur, MW, Milling, LE, Prathima, P (2025). "A STUB1–CHIC2 complex inhibits CD8+ T cells to restrain tumor immunity". Nature Immunology. doi:10.1038/s41590-025-02231-6.
- Page Module:Citation/CS1/styles.css has no content.Patterson C (Jan 2002). "A new gun in town: the U box is a ubiquitin ligase domain". Science's STKE. 2002 (116): pe4. doi:10.1126/stke.2002.116.pe4. PMID 11805346. S2CID 31977936.
- Page Module:Citation/CS1/styles.css has no content.Scanlan MJ, Chen YT, Williamson B, Gure AO, Stockert E, Gordan JD, Türeci O, Sahin U, Pfreundschuh M, Old LJ (May 1998). "Characterization of human colon cancer antigens recognized by autologous antibodies". International Journal of Cancer. 76 (5): 652–8. doi:10.1002/(SICI)1097-0215(19980529)76:5<652::AID-IJC7>3.0.CO;2-P. PMID 9610721.
- Page Module:Citation/CS1/styles.css has no content.Ballinger CA, Connell P, Wu Y, Hu Z, Thompson LJ, Yin LY, Patterson C (Jun 1999). "Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions". Molecular and Cellular Biology. 19 (6): 4535–45. doi:10.1128/mcb.19.6.4535. PMC 104411. PMID 10330192.
- Page Module:Citation/CS1/styles.css has no content.Connell P, Ballinger CA, Jiang J, Wu Y, Thompson LJ, Höhfeld J, Patterson C (Jan 2001). "The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins". Nature Cell Biology. 3 (1): 93–6. doi:10.1038/35050618. PMID 11146632. S2CID 19161960.
- Page Module:Citation/CS1/styles.css has no content.Daniels RJ, Peden JF, Lloyd C, Horsley SW, Clark K, Tufarelli C, Kearney L, Buckle VJ, Doggett NA, Flint J, Higgs DR (Feb 2001). "Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16". Human Molecular Genetics. 10 (4): 339–52. doi:10.1093/hmg/10.4.339. PMID 11157797.
- Page Module:Citation/CS1/styles.css has no content.Jiang J, Ballinger CA, Wu Y, Dai Q, Cyr DM, Höhfeld J, Patterson C (Nov 2001). "CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation". The Journal of Biological Chemistry. 276 (46): 42938–44. doi:10.1074/jbc.M101968200. PMID 11557750.
- Page Module:Citation/CS1/styles.css has no content.Demand J, Alberti S, Patterson C, Höhfeld J (Oct 2001). "Cooperation of a ubiquitin domain protein and an E3 ubiquitin ligase during chaperone/proteasome coupling". Current Biology. 11 (20): 1569–77. Bibcode:2001CBio...11.1569D. doi:10.1016/S0960-9822(01)00487-0. PMID 11676916. S2CID 2021754.
- Page Module:Citation/CS1/styles.css has no content.Imai Y, Soda M, Hatakeyama S, Akagi T, Hashikawa T, Nakayama KI, Takahashi R (Jul 2002). "CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity". Molecular Cell. 10 (1): 55–67. doi:10.1016/S1097-2765(02)00583-X. PMID 12150907.
- Page Module:Citation/CS1/styles.css has no content.Krackhardt AM, Witzens M, Harig S, Hodi FS, Zauls AJ, Chessia M, Barrett P, Gribben JG (Sep 2002). "Identification of tumor-associated antigens in chronic lymphocytic leukemia by SEREX". Blood. 100 (6): 2123–31. doi:10.1182/blood-2002-02-0513. PMID 12200376.
- Page Module:Citation/CS1/styles.css has no content.Cardozo CP, Michaud C, Ost MC, Fliss AE, Yang E, Patterson C, Hall SJ, Caplan AJ (Feb 2003). "C-terminal Hsp-interacting protein slows androgen receptor synthesis and reduces its rate of degradation". Archives of Biochemistry and Biophysics. 410 (1): 134–40. doi:10.1016/S0003-9861(02)00680-X. PMID 12559985.
- Page Module:Citation/CS1/styles.css has no content.Zhou P, Fernandes N, Dodge IL, Reddi AL, Rao N, Safran H, DiPetrillo TA, Wazer DE, Band V, Band H (Apr 2003). "ErbB2 degradation mediated by the co-chaperone protein CHIP". The Journal of Biological Chemistry. 278 (16): 13829–37. doi:10.1074/jbc.M209640200. PMID 12574167.
- Page Module:Citation/CS1/styles.css has no content.Shimura H, Schwartz D, Gygi SP, Kosik KS (Feb 2004). "CHIP-Hsc70 complex ubiquitinates phosphorylated tau and enhances cell survival". The Journal of Biological Chemistry. 279 (6): 4869–76. doi:10.1074/jbc.M305838200. PMID 14612456.
- Page Module:Citation/CS1/styles.css has no content.Li L, Xin H, Xu X, Huang M, Zhang X, Chen Y, Zhang S, Fu XY, Chang Z (Jan 2004). "CHIP mediates degradation of Smad proteins and potentially regulates Smad-induced transcription". Molecular and Cellular Biology. 24 (2): 856–64. doi:10.1128/MCB.24.2.856-864.2004. PMC 343794. PMID 14701756.
- Page Module:Citation/CS1/styles.css has no content.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 (Apr 2004). "CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation". Human Molecular Genetics. 13 (7): 703–14. doi:10.1093/hmg/ddh083. PMID 14962978.
- Page Module:Citation/CS1/styles.css has no content.Galigniana MD, Harrell JM, Housley PR, Patterson C, Fisher SK, Pratt WB (Apr 2004). "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". Brain Research. Molecular Brain Research. 123 (1–2): 27–36. doi:10.1016/j.molbrainres.2003.12.015. hdl:11336/29101. PMID 15046863.
- Page Module:Citation/CS1/styles.css has no content.He B, Bai S, Hnat AT, Kalman RI, Minges JT, Patterson C, Wilson EM (Jul 2004). "An androgen receptor NH2-terminal conserved motif interacts with the COOH terminus of the Hsp70-interacting protein (CHIP)". The Journal of Biological Chemistry. 279 (29): 30643–53. doi:10.1074/jbc.M403117200. PMID 15107424.
- Page Module:Citation/CS1/styles.css has no content.Alberti S, Böhse K, Arndt V, Schmitz A, Höhfeld J (Sep 2004). "The cochaperone HspBP1 inhibits the CHIP ubiquitin ligase and stimulates the maturation of the cystic fibrosis transmembrane conductance regulator". Molecular Biology of the Cell. 15 (9): 4003–10. doi:10.1091/mbc.E04-04-0293. PMC 515335. PMID 15215316.
- Page Module:Citation/CS1/styles.css has no content.Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (Aug 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–5. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
External links
- STUB1 human gene location in the UCSC Genome Browser.
- STUB1 human gene details in the UCSC Genome Browser.
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