STUB1

STUB1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4KBQ
Identifiers
Aliases	STUB1, CHIP, HSPABP2, NY-CO-7, SCAR16, SDCCAG7, UBOX1, STIP1 homology and U-box containing protein 1, SCA48
External IDs	OMIM: 607207 MGI: 1891731 HomoloGene: 4281 GeneCards: STUB1
Gene location (Human) Chr. Chromosome 16 (human) Band 16p13.3 Start 680,224 bp End 682,870 bp
Gene location (Mouse) Chr. Chromosome 17 (mouse) Band 17 A3.3|17 12.93 cM Start 26,049,479 bp End 26,052,378 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in postcentral gyrus external globus pallidus spinal ganglia superior vestibular nucleus ventral tegmental area parotid gland pons nipple trigeminal ganglion renal medulla Top expressed in neural tube lens bone marrow islet of Langerhans mesencephalon adrenal gland rhombencephalon hypothalamus urinary bladder cerebellar cortex More reference expression data BioGPS More reference expression data
Gene ontology Molecular function Hsp90 protein binding protein-macromolecule adaptor activity protein homodimerization activity misfolded protein binding ubiquitin protein ligase activity ubiquitin-protein transferase activity ubiquitin-ubiquitin ligase activity kinase binding protein binding enzyme binding TPR domain binding G protein-coupled receptor binding ubiquitin protein ligase binding transferase activity Hsp70 protein binding SMAD binding heat shock protein binding tau protein binding chaperone binding Cellular component cytoplasm ubiquitin ligase complex nucleoplasm Z disc endoplasmic reticulum nuclear inclusion body extracellular exosome ubiquitin conjugating enzyme complex nucleus cytosol chaperone complex Biological process positive regulation of chaperone-mediated protein complex assembly regulation of protein stability ubiquitin-dependent protein catabolic process regulation of glucocorticoid metabolic process protein K63-linked ubiquitination protein maturation protein polyubiquitination protein quality control for misfolded or incompletely synthesized proteins negative regulation of protein binding ubiquitin-dependent SMAD protein catabolic process cellular response to DNA damage stimulus endoplasmic reticulum unfolded protein response positive regulation of ubiquitin-protein transferase activity protein ubiquitination positive regulation of protein ubiquitination positive regulation of proteasomal ubiquitin-dependent protein catabolic process DNA repair proteasome-mediated ubiquitin-dependent protein catabolic process protein autoubiquitination cellular response to misfolded protein ERBB2 signaling pathway negative regulation of transforming growth factor beta receptor signaling pathway ubiquitin-dependent ERAD pathway response to ischemia cellular response to heat chaperone-mediated autophagy cellular response to hypoxia Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10273 56424 Ensembl ENSG00000103266 ENSMUSG00000039615 UniProt Q9UNE7 Q9WUD1 RefSeq (mRNA) NM_005861 NM_001293197 NM_019719 RefSeq (protein) NP_001280126 NP_005852 NP_062693 Location (UCSC) Chr 16: 0.68 – 0.68 Mb Chr 17: 26.05 – 26.05 Mb PubMed search
Wikidata
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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).

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. In addition, CHIP possesses E3 ubiquitin ligase activity and promotes ubiquitylation, 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.

Mutations in STUB1 cause spinocerebellarataxiatype 16.

Interactions

STUB1 has been shown to interact with:

• C-Raf,
• DNAJB1,
• HSPA1A,
• HSPA4,
• HSPA8,
• Parkin (ligase), and
• RUNX2.

Further reading

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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. doi:10.1016/S0960-9822(01)00487-0. PMID 11676916. S2CID 2021754.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.