From Wikipedia, the free encyclopedia
Jump to: navigation, search
STIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase
Protein STUB1 PDB 2c2l.png
PDB rendering based on 2c2l.
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM607207 MGI1891731 HomoloGene4281 GeneCards: STUB1 Gene
RNA expression pattern
PBB GE STUB1 217934 x at tn.png
More reference expression data
Species Human Mouse
Entrez 10273 56424
Ensembl ENSG00000103266 ENSMUSG00000039615
UniProt Q9UNE7 Q9WUD1
RefSeq (mRNA) NM_001293197 NM_019719
RefSeq (protein) NP_001280126 NP_062693
Location (UCSC) Chr 16:
0.73 – 0.73 Mb
Chr 17:
25.83 – 25.83 Mb
PubMed search [1] [2]

STUB1 (STIP1 homology and U-Box containing protein 1), also known as CHIP (C terminus of HSC70-Interacting Protein), is a human gene.[1][2]


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] 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 ataxia .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.  edit


STUB1 has been shown to interact with C-Raf,[5] Parkin (ligase),[6] DNAJB1,[2] HSPA8,[2] RUNX2,[7] HSPA1A[2][6] and HSPA4.[2]


  1. ^ "Entrez Gene: STUB1 STIP1 homology and U-box containing protein 1". 
  2. ^ a b c d e f Ballinger CA, Connell P, Wu Y, Hu Z, Thompson LJ, Yin LY, Patterson C (1 June 1999). "Identification of CHIP, a Novel Tetratricopeptide Repeat-Containing Protein That Interacts with Heat Shock Proteins and Negatively Regulates Chaperone Functions". Mol. Cell. Biol. 19 (6): 4535–45. PMC 104411. PMID 10330192. 
  3. ^ Jiang J, Ballinger CA, Wu Y, Dai Q, Cyr DM, Höhfeld J, Patterson C (November 2001). "CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation". J. Biol. Chem. 276 (46): 42938–44. doi:10.1074/jbc.M101968200. PMID 11557750. 
  4. ^ Qian SB, McDonough H, Boellmann F, Cyr DM, Patterson C (March 2006). "CHIP-mediated stress recovery by sequential ubiquitination of substrates and Hsp70". Nature 440 (7083): 551–5. doi:10.1038/nature04600. PMID 16554822. 
  5. ^ Dogan, Taner; Harms Gregory S; Hekman Mirko; Karreman Christiaan; Oberoi Tripat Kaur; Alnemri Emad S; Rapp Ulf R; Rajalingam Krishnaraj (Dec 2008). "X-linked and cellular IAPs modulate the stability of C-RAF kinase and cell motility". Nat. Cell Biol. (England) 10 (12): 1447–55. doi:10.1038/ncb1804. PMID 19011619. 
  6. ^ a b Imai, Yuzuru; Soda Mariko; Hatakeyama Shigetsugu; Akagi Takumi; Hashikawa Tsutomu; Nakayama Kei Ichi; Takahashi Ryosuke (Jul 2002). "CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity". Mol. Cell (United States) 10 (1): 55–67. doi:10.1016/S1097-2765(02)00583-X. ISSN 1097-2765. PMID 12150907. 
  7. ^ Li, Xueni; Huang Mei, Zheng Huiling, Wang Yinyin, Ren Fangli, Shang Yu, Zhai Yonggong, Irwin David M, Shi Yuguang, Chen Di, Chang Zhijie (Jun 2008). "CHIP promotes Runx2 degradation and negatively regulates osteoblast differentiation". J. Cell Biol. (United States) 181 (6): 959–72. doi:10.1083/jcb.200711044. PMC 2426947. PMID 18541707. 

Further reading[edit]

External links[edit]