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Heat shock 70kDa protein 8
Protein HSPA8 PDB 1atr.png
PDB rendering based on 1atr.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols HSPA8 ; HEL-33; HEL-S-72p; HSC54; HSC70; HSC71; HSP71; HSP73; HSPA10; LAP-1; LAP1; NIP71
External IDs OMIM600816 MGI105384 HomoloGene68524 ChEMBL: 1275223 GeneCards: HSPA8 Gene
RNA expression pattern
PBB GE HSPA8 210338 s at tn.png
PBB GE HSPA8 208687 x at tn.png
PBB GE HSPA8 221891 x at tn.png
More reference expression data
Species Human Mouse
Entrez 3312 15481
Ensembl ENSG00000109971 ENSMUSG00000015656
UniProt P11142 P63017
RefSeq (mRNA) NM_006597 NM_031165
RefSeq (protein) NP_006588 NP_112442
Location (UCSC) Chr 11:
122.93 – 122.93 Mb
Chr 9:
40.8 – 40.81 Mb
PubMed search [1] [2]

Heat shock 70 kDa protein 8 also known as heat shock cognate 71 kDa protein or Hsc70 or Hsp73 is a heat shock protein that in humans is encoded by the HSPA8 gene.[1]


The heat shock protein 70 (Hsp70) family contains both heat-inducible and constitutively expressed members. The latter are called heat-shock cognate (Hsc) proteins. The heat shock 70 kDa protein 8 also known as Hsc70 belongs to the heat-shock cognate subgroup. This protein binds to nascent polypeptides to facilitate correct protein folding. It also functions as an ATPase in the disassembly of clathrin-coated vesicles during transport of membrane components through the cell. Two alternatively spliced variants have been characterized to date.[1]

HSPA8 is ATPase that works with auxilin to remove clathrin coated vesicles. In neurons, synaptojanin is also an important protein involved in vesicle uncoating.

Hsc70 is a key component of chaperone-mediated autophagy wherein it imparts selectivity to the proteins being degraded by this lysosomal pathway.

Hsc70 vs Hsp70 comparison[edit]

Human Hsc70 has 85% identity with human Hsp70 (SDSC workbench, blosom26 default analysis). The scientific community has long assumed that Hsp70 and Hsc70 have similar cellular roles, but this assumption proved erroneous.[2]

Unlike canonical heat shock proteins, Hsc70 is constitutively expressed and performs functions related to normal cellular processes. Hsc70 was placed in the heat shock protein family due to homology with other heat shock proteins.


HSPA8 has been shown to interact with STUB1,[3] BAG3,[4] BAG4,[5] Parkin (ligase),[6] BAG2,[4] HSPBP1,[7][8] CDC5L,[9] BAG1,[4][10] DNAJA3[11] and CITED1.[12]


  1. ^ a b "Entrez Gene: HSPA8 heat shock 70kDa protein 8". 
  2. ^ Goldfarb S, Kashlan O, Watkins J, Suaud L, Yan W, Kleyman T, Rubenstein R (2006). "Differential effects of Hsc70 and Hsp70 on the intracellular trafficking and functional expression of epithelial sodium channels". Proc Natl Acad Sci USA 103 (15): 5817–22. doi:10.1073/pnas.0507903103. PMC 1458656. PMID 16585520. 
  3. ^ Ballinger, C A; Connell P; Wu Y; Hu Z; Thompson L J; Yin L Y; Patterson C (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. (UNITED STATES) 19 (6): 4535–45. ISSN 0270-7306. PMC 104411. PMID 10330192. 
  4. ^ a b c Takayama, S; Xie Z; Reed J C (January 1999). "An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators". J. Biol. Chem. (UNITED STATES) 274 (2): 781–6. doi:10.1074/jbc.274.2.781. ISSN 0021-9258. PMID 9873016. 
  5. ^ Miki, Kiyoshi; Eddy Edward M (April 2002). "Tumor necrosis factor receptor 1 is an ATPase regulated by silencer of death domain". Mol. Cell. Biol. (United States) 22 (8): 2536–43. doi:10.1128/MCB.22.8.2536-2543.2002. ISSN 0270-7306. PMC 133739. PMID 11909948. 
  6. ^ Imai, Yuzuru; Soda Mariko; Hatakeyama Shigetsugu; Akagi Takumi; Hashikawa Tsutomu; Nakayama Kei Ichi; Takahashi Ryosuke (July 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. ^ Rual, Jean-François; Venkatesan Kavitha, Hao Tong, Hirozane-Kishikawa Tomoko, Dricot Amélie, Li Ning, Berriz Gabriel F, Gibbons Francis D, Dreze Matija, Ayivi-Guedehoussou Nono, Klitgord Niels, Simon Christophe, Boxem Mike, Milstein Stuart, Rosenberg Jennifer, Goldberg Debra S, Zhang Lan V, Wong Sharyl L, Franklin Giovanni, Li Siming, Albala Joanna S, Lim Janghoo, Fraughton Carlene, Llamosas Estelle, Cevik Sebiha, Bex Camille, Lamesch Philippe, Sikorski Robert S, Vandenhaute Jean, Zoghbi Huda Y, Smolyar Alex, Bosak Stephanie, Sequerra Reynaldo, Doucette-Stamm Lynn, Cusick Michael E, Hill David E, Roth Frederick P, Vidal Marc (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature (England) 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. 
  8. ^ Stelzl, Ulrich; Worm Uwe, Lalowski Maciej, Haenig Christian, Brembeck Felix H, Goehler Heike, Stroedicke Martin, Zenkner Martina, Schoenherr Anke, Koeppen Susanne, Timm Jan, Mintzlaff Sascha, Abraham Claudia, Bock Nicole, Kietzmann Silvia, Goedde Astrid, Toksöz Engin, Droege Anja, Krobitsch Sylvia, Korn Bernhard, Birchmeier Walter, Lehrach Hans, Wanker Erich E (September 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell (United States) 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. ISSN 0092-8674. PMID 16169070. 
  9. ^ Ajuh, P; Kuster B; Panov K; Zomerdijk J C; Mann M; Lamond A I (December 2000). "Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry". EMBO J. (ENGLAND) 19 (23): 6569–81. doi:10.1093/emboj/19.23.6569. ISSN 0261-4189. PMC 305846. PMID 11101529. 
  10. ^ Takayama, S; Bimston D N; Matsuzawa S; Freeman B C; Aime-Sempe C; Xie Z; Morimoto R I; Reed J C (August 1997). "BAG-1 modulates the chaperone activity of Hsp70/Hsc70". EMBO J. (ENGLAND) 16 (16): 4887–96. doi:10.1093/emboj/16.16.4887. ISSN 0261-4189. PMC 1170124. PMID 9305631. 
  11. ^ Sarkar, S; Pollack B P; Lin K T; Kotenko S V; Cook J R; Lewis A; Pestka S (December 2001). "hTid-1, a human DnaJ protein, modulates the interferon signaling pathway". J. Biol. Chem. (United States) 276 (52): 49034–42. doi:10.1074/jbc.M103683200. ISSN 0021-9258. PMID 11679576. 
  12. ^ Yahata, T; de Caestecker M P; Lechleider R J; Andriole S; Roberts A B; Isselbacher K J; Shioda T (March 2000). "The MSG1 non-DNA-binding transactivator binds to the p300/CBP coactivators, enhancing their functional link to the Smad transcription factors". J. Biol. Chem. (UNITED STATES) 275 (12): 8825–34. doi:10.1074/jbc.275.12.8825. ISSN 0021-9258. PMID 10722728. 

Further reading[edit]

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