| Identity |
| Other names | HSP60 |
| HSP65 | |
| HuCHA60 | |
| Chaperonin 60kDa (CPN60) | |
| GROEL | |
| SPG13 | |
| HGNC | HSPD1 |
| Location | 2q33.1 |
| Location_base_pair | Starts at 198059553 and ends at 198072885 bp from pter ( according to hg18-Mar_2006). |
| DNA/RNA |
| Description | The HSP60 gene contains 12 exons and 11 introns and was predicted to span over approximately 13 kb of the genomic DNA. The first exon is non-coding region. |
| Transcription | Two transcript variants encoding the same protein have been identified for HSP60 gene. This variant which was named HSP60s1 and HSP60s2 (s for short) comparing it to the much longer regular HSP60 gene. |
| Pseudogene | Twelve pseudogenes located on chromosome 3, 4, 5, 6, 8 and 12 have been associated with HSP60. |
| Protein |
| Description | The HSP60 consists of 573 amino acids corresponding to a molecular weight of 61.05 kDa. The HSP60 proteins are ubiquitous abundant proteins of eubacterial genomes and also known as the Chaperonin. The Chapenonins divided into 2 subfamilies: Type I (HSP60/GROEL) and type II (TCP-1 ring complex). Type I are present in prokaryotes (eubacteria) and organelles (mitochondria and chloroplast). Type II are presents in archabacteria and in the eukaryotic cytosol. HSP60 family have the ring-shape oligomeric protein complex with a large central cavity, and composed of 14 proteins which organized into two 7-protein ring that are stacked on each other like double donut. This structure is reversible dissociate in the presence of Mg2+ and ATP, ATPase activity, and have role in folding and assembly of oligomeric protein structures. |
| Expression | HSP60 expression is ubiquitous in the pre-natal, different organ system, immune system, blood, epithelial tissue and cells. |
| Localisation | Mainly in the mitochondria, but growing body of evidence showed that there are also extra-mitochondrial such as in the cell surface, peroxisomes and the endoplasmic reticulum. |
| Function | Assisting mitochondrial protein folding, unfolding, and degradation. HSP60 also have anti-apoptosis and pro-apoptosis roles. |
| Homology | Up to now more than 150 homologues of HSP60 sequences with pair-wise similarity extending from 40-100% at the amino acid level. Among them: in rat (Rattus norvegicus), pufferfish (Fugu rubripes), zebrafish (Danio rerio), the nematode Caenorhabditis elegans and the mouse (Mus musculus). |
| Mutations |
| Germinal | Not known in Homo sapiens. |
| Somatic | Hereditary spastic paraplegia (SPG13) is associated with a mutation in the HSP60 gene: The amino acid 72 Valine is changed to Isoleucin. In Sudden Death Infant Syndrome (SIDS), there are two mutations reported in the coding region of HSP60: N158S and G573A. |
| Implicated in |
| Entity | Various carcinomas. |
| Disease | HSP60 reported to be over-expressed in exo-cervix cancer, colorectal cancer and prostate carcinoma. But down-regulate its expression in bladder cancer and lung carcinoma. |
| Prognosis | Controversy; worse prognosis in bladder cancer and acute myeloid leukemia. Others shows favorable prognosis, such as in ovarian cancer, osteo sarcoma and esophageal cancer. |
| Oncogenesis | The discrepancy of HSP60 expression and/or prognosis during carcinogenesis might be due to its pro- and anti-apoptotic roles in the cancer cells. The cytosolic and organellar forms of HSP60 might explain the anti- and pro-apoptotic roles. |
| Entity | Diseases linked to deficiency of HSP60. |
| Disease | There is a few reports on HSP60 deficiency in human. Studies reported a patient with systemic mitochondrial encephalopathy, which had lower HSP60 concentration than normal person. Another HSP60 deficient patient presented with congenital lactic acidemia. In short chain acyl-CoA dehydrogenase, SCAD. HSP deficiency also reported in fibroblast derived from a patient with a fatal systemic mitochondrial disease leading to deficiency of multiple mitochondrial enzyme and mitochondrial abnormality. |
| Entity | Autoimmune diseases. |
| Note | First clinical trials using HSP60 (peptide 277) has been tested in type-2 diabetes. |
| Disease | HSP60 have been implicated in T cell activation and cause inflammatory reaction. It involved in the pathogenesis of a number of autoimmune diseases in inflammatory conditions such as type-1 diabetes, juvenile chronic arthritis, atherosclerosis, Cohn disease, autoimmunity in women, rheumatoid arthritis, systemic lupus erythematodes, Sjogren syndrome and mix connective tissue diseases. |
| External links |
| Bibliography |
| Primary structure of a human mitochondrial protein homologous to the bacterial and plant chaperonins and to the 65-kilodalton mycobacterial antigen. |
| Jindal S, Dudani AK, Singh B, Harley CB, Gupta RS |
| Molecular and cellular biology. 1989 ; 9 (5) : 2279-2283. |
| PMID 2568584 |
| The mitochondrial chaperonin hsp60 is required for its own assembly. |
| Cheng MY, Hartl FU, Horwich AL |
| Nature. 1990 ; 348 (6300) : 455-458. |
| PMID 1978929 |
| Nucleotide sequences and novel structural features of human and Chinese hamster hsp60 (chaperonin) gene families. |
| Venner TJ, Singh B, Gupta RS |
| DNA and cell biology. 1990 ; 9 (8) : 545-552. |
| PMID 1980192 |
| Antifolding activity of hsp60 couples protein import into the mitochondrial matrix with export to the intermembrane space. |
| Koll H, Guiard B, Rassow J, Ostermann J, Horwich AL, Neupert W, Hartl FU |
| Cell. 1992 ; 68 (6) : 1163-1175. |
| PMID 1347713 |
| Evolution of the chaperonin families (Hsp60, Hsp10 and Tcp-1) of proteins and the origin of eukaryotic cells. |
| Gupta RS |
| Molecular microbiology. 1995 ; 15 (1) : 1-11. |
| PMID 7752884 |
| Genetic complexity of the human hsp 60 gene. |
| Pochon NA, Mach B |
| International immunology. 1996 ; 8 (2) : 221-230. |
| PMID 8671607 |
| The genes encoding mammalian chaperonin 60 and chaperonin 10 are linked head-to-head and share a bidirectional promoter. |
| Ryan MT, Herd SM, Sberna G, Samuel MM, Hoogenraad NJ, Hˆ½j PB |
| Gene. 1997 ; 196 (1-2) : 9-17. |
| PMID 9322735 |
| The Hsp70 and Hsp60 chaperone machines. |
| Bukau B, Horwich AL |
| Cell. 1998 ; 92 (3) : 351-366. |
| PMID 9476895 |
| Chaperone-mediated protein folding. |
| Fink AL |
| Physiological reviews. 1999 ; 79 (2) : 425-449. |
| PMID 10221986 |
| Mitochondrial-matrix proteins at unexpected locations: are they exported? |
| Soltys BJ, Gupta RS |
| Trends in biochemical sciences. 1999 ; 24 (5) : 174-177. |
| PMID 10322429 |
| Chaperonins are cell-signalling proteins: the unfolding biology of molecular chaperones. |
| Ranford JC, Coates AR, Henderson B |
| Expert reviews in molecular medicine. 2000 ; 2 (8) : 1-17. |
| PMID 14585136 |
| Linkage disequilibrium in humans: models and data. |
| Pritchard JK, Przeworski M |
| American journal of human genetics. 2001 ; 69 (1) : 1-14. |
| PMID 11410837 |
| Unfolding the role of chaperones and chaperonins in human disease. |
| Slavotinek AM, Biesecker LG |
| Trends in genetics : TIG. 2001 ; 17 (9) : 528-535. |
| PMID 11525836 |
| Heat shock proteins: the 'Swiss Army Knife' vaccines against cancers and infectious agents. |
| Srivastava PK, Amato RJ |
| Vaccine. 2001 ; 19 (17-19) : 2590-2597. |
| PMID 11257397 |
| Chaperonin-mediated protein folding. |
| Thirumalai D, Lorimer GH |
| Annual review of biophysics and biomolecular structure. 2001 ; 30 : 245-269. |
| PMID 11340060 |
| Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60. |
| Hansen JJ, Dˆºrr A, Cournu-Rebeix I, Georgopoulos C, Ang D, Nielsen MN, Davoine CS, Brice A, Fontaine B, Gregersen N, Bross P |
| American journal of human genetics. 2002 ; 70 (5) : 1328-1332. |
| PMID 11898127 |
| Chaperonin 60 unfolds its secrets of cellular communication. |
| Maguire M, Coates AR, Henderson B |
| Cell stress & chaperones. 2002 ; 7 (4) : 317-329. |
| PMID 12653476 |
| Chaperonins in disease: mechanisms, models, and treatments. |
| Ranford JC, Henderson B |
| Molecular pathology : MP. 2002 ; 55 (4) : 209-213. |
| PMID 12147708 |
| Investigating a possible relation between the amino acid variation N158S of the human heat shock protein HSP60 and increased susceptibility to Sudden Infant Death Syndrome (SIDS). |
| Teske A, et al |
| Am J Hum Genet. 2002 ; 71. |
| Genomic structure of the human mitochondrial chaperonin genes: HSP60 and HSP10 are localised head to head on chromosome 2 separated by a bidirectional promoter. |
| Hansen JJ, Bross P, Westergaard M, Nielsen MN, Eiberg H, Bˆ½rglum AD, Mogensen J, Kristiansen K, Bolund L, Gregersen N |
| Human genetics. 2003 ; 112 (1) : 71-77. |
| PMID 12483302 |
| Mitochondrial chaperones in cancer: from molecular biology to clinical diagnostics. |
| Czarnecka AM, Campanella C, Zummo G, Cappello F |
| Cancer biology & therapy. 2006 ; 5 (7) : 714-720. |
| PMID 16861898 |
| Single-nucleotide variations in the genes encoding the mitochondrial Hsp60/Hsp10 chaperone system and their disease-causing potential. |
| Bross P, Li Z, Hansen J, Hansen JJ, Nielsen MN, Corydon TJ, Georgopoulos C, Ang D, Lundemose JB, Niezen-Koning K, Eiberg H, Yang H, Kˆ½lvraa S, Bolund L, Gregersen N |
| Journal of human genetics. 2007 ; 52 (1) : 56-65. |
| PMID 17072495 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 02-2007 | Ahmad Faried, Leri S Faried |
| Citation |
| This paper should be referenced as such : |
| Faried A, Faried LS . HSPD1 (Heat Shock 60kDa Protein 1). Atlas Genet Cytogenet Oncol Haematol. February 2007 . URL : http://AtlasGeneticsOncology.org/Genes/HSPD1ID40888ch2q33.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Thu Nov 27 13:23:49 2008 |
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