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HSPD1 (Heat Shock 60kDa Protein 1)

Written2007-02Ahmad Faried, Leri S Faried
Department of General Surgical Science (Surgery I), Graduate School of Medicine, Gunma University, Maebashi, Japan
Updated2014-10Cappello Francesco, Conway de Macario Everly , Macario Alberto JL
Department of Experimental Biomedicine, Clinical Neuroscience, Section of Human Anatomy, University of Palermo, Palermo, Italy;, Euro-Mediterranean Institute of Science, Technology, Palermo, Italy (FC); Department of Microbiology, Immunology, School of Medicine, University of Maryland at Baltimore; Institute of Marine, Environmental Technology (IMET); Columbus Center, Baltimore, MD 21202, USA (ECdeM); Department of Microbiology, Immunology, School of Medicine, University of Maryland at Baltimore,, Institute of Marine, Environmental Technology (IMET), Columbus Center, Baltimore, MD 21202, USA;, Euro-Mediterranean Institute of Science, Technology, Palermo, Italy (AJLM)

Abstract The HSPD1 gene encodes a protein known as HSP60 or Hsp60, also commonly referred to as Cpn60. This protein is a molecular chaperone typically localized inside mitochondria where it forms a chaperoning machine with HSP10 (encoded by the HSPE1 gene), also called Cpn10, to assist protein folding inside the organelle. Hsp60 also occurs in the cytosol, plasma-cell membrane, intercellular space, and blood. Its functions in all these extramitochondrial locations are poorly understood. While the canonical functions of Hsp60 are considered to be cytoprotective, anti-stress and maintenance of protein homeostasis, other roles are currently being investigated. For example, Hsp60 participates in the pathogenesis of diseases in various ways in certain types of cancer, and chronic inflammatory and autoimmune pathological conditions. These are considered chaperonopathies by mistake, in which a normal chaperone (normal at least as far as it can be determined by current methods to study the structure of a molecule available only at extremely low concentrations and quantities) turns against the organism instead of protecting it, favouring the growth and dissemination of cancer cells, or the initiation-progression of inflammation, for instance. In addition, Hsp60 mutations cause at least two types of severe genetic chaperonopathies. All this knowledge is expanding nowadays clearly pointing to Hsp60 as a potential target for chaperonotherapy by replacement when it is defective or by inhibition when it is pathogenic.

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Identity

Other namesHSP60
HSP65
HuCHA60
Chaperonin 60kDa (CPN60)
GROEL
SPG13
HGNC (Hugo) HSPD1
LocusID (NCBI) 3329
Atlas_Id 40888
Location 2q33.1  [Link to chromosome band 2q33]
Location_base_pair Starts at 198351308 and ends at 198364640 bp from pter ( according to hg19-Feb_2009)  [Mapping HSPD1.png]
 
  Hsp60 and Hsp10 protein/gene/genomic data.
Fusion genes
(updated 2016)
CDH12 (5p14.3) / HSPD1 (2q33.1)HSPA8 (11q24.1) / HSPD1 (2q33.1)IMMT (2p11.2) / HSPD1 (2q33.1)
LOC728190 () / HSPD1 (2q33.1)

DNA/RNA

 
  The human hsp60 genes and pseudogenes: genomic data. Source: Mukherjee et al. BMC Evolutionary Biology 2010 10:64. PMID 20193073
Description The human HSP60 gene (HSPD1) 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 (Hansen et al., 2003; Mukherjee et al., 2010).
Transcription Two transcript variants encoding the same protein have been identified for HSPD1 http://www.ncbi.nlm.nih.gov/gene/3329; Mukherjee et al., 2010).
Pseudogene Twelve pseudogenes located on chromosome 3, 4, 5, 6, 8 and 12 have been associated with HSP60 (Mukherjee et al., 2010).

Protein

 
  The molecular anatomy of the human Hsp60: structural domains.
Left: The anatomy of the human Hsp60: structural domains. The cartoon represents a three-dimensional model of the human Hsp60 monomer showing its three structural domains: apical in green, intermediate in yellow and equatorial in red. Right: This picture presents the ATP and Mg+/K+ binding sites on Hsp60. Particularly it shows two highly conserved sequences: 52-DGVTVAKEI-60 (orange-brown), and 85-AGDGTTTATVL-95 (magenta) corresponding to the binding sites for Mg+/K+ (green and yellow spheres, respectively) and ATP/ADP (red). Source: Cappello et al., Expert Opin Ther Targets. 2014 ; 18 (2) : 185-208. PMID 24286280.
Description The HSP60 consists of 573 amino acids corresponding to a molecular weight of 61.05 kDa (Mukherjee et al., 2010). The HSP60 protein are abundant proteins of eubacteria genomes and mitochondria in eukaryotes, and also occurs in other locations, such as the cellular cytosol, plasma-cell membrane, and extracellular space (including blood) in eukaryotic organisms.
HSP60 belongs to the chaperone subgroup called chaperonins, of which two varieties are known: chaperonins of Group I and chaperonins of Group II. The former include the human HSP60 typically present in the mitochondria (but also occurring in other locations as described above) and the bacterial GroEL. Chaperonins of Group II include the archaeal thermosome subunits and the cytosolic chaperonin CCT (Chaperonin-containing TCP-1). The human HSP60 and the bacterial GroEL form oligomers: seven monomers associate to form a ring and two rings associate end to end to build a large chaperoning machine of fourteen subunits, all identical. This tetradecamer is the HSP60 functional chaperoning complex that associates with Hsp60 and requires ATP and ATPase activity for the folding of substrates (Cappello et al., 2014).
Expression HSP60 expression is virtually ubiquitous, since it can be found in cells of different tissues and organs, including immune system, epithelial tissue and other cells (Cappello et al., 2011a). However, sometimes its levels can be under the threshold of detectability by immunomorphology or immunoblotting. It can also be found in the blood (Shamaei-Tousi et al., 2007).
 
  Hsp60 presence and localization in normal tissues.
Top: Normal human bronchial mucosa. Ciliated cells present Hsp60 positivity by immunohistochemistry (IHC) in the cytosol (red spots, see arrow for example). Bottom: Normal human colonic mucosa. Intestinal cells do not show any positivity for Hsp60 at IHC, since the protein is under the threshold of detectability. Modified from: Cappello et al., Methods Mol Biol. 2011 ; 787 : 245-254. PMID 21898240
Localisation LOCALISATION HSP60 subcellular localization is mainly in the mitochondria, but it also occurs in extra-mitochondrial sites such as the cytosol, cell surface, peroxisomes, and the endoplasmic reticulum (Soltys and Gupta, 1996; Soltys and Gupta, 1999; Gupta et al., 2008). Levels of extramitochondrial localization increase during inflammatory states (Rodolico et al., 2010; Tomasello et al., 2011; Cappello et al., 2011b) and tumorigenesis (Cappello et al., 2008; Cappello et al., 2011c; Campanella et al., 2012; Rappa et al., 2012).
 
  Hsp60 localization localization in pathologic tissues.
Top: Epithelial cell of inflamed colonic mucosa (patient with ulcerative colitis) showing Hsp60 positivity (immunogold) in cytosol (arrows). Modfied from Tomasello et al., 2011). Bottom: Pulmonary mucoepidermoid carcinoma cell (H292) showing Hsp60 positivity (immunogold) in cytosol and at plasma-cell membrane level (arrows). Inset: a classical mitochondrial positivity for Hsp60. Modified from Campanella et al., PLoS One. 2012 ; 7 (7) : e42008. PMID 22848686
Function FUNCTION Assisting mitochondrial protein folding, unfolding, and degradation (Bukau and Horwich, 1998; Fink, 1999; Slavotinek and Biesecker, 2001; Thirumalai and Lorimer, 2001; Corrao et al., 2010). HSP60 also have anti-apoptosis and pro-apoptosis roles in different pathophysiologic conditions such as heart failure (Knowlton et al., 1998; Kirchhoff et al., 2002; Gupta and Knowlton, 2005; Lin et al, 2007; Kim et al., 2009) and cancer (Chandra et al., 2007; Campanella et al., 2008).
 
  Hsp60 function.
Hsp60 works in cooperation with Hsp10, its co-chaperonin, to assist protein folding of unfolded mitochondrial proteins by an ATP dependent mechanism. Modified from www.pdbj.org.
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 these homologues one can mention those from rat rat (Rattus norvegicus), pufferfish (Fugu rubripes), zebrafish (Danio rerio), the nematode Caenorhabditis elegans, mouse (Mus musculus), and Chlamydia trachomatis (Gupta, 1995). Moreover, Hsp60 presents a high structural homology with other human proteins, that may act as autoantigen, such as acetylcholine receptor, thyroglobulin, etc. (Jones et al., 1993). The high homology between Hsp60 of several bacterial species and the human protein led to postulate its involvement in molecular mimicry phenomena with pathogenic implications (Campanella et al., 2009; Cappello et al., 2009). Moreover, the high homology between human and bacterial Hsp60 and other human autoantigens led to postulate its role in the autoimmune manifestations of some autoimmune diseases, such as myasthenia gravis (Cappello et al., 2010; Marino Gammazza et al., 2012) and Hashimoto's thyroiditis (Marino Gammazza et al., 2014).
  Hsp60 homology and cross-reactivity.
Comparison between the structures of Chlamydia trachomatis (ct-) and human- (h-) Hsp60. Shown are the positions of the four epitopes with 100% homologies. Circle: apical domain; arrow: intermediate domain; arrowhead: equatorial domain. Source: Cappello et al., PLoS Pathog. 2009 ; 5 (8) :e1000552. PMID 19714222.

Mutations

 
  Mutations that cripple Hsp60 and cause disease in humans.
Left: wild type Hsp60, with the amino acids V98 (yellow) and D29 (red) highlighted. Right: the mutants V98I, causing spastic paraplegia SPG13 (yellow), and D29G, causing MitCHAP-60 disease (red), are highlighted. These mutations appear to alter the molecular anatomy of Hsp60 to the point of making it functionally defective. Source: Cappello et al., Expert Opin Ther Targets. 2014 ; 18 (2) : 185-208. PMID 24286280
Epigenetics 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 Isoleucine (Hansen et al., 2002). MitCHAP-60 disease is associated with a mutation in the HSP60 gene: The amino acid 29 Aspartic acid is changed to Glycine (Magen et al., 2008).
General note:
HSP60 expression (mRNA) and levels (protein) were elevated, decreased or without changes in a number of cancers studied by independent groups with various techniques. For a review on this topic see: Czarnecka et al., 2006; Cappello et al., 2008; Rappa et al., 2012; Macario et al., 2013). Moreover, cancer cells, but not the normal counterparts release HSP60 via exosomes (Merendino et al., 2010; Campanella et al., 2012). Further studies on this topic are currently under way to better understand why Hsp60 levels change during carcinogenesis and what is the role of this protein in cancer progression

Implicated in

Note
Entity Autoimmune diseases
Note First clinical trials using HSP60 (peptide 277) has been tested in type-2 diabetes.
Disease HSP60 has been implicated in T cell activation and cause inflammatory reaction. It has been involved in the pathogenesis of a number of autoimmune diseases and inflammatory conditions such as type-1 diabetes, juvenile chronic arthritis, atherosclerosis, Crohn disease, rheumatoid arthritis, systemic lupus erythematosus, Sjogren syndrome, Hashimoto thyroiditis, and myasthenia gravis (Campanella et al., 2009; Cappello et al., 2009; Cappello et al., 2010; Marino Gammazza et al., 2012; Marino Gammazza et al., 2014).
  
Entity Colon cancer
Note For a review on Hsp60 in colon cancer, see Cappello et al., 2011c.
Disease Hsp60 expression and levels were increased in colon cancer of various grades and stages compared to controls (Cappello et al., 2005a). This has been confirmed by other independent groups (Mori et al., 2005; He et al., 2007).
Prognosis Hsp60 has been described as a potential serum marker for colorectal cancer (Hamelin et al., 2011).
Oncogenesis Hsp60 levels increase gradually through the carcinogenic steps (i.e., normal-to-dysplasia-to-carcinoma sequence) and Hsp60 is a good marker to distinguish dysplastic from normal cells (Cappello et al., 2003a).
  
Entity Lung cancer.
Note The four major histological types of carcinoma of the lung are: squamous cell carcinoma (SCC), adenocarcinoma (AD), small cell carcinoma (SCLC), and large cell carcinoma (LCC). In some cases there can be a combination of histological patterns (Husain and Kumar, 2005).
Disease Hsp60 levels were decreased in adenocarcinoma and adenosquamous carcinoma compared to controls (Cappello et al., 2005b; Cappello et al., 2006a). However, this has not been confirmed by another independent group (Xu et al., 2011) that in a series of lung adenocarcinomas found increased levels of Hsp60 compared to controls. The authors postulated that the possible reason to explain this contrasting data may be two: different TNM stages and different part of the tumor biopsied (e.g., central versus periphery).
Prognosis Hsp60 levels were significantly correlated with TNM stage of the tumor and Eastern Cooperative Oncology Group performance status (Xu et al., 2011). Multivariate statistical analysis showed that patient age, pathological T stage, N stage, and Hsp60 expression were independent prognostic indicators with regard to disease-free survival (Xu et al., 2011).
Oncogenesis Hsp60 levels decrease gradually through carcinogenetic steps of lung (i.e., normal-to-dysplasia-to-carcinoma sequence) (Cappello et al., 2005b; Cappello et al., 2006a).
  
Entity Prostate cancer
Note Prostate cancer is preceded by the so called 'prostate intraneoplastic lesion' or PIN, a dysplastic (pretumoral) lesion. Prostatic hyperplasia is not considered a preneoplastic condition (Bostwick and Chen, 2012). Gleason score is an index of malignancy: the higher it is, the worse is the prognosis (Egevad et al., 2012). Prostate specific antigen (PSA) is a serum marker used for prostate cancer diagnosis and follow-up (Loeb et al., 2014).
Disease Many studies have shown that Hsp60 levels are increased in prostate cancer, using immunohistochemistry (Cornford et al., 2000; Cappello et al., 2003b; Johansson et al., 2006), and proteomics (Skyortsov et al., 2011). HSP60 was significantly increased in both early and advanced prostate cancers when compared with non-neoplastic prostatic epithelium (Cornford et al., 2000). In non-malignant prostate, HSP60-staining is localized in the glandular compartment, particularly basal epithelial cells. In prostate cancer, most epithelial cells showed moderate to strong staining without apparent correlation between staining intensity and Gleason grade (Johansson et al., 2006).
Prognosis Recurrence-free survival in patients with strong HSP60 staining was shorter than in those with weak levels (Glaessgen et al., 2008). In another study, the levels of HSP60 were significantly increased in tumors with high Gleason score. HSP60 expression was also significantly associated with initial serum PSA levels and with the presence of lymph node metastasis (Castilla et al., 2010).
Oncogenesis HSP60 levels increase gradually through carcinogenic steps (from PIN to carcinoma) of prostate (Cappello et al., 2003b).
  
Entity Exocervical cancer
Note Exocervical cancer is preceded by the so called 'squamous intraepithelial lesion' or SIL, a dysplastic (pretumoral) lesion (Garrett and McCann, 2013). SIL, as well as exocervical cancer, have been related to infection by Human Papilloma Virus (HPV) (Garrett and McCann, 2013).
Disease Hsp60 levels are increased in exocervical cancer, as shown by immunohistochemistry (Cappello et al., 2002-2003; Castle et al., 2005).
Oncogenesis HSP60 levels increase gradually through carcinogenic steps (from SIL to carcinoma) of exocervix (Cappello et al., 2002-2003).
  
Entity Vesical cancer
Disease HSP60 levels are decreased in vesical cancers such as bladder carcinoma (Lebret et al., 2003; Cappello et al., 2006b).
Prognosis HSP60 is considered a useful marker for patients with superficial bladder carcinoma for predicting disease progression: lower levels correlate with worse outcome of local treatments. Particularly, HSP60 levels are considered useful prognostic marker to identify patients for whom local treatment would be insufficient (Lebret et al., 2003). Hsp60 levels may predict response to neoadjuvant chemoradiotherapy in invasive or high-risk superficial bladder cancer (Urushibara et al., 2007).
  

To be noted

HSP60 may participate in the process of carcinogenesis, representing cases of chaperonopathies by mistake or collaborationism in which a normal chaperone (at least considering the methods available nowadays to characterize intracellular molecules, or extracellular molecules at very low concentrations) contributes to cancer development (Macario et al., 2013).
HSP60 may participate also in the process of chronic inflammation (Cappello et al., 2011b) and autoimmune diseases (Cappello et al., 2009), also by molecular mimicry phenomena. For example, atherosclerosis has been postulated to be an autoimmune disease due to an immune reaction against heat-shock protein 60 (Wick et al., 2014).

Bibliography

The lung.
Husain A, Kumar V
In: Robbins, Cotran. Pathologic Basis of Disease, 7th edn. Philadelphia: Saunders;2005, 711-772.
 
Expression of heat shock proteins HSP10, HSP27, HSP60, HSP70, and HSP90 in urothelial carcinoma of urinary bladder
Cappello F, David S, Ardizzone N, Rappa F, Marasà L, Bucchieri F, Zummo G
Journal of Cancer Molecule. 2006b ; 2 (2) : 73-77.
 
The Chaperonopathies. Diseases with Defective Molecular Chaperones.
Macario AJL, Conway de Macario AJL, Cappello F
SpringerBriefs in Biochemistry and Molecular Biology. 2013, XVI, pp 75-79. http://www.springer.com/biomed/book/978-94-007-4666-4
 
Sequence homologies between hsp60 and autoantigens
Jones DB, Coulson AF, Duff GW
Immunol Today 1993 Mar;14(3):115-8
PMID 8466626
 
Immunoelectron microscopic localization of the 60-kDa heat shock chaperonin protein (Hsp60) in mammalian cells
Soltys BJ, Gupta RS
Exp Cell Res 1996 Jan 10;222(1):16-27
PMID 8549659
 
Differential expression of heat shock proteins in normal and failing human hearts
Knowlton AA, Kapadia S, Torre-Amione G, Durand JB, Bies R, Young J, Mann DL
J Mol Cell Cardiol 1998 Apr;30(4):811-8
PMID 9602430
 
The Hsp70 and Hsp60 chaperone machines
Bukau B, Horwich AL
Cell 1998 Feb 6;92(3):351-66
PMID 9476895
 
Chaperone-mediated protein folding
Fink AL
Physiol Rev 1999 Apr;79(2):425-49
PMID 10221986
 
Mitochondrial-matrix proteins at unexpected locations: are they exported? Trends Biochem Sci
Soltys BJ, Gupta RS
1999 May;24(5):174-7 Review
PMID 10322429
 
Heat shock protein expression independently predicts clinical outcome in prostate cancer
Cornford PA, Dodson AR, Parsons KF, Desmond AD, Woolfenden A, Fordham M, Neoptolemos JP, Ke Y, Foster CS
Cancer Res 2000 Dec 15;60(24):7099-105
PMID 11156417
 
Unfolding the role of chaperones and chaperonins in human disease
Slavotinek AM, Biesecker LG
Trends Genet 2001 Sep;17(9):528-35
PMID 11525836
 
Chaperonin-mediated protein folding
Thirumalai D, Lorimer GH
Annu Rev Biophys Biomol Struct 2001;30:245-69
PMID 11340060
 
Expression of 60-kD heat shock protein increases during carcinogenesis in the uterine exocervix
Cappello F, Bellafiore M, Palma A, Marciano V, Martorana G, Belfiore P, Martorana A, Farina F, Zummo G, Bucchieri F
Pathobiology 2002-2003;70(2):83-8
PMID 12476033
 
Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60
Hansen JJ, Dürr A, Cournu-Rebeix I, Georgopoulos C, Ang D, Nielsen MN, Davoine CS, Brice A, Fontaine B, Gregersen N, Bross P
Am J Hum Genet 2002 May;70(5):1328-32
PMID 11898127
 
Cytosolic heat shock protein 60, apoptosis, and myocardial injury
Kirchhoff SR, Gupta S, Knowlton AA
Circulation 2002 Jun 18;105(24):2899-904
PMID 12070120
 
60KDa chaperonin (HSP60) is over-expressed during colorectal carcinogenesis
Cappello F, Bellafiore M, Palma A, David S, Marcianò V, Bartolotta T, Sciumè C, Modica G, Farina F, Zummo G, Bucchieri F
Eur J Histochem 2003;47(2):105-10
PMID 12777205
 
Immunohistochemical evaluation of PCNA, p53, HSP60, HSP10 and MUC-2 presence and expression in prostate carcinogenesis
Cappello F, Rappa F, David S, Anzalone R, Zummo G
Anticancer Res 2003 Mar-Apr;23(2B):1325-31
PMID 12820390
 
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, Børglum AD, Mogensen J, Kristiansen K, Bolund L, Gregersen N
Hum Genet 2003 Jan;112(1):71-7
PMID 12483302
 
Heat shock proteins HSP27, HSP60, HSP70, and HSP90: expression in bladder carcinoma
Lebret T, Watson RW, Molinié V, O'Neill A, Gabriel C, Fitzpatrick JM, Botto H
Cancer 2003 Sep 1;98(5):970-7
PMID 12942564
 
The expression of HSP60 and HSP10 in large bowel carcinomas with lymph node metastase
Cappello F, David S, Rappa F, Bucchieri F, Marasà L, Bartolotta TE, Farina F, Zummo G
BMC Cancer 2005 Oct 28;5:139
PMID 16253146
 
Immunopositivity of heat shock protein 60 as a biomarker of bronchial carcinogenesis
Cappello F, Di Stefano A, D'Anna SE, Donner CF, Zummo G
Lancet Oncol 2005 Oct;6(10):816
PMID 16198989
 
Immunohistochemical evaluation of heat shock proteins in normal and preinvasive lesions of the cervix
Castle PE, Ashfaq R, Ansari F, Muller CY
Cancer Lett 2005 Nov 18;229(2):245-52
PMID 16112431
 
HSP60, Bax, apoptosis and the heart
Gupta S, Knowlton AA
J Cell Mol Med 2005 Jan-Mar;9(1):51-8
PMID 15784164
 
Differential expression of Janus kinase 3 (JAK3), matrix metalloproteinase 13 (MMP13), heat shock protein 60 (HSP60), and mouse double minute 2 (MDM2) in human colorectal cancer progression using human cancer cDNA microarrays
Mori D, Nakafusa Y, Miyazaki K, Tokunaga O
Pathol Res Pract 2005;201(12):777-89
PMID 16308103
 
Hsp60 and Hsp10 down-regulation predicts bronchial epithelial carcinogenesis in smokers with chronic obstructive pulmonary disease
Cappello F, Di Stefano A, David S, Rappa F, Anzalone R, La Rocca G, D'Anna SE, Magno F, Donner CF, Balbi B, Zummo G
Cancer 2006 Nov 15;107(10):2417-24
PMID 17048249
 
Mitochondrial chaperones in cancer: from molecular biology to clinical diagnostics
Czarnecka AM, Campanella C, Zummo G, Cappello F
Cancer Biol Ther 2006 Jul;5(7):714-20
PMID 16861898
 
Proteomic comparison of prostate cancer cell lines LNCaP-FGC and LNCaP-r reveals heatshock protein 60 as a marker for prostate malignancy
Johansson B, Pourian MR, Chuan YC, Byman I, Bergh A, Pang ST, Norstedt G, Bergman T, Pousette A
Prostate 2006 Sep 1;66(12):1235-44
PMID 16705742
 
Proteomics-based identification of HSP60 as a tumor-associated antigen in colorectal cancer
He Y, Wu Y, Mou Z, Li W, Zou L, Fu T, Zhang A, Xiang D, Xiao H, Wang X
Proteomics Clin Appl 2007 Mar;1(3):336-42
PMID 21136683
 
HSP60 in heart failure: abnormal distribution and role in cardiac myocyte apoptosis
Lin L, Kim SC, Wang Y, Gupta S, Davis B, Simon SI, Torre-Amione G, Knowlton AA
Am J Physiol Heart Circ Physiol 2007 Oct;293(4):H2238-47
PMID 17675567
 
Plasma heat shock protein 60 and cardiovascular disease risk: the role of psychosocial, genetic, and biological factors
Shamaei-Tousi A, Steptoe A, O'Donnell K, Palmen J, Stephens JW, Hurel SJ, Marmot M, Homer K, D'Aiuto F, Coates AR, Humphries SE, Henderson B
Cell Stress Chaperones 2007 Winter;12(4):384-92
PMID 18229457
 
HSP60 may predict good pathological response to neoadjuvant chemoradiotherapy in bladder cancer
Urushibara M, Kageyama Y, Akashi T, Otsuka Y, Takizawa T, Koike M, Kihara K
Jpn J Clin Oncol 2007 Jan;37(1):56-61
PMID 17095522
 
Upon oxidative stress, the antiapoptotic Hsp60/procaspase-3 complex persists in mucoepidermoid carcinoma cells
Campanella C, Bucchieri F, Ardizzone NM, Marino Gammazza A, Montalbano A, Ribbene A, Di Felice V, Bellafiore M, David S, Rappa F, Marasà M, Peri G, Farina F, Czarnecka AM, Conway de Macario E, Macario AJ, Zummo G, Cappello F
Eur J Histochem 2008 Oct-Dec;52(4):221-8
PMID 19109096
 
Hsp60 expression, new locations, functions and perspectives for cancer diagnosis and therapy
Cappello F, Conway de Macario E, Marasà L, Zummo G, Macario AJ
Cancer Biol Ther 2008 Jun;7(6):801-9
PMID 18497565
 
Heat shock proteins 27, 60 and 70 as prognostic markers of prostate cancer
Glaessgen A, Jonmarker S, Lindberg A, Nilsson B, Lewensohn R, Ekman P, Valdman A, Egevad L
APMIS 2008 Oct;116(10):888-95
PMID 19132982
 
Unusual cellular disposition of the mitochondrial molecular chaperones Hsp60, Hsp70 and Hsp10
Gupta RS, Ramachandra NB, Bowes T, Singh B
Novartis Found Symp 2008;291:59-68; discussion 69-73, 137-40
PMID 18575266
 
Mitochondrial hsp60 chaperonopathy causes an autosomal-recessive neurodegenerative disorder linked to brain hypomyelination and leukodystrophy
Magen D, Georgopoulos C, Bross P, Ang D, Segev Y, Goldsher D, Nemirovski A, Shahar E, Ravid S, Luder A, Heno B, Gershoni-Baruch R, Skorecki K, Mandel H
Am J Hum Genet 2008 Jul;83(1):30-42
PMID 18571143
 
A comparative analysis of the products of GROEL-1 gene from Chlamydia trachomatis serovar D and the HSP60 var1 transcript from Homo sapiens suggests a possible autoimmune response
Campanella C, Marino Gammazza A, Mularoni L, Cappello F, Zummo G, Di Felice V
Int J Immunogenet 2009 Feb;36(1):73-8
PMID 19207939
 
Chlamydia trachomatis infection and anti-Hsp60 immunity: the two sides of the coin
Cappello F, Conway de Macario E, Di Felice V, Zummo G, Macario AJ
PLoS Pathog 2009 Aug;5(8):e1000552
PMID 19714222
 
Extracellular heat shock protein 60, cardiac myocytes, and apoptosis
Kim SC, Stice JP, Chen L, Jung JS, Gupta S, Wang Y, Baumgarten G, Trial J, Knowlton AA
Circ Res 2009 Dec 4;105(12):1186-95
PMID 19875724
 
Hsp60 and AChR cross-reactivity in myasthenia gravis: An update
Cappello F, Marino Gammazza A, Zummo L, Conway de Macario E, Macario AJ
J Neurol Sci 2010 May 15;292(1-2):117-8
PMID 20236663
 
Immunohistochemical expression of Hsp60 correlates with tumor progression and hormone resistance in prostate cancer
Castilla C, Congregado B, Conde JM, Medina R, Torrubia FJ, Japón MA, Sáez C
Urology 2010 Oct;76(4):1017
PMID 20708221
 
Human Hsp10 and Early Pregnancy Factor (EPF) and their relationship and involvement in cancer and immunity: current knowledge and perspectives
Corrao S, Campanella C, Anzalone R, Farina F, Zummo G, Conway de Macario E, Macario AJ, Cappello F, La Rocca G
Life Sci 2010 Jan 30;86(5-6):145-52
PMID 19913561
 
Hsp60 is actively secreted by human tumor cells
Merendino AM, Bucchieri F, Campanella C, Marcianò V, Ribbene A, David S, Zummo G, Burgio G, Corona DF, Conway de Macario E, Macario AJ, Cappello F
PLoS One 2010 Feb 16;5(2):e9247
PMID 20169074
 
Chaperonin genes on the rise: new divergent classes and intense duplication in human and other vertebrate genomes
Mukherjee K, Conway de Macario E, Macario AJ, Brocchieri L
BMC Evol Biol 2010 Mar 1;10:64
PMID 20193073
 
Hsp60 and Hsp10 increase in colon mucosa of Crohns disease and ulcerative colitis
Rodolico V, Tomasello G, Zerilli M, Martorana A, Pitruzzella A, Gammazza AM, David S, Zummo G, Damiani P, Accomando S, Conway de Macario E, Macario AJ, Cappello F
Cell Stress Chaperones 2010 Nov;15(6):877-84
PMID 20390473
 
Immunohistochemistry of human Hsp60 in health and disease: from autoimmunity to cancer
Cappello F, de Macario EC, Zummo G, Macario AJ
Methods Mol Biol 2011;787:245-54
PMID 21898240
 
Convergent sets of data from in vivo and in vitro methods point to an active role of Hsp60 in chronic obstructive pulmonary disease pathogenesis
Cappello F, Caramori G, Campanella C, Vicari C, Gnemmi I, Zanini A, Spanevello A, Capelli A, La Rocca G, Anzalone R, Bucchieri F, D'Anna SE, Ricciardolo FL, Brun P, Balbi B, Carone M, Zummo G, Conway de Macario E, Macario AJ, Di Stefano A
PLoS One 2011;6(11):e28200
PMID 22140545
 
Hsp60: molecular anatomy and role in colorectal cancer diagnosis and treatment
Cappello F, David S, Peri G, Farina F, Conway de Macario E, Macario AJ, Zummo G
Front Biosci (Schol Ed) 2011 Jan 1;3:341-51
PMID 21196380
 
Identification and verification of heat shock protein 60 as a potential serum marker for colorectal cancer
Hamelin C, Cornut E, Poirier F, Pons S, Beaulieu C, Charrier JP, Haïdous H, Cotte E, Lambert C, Piard F, Ataman-Önal Y, Choquet-Kastylevsky G
FEBS J 2011 Dec;278(24):4845-59
PMID 21973086
 
Proteomics profiling of microdissected low- and high-grade prostate tumors identifies Lamin A as a discriminatory biomarker
Skvortsov S, Schäfer G, Stasyk T, Fuchsberger C, Bonn GK, Bartsch G, Klocker H, Huber LA
J Proteome Res 2011 Jan 7;10(1):259-68
PMID 20977276
 
Changes in immunohistochemical levels and subcellular localization after therapy and correlation and colocalization with CD68 suggest a pathogenetic role of Hsp60 in ulcerative colitis
Tomasello G, Rodolico V, Zerilli M, Martorana A, Bucchieri F, Pitruzzella A, Marino Gammazza A, David S, Rappa F, Zummo G, Damiani P, Accomando S, Rizzo M, de Macario EC, Macario AJ, Cappello F
Appl Immunohistochem Mol Morphol 2011 Dec;19(6):552-61
PMID 21441812
 
Heat shock protein-60 expression was significantly correlated with the prognosis of lung adenocarcinoma
Xu X, Wang W, Shao W, Yin W, Chen H, Qiu Y, Mo M, Zhao J, Deng Q, He J
J Surg Oncol 2011 Nov 1;104(6):598-603
PMID 21671464
 
Precursors of prostate cancer
Bostwick DG, Cheng L
Histopathology 2012 Jan;60(1):4-27
PMID 22212075
 
The odyssey of Hsp60 from tumor cells to other destinations includes plasma membrane-associated stages and Golgi and exosomal protein-trafficking modalities
Campanella C, Bucchieri F, Merendino AM, Fucarino A, Burgio G, Corona DF, Barbieri G, David S, Farina F, Zummo G, de Macario EC, Macario AJ, Cappello F
PLoS One 2012;7(7):e42008
PMID 22848686
 
Implications of the International Society of Urological Pathology modified Gleason grading system
Egevad L, Mazzucchelli R, Montironi R
Arch Pathol Lab Med 2012 Apr;136(4):426-34
PMID 22458905
 
The molecular anatomy of human Hsp60 and its similarity with that of bacterial orthologs and acetylcholine receptor reveal a potential pathogenetic role of anti-chaperonin immunity in myasthenia gravis
Gammazza AM, Bucchieri F, Grimaldi LM, Benigno A, de Macario EC, Macario AJ, Zummo G, Cappello F
Cell Mol Neurobiol 2012 Aug;32(6):943-7
PMID 22258649
 
HSP-molecular chaperones in cancer biogenesis and tumor therapy: an overview
Rappa F, Farina F, Zummo G, David S, Campanella C, Carini F, Tomasello G, Damiani P, Cappello F, DE Macario EC, Macario AJ
Anticancer Res 2012 Dec;32(12):5139-50
PMID 23225410
 
Abnormal cytology in 2012: management of atypical squamous cells, low-grade intraepithelial neoplasia, and high-grade intraepithelial neoplasia
Garrett LA, McCann CK
Clin Obstet Gynecol 2013 Mar;56(1):25-34
PMID 23337842
 
Hsp60 chaperonopathies and chaperonotherapy: targets and agents
Cappello F, Marino Gammazza A, Palumbo Piccionello A, Campanella C, Pace A, Conway de Macario E, Macario AJ
Expert Opin Ther Targets 2014 Feb;18(2):185-208
PMID 24286280
 
Active Surveillance for Prostate Cancer: A Systematic Review of Clinicopathologic Variables and Biomarkers for Risk Stratification
Loeb S, Bruinsma SM, Nicholson J, Briganti A, Pickles T, Kakehi Y, Carlsson SV, Roobol MJ
Eur Urol 2015 Apr;67(4):619-626
PMID 25457014
 
Elevated blood Hsp60, its structural similarities and cross-reactivity with thyroid molecules, and its presence on the plasma membrane of oncocytes point to the chaperonin as an immunopathogenic factor in Hashimoto's thyroiditis
Marino Gammazza A, Rizzo M, Citarrella R, Rappa F, Campanella C, Bucchieri F, Patti A, Nikolic D, Cabibi D, Amico G, Conaldi PG, San Biagio PL, Montalto G, Farina F, Zummo G, Conway de Macario E, Macario AJ, Cappello F
Cell Stress Chaperones 2014 May;19(3):343-53
PMID 24057177
 
The role of heat shock proteins in atherosclerosis
Wick G, Jakic B, Buszko M, Wick MC, Grundtman C
Nat Rev Cardiol 2014 Sep;11(9):516-29
PMID 25027488
 

Citation

This paper should be referenced as such :
Cappello F, Conway de Macario E, Macario AJL
HSPD1 (Heat Shock 60kDa Protein 1);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/HSPD1ID40888ch2q33.html
History of this paper:
Faried, LS ; Faried, A. HSPD1 (heat shock 60kDa protein 1). Atlas Genet Cytogenet Oncol Haematol. 2007;11(3):194-196.
http://documents.irevues.inist.fr/bitstream/handle/2042/38438/02-2007-HSPD1ID40888ch2q33.pdf


External links

Nomenclature
HGNC (Hugo)HSPD1   5261
Cards
AtlasHSPD1ID40888ch2q33
Entrez_Gene (NCBI)HSPD1  3329  heat shock protein family D (Hsp60) member 1
AliasesCPN60; GROEL; HLD4; HSP-60; 
HSP60; HSP65; HuCHA60; SPG13
GeneCards (Weizmann)HSPD1
Ensembl hg19 (Hinxton)ENSG00000144381 [Gene_View]  chr2:198351308-198364640 [Contig_View]  HSPD1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000144381 [Gene_View]  chr2:198351308-198364640 [Contig_View]  HSPD1 [Vega]
ICGC DataPortalENSG00000144381
TCGA cBioPortalHSPD1
AceView (NCBI)HSPD1
Genatlas (Paris)HSPD1
WikiGenes3329
SOURCE (Princeton)HSPD1
Genomic and cartography
GoldenPath hg19 (UCSC)HSPD1  -     chr2:198351308-198364640 -  2q33.1   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)HSPD1  -     2q33.1   [Description]    (hg38-Dec_2013)
EnsemblHSPD1 - 2q33.1 [CytoView hg19]  HSPD1 - 2q33.1 [CytoView hg38]
Mapping of homologs : NCBIHSPD1 [Mapview hg19]  HSPD1 [Mapview hg38]
OMIM118190   605280   612233   
Gene and transcription
Genbank (Entrez)AK297305 AK298368 AK298632 AK298844 AK301276
RefSeq transcript (Entrez)NM_002156 NM_199440
RefSeq genomic (Entrez)NC_000002 NC_018913 NG_008915 NT_005403 NW_004929305
Consensus coding sequences : CCDS (NCBI)HSPD1
Cluster EST : UnigeneHs.727543 [ NCBI ]
CGAP (NCI)Hs.727543
Alternative Splicing GalleryENSG00000144381
Gene ExpressionHSPD1 [ NCBI-GEO ]   HSPD1 [ EBI - ARRAY_EXPRESS ]   HSPD1 [ SEEK ]   HSPD1 [ MEM ]
Gene Expression Viewer (FireBrowse)HSPD1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)3329
GTEX Portal (Tissue expression)HSPD1
Protein : pattern, domain, 3D structure
UniProt/SwissProtP10809 (Uniprot)
NextProtP10809  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP10809
Splice isoforms : SwissVarP10809 (Swissvar)
PhosPhoSitePlusP10809
Domaine pattern : Prosite (Expaxy)CHAPERONINS_CPN60 (PS00296)   
Domains : Interpro (EBI)Chaperonin_Cpn60_CS    Chaprnin_Cpn60    Cpn60/TCP-1    GroEL-like_apical_dom    GROEL-like_equatorial   
Domain families : Pfam (Sanger)Cpn60_TCP1 (PF00118)   
Domain families : Pfam (NCBI)pfam00118   
DMDM Disease mutations3329
Blocks (Seattle)HSPD1
PDB (SRS)4PJ1   
PDB (PDBSum)4PJ1   
PDB (IMB)4PJ1   
PDB (RSDB)4PJ1   
Structural Biology KnowledgeBase4PJ1   
SCOP (Structural Classification of Proteins)4PJ1   
CATH (Classification of proteins structures)4PJ1   
SuperfamilyP10809
Human Protein AtlasENSG00000144381
Peptide AtlasP10809
HPRD00318
IPIIPI00784154   IPI00917575   IPI00916653   IPI00917983   IPI00917789   IPI00917686   IPI00973036   IPI00969594   IPI00915941   
Protein Interaction databases
DIP (DOE-UCLA)P10809
IntAct (EBI)P10809
FunCoupENSG00000144381
BioGRIDHSPD1
STRING (EMBL)HSPD1
ZODIACHSPD1
Ontologies - Pathways
QuickGOP10809
Ontology : AmiGOlipopolysaccharide binding  p53 binding  B cell cytokine production  MyD88-dependent toll-like receptor signaling pathway  positive regulation of T cell mediated immune response to tumor cell  DNA replication origin binding  single-stranded DNA binding  double-stranded RNA binding  protein binding  ATP binding  extracellular space  cytoplasm  mitochondrion  mitochondrial inner membrane  mitochondrial matrix  early endosome  cytosol  coated pit  'de novo' protein folding  activation of cysteine-type endopeptidase activity involved in apoptotic process  response to unfolded protein  response to cold  cell surface  membrane  viral process  ATPase activity  cyclin-dependent protein kinase activating kinase holoenzyme complex  coated vesicle  secretory granule  ubiquitin protein ligase binding  positive regulation of interferon-alpha production  positive regulation of interferon-gamma production  positive regulation of interferon-gamma production  positive regulation of interleukin-10 production  positive regulation of interleukin-12 production  positive regulation of interleukin-6 production  protein refolding  B cell proliferation  T cell activation  B cell activation  positive regulation of macrophage activation  positive regulation of apoptotic process  negative regulation of apoptotic process  protein complex  poly(A) RNA binding  lipopolysaccharide receptor complex  isotype switching to IgG isotypes  protein stabilization  protein stabilization  positive regulation of T cell activation  positive regulation of T cell activation  unfolded protein binding  unfolded protein binding  chaperone binding  chaperone-mediated protein complex assembly  protein maturation  extracellular exosome  
Ontology : EGO-EBIlipopolysaccharide binding  p53 binding  B cell cytokine production  MyD88-dependent toll-like receptor signaling pathway  positive regulation of T cell mediated immune response to tumor cell  DNA replication origin binding  single-stranded DNA binding  double-stranded RNA binding  protein binding  ATP binding  extracellular space  cytoplasm  mitochondrion  mitochondrial inner membrane  mitochondrial matrix  early endosome  cytosol  coated pit  'de novo' protein folding  activation of cysteine-type endopeptidase activity involved in apoptotic process  response to unfolded protein  response to cold  cell surface  membrane  viral process  ATPase activity  cyclin-dependent protein kinase activating kinase holoenzyme complex  coated vesicle  secretory granule  ubiquitin protein ligase binding  positive regulation of interferon-alpha production  positive regulation of interferon-gamma production  positive regulation of interferon-gamma production  positive regulation of interleukin-10 production  positive regulation of interleukin-12 production  positive regulation of interleukin-6 production  protein refolding  B cell proliferation  T cell activation  B cell activation  positive regulation of macrophage activation  positive regulation of apoptotic process  negative regulation of apoptotic process  protein complex  poly(A) RNA binding  lipopolysaccharide receptor complex  isotype switching to IgG isotypes  protein stabilization  protein stabilization  positive regulation of T cell activation  positive regulation of T cell activation  unfolded protein binding  unfolded protein binding  chaperone binding  chaperone-mediated protein complex assembly  protein maturation  extracellular exosome  
Pathways : KEGGRNA degradation    Type I diabetes mellitus    Legionellosis    Tuberculosis   
REACTOMEP10809 [protein]
REACTOME PathwaysR-HSA-1268020 Mitochondrial protein import [pathway]
NDEx Network
Atlas of Cancer Signalling NetworkHSPD1
Wikipedia pathwaysHSPD1
Orthology - Evolution
OrthoDB3329
GeneTree (enSembl)ENSG00000144381
Phylogenetic Trees/Animal Genes : TreeFamHSPD1
Homologs : HomoloGeneHSPD1
Homology/Alignments : Family Browser (UCSC)HSPD1
Gene fusions - Rearrangements
Polymorphisms : SNP, variants
NCBI Variation ViewerHSPD1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)HSPD1
dbVarHSPD1
ClinVarHSPD1
1000_GenomesHSPD1 
Exome Variant ServerHSPD1
ExAC (Exome Aggregation Consortium)HSPD1 (select the gene name)
Genetic variants : HAPMAP3329
Genomic Variants (DGV)HSPD1 [DGVbeta]
Mutations
ICGC Data PortalHSPD1 
TCGA Data PortalHSPD1 
Broad Tumor PortalHSPD1
OASIS PortalHSPD1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICHSPD1 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)MSeqDR-LSDB Mitochondrial Disease Locus Specific Database
BioMutasearch HSPD1
DgiDB (Drug Gene Interaction Database)HSPD1
DoCM (Curated mutations)HSPD1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)HSPD1 (select a term)
intoGenHSPD1
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)2:198351308-198364640  ENSG00000144381
CONAN: Copy Number AnalysisHSPD1 
Mutations and Diseases : HGMDHSPD1
OMIM118190    605280    612233   
MedgenHSPD1
Genetic Testing Registry HSPD1
NextProtP10809 [Medical]
TSGene3329
GENETestsHSPD1
Huge Navigator HSPD1 [HugePedia]
snp3D : Map Gene to Disease3329
BioCentury BCIQHSPD1
ClinGenHSPD1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD3329
Chemical/Pharm GKB GenePA29527
Clinical trialHSPD1
Miscellaneous
canSAR (ICR)HSPD1 (select the gene name)
Probes
Litterature
PubMed354 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineHSPD1
EVEXHSPD1
GoPubMedHSPD1
iHOPHSPD1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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