60 kDa heat shock protein, mitochondrial (HSPD1)
The protein contains 573 amino acids for an estimated molecular weight of 61055 Da.
Chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp10, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix (PubMed:1346131, PubMed:11422376). The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein (Probable). (updated: Jan. 31, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
Biological Process
'de novo' protein folding
Activation of cysteine-type endopeptidase activity involved in apoptotic process
Apoptotic mitochondrial changes
B cell activation
B cell cytokine production
B cell proliferation
Biological process involved in interaction with symbiont
Cellular response to heat
Cellular response to interleukin-7
Chaperone-mediated protein complex assembly
Chaperone-mediated protein folding
Isotype switching to IgG isotypes
Mitochondrial unfolded protein response
Mitochondrion organization
MyD88-dependent toll-like receptor signaling pathway
Negative regulation of apoptotic process
Negative regulation of apoptotic process in bone marrow cell
Negative regulation of neuron apoptotic process
Negative regulation of reactive oxygen species biosynthetic process
Positive regulation of apoptotic process
Positive regulation of inflammatory response
Positive regulation of interferon-alpha 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
Positive regulation of interleukin-6 secretion
Positive regulation of macrophage activation
Positive regulation of T cell activation
Positive regulation of T cell mediated immune response to tumor cell
Positive regulation of tumor necrosis factor secretion
Protein folding
Protein import into mitochondrial intermembrane space
Protein maturation
Protein refolding
Protein stabilization
Regulation of transcription by RNA polymerase II
Response to activity
Response to ATP
Response to cocaine
Response to cold
Response to drug
Response to estrogen
Response to glucocorticoid
Response to hydrogen peroxide
Response to hypoxia
Response to ischemia
Response to lipopolysaccharide
Response to unfolded protein
T cell activation
Viral process
Cellular Component
Cell surface
Clathrin-coated pit
Coated vesicle
Cytoplasm
Cytosol
Early endosome
Extracellular exosome
Extracellular matrix
Extracellular space
Golgi apparatus
Lipopolysaccharide receptor complex
Membrane
Membrane raft
Mitochondrial crista
Mitochondrial inner membrane
Mitochondrial matrix
Mitochondrion
Myelin sheath
Peroxisomal matrix
Plasma membrane
Protein complex
Protein-containing complex
Rough endoplasmic reticulum
Secretory granule
Zymogen granule
Molecular Function
Apolipoprotein A-I binding
Apolipoprotein binding
ATP binding
ATPase
Chaperone binding
DNA replication origin binding
Double-stranded RNA binding
Enzyme binding
High-density lipoprotein particle binding
Insulin binding
Isomerase activity
Lipopolysaccharide binding
Modification-dependent protein binding
P53 binding
Poly(A) RNA binding
Protease binding
Protein folding chaperone
RNA binding
Single-stranded DNA binding
Ubiquitin protein ligase binding
Unfolded protein binding
The reference OMIM entry for this protein is 118190
Heat-shock 60-kd protein 1; hspd1
Hsp60
Chaperonin, 60-kd; cpn60
Groel, e. coli, homolog of
DESCRIPTION
It had long been assumed that all information necessary for proper folding of proteins and their assembly into oligomeric complexes was contained within the primary sequence of the polypeptides and that no catalyst or other accessory proteins were involved in this process. However, this basic tenet of biochemistry was challenged by the discovery of chaperonins, which are involved in the folding and assembly of a number of different proteins (Cheng et al., 1989; Ellis, 1990; Rothman, 1989). Members of the chaperonin family include the GroEL protein of E. coli and HSP60, a protein present in eukaryotic cell mitochondria. In both prokaryotic and eukaryotic systems, synthesis of these proteins is induced in response to stresses, such as heat shock (Venner et al., 1990).CLONING
Venner et al. (1990) presented evidence of the existence of multiple copies of the HSP60 gene in the human. All except one of these genes are nonfunctional pseudogenes containing numerous changes such as base substitutions, insertions, and deletions.BIOCHEMICAL FEATURES
Azem et al. (1994) performed chemical crosslinking and electron microscopy studies on bacterial chaperonins GroEL and GroES (HSPE1; 600141) to determine how they interact with unfolded proteins. GroEL is an oligomer of 14 identical 57.3-kD subunits, with a structure of 2 stacked heptameric rings arranged around a 2-fold axis of symmetry (Saibil et al., 1991). It appears as a hollow cylinder. In the presence of ATP, 2 GroES rings (each made of 7 identical 10.4-kD subunits) can successively bind a single GroEL core to make a functional symmetric heterodimer. Although the central core of GroEL is obstructed by the 2 GroES rings at each end, this heterodimer can stably bind and assist the refolding of the RuBisCo enzyme. While binding was thought to occur in the central cavity, these data indicate that unfolded proteins may bind and fold on the external envelope of some chaperonins (Azem et al., 1994). Schmidt et al. (1994) suggested that the symmetric chaperonin complex is functionally significant because complete folding of a nonnative substrate protein in the presence of GroEL and GroES occurs only in the presence of ATP, and not with ADP. Chaperonin-assisted folding occurs by a catalytic cycle in which one ATP is hydrolyzed by one ring of GroEL in a quantized manner with each turnover. Todd et al. (1994) proposed a unifying model for chaperonin-facilitated protein folding based on successive rounds of binding and release, and partitioning between committed and kinetically trapped intermediates.GENE FUNCTION
Zal et al. (2004) examined the antigen recognition of CD4 (186940)-positive/CD28 (186760)-null T lymphocytes from 21 patients with acute coronary syndrome (ACS), 12 with chronic stable angina, and 9 healthy controls. CD4-positive/CD28-null cells from 12 of 21 patients with ACS reacted with HSPD1; no response was detected to human cytomegalovirus, Chlamydia pneumoniae, or oxidized LDL. CD4-positive/CD28-null cells from patients with chronic stable angina and controls did not react to any of the antigens. Zal et al. (2004) concluded that HSPD1 is an antigen recognized by CD4-positive/CD28-null T cells of patients with acute coronary syndrome and suggested that HSPD1-specific CD4-positive/CD28-null cells may contribute to vascular damage in these patients. Zanin-Zhorov et al. (2006) reported that HSP60, as well as a synthetic peptide derived fr ... More on the omim web site
Feb. 5, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 15, 2016: Protein entry updated
Automatic update: OMIM entry 118190 was added.