Heat shock-related 70 kDa protein 2 (HSPA2)
The protein contains 639 amino acids for an estimated molecular weight of 70021 Da.
Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release (PubMed:26865365). Plays a role in spermatogenesis. In association with SHCBP1L may participate in the maintenance of spindle integrity during meiosis in male germ cells (By similarity). (updated: Nov. 22, 2017)
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.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- 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.
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| Variant | Description |
|---|---|
| dbSNP:rs45456191 | |
| dbSNP:rs45447398 |
Biological Process
Cellular response to heat
Cellular response to unfolded protein
Chaperone cofactor-dependent protein refolding
Male meiosis I
Male meiotic nuclear division
Negative regulation of inclusion body assembly
Positive regulation of ATPase activity
Positive regulation of ATPase-coupled calcium transmembrane transporter activity
Positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G2/M transition of mitotic cell cycle
Positive regulation of G2/M transition of mitotic cell cycle
Positive regulation of protein phosphorylation
Protein refolding
Response to cold
Response to heat
Response to unfolded protein
Spermatid development
Spermatogenesis
Synaptonemal complex disassembly
Vesicle-mediated transport
The reference OMIM entry for this protein is 140560
Heat-shock 70-kd protein 2; hspa2
Heat-shock protein, 70-kd, 2
Hsp70-2
Heat-shock protein, 70-kd, 3
Hsp70-3
CLONING
Bonnycastle et al. (1994) isolated a genomic clone for HSPA2 and found that it has a single open reading frame of 1,917 basepairs that encodes a 639-amino acid protein with a predicted molecular mass of 70,030 Da. Analysis of the sequence indicated that HSPA2 is the human homolog of the murine Hsp70-2 gene, with 91.7% identity in the nucleotide coding sequence and 98.2% in the corresponding amino acid sequence. HSPA2 has less amino acid homology to the other members of the human HSP70 gene family. HSPA2 is constitutively expressed in most tissues, with very high levels in testis and skeletal muscle. Roux et al. (1994) also cloned the HSPA2 gene, using a genomic probe derived from one of the HSP genes in the major histocompatibility complex (MHC) on chromosome 6, which had previously been shown to detect sequences on chromosome 14 as well. HSPA2 is expressed abundantly in muscle, heart, esophagus, and brain, and to a lesser extent in testis. Using Western blot analysis, Son et al. (1999) found significant expression of a 70-kD HSPA2 protein in testis, but only low expression in testis with Sertoli cell-only syndrome (see 305700). A small amount of HSPA2 was detected in breast, stomach, prostate, colon, liver, ovary, and epididymis. Immunohistochemical analysis of normal testis detected HSPA2 in spermatocytes and spermatids with normal spermatogenesis, whereas little to no immunoreactivity was detected in testis with Sertoli cell-only syndrome. Huszar et al. (2000) determined that HSPA2 is identical to sperm CKM, a marker of sperm maturity and function. Immunohistochemical analysis detected weak expression of HSPA2 in spermatocytes and stronger expression in spermatids and in the tail of mature sperm.GENE FUNCTION
During spermiogenesis, both cytoplasmic extrusion and plasma membrane remodeling, which facilitate the formation of the zona pellucida-binding site, involve major intrasperm protein transport. Huszar et al. (2000) noted that immature human sperm, which fail to express HSPA2, show cytoplasmic retention and lack zona pellucida binding. They suggested that HSPA2 may be critical to sperm maturation through its role as a protein chaperone. Rohde et al. (2005) found elevated expression of HSP70-2 in 5 of 16 (31%) and 4 of 9 (44%) samples from primary and metastatic breast cancer tissue, respectively, compared with 13 samples from adjacent normal breast tissue. Cancer cells depleted of HSP70 (HSPA1A; 140550) and HSP70-2 by small interfering RNA displayed strikingly different morphologies (detached and round vs flat senescent-like), cell cycle distribution (G2/M vs G1 arrest), and gene expression profiles. Concomitant depletion of HSP70 and HSP70-2 had a synergistic antiproliferative effect on cancer cells.MAPPING
Several heat-shock protein genes, such as HSPA1, are located in the MHC on chromosome 6. However, the HSPA2 gene is located on chromosome 14q22-q24 (Harrison et al., 1987). By fluorescence in situ hybridization, Bonnycastle et al. (1994) mapped a 670-kb YAC containing HSPA2 to chromosome 14q24.1. Roux et al. (1994) localized HSPA2 to chromosome 14q22 by study of a somatic cell hybrid panel and by FISH analysis. Hunt et al. (1993) found that the corresponding gene in the mouse is located in a region of chromosome 12 homologous to human chromosome 14.MOLECULAR GENETICS
For a discussion of a possible association between variation in the HSPA2 gene and noise-induced hearing lo ... More on the omim web site
Feb. 10, 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 16, 2016: Protein entry updated
Automatic update: OMIM entry 140560 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed