Stress-70 protein, mitochondrial (HSPA9)
The protein contains 679 amino acids for an estimated molecular weight of 73680 Da.
Chaperone protein which plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis. Interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU (PubMed:26702583). Regulates erythropoiesis via stabilization of ISC assembly (PubMed:21123823, PubMed:26702583). May play a role in the control of cell proliferation and cellular aging (By similarity). (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.
- 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.
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Biological Process
Cellular protein metabolic process
Cellular response to heat
Cellular response to unfolded protein
Chaperone cofactor-dependent protein refolding
Erythrocyte differentiation
Inner mitochondrial membrane organization
Interleukin-12-mediated signaling pathway
Iron-sulfur cluster assembly
Negative regulation of apoptotic process
Negative regulation of erythrocyte differentiation
Negative regulation of hematopoietic stem cell differentiation
Negative regulation of hemopoiesis
Protein export from nucleus
Protein folding
Protein refolding
Protein targeting to mitochondrion
Regulation of erythrocyte differentiation
Response to unfolded protein
The reference OMIM entry for this protein is 600548
Heat-shock 70-kd protein 9; hspa9
Hspa9b
Mortalin
Mortalin 2; mot2
Mortalin, perinuclear
Glucose-regulated protein, 75-kd; grp75
DESCRIPTION
HSPA9 is a highly conserved member of the HSP70 family of proteins (see 140550). It functions as a chaperone in the mitochondria, cytoplasm, and centrosome (summary by Chen et al., 2011).CLONING
Mortalin has been shown to exhibit differential distributions in cells with mortal and immortal phenotypes. All immortal human and mouse cells that have been tested are devoid of the uniformly distributed cytosolic form of the protein that is characteristic of normal cells. Kaul et al. (1995) cloned mortalin cDNA from an immortal cell line, RS-4, established from mouse fibroblasts. The cDNA exhibited the structure of the perinuclear form, Mot2.GENE FUNCTION
By immunoprecipitation analysis of mitochondria from human lymphoblasts and transfected COS-7 cells, Shan et al. (2007) showed that frataxin (FXN; 606829), which is encoded by the gene mutated in Friedreich ataxia (229300), interacted directly with several mitochondrial proteins, including the mitochondrial chaperone HSPA9. Reciprocal immunoprecipitation analysis confirmed the interaction of FXN and HSPA9 in transfected HEK293 cells. Heterozygous deletions spanning chromosome 5q31.2 occur frequently in myelodysplastic syndromes (153550). Chen et al. (2011) purified human cord blood hematopoietic progenitor cells and grew them under culture conditions that supported erythroid, myeloid, or megakaryocytic cell growth. They found that short hairpin RNA-mediated knockdown of HSPA9 in these progenitors reduced growth predominantly in erythroid progenitors. Knockdown of HSPA9 in erythroid cultures was associated with an increased number of cells in the G0/G1 phase of the cell cycle and accelerated apoptosis. Knockdown of Hspa9 in mouse bone marrow cells, followed by transplantation into wildtype recipients, also resulted in loss of erythroid cell number. Chen et al. (2011) concluded that haploinsufficiency for HSPA9 may contribute to abnormal hematopoiesis in myelodysplastic syndromes with deletions spanning chromosome 5q31.2.MAPPING
Using FISH, Kaul et al. (1995) mapped the human mortalin gene to chromosome 5q31.1. Gross (2011) mapped the HSPA9 gene to chromosome 5q31.2 based on an alignment of the HSPA9 sequence (GenBank GENBANK AK222758) with the genomic sequence. In mouse, Kaul et al. (1995) mapped mortalin-related genes to chromosomes 18 and X. ... 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600548 was added.
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed