Heat shock protein 75 kDa, mitochondrial (TRAP1)
The protein contains 704 amino acids for an estimated molecular weight of 80110 Da.
Chaperone that expresses an ATPase activity. Involved in maintaining mitochondrial function and polarization, downstream of PINK1 and mitochondrial complex I. Is a negative regulator of mitochondrial respiration able to modulate the balance between oxidative phosphorylation and aerobic glycolysis. The impact of TRAP1 on mitochondrial respiration is probably mediated by modulation of mitochondrial SRC and inhibition of SDHA. (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.
- 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.
- 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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| Variant | Description |
|---|---|
| dbSNP:rs13926 | |
| dbSNP:rs1136948 | |
| dbSNP:rs55766649 | |
| dbSNP:rs2791 |
Biological Process
Chaperone-mediated protein folding
Negative regulation of cellular respiration
Negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide
Negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
Negative regulation of reactive oxygen species biosynthetic process
Protein folding
Response to stress
Translational attenuation
The reference OMIM entry for this protein is 606219
Tumor necrosis factor receptor-associated protein 1; trap1
Tnfr-associated protein 1 heat-shock protein, 75-kd; hsp75
Hsp90-like protein; hsp90l
DESCRIPTION
HSP90 proteins are highly conserved molecular chaperones that have key roles in signal transduction, protein folding, protein degradation, and morphologic evolution. HSP90 proteins normally associate with other cochaperones and play important roles in folding newly synthesized proteins or stabilizing and refolding denatured proteins after stress. TRAP1 is a mitochondrial HSP90 protein. Other HSP90 proteins are found in cytosol (see HSP90AA1; 140571) and endoplasmic reticulum (HSP90B1; 191175) (Chen et al., 2005).CLONING
Using a yeast 2-hybrid screen of a Gal4/HeLa cDNA library with the intracellular domain of TNFR1 (191190) as bait, followed by 5-prime RACE, Song et al. (1995) isolated a partial cDNA encoding TRAP1. The deduced 661-amino acid protein is 60% similar to HSP90 family members, although it lacks the highly charged domain found in HSP90 proteins. Northern blot analysis revealed variable but ubiquitous expression of a 2.7-kb TRAP1 transcript. By yeast 2-hybrid screening of several cDNA libraries with an N-terminally truncated retinoblastoma protein (RB1; 614041) as bait, Chen et al. (1996) obtained a nearly complete cDNA encoding TRAP1, which they termed HSP75. HSP75 has 698 amino acids. Immunoprecipitation, immunoblot analysis, and immunofluorescence microscopy demonstrated expression of a 75-kD cytoplasmic protein that colocalized with RB1 during mitosis but not during other phases. During heat shock, HSP75 migrated to the nucleus. In a yeast 2-hybrid screen with exostosin-2 (EXT2; 608210) as bait, Simmons et al. (1999) isolated TRAP1. They reported that the full-length cDNA sequence encodes a 704-amino acid protein (GenBank GENBANK AF154108). Using immunofluorescence microscopy, Felts et al. (2000) demonstrated a mitochondrial localization for TRAP1. TRAP1 possesses a mitochondrial localization sequence, STQTAED, beginning after cleavage at position 59. Sequence analysis predicted that TRAP1 is 54% identical to a Drosophila homolog. By database analysis, Chen et al. (2005) identified several TRAP1 variants. Like other HSP90 proteins, the 704-amino acid TRAP1 protein has a highly conserved N-terminal domain, a middle domain involved in ATPase activity, a charged domain, and a C-terminal domain, but it lacks the charged domain found immediately after the N-terminal domain in other HSP90 proteins. It also has a signal peptide and gln-rich region.GENE FUNCTION
Using yeast 2-hybrid and GST pull-down analyses, Song et al. (1995) found that TRAP1 interacted with the N-terminal half of TNFR1. Binding analysis by Chen et al. (1996) showed that HSP75 used an LxCxE motif to bind to the T antigen-binding domains of RB1. Western blot analysis indicated that HSP75 could refold denatured RB1, suggesting that HSP75 acts as a chaperone for RB1. Binding analysis by Simmons et al. (1999) showed that TRAP1 interacted with the C-terminal ends of the proteins encoded by both multiple exostoses-causing genes, EXT1 (608177) and EXT2, but not with EXTL1 (601738) or EXTL3 (605744). The interaction required the presence of a his residue in the EXT proteins, the loss of which had been identified in a single family with type I multiple exostoses (133700) by Raskind et al. (1998). Felts et al. (2000) reported that TRAP1 lacked the chaperone activities of HSP90 and also failed to interact with cochaperones of HSP90. However, TRAP1 did bind ATP and expressed an ATPase activity that could be blocked by the HSP ... 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 606219 was added.