Heat shock protein 105 kDa (HSPH1)
The protein contains 858 amino acids for an estimated molecular weight of 96865 Da.
Acts as a nucleotide-exchange factor (NEF) for chaperone proteins HSPA1A and HSPA1B, promoting the release of ADP from HSPA1A/B thereby triggering client/substrate protein release (PubMed:24318877). Prevents the aggregation of denatured proteins in cells under severe stress, on which the ATP levels decrease markedly. Inhibits HSPA8/HSC70 ATPase and chaperone activities (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.
- 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.
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Biological Process
Chaperone cofactor-dependent protein refolding
Negative regulation of establishment of protein localization to mitochondrion
Negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide
Negative regulation of p38MAPK cascade
Positive regulation of MHC class I biosynthetic process
Positive regulation of NK T cell activation
Positive regulation of protein tyrosine kinase activity
Positive regulation of transcription by RNA polymerase II
Receptor-mediated endocytosis
Regulation of cellular response to heat
Response to unfolded protein
Cellular Component
Cytoplasm
Cytosol
Endocytic vesicle lumen
Extracellular exosome
Extracellular region
Microtubule
Nucleoplasm
Nucleus
Protein complex
Protein-containing complex
Molecular Function
Adenyl-nucleotide exchange factor activity
Alpha-tubulin binding
ATP binding
ATPase
The reference OMIM entry for this protein is 610703
Heat-shock 105/110-kd protein 1; hsph1
Heat-shock protein, 105-kd; hsp105
Heat-shock protein, 110-kd; hsp110
Kiaa0201
CLONING
By sequencing clones obtained from an immature myeloid leukemia cell line cDNA library, Nagase et al. (1996) cloned HSPH1, which they designated KIAA0201. The deduced 858-amino acid protein contains an HSP70 (see HSPA1A; 140550)-like motif and shares 93.4% identity with mouse Hsph1-alpha. Northern blot analysis detected highest expression in brain, lung, and testis. Expression was lower in heart, skeletal muscle, kidney, pancreas, spleen, ovary, small intestine, colon, and peripheral blood leukocytes, and weak in liver. No expression was detected in thymus and prostate. Using mouse Hsph1 to screen a cDNA library derived from heat-shocked HeLa cells, Ishihara et al. (1999) cloned 2 splice variants of HSPH1, which they called HSP105-alpha and HSP105-beta. The HSP105-alpha and HSP105-beta proteins contain 858 and 814 amino acids, respectively, and both have an N-terminal ATP-binding domain. Northern blot analysis detected a 4-kb HSP105 transcript in HeLa cells. Immunohistochemical analysis localized HSP105 mainly in the cytoplasm. Database analysis indicated that both HSP105 isoforms are highly conserved during evolution.GENE FUNCTION
Using Northern blot analysis, Ishihara et al. (1999) found that both HSP105-alpha and HSP105-beta were upregulated in HeLa cells exposed to heat shock. HSP105-alpha, but not HSP105-beta, was also upregulated in response to other cell stresses. Following heat shock, HSP105 relocalized from a cytoplasmic to perinuclear position. In mice, Olszak et al. (2014) showed that while bone marrow-derived Cd1d (188410) signals contribute to natural killer T (NKT) cell-mediated intestinal inflammation, engagement of epithelial Cd1d elicits protective effects through the activation of Stat3 (102582) and Stat3-dependent transcription of Il10 (124092), Hsp110, and Cd1d itself. All of these epithelial elements are critically involved in controlling CD1D-mediated intestinal inflammation. This was demonstrated by severe NKT cell-mediated colitis upon intestinal epithelial cell-specific deletion of IL10, CD1D, and its critical regulator microsomal triglyceride transfer protein (MTP; 157147), as well as deletion of HSP110 in the radioresistant compartment. Olszak et al. (2014) concluded that these studies uncovered a novel pathway of intestinal epithelial cell-dependent regulation of mucosal homeostasis as well as highlighted a critical role for IL10 in the intestinal epithelium, with broad implications for diseases such as inflammatory bowel disease.MOLECULAR GENETICS
Dorard et al. (2011) identified a mutant of HSP110, which they called HSP110-delta-E9, in colorectal cancer (114500) showing microsatellite instability (MSI CRC), generated from an aberrantly spliced mRNA and lacking the HSP110 substrate-binding domain. This mutant was expressed at variable levels in almost all MSI CRC cell lines and primary tumors tested. HSP110-delta-E9 impaired both the normal cellular localization of HSP110 and its interaction with other HSPs, thus abrogating the chaperone activity and antiapoptotic function of HSP110 in a dominant-negative manner. HSP110-delta-E9 overexpression caused the sensitization of cells to anticancer agents such as oxaliplatin and 5-fluorouracil, which are routinely prescribed in the adjuvant treatment of people with colorectal cancer. The survival and response to chemotherapy of subjects with colorectal cancer showing microsatellite instability was associated with the tumor e ... 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 610703 was added.