Bleomycin hydrolase (BLMH)
The protein contains 455 amino acids for an estimated molecular weight of 52562 Da.
The normal physiological role of BLM hydrolase is unknown, but it catalyzes the inactivation of the antitumor drug BLM (a glycopeptide) by hydrolyzing the carboxamide bond of its B-aminoalaninamide moiety thus protecting normal and malignant cells from BLM toxicity. (updated: March 4, 2015)
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.
- 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.
- 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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| Variant | Description |
|---|---|
| dbSNP:rs1050565 |
The reference OMIM entry for this protein is 602403
Bleomycin hydrolase; blmh
Bmh
CLONING
The gene encoding bleomycin hydrolase (BMH) was cloned and found to encode a 455-amino acid protein containing the signature active site residues of the cysteine protease papain superfamily (Bromme et al., 1996; Ferrando et al., 1996). The protein had aminopeptidase activity that was blocked by the irreversible cysteine protease inhibitor E-64. Ferrando et al. (1996) found the BMH protein to be approximately 40% identical to that of the yeast homolog Gal6. Both yeast and human BMH also possess endopeptidase activity. The gene is expressed in many human tissues with elevated expression levels found in testis, skeletal muscle, and pancreas, and low levels of expression in colon and peripheral blood leukocytes (Bromme et al., 1996).MAPPING
Montoya et al. (1997) mapped the BLMH gene to chromosome 17 using a human/rodent hybrid mapping panel and localized it to 17q11.1-q11.2 by linkage analysis using the CEPH reference database. By fluorescence in situ hybridization, Ferrando et al. (1997) mapped the BLMH gene to 17q11.2, very close to the locus of the NF1 gene (613113).GENE STRUCTURE
Montoya et al. (1997) found that the BLMH gene contains 11 exons ranging in size from 69 to 198 bp separated by introns of approximately 1 kb, reflecting the archetypal genomic structure of the cysteine protease family. Ferrando et al. (1997) concluded that BLMH contains 12 coding exons and spans more than 30 kb. They also concluded that the number and distribution of exons and introns differ from those reported for other human cysteine proteinases, indicating that these genes are only distantly related. The nuclear sequence of the 5-prime flanking region of the gene had characteristics of housekeeping genes, consistent with the widespread expression of bleomycin hydrolase in human tissues. The 5-prime flanking region of the gene also contains a polymorphic CCG trinucleotide repeat that may be a target of genetic instability events and affect its transcriptional activity.GENE FUNCTION
Bleomycin hydrolase is highly conserved through evolution; however, the only known activity of the enzyme is metabolic inactivation of the glycopeptide bleomycin (BLM), a component of combination chemotherapy regimens for cancer. Even in low doses, bleomycin has the unfortunate property of inducing pulmonary toxicity in approximately 3 to 5% of patients; cumulative doses greater than 450 mg induced potentially lethal pulmonary toxicity in up to 10% of patients. Lazo and Humphreys (1983) considered the BMH gene to be a primary candidate for protection against potential fatal bleomycin-induced pulmonary fibrosis and bleomycin resistance in tumors. Haston et al. (1996) presented evidence for a genetic basis for susceptibility to BMH-induced pulmonary fibrosis. The yeast Gal6 protein forms a barrel structure with the active sites embedded in a channel as in the proteasome. The C termini lie in the active site clefts. Zheng et al. (1998) showed that Gal6 acts as a carboxypeptidase on its C terminus to convert itself to an aminopeptidase and peptide ligase. The substrate specificity of the peptidase activity is determined by the position of the C terminus of Gal6 rather than the sequence of the substrate. The authors proposed a model to explain these diverse activities and the ability of yeast Gal6 to inactivate bleomycin. Southern blot analysis of DNA from leukocytes and autologous breast tumors showed that the bleomycin hydrolase ... More on the omim web site
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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602403 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed