Biliverdin reductase A (BLVRA)
The protein contains 296 amino acids for an estimated molecular weight of 33428 Da.
Reduces the gamma-methene bridge of the open tetrapyrrole, biliverdin IX alpha, to bilirubin with the concomitant oxidation of a NADH or NADPH cofactor. (updated: April 1, 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.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs699512 | |
| dbSNP:rs17245918 | |
| dbSNP:rs1050916 |
The reference OMIM entry for this protein is 109750
Biliverdin reductase a; blvra
Biliverdin ix-alpha reductase
Bvr
Blvr
Bvra
DESCRIPTION
Biliverdin reductases, such as BLVRA (EC 1.3.1.24), catalyze the conversion of biliverdin to bilirubin in the presence of NADPH or NADH (Komuro et al., 1996).CLONING
Meera Khan et al. (1983) used a simple chromogenic staining procedure for specific identification of BLVR after gel electrophoresis. The study indicated that both NADH-dependent and NADPH-dependent BLVR activity is due to 1 enzyme which is probably coded by a single gene and is a monomer in its functional configuration. By RT-PCR of erythroleukemia cell line RNA, followed by screening a cDNA library of a second human leukemia cell line, Komuro et al. (1996) cloned BLVRA, which they called biliverdin IX-alpha reductase. The deduced 296-amino acid protein has a calculated molecular mass of 33.2 kD. Removal of 2 N-terminal amino acids results in a 294-amino acid mature protein with an N-terminal threonine. The N-terminal region contains the NADH/NADPH-binding consensus sequence. BLVRA shares 82.8% amino acid identity with rat Blvra, but it does not share significant homology with BLVRB (600941). Northern blot analysis detected BLVRA at 1.35 kb in all 8 tissues examined. Expression was highest in brain, pancreas, and lung, and lowest in liver and placenta. By RT-PCR, Maines et al. (1996) cloned BVR from placenta RNA. Northern blot analysis detected BVR at about 1.2 kb in kidney mRNA. Western blot analysis detected a single protein, but isoelectric focusing detected several charge variants. Atomic absorption spectroscopy indicated that the protein purified from human liver contains zinc at an approximately 1:1 molar ratio. Lerner-Marmarosh et al. (2005) found that BVR shares similarity with insulin receptor (INSR; 147670) in residues necessary for tyrosine kinase activity. The C terminus of BVR contains a 6-stranded beta sheet that may provide a docking site or protein-protein interaction site.GENE STRUCTURE
Gafvels et al. (2009) noted that the BLVRA gene contains 7 exons.MAPPING
Hartz (2011) mapped the BLVRA gene to chromosome 7p13 based on an alignment of the BLVRA sequence (GenBank GENBANK U34877) with the genomic sequence (GRCh37). Through a study of mouse-human hybrids, Meera Khan et al. (1982) assigned the structural gene for biliverdin reductase to chromosome 7 (7p14-cen). Peters et al. (1989) mapped Blvr to mouse chromosome 2 using an electrophoretic variant in linkage studies. Thomas et al. (2003) described the sequencing and annotation of a 341-kb region of mouse chromosome 2 containing 9 genes, including Blvra, and its comparison with the orthologous regions of the human and rat genomes. These analyses revealed that the conserved synteny between mouse chromosome 2 and human chromosome 7 reflects an interval containing a single gene (Blvra/BLVRA) that is, at most, only 34 kb in the mouse genome. In the mouse, this segment is flanked proximally by genes orthologous to human chromosome 15q21 and distally by genes orthologous to human chromosome 2q11. These findings illustrated that some small genomic regions outside the large mouse-human conserved segments can contain a single gene as well as sequences that are apparently unique to 1 genome.GENE FUNCTION
Maines et al. (1996) found that zinc inhibited NADPH-dependent but not NADH-dependent reductase activity, suggesting that the NADH- and NADPH-binding regions differ in their ability to interact with zinc. Fe-hematoporphyrin, however, inhibited both NA ... 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 109750 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed