Flavin reductase (NADPH) (BLVRB)

The protein contains 206 amino acids for an estimated molecular weight of 22119 Da.

 

Broad specificity oxidoreductase that catalyzes the NADPH-dependent reduction of a variety of flavins, such as riboflavin, FAD or FMN, biliverdins, methemoglobin and PQQ (pyrroloquinoline quinone). Contributes to heme catabolism and metabolizes linear tetrapyrroles. Can also reduce the complexed Fe(3+) iron to Fe(2+) in the presence of FMN and NADPH. In the liver, converts biliverdin to bilirubin. (updated: April 1, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. 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.
  3. 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.
  4. 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.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. 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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology.


Interpro domains
Total structural coverage: 100%
Model score: 100

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VariantDescription
dbSNP:rs11547746

The reference OMIM entry for this protein is 600941

Biliverdin reductase b; blvrb
Bvrb
Nadph-flavin reductase; flr
Methemoglobin reductase
Nadph reductase

DESCRIPTION

The final step in heme metabolism in mammals is catalyzed by the cytosolic biliverdin reductase enzymes A and B (EC 1.3.1.24).

CLONING

Yamaguchi et al. (1993) isolated 2 biliverdin reductases. BLVRB, which they called biliverdin-IX beta-reductase, is found predominantly in fetal liver. BLVRA (109750), which they called biliverdin-IX alpha-reductase, is a major component of human adult liver and is identical to the enzyme previously reported as biliverdin reductase. Chikuba et al. (1994) isolated a cDNA encoding human erythrocyte NADPH-flavin reductase (FLR) from a human reticulocyte library. The FLR cDNA, which appeared to be identical to the BLVRB cDNA, encodes a deduced 206-amino acid protein. Western blot analysis of rat tissues showed highest levels of FLR in the erythrocytes and liver. Northern blot analysis detected a 1.1-kb transcript in human tissues. FLR had previously been isolated as an NADPH-dependent diaphorase, designated diaphorase-2 (DIA2), by Fisher et al. (1977) and has also been called methemoglobin reductase and NADPH reductase. Yubisui et al. (1977, 1979) found that flavins are the effective electron acceptor of the enzyme and purified FLR to homogeneity. Quandt and Hultquist (1994) cloned bovine liver NADPH-flavin reductase. The deduced bovine FLR protein shares 91% sequence homology with human BLVRB. Komuro et al. (1994) confirmed the identity of the human BLVRB and FLR proteins. Northern blot analysis detected highest expression of BLVRB in fetal liver and adult skeletal muscle and liver.

MAPPING

By fluorescence in situ hybridization using a 0.76-kb cDNA fragment as a probe, Saito et al. (1995) mapped the BLVRB gene to chromosome 19q13.13-q13.2. The BLVRA gene maps to 7p14-cen. ... More on the omim web site

Subscribe to this protein entry history

May 12, 2019: Protein entry updated
Automatic update: model status changed

Nov. 17, 2018: Protein entry updated
Automatic update: model status changed

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

Oct. 27, 2017: Protein entry updated
Automatic update: model status changed

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600941 was added.

Feb. 25, 2016: Protein entry updated
Automatic update: model status changed

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed