Flavin reductase (NADPH)
Details
- Name
- Flavin reductase (NADPH)
- Kind
- protein
- Synonyms
- 1.5.1.30
- Biliverdin reductase B
- Biliverdin-IX beta-reductase
- BVR-B
- FLR
- FR
- GHBP
- Green heme-binding protein
- NADPH-dependent diaphorase
- NADPH-flavin reductase
- S-nitroso-CoA-assisted nitrosyltransferase
- SCAN
- SNO-CoA-assisted nitrosyltransferase
- Gene Name
- BLVRB
- UniProtKB Entry
- P30043Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0010413|Flavin reductase (NADPH) MAVKKIAIFGATGQTGLTTLAQAVQAGYEVTVLVRDSSRLPSEGPRPAHVVVGDVLQAAD VDKTVAGQDAVIVLLGTRNDLSPTTVMSEGARNIVAAMKAHGVDKVVACTSAFLLWDPTK VPPRLQAVTDDHIRMHKVLRESGLKYVAVMPPHIGDQPLTGAYTVTLDGRGPSRVISKHD LGHFMLRCLTTDEYDGHSTYPSHQYQ
- Number of residues
- 206
- Molecular Weight
- 22119.215
- Theoretical pI
- 7.76
- GO Classification
- Functionsbiliberdin reductase NAD+ activity / biliverdin reductase (NAD(P)H) activity / biliverdin reductase (NADPH) activity / FMN reductase (NAD(P)H) activity / FMN reductase (NADH) activity / FMN reductase (NADPH) activity / peptidyl-cysteine S-nitrosylase activityProcessesmegakaryocyte differentiation / negative regulation of insulin receptor signaling pathwayComponentsintracellular membrane-bounded organelle
- General Function
- Enzyme that can both act as a NAD(P)H-dependent reductase and a S-nitroso-CoA-dependent nitrosyltransferase (PubMed:10620517, PubMed:18241201, PubMed:27207795, PubMed:38056462, PubMed:7929092). Promotes fetal heme degradation during development (PubMed:10858451, PubMed:18241201, PubMed:7929092). Also expressed in adult tissues, where it acts as a regulator of hematopoiesis, intermediary metabolism (glutaminolysis, glycolysis, TCA cycle and pentose phosphate pathway) and insulin signaling (PubMed:27207795, PubMed:29500232, PubMed:38056462). Has a broad specificity oxidoreductase activity by catalyzing the NAD(P)H-dependent reduction of a variety of flavins, such as riboflavin, FAD or FMN, biliverdins, methemoglobin and PQQ (pyrroloquinoline quinone) (PubMed:10620517, PubMed:18241201, PubMed:7929092). Contributes to fetal heme catabolism by catalyzing reduction of biliverdin IXbeta into bilirubin IXbeta in the liver (PubMed:10858451, PubMed:18241201, PubMed:7929092). Biliverdin IXbeta, which constitutes the major heme catabolite in the fetus is not present in adult (PubMed:10858451, PubMed:18241201, PubMed:7929092). Does not reduce bilirubin IXalpha (PubMed:10858451, PubMed:18241201, PubMed:7929092). Can also reduce the complexed Fe(3+) iron to Fe(2+) in the presence of FMN and NADPH (PubMed:10620517). Acts as a protein nitrosyltransferase by catalyzing nitrosylation of cysteine residues of target proteins, such as HMOX2, INSR and IRS1 (PubMed:38056462). S-nitroso-CoA-dependent nitrosyltransferase activity is mediated via 'ping-pong' mechanism: BLVRB first associates with both S-nitroso-CoA and protein substrate, nitric oxide group is then transferred from S-nitroso-CoA to Cys-109 and Cys-188 residues of BLVRB and from S-nitroso-BLVRB to the protein substrate (PubMed:38056462). Inhibits insulin signaling by mediating nitrosylation of INSR and IRS1, leading to their inhibition (PubMed:38056462)
- Specific Function
- biliberdin reductase NAD+ activity
- Pfam Domain Function
- NAD_binding_10 (PF13460)
- Signal Regions
- Not Available
- Transmembrane Regions
- Not Available
- Cellular Location
- Cytoplasm
- Gene sequence
>lcl|BSEQ0010414|Flavin reductase (NADPH) (BLVRB) ATGGCCGTCAAGAAGATCGCGATCTTCGGCGCCACTGGCCAGACCGGGCTCACCACCCTG GCGCAGGCGGTGCAAGCAGGTTACGAAGTGACAGTGCTGGTGCGGGACTCCTCCAGGCTG CCATCAGAGGGGCCCCGGCCGGCCCACGTGGTAGTGGGAGATGTTCTGCAGGCAGCCGAT GTGGACAAGACCGTGGCTGGGCAGGACGCTGTCATCGTGCTGCTGGGCACCCGCAATGAC CTCAGTCCCACGACAGTGATGTCCGAGGGCGCCCGGAACATTGTGGCAGCCATGAAGGCT CATGGTGTGGACAAGGTCGTGGCCTGCACCTCGGCTTTCCTGCTCTGGGACCCTACCAAG GTGCCCCCACGACTGCAGGCTGTGACTGATGACCACATCCGGATGCACAAGGTGCTGCGG GAATCAGGCCTGAAGTACGTGGCTGTGATGCCGCCACACATAGGAGACCAGCCACTAACT GGGGCGTACACAGTGACCCTGGATGGACGAGGGCCCTCAAGGGTCATCTCCAAACATGAC CTGGGCCATTTCATGCTGCGCTGCCTCACCACCGATGAGTACGACGGACACAGCACCTAC CCCTCCCACCAGTACCAGTAG
- Chromosome Location
- 19
- Locus
- 19q13.2
- External Identifiers
Resource Link UniProtKB ID P30043 UniProtKB Entry Name BLVRB_HUMAN GenBank Protein ID 1384068 GenBank Gene ID D26308 GeneCard ID BLVRB GenAtlas ID BLVRB HGNC ID HGNC:1063 PDB ID(s) 1HDO, 1HE2, 1HE3, 1HE4, 1HE5, 5OOG, 5OOH, 6OPL, 7ER6, 7ER7, 7ER8, 7ER9, 7ERA, 7ERB, 7ERC, 7ERD, 7ERE, 8ELL, 8ELM KEGG ID hsa:645 NCBI Gene ID 645 - General References
- Chikuba K, Yubisui T, Shirabe K, Takeshita M: Cloning and nucleotide sequence of a cDNA of the human erythrocyte NADPH-flavin reductase. Biochem Biophys Res Commun. 1994 Feb 15;198(3):1170-6. [Article]
- Komuro A, Tobe T, Hashimoto K, Nakano Y, Yamaguchi T, Nakajima H, Tomita M: Molecular cloning and expression of human liver biliverdin-IX beta reductase. Biol Pharm Bull. 1996 Jun;19(6):796-804. [Article]
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- Yamaguchi T, Komuro A, Nakano Y, Tomita M, Nakajima H: Complete amino acid sequence of biliverdin-IX beta reductase from human liver. Biochem Biophys Res Commun. 1993 Dec 30;197(3):1518-23. [Article]
- Yamaguchi T, Komoda Y, Nakajima H: Biliverdin-IX alpha reductase and biliverdin-IX beta reductase from human liver. Purification and characterization. J Biol Chem. 1994 Sep 30;269(39):24343-8. [Article]
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- Cunningham O, Gore MG, Mantle TJ: Initial-rate kinetics of the flavin reductase reaction catalysed by human biliverdin-IXbeta reductase (BVR-B). Biochem J. 2000 Jan 15;345 Pt 2:393-9. [Article]
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Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Riboflavin approved, investigational, nutraceutical, vet_approved yes target product of Details NADH approved, nutraceutical unknown target Details Biliverdine IX Alpha experimental unknown target Details Flavin mononucleotide approved, investigational unknown target Details Nicotinamide adenine dinucleotide phosphate experimental unknown target Details Lumichrome experimental unknown target Details Mesobiliverdin IV alpha experimental unknown target Details Methylene blue approved, investigational no enzyme substrate Details