Overview
| Uniprot ID | P30043 |
|---|
| Protein Name | Flavin reductase (NADPH) |
|---|
| Gene Name | BLVRB |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 178 |
GPSRVISKHDLGHFM |
| 99 |
RNIVAAMKAHGVDKV |
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 a '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)
Protein Sequence
10
MAVKKIAIFG
20
ATGQTGLTTL
30
AQAVQAGYEV
40
TVLVRDSSRL
50
PSEGPRPAHV
60
VVGDVLQAAD
70
VDKTVAGQDA
80
VIVLLGTRND
90
LSPTTVMSEG
100
ARNIVAAMKA
110
HGVDKVVACT
120
SAFLLWDPTK
130
VPPRLQAVTD
140
DHIRMHKVLR
150
ESGLKYVAVM
160
PPHIGDQPLT
170
GAYTVTLDGR
180
GPSRVISKHD
190
LGHFMLRCLT
200
TDEYDGHSTY
PSHQYQ
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0070062 |
extracellular exosome |
| Molecular Function |
GO:0004074 |
biliverdin reductase [NAD(P)H] activity |
| Molecular Function |
GO:0052874 |
FMN reductase (NADH) activity |
| Molecular Function |
GO:0052873 |
FMN reductase (NADPH) activity |
| Molecular Function |
GO:0035605 |
peptidyl-cysteine S-nitrosylase activity |
| Molecular Function |
GO:0042602 |
riboflavin reductase (NADPH) activity |
| Biological Process |
GO:0042167 |
heme catabolic process |
| Biological Process |
GO:0030219 |
megakaryocyte differentiation |
| Biological Process |
GO:0046627 |
negative regulation of insulin receptor signaling pathway |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.