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P30043 (BLVRB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Flavin reductase (NADPH)

Short name=FR
EC=1.5.1.30
Alternative name(s):
Biliverdin reductase B
Short name=BVR-B
EC=1.3.1.24
Biliverdin-IX beta-reductase
Green heme-binding protein
Short name=GHBP
NADPH-dependent diaphorase
NADPH-flavin reductase
Short name=FLR
Gene names
Name:BLVRB
Synonyms:FLR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length206 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 Fe3+ iron to Fe2+ in the presence of FMN and NADPH. In the liver, converts biliverdin to bilirubin. Ref.14

Catalytic activity

Reduced riboflavin + NADP+ = riboflavin + NADPH. Ref.9 Ref.14 Ref.15

Bilirubin + NAD(P)+ = biliverdin + NAD(P)H. Ref.9 Ref.14 Ref.15

Enzyme regulation

Mesobiliverdin acts as competitve inhibitor for flavin reduction, indicating that flavin and tetrapyrrole substrates compete for the same site. Ref.14

Subunit structure

Monomer. Ref.9 Ref.17

Subcellular location

Cytoplasm Ref.9.

Tissue specificity

Predominantly expressed in liver and erythrocytes. At lower levels in heart, lung, adrenal gland and cerebrum. Ref.9

Biophysicochemical properties

Kinetic parameters:

KM=36 µM for NADP Ref.9 Ref.14

KM=5.6 mM for NADH

KM=0.3 µM for biliverdin IX-beta

KM=52 µM for FMN

KM=125 µM for FAD

KM=53 µM for riboflavin

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.1 Ref.8 Ref.9 Ref.10 Ref.11
Chain2 – 206205Flavin reductase (NADPH)
PRO_0000064948

Regions

Nucleotide binding10 – 156NADP
Nucleotide binding54 – 552NADP
Nucleotide binding75 – 784NADP

Sites

Binding site351NADP
Binding site1321NADP
Binding site1531Substrate
Binding site1541NADP; via amide nitrogen

Natural variations

Natural variant461R → Q. Ref.4
Corresponds to variant rs11547746 [ dbSNP | Ensembl ].
VAR_019168

Experimental info

Mutagenesis1531H → A: Reduced affinity for biliverdin. Ref.15
Sequence conflict161G → C AA sequence Ref.9

Secondary structure

.......................................... 206
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P30043 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 3057E6D69A9F9F9F

FASTA20622,119
        10         20         30         40         50         60 
MAVKKIAIFG ATGQTGLTTL AQAVQAGYEV TVLVRDSSRL PSEGPRPAHV VVGDVLQAAD 

        70         80         90        100        110        120 
VDKTVAGQDA VIVLLGTRND LSPTTVMSEG ARNIVAAMKA HGVDKVVACT SAFLLWDPTK 

       130        140        150        160        170        180 
VPPRLQAVTD DHIRMHKVLR ESGLKYVAVM PPHIGDQPLT GAYTVTLDGR GPSRVISKHD 

       190        200 
LGHFMLRCLT TDEYDGHSTY PSHQYQ 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and nucleotide sequence of a cDNA of the human erythrocyte NADPH-flavin reductase."
Chikuba K., Yubisui T., Shirabe K., Takeshita M.
Biochem. Biophys. Res. Commun. 198:1170-1176(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-34; 63-87 AND 98-206.
Tissue: Erythrocyte and Reticulocyte.
[2]"Molecular cloning and expression of human liver biliverdin-IXbeta reductase."
Komuro A., Tobe T., Hashimoto K., Nakano Y., Yamaguchi T., Nakajima H., Tomita M.
Biol. Pharm. Bull. 19:796-804(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Cerebellum.
[4]NIEHS SNPs program
Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLN-46.
[5]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Pancreas.
[8]"Complete amino acid sequence of biliverdin-IX beta reductase from human liver."
Yamaguchi T., Komuro A., Nakano Y., Tomita M., Nakajima H.
Biochem. Biophys. Res. Commun. 197:1518-1523(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-205.
Tissue: Liver.
[9]"Biliverdin-IX alpha reductase and biliverdin-IX beta reductase from human liver. Purification and characterization."
Yamaguchi T., Komoda Y., Nakajima H.
J. Biol. Chem. 269:24343-24348(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-21, SUBUNIT, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
Tissue: Liver.
[10]"Human liver protein map: a reference database established by microsequencing and gel comparison."
Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F., Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R., Appel R.D., Hughes G.J.
Electrophoresis 13:992-1001(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-11.
Tissue: Liver.
[11]"Plasma and red blood cell protein maps: update 1993."
Golaz O., Hughes G.J., Frutiger S., Paquet N., Bairoch A., Pasquali C., Sanchez J.-C., Tissot J.-D., Appel R.D., Walzer C., Balant L., Hochstrasser D.F.
Electrophoresis 14:1223-1231(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-11.
Tissue: Erythrocyte.
[12]Lubec G., Vishwanath V., Chen W.-Q., Sun Y.
Submitted (DEC-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 40-92; 64-78; 106-124 AND 146-170, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[13]"Evidence that biliverdin-IX beta reductase and flavin reductase are identical."
Shalloe F., Elliott G., Ennis O., Mantle T.J.
Biochem. J. 316:385-387(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTITY OF FR AND BVR-B.
[14]"Initial-rate kinetics of the flavin reductase reaction catalysed by human biliverdin-IXbeta reductase (BVR-B)."
Cunningham O., Gore M.G., Mantle T.J.
Biochem. J. 345:393-399(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
[15]"Computational and experimental studies on the catalytic mechanism of biliverdin-IXbeta reductase."
Smith L.J., Browne S., Mulholland A.J., Mantle T.J.
Biochem. J. 411:475-484(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-153.
[16]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"Structure of human biliverdin IXbeta reductase, an early fetal bilirubin IXbeta producing enzyme."
Pereira P.J., Macedo-Ribeiro S., Parraga A., Perez-Luque R., Cunningham O., Darcy K., Mantle T.J., Coll M.
Nat. Struct. Biol. 8:215-220(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS) IN COMPLEXES WITH MESOBILIVERDIN; BILIVERDIN; FLAVIN MONONUCLEOTIDE; LUMICHROME AND NADP, SUBUNIT.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D26308 mRNA. Translation: BAA05370.1.
D32143 mRNA. Translation: BAA06874.1.
AK312137 mRNA. Translation: BAG35073.1.
AY340485 Genomic DNA. Translation: AAP88933.1.
AC010271 Genomic DNA. No translation available.
CH471126 Genomic DNA. Translation: EAW56969.1.
BC109371 mRNA. Translation: AAI09372.1.
PIRJC2070.
RefSeqNP_000704.1. NM_000713.2.
UniGeneHs.515785.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1HDOX-ray1.15A1-206[»]
1HE2X-ray1.20A1-206[»]
1HE3X-ray1.40A1-206[»]
1HE4X-ray1.40A1-206[»]
1HE5X-ray1.50A1-206[»]
ProteinModelPortalP30043.
SMRP30043. Positions 1-205.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107114. 4 interactions.
IntActP30043. 5 interactions.
MINTMINT-5001335.
STRING9606.ENSP00000263368.

Chemistry

DrugBankDB00157. NADH.
DB00140. Riboflavin.

PTM databases

PhosphoSiteP30043.

Polymorphism databases

DMDM1706870.

2D gel databases

DOSAC-COBS-2DPAGEP30043.
REPRODUCTION-2DPAGEIPI00783862.
SWISS-2DPAGEP30043.
UCD-2DPAGEP30043.

Proteomic databases

PaxDbP30043.
PRIDEP30043.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263368; ENSP00000263368; ENSG00000090013.
GeneID645.
KEGGhsa:645.
UCSCuc002onw.2. human.

Organism-specific databases

CTD645.
GeneCardsGC19M040953.
HGNCHGNC:1063. BLVRB.
HPAHPA041698.
HPA041937.
MIM600941. gene.
neXtProtNX_P30043.
PharmGKBPA25374.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG239698.
HOGENOMHOG000262432.
HOVERGENHBG050695.
InParanoidP30043.
KOK05901.
OMATDEYNGH.
PhylomeDBP30043.
TreeFamTF324063.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressP30043.
BgeeP30043.
CleanExHS_BLVRB.
GenevestigatorP30043.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
InterProIPR016040. NAD(P)-bd_dom.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP30043.
GenomeRNAi645.
NextBio2618.
PROP30043.
SOURCESearch...

Entry information

Entry nameBLVRB_HUMAN
AccessionPrimary (citable) accession number: P30043
Secondary accession number(s): A6NKD8 expand/collapse secondary AC list , B2R5C6, P32078, P53005, Q32LZ2
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 143 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM