P30043 (BLVRB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	206 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	heme catabolic process Inferred from direct assay Ref.9. Source: UniProtKB small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Inferred from direct assay Ref.9. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay. Source: HPA
Molecular_function	biliverdin reductase activity Inferred from direct assay Ref.9. Source: UniProtKB nucleotide binding Inferred from electronic annotation. Source: InterPro riboflavin reductase (NADPH) activity Inferred from direct assay Ref.17. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.1 Ref.8 Ref.9 Ref.10 Ref.11

Chain

2 – 206

205

Flavin reductase (NADPH)

PRO_0000064948

Regions

Nucleotide binding

10 – 15

6

NADP

Nucleotide binding

54 – 55

2

NADP

Nucleotide binding

75 – 78

4

NADP

Sites

Binding site

35

1

NADP

Binding site

132

1

NADP

Binding site

153

1

Substrate

Binding site

154

1

NADP; via amide nitrogen

Natural variations

Natural variant

46

1

R → Q. Ref.4
Corresponds to variant rs11547746 [ dbSNP | Ensembl ].

VAR_019168

Experimental info

Mutagenesis

153

1

H → A: Reduced affinity for biliverdin. Ref.15

Sequence conflict

16

1

G → C AA sequence Ref.9

Secondary structure

1

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206

Helix Strand Turn

Details...

Beta strand

5 – 10

6

Helix

14 – 25

12

Beta strand

29 – 35

7

Helix

37 – 39

3

Beta strand

42 – 44

3

Beta strand

48 – 53

6

Helix

58 – 65

8

Beta strand

69 – 73

5

Helix

86 – 101

16

Beta strand

105 – 109

5

Helix

112 – 114

3

Helix

118 – 120

3

Helix

123 – 125

3

Helix

126 – 141

16

Beta strand

144 – 149

6

Beta strand

152 – 155

4

Beta strand

164 – 169

6

Beta strand

174 – 177

4

Helix

178 – 187

10

Helix

188 – 190

3

Turn

193 – 196

4

Beta strand

198 – 202

5

Sequences

	Sequence		Length	Mass (Da)
	P30043 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 3057E6D69A9F9F9F	FASTA	206	22,119
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, 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

NIEHS-SNPs

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.

IPI

IPI00783862.

PIR

JC2070.

RefSeq

NP_000704.1. NM_000713.2.

UniGene

Hs.515785.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HDO	X-ray	1.15	A	1-206	[»]
1HE2	X-ray	1.20	A	1-206	[»]
1HE3	X-ray	1.40	A	1-206	[»]
1HE4	X-ray	1.40	A	1-206	[»]
1HE5	X-ray	1.50	A	1-206	[»]

ProteinModelPortal

P30043.

ModBase

Search...

Protein-protein interaction databases

IntAct

P30043. 5 interactions.

STRING

9606.ENSP00000263368.

PTM databases

PhosphoSite

P30043.

Polymorphism databases

DMDM

1706870.

2D gel databases

DOSAC-COBS-2DPAGE

P30043.

REPRODUCTION-2DPAGE

IPI00783862.

SWISS-2DPAGE

P30043.

UCD-2DPAGE

P30043.

Proteomic databases

PaxDb

P30043.

PRIDE

P30043.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000263368; ENSP00000263368; ENSG00000090013.

GeneID

645.

KEGG

hsa:645.

UCSC

uc002onw.2. human.

Organism-specific databases

CTD

645.

GeneCards

GC19M040953.

HGNC

HGNC:1063. BLVRB.

HPA

HPA041698.
HPA041937.

MIM

600941. gene.

neXtProt

NX_P30043.

PharmGKB

PA25374.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG239698.

HOGENOM

HOG000262432.

HOVERGEN

HBG050695.

InParanoid

P30043.

KO

K05901.

OMA

PHIADEP.

OrthoDB

EOG4M0F2R.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

Bgee

P30043.

CleanEx

HS_BLVRB.

Genevestigator

P30043.

GermOnline

ENSG00000090013. Homo sapiens.

Family and domain databases

Gene3D

3.40.50.720. 1 hit.

InterPro

IPR016040. NAD(P)-bd_dom.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL5019.

DrugBank

DB00157. NADH.
DB00140. Riboflavin.

EvolutionaryTrace

P30043.

GenomeRNAi

645.

NextBio

2618.

SOURCE

Search...

Entry information

Entry name

BLVRB_HUMAN

Accession

Primary (citable) accession number: P30043
Secondary accession number(s): A6NKD8 , B2R5C6, P32078, P53005, Q32LZ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 133 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.