Reviewed, UniProtKB/Swiss-Prot P30043 (BLVRB_HUMAN)

Names and origin

Protein names

Recommended name:
    Flavin reductase
      Short name=FR
    EC=1.5.1.30
Alternative name(s):
    NADPH-dependent diaphorase
    NADPH-flavin reductase
      Short name=FLR
    Biliverdin reductase B
      Short name=BVR-B
    EC=1.3.1.24
    Biliverdin-IX beta-reductase
    Green heme-binding protein
      Short name=GHBP

Gene names

Name:	BLVRB
Synonyms:	FLR

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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	Catalyzes electron transfer from reduced pyridine nucleotides to flavins as well as methylene blue, pyrroloquinoline quinone, riboflavin, or methemoglobin. Possible role in protecting cells from oxidative damage or in regulating iron metabolism. In the liver, converts biliverdin to bilirubin.
Catalytic activity	Reduced riboflavin + NADP+ = riboflavin + NADPH. Bilirubin + NAD(P)+ = biliverdin + NAD(P)H.
Subunit structure	Monomer.
Subcellular location	Cytoplasm Potential.
Tissue specificity	Predominantly expressed in liver and erythrocytes. At lower levels in heart, lung, adrenal gland and cerebrum.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	3D-structure Direct protein sequencing Multifunctional enzyme
Gene Ontology (GO)
Biological process	cellular metabolic process Inferred from electronic annotation. Source: InterPro oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	biliverdin reductase activity Ref.1 Traceable author statement. Source: ProtInc coenzyme binding Inferred from electronic annotation. Source: InterPro flavin reductase activity Inferred from electronic annotation. Source: EC
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

PRO_0000064948

Regions

Nucleotide binding

5 – 36

32

NAD or NADP Potential

Natural variations

Natural variant

46

1

R → Q: dbSNP rs11547746. Ref.4

VAR_019168

Experimental info

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

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

Turn

193 – 196

4

Beta strand

198 – 202

5

Sequences

	Sequence		Length	Mass (Da)
	P30043-1 [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: 8117274] [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: 8799475] [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: 14702039] [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: 15057824] [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: 15489334] [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: 8280170] [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: 7929092] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-21. 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: 1286669] [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: 8313871] [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: 8687377] [Abstract] Cited for: IDENTITY OF FR AND BVR-B.
[14]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[15]	"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: 11224564] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

UniGene

Hs.515785

3D structure databases

PDBPDBe

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	[»]

ModBase

Search...

2-D gel databases

SWISS-2DPAGE

P30043.

DOSAC-COBS-2DPAGE

P30043.

REPRODUCTION-2DPAGE

IPI00783862.

Proteomic databases

PRIDE

P30043.

Genome annotation databases

Ensembl

ENSG00000090013. Homo sapiens. [Contig view]

GeneID

645.

KEGG

hsa:645.

Organism-specific databases

GeneCards

GC19M045645.

H-InvDB

HIX0040129.

HGNC

HGNC:1063. BLVRB.

MIM

600941. gene.

PharmGKB

PA25374.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P30043.

OMA

P30043. TMMSEGT.

Enzyme and pathway databases

BRENDA

1.3.1.24. 247.
1.5.1.30. 247.

Gene expression databases

ArrayExpress

P30043.

Bgee

P30043.

CleanEx

HS_BLVRB.

GermOnline

ENSG00000090013. Homo sapiens.

Family and domain databases

InterPro

IPR001509. Epimerase_deHydtase.
IPR016040. NAD(P)-bd_dom.
[Graphical view]

Gene3D

G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.

Pfam

PF01370. Epimerase. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00157. NADH.
DB00140. Riboflavin.

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:	June 16, 2009
This is version 92 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)