Reviewed, UniProtKB/Swiss-Prot P53004 (BIEA_HUMAN)

Names and origin

Protein names

Recommended name:
    Biliverdin reductase A
      Short name=BVR A
    EC=1.3.1.24
Alternative name(s):
    Biliverdin-IX alpha-reductase

Gene names

Name:	BLVRA
Synonyms:	BLVR, BVR

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	296 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	Reduces the gamma-methene bridge of the open tetrapyrrole, biliverdin IX alpha, to bilirubin with the concomitant oxidation of a NADH or NADPH cofactor.
Catalytic activity	Bilirubin + NAD(P)(+) = biliverdin + NAD(P)H.
Cofactor	Binds 1 zinc ion per subunit.
Pathway	Porphyrin metabolism; protoheme degradation.
Subunit structure	Monomer.
Subcellular location	Cytoplasm.
Tissue specificity	Liver.
Miscellaneous	Uses the reactants NADH or NADPH depending on the pH; NADH is used at the acidic pH range (6-6.9) and NADPH at the alkaline range (8.5-8.7). NADPH, however, is the probable reactant in biological systems.
Sequence similarities	Belongs to the gfo/idh/mocA family. Biliverdin reductase subfamily.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	Metal-binding NAD NADP Zinc
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	heme catabolic process Traceable author statement. Source: UniProtKB oxidation reduction Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	biliverdin reductase activity Inferred from direct assay. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Propeptide

1 – 2

2

PRO_0000010852

Chain

3 – 296

294

Biliverdin reductase A

PRO_0000010853

Regions

Compositional bias

11 – 16

6

Poly-Val

Sites

Metal binding

280

1

Zinc Potential

Metal binding

281

1

Zinc Potential

Metal binding

292

1

Zinc Potential

Metal binding

293

1

Zinc Potential

Amino acid modifications

Modified residue

230

1

Phosphoserine

Natural variations

Natural variant

3

1

A → T: dbSNP rs699512.

VAR_019230

Natural variant

37

1

L → V: dbSNP rs17245918.

VAR_019231

Natural variant

56

1

Q → R: dbSNP rs1050916.

VAR_014851

Experimental info

Sequence conflict

121

1

L → S in AAH05902. Ref.5

Sequence conflict

154 – 155

2

AG → SD in CAA63635. Ref.1

Sequence conflict

160

1

E → D in CAA63635. Ref.1

Secondary structure

1

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296

Helix Strand Turn

Details...

Beta strand

9 – 14

6

Helix

18 – 28

11

Helix

33 – 36

4

Beta strand

37 – 43

7

Beta strand

50 – 53

4

Helix

59 – 64

6

Beta strand

70 – 73

4

Helix

77 – 89

13

Beta strand

93 – 98

6

Helix

104 – 117

14

Beta strand

121 – 124

4

Helix

126 – 129

4

Helix

131 – 140

10

Beta strand

145 – 154

10

Helix

159 – 162

4

Helix

165 – 168

4

Helix

170 – 180

11

Beta strand

182 – 193

12

Beta strand

198 – 207

10

Beta strand

212 – 219

8

Beta strand

226 – 235

10

Helix

250 – 262

13

Helix

268 – 290

23

Sequences

	Sequence		Length	Mass (Da)
	P53004-1 [UniParc]. Last modified October 10, 2002. Version 2. Checksum: 2CF2AA7F1CDDB707	FASTA	296	33,428
	10 20 30 40 50 60 MNAEPERKFG VVVVGVGRAG SVRMRDLRNP HPSSAFLNLI GFVSRRELGS IDGVQQISLE 70 80 90 100 110 120 DALSSQEVEV AYICSESSSH EDYIRQFLNA GKHVLVEYPM TLSLAAAQEL WELAEQKGKV 130 140 150 160 170 180 LHEEHVELLM EEFAFLKKEV VGKDLLKGSL LFTAGPLEEE RFGFPAFSGI SRLTWLVSLF 190 200 210 220 230 240 GELSLVSATL EERKEDQYMK MTVCLETEKK SPLSWIEEKG PGLKRNRYLS FHFKSGSLEN 250 260 270 280 290 VPNVGVNKNI FLKDQNIFVQ KLLGQFSEKE LAAEKKRILH CLGLAEEIQK YCCSRK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human biliverdin IXalpha reductase is a zinc-metalloprotein. Characterization of purified and Escherichia coli expressed enzymes." Maines M.D., Polevoda B.V., Huang T.-J., McCoubrey W.K. Jr. Eur. J. Biochem. 235:372-381(1996) [PubMed: 8631357] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	Komuro A., Tobe T., Nakano Y., Yamaguchi T., Tomita M. Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE, VARIANT THR-3.
[3]	"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Livingston R.J., Rieder M.J., Chung M.-W., Ritchie T.K., Olson A.N., Nguyen C.P., Nguyen D.A., Poel C.L., Chambers S.W., Schackwitz W.S., Sherwood J.K., Sherwood A.M., Leithauser B.J., Nickerson D.A. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-3; VAL-37 AND ARG-56.
[4]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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], VARIANT THR-3. Tissue: Brain and Prostate.
[6]	"Purification and characterization of human biliverdin reductase." Maines M.D., Trakshel G.M. Arch. Biochem. Biophys. 300:320-326(1993) [PubMed: 8424666] [Abstract] Cited for: PROTEIN SEQUENCE OF 3-36; 48-74 AND 228-248. Tissue: Liver.
[7]	"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 3-22. Tissue: Liver.
[8]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-230, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X93086 mRNA. Translation: CAA63635.1.
U34877 mRNA. Translation: AAC35588.1.
AY616754 Genomic DNA. Translation: AAT11126.1.
AC005189 Genomic DNA. No translation available.
AC004939 Genomic DNA. Translation: AAD05025.1.
AC004985 Genomic DNA. Translation: AAP21879.1.
BC005902 mRNA. Translation: AAH05902.1.
BC008456 mRNA. Translation: AAH08456.1.

PIR

G02066.
S62624.

RefSeq

NP_000703.2.

UniGene

Hs.488143

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2H63	X-ray	2.70	A/B/C/D	7-296	[»]

SMR

P53004. Positions 1-292.

ModBase

Search...

PTM databases

PhosphoSite

P53004.

Polymorphism databases

NIEHS-SNPs

Search...

2-D gel databases

OGP

P53004.

REPRODUCTION-2DPAGE

IPI00294158.

Proteomic databases

PeptideAtlas

P53004.

Genome annotation databases

Ensembl

ENSG00000106605. Homo sapiens. [Contig view]

GeneID

644.

KEGG

hsa:644.

Organism-specific databases

H-InvDB

HIX0006633.

HGNC

HGNC:1062. BLVRA.

MIM

109750. gene.

PharmGKB

PA25373.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

P53004.

HOVERGEN

P53004.

Enzyme and pathway databases

BioCyc

MetaCyc:MON-13862.

Gene expression databases

ArrayExpress

P53004.

CleanEx

HS_BLVRA.

GermOnline

ENSG00000106605. Homo sapiens.

Family and domain databases

InterPro

IPR017094. Biliverdin_Rdtase_A.
IPR015249. Biliverdin_Rdtase_cat.
IPR000683. GFO/IDH/MocA_N.
IPR016040. NAD(P)-bd.
[Graphical view]

Gene3D

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

Pfam

PF09166. Biliv-reduc_cat. 1 hit.
PF01408. GFO_IDH_MocA. 1 hit.
[Graphical view]

PIRSF

PIRSF037032. Biliverdin_reductase_A. 1 hit.

ProtoNet

Search...

Other Resources

DrugBank

DB00157. NADH.

NextBio

2614.

SOURCE

Search...

Entry information

Entry name

BIEA_HUMAN

Accession

Primary (citable) accession number: P53004
Secondary accession number(s): O95019 , Q86UX0, Q96QL4, Q9BRW8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 10, 2002
Last modified:	November 25, 2008
This is version 82 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)