P46844 (BIEA_RAT) Reviewed, UniProtKB/Swiss-Prot

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

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	295 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 By similarity.
Subcellular location	Cytoplasm.
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
Ligand	Metal-binding NAD NADP Zinc
Molecular function	Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	heme catabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	biliverdin reductase activity Traceable author statement Ref.1. Source: RGD nucleotide binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Propeptide

1 – 2

2

PRO_0000010856

Chain

3 – 295

293

Biliverdin reductase A

PRO_0000010857

Regions

Nucleotide binding

15 – 20

6

NAD or NADP

Nucleotide binding

76 – 79

4

NAD or NADP

Compositional bias

11 – 16

6

Poly-Val

Sites

Metal binding

279

1

Zinc Potential

Metal binding

280

1

Zinc Potential

Metal binding

291

1

Zinc Potential

Metal binding

292

1

Zinc Potential

Binding site

97

1

NAD or NADP; via carbonyl oxygen

Amino acid modifications

Modified residue

1

1

N-acetylmethionine By similarity

Modified residue

173

1

Phosphothreonine By similarity

Modified residue

177

1

Phosphoserine By similarity

Modified residue

236

1

Phosphoserine By similarity

Modified residue

247

1

N6-acetyllysine By similarity

Modified residue

252

1

N6-acetyllysine By similarity

Experimental info

Mutagenesis

73

1

C → A: Loss of activity.

Mutagenesis

280

1

C → A: Reduced activity.

Mutagenesis

291

1

C → A: Reduced activity.

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

295

Helix Strand Turn

Details...

Beta strand

7 – 14

8

Helix

18 – 27

10

Helix

30 – 33

4

Beta strand

36 – 42

7

Beta strand

53 – 55

3

Helix

58 – 63

6

Beta strand

69 – 72

4

Helix

76 – 78

3

Helix

79 – 88

10

Beta strand

92 – 97

6

Helix

103 – 116

14

Beta strand

120 – 123

4

Helix

125 – 128

4

Helix

130 – 139

10

Beta strand

144 – 153

10

Helix

158 – 161

4

Helix

164 – 167

4

Helix

169 – 179

11

Beta strand

183 – 192

10

Helix

193 – 195

3

Beta strand

197 – 205

9

Beta strand

211 – 218

8

Beta strand

225 – 232

8

Beta strand

235 – 237

3

Helix

249 – 261

13

Helix

267 – 291

25

Sequences

	Sequence		Length	Mass (Da)
	P46844 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 219C8EA96C150588	FASTA	295	33,566
	10 20 30 40 50 60 MDAEPKRKFG VVVVGVGRAG SVRLRDLKDP RSAAFLNLIG FVSRRELGSL DEVRQISLED 70 80 90 100 110 120 ALRSQEIDVA YICSESSSHE DYIRQFLQAG KHVLVEYPMT LSFAAAQELW ELAAQKGRVL 130 140 150 160 170 180 HEEHVELLME EFEFLRREVL GKELLKGSLR FTASPLEEER FGFPAFSGIS RLTWLVSLFG 190 200 210 220 230 240 ELSLISATLE ERKEDQYMKM TVQLETQNKG LLSWIEEKGP GLKRNRYVNF QFTSGSLEEV 250 260 270 280 290 PSVGVNKNIF LKDQDIFVQK LLDQVSAEDL AAEKKRIMHC LGLASDIQKL CHQKK

References

[1]	"Expression and characterization of a cDNA for rat kidney biliverdin reductase. Evidence suggesting the liver and kidney enzymes are the same transcript product." Fakhrai H., Maines M.D. J. Biol. Chem. 267:4023-4029(1992) [PubMed: 1371282] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Kidney.
[2]	Lubec G., Afjehi-Sadat L. Submitted (NOV-2006) to UniProtKB Cited for: PROTEIN SEQUENCE OF 119-136, MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Spinal cord.
[3]	"Site-directed mutagenesis of cysteine residues in biliverdin reductase. Roles in substrate and cofactor binding." McCoubrey W.K. Jr., Maines M.D. Eur. J. Biochem. 222:597-603(1994) [PubMed: 8020496] [Abstract] Cited for: MUTAGENESIS.
[4]	"Crystallization and preliminary X-ray diffraction analysis of a rat biliverdin reductase." Sun D., Sato M., Yoshida T., Shimizu H., Miyatake H., Adachi S., Shiro Y., Kikuchi A. Acta Crystallogr. D 56:1180-1182(2000) [PubMed: 10957639] [Abstract] Cited for: CRYSTALLIZATION.
[5]	"Crystal structure of a biliverdin IXalpha reductase enzyme-cofactor complex." Whitby F.G., Phillips J.D., Hill C.P., McCoubrey W.K. Jr., Maines M.D. J. Mol. Biol. 319:1199-1210(2002) [PubMed: 12079357] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 8-291 IN COMPLEX WITH NAD.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M81681 mRNA. Translation: AAA40830.1.

IPI

IPI00230874.

PIR

A42268.

RefSeq

NP_446302.1. NM_053850.1.

UniGene

Rn.9865.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1GCU	X-ray	1.40	A	1-295	[»]
1LC0	X-ray	1.20	A	8-295	[»]
1LC3	X-ray	1.50	A	8-295	[»]

ProteinModelPortal

P46844.

SMR

P46844. Positions 1-292.

ModBase

Search...

Protein-protein interaction databases

STRING

P46844.

Proteomic databases

PRIDE

P46844.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

116599.

KEGG

rno:116599.

UCSC

NM_053850. rat.

Organism-specific databases

CTD

644.

RGD

620721. Blvra.

Phylogenomic databases

eggNOG

roNOG13983.

HOVERGEN

HBG003218.

InParanoid

P46844.

OrthoDB

EOG46HGB7.

Gene expression databases

Genevestigator

P46844.

GermOnline

ENSRNOG00000011778. Rattus norvegicus.

Family and domain databases

InterPro

IPR017094. Biliverdin_Rdtase_A.
IPR015249. Biliverdin_Rdtase_cat.
IPR016040. NAD(P)-bd_dom.
IPR000683. Oxidoreductase_N.
[Graphical view]

Gene3D

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

KO

K00214.

Pfam

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

PIRSF

PIRSF037032. Biliverdin_reductase_A. 1 hit.

ProDom

PD040165. Biliverdin_Rdtase_cat. 1 hit.
[Graphical view] [Entries sharing at least one domain]

ProtoNet

Search...

Other

NextBio

619303.

Entry information

Entry name

BIEA_RAT

Accession

Primary (citable) accession number: P46844

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	December 14, 2011
This is version 96 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program