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P53004 (BIEA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | 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:
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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length296 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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-containing compound metabolism; protoheme degradation.

Subunit structure

Monomer.

Subcellular location

Cytoplasm.

Tissue specificity

Liver.

Involvement in disease

Hyperbiliverdinemia (HBLVD) [MIM:614156]: A condition characterized by a green discoloration of the skin, urine, serum, and other bodily fluids. It is due to increased biliverdin resulting from inefficient conversion to bilirubin. Affected individuals appear to have symptoms only in the context of obstructive cholestasis and/or liver failure. In some cases, green jaundice can resolve after resolution of obstructive cholestasis.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Propeptide1 – 22
PRO_0000010852
Chain3 – 296294Biliverdin reductase A Ref.2
PRO_0000010853

Regions

Nucleotide binding15 – 206NAD or NADP
Nucleotide binding44 – 463NAD or NADP
Nucleotide binding77 – 804NAD or NADP
Compositional bias11 – 166Poly-Val

Sites

Metal binding2801Zinc Potential
Metal binding2811Zinc Potential
Metal binding2921Zinc Potential
Metal binding2931Zinc Potential
Binding site981NAD or NADP; via carbonyl oxygen

Amino acid modifications

Modified residue1741Phosphothreonine Ref.12
Modified residue1781Phosphoserine Ref.12
Modified residue2301Phosphoserine Ref.9
Modified residue2481N6-acetyllysine Ref.13
Modified residue2531N6-acetyllysine Ref.13

Natural variations

Natural variant31A → T. Ref.1 Ref.4 Ref.6
Corresponds to variant rs699512 [ dbSNP | Ensembl ].
VAR_019230
Natural variant371L → V. Ref.4
Corresponds to variant rs17245918 [ dbSNP | Ensembl ].
VAR_019231
Natural variant561Q → R. Ref.4
Corresponds to variant rs1050916 [ dbSNP | Ensembl ].
VAR_014851

Experimental info

Sequence conflict1211L → S in AAH05902. Ref.6
Sequence conflict154 – 1552AG → SD in CAA63635. Ref.2
Sequence conflict1601E → D in CAA63635. Ref.2

Secondary structure

.............................................. 296
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P53004 [UniParc].

Last modified October 10, 2002. Version 2.
Checksum: 2CF2AA7F1CDDB707

FASTA29633,428
        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 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of the cDNA encoding human biliverdin-IX alpha reductase."
Komuro A., Tobe T., Nakano Y., Yamaguchi T., Tomita M.
Biochim. Biophys. Acta 1309:89-99(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-3.
[2]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Placenta.
[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: Skeletal muscle.
[4]NIEHS SNPs program
Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-3; VAL-37 AND ARG-56.
[5]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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], VARIANT THR-3.
Tissue: Brain and Prostate.
[7]"Purification and characterization of human biliverdin reductase."
Maines M.D., Trakshel G.M.
Arch. Biochem. Biophys. 300:320-326(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 3-36; 48-74 AND 228-248.
Tissue: Liver.
[8]"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 3-22.
Tissue: Liver.
[9]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-230, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"A novel mutation in the biliverdin reductase-A gene combined with liver cirrhosis results in hyperbiliverdinaemia (green jaundice)."
Gafvels M., Holmstrom P., Somell A., Sjovall F., Svensson J.O., Stahle L., Broome U., Stal P.
Liver Int. 29:1116-1124(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN HBLVD.
[12]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-174 AND SER-178, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[13]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-248 AND LYS-253, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"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].
[15]"Crystal structure of human biliverdin reductase A."
Structural genomics consortium (SGC)
Submitted (FEB-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 7-296 IN COMPLEX WITH NADP.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U34877 mRNA. Translation: AAC35588.1.
X93086 mRNA. Translation: CAA63635.1.
AK291862 mRNA. Translation: BAF84551.1.
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.
PIRG02066.
S62624.
RefSeqNP_000703.2. NM_000712.3.
NP_001240752.1. NM_001253823.1.
UniGeneHs.488143.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2H63X-ray2.70A/B/C/D7-296[»]
ProteinModelPortalP53004.
SMRP53004. Positions 7-291.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107113. 3 interactions.
DIPDIP-42180N.
MINTMINT-1212210.
STRING9606.ENSP00000265523.

Chemistry

DrugBankDB00157. NADH.

PTM databases

PhosphoSiteP53004.

Polymorphism databases

DMDM23830892.

2D gel databases

OGPP53004.
REPRODUCTION-2DPAGEIPI00294158.

Proteomic databases

PaxDbP53004.
PeptideAtlasP53004.
PRIDEP53004.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265523; ENSP00000265523; ENSG00000106605.
ENST00000402924; ENSP00000385757; ENSG00000106605.
GeneID644.
KEGGhsa:644.
UCSCuc003tir.3. human.

Organism-specific databases

CTD644.
GeneCardsGC07P043798.
HGNCHGNC:1062. BLVRA.
HPAHPA042865.
MIM109750. gene.
614156. phenotype.
neXtProtNX_P53004.
Orphanet276405. Hyperbiliverdinemia.
PharmGKBPA25373.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG114525.
HOGENOMHOG000231884.
HOVERGENHBG003218.
InParanoidP53004.
KOK00214.
OMAKRILHCL.
OrthoDBEOG78WKS5.
PhylomeDBP53004.
TreeFamTF342889.

Enzyme and pathway databases

BioCycMetaCyc:HS02928-MONOMER.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00684.

Gene expression databases

ArrayExpressP53004.
BgeeP53004.
CleanExHS_BLVRA.
GenevestigatorP53004.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
InterProIPR017094. Biliverdin_Rdtase_A.
IPR015249. Biliverdin_Rdtase_cat.
IPR016040. NAD(P)-bd_dom.
IPR000683. Oxidoreductase_N.
[Graphical view]
PfamPF09166. Biliv-reduc_cat. 1 hit.
PF01408. GFO_IDH_MocA. 1 hit.
[Graphical view]
PIRSFPIRSF037032. Biliverdin_reductase_A. 1 hit.
ProDomPD040165. Biliverdin_Rdtase_cat. 1 hit.
[Graphical view] [Entries sharing at least one domain]
ProtoNetSearch...

Other

EvolutionaryTraceP53004.
GenomeRNAi644.
NextBio2614.
PROP53004.
SOURCESearch...

Entry information

Entry nameBIEA_HUMAN
AccessionPrimary (citable) accession number: P53004
Secondary accession number(s): A8K747 expand/collapse secondary AC list , O95019, Q86UX0, Q96QL4, Q9BRW8
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 10, 2002
Last modified: April 16, 2014
This is version 136 of the entry and version 2 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

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

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 7

Human chromosome 7: entries, gene names and cross-references to MIM