ID   BIEA_HUMAN              Reviewed;         296 AA.
AC   P53004; A8K747; O95019; Q86UX0; Q96QL4; Q9BRW8;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   10-OCT-2002, sequence version 2.
DT   27-MAR-2024, entry version 208.
DE   RecName: Full=Biliverdin reductase A {ECO:0000303|PubMed:8631357};
DE            Short=BVR A {ECO:0000303|PubMed:8631357};
DE            EC=1.3.1.24 {ECO:0000269|PubMed:7929092, ECO:0000269|PubMed:8424666, ECO:0000269|PubMed:8631357};
DE   AltName: Full=Biliverdin-IX alpha-reductase {ECO:0000303|PubMed:8950184};
DE   Flags: Precursor;
GN   Name=BLVRA {ECO:0000312|HGNC:HGNC:1062};
GN   Synonyms=BLVR, BVR {ECO:0000303|PubMed:8631357};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT THR-3.
RX   PubMed=8950184; DOI=10.1016/s0167-4781(96)00099-1;
RA   Komuro A., Tobe T., Nakano Y., Yamaguchi T., Tomita M.;
RT   "Cloning and characterization of the cDNA encoding human biliverdin-IX
RT   alpha reductase.";
RL   Biochim. Biophys. Acta 1309:89-99(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND COFACTOR.
RC   TISSUE=Placenta;
RX   PubMed=8631357; DOI=10.1111/j.1432-1033.1996.00372.x;
RA   Maines M.D., Polevoda B.V., Huang T.-J., McCoubrey W.K. Jr.;
RT   "Human biliverdin IXalpha reductase is a zinc-metalloprotein.
RT   Characterization of purified and Escherichia coli expressed enzymes.";
RL   Eur. J. Biochem. 235:372-381(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Skeletal muscle;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-3; VAL-37 AND ARG-56.
RG   NIEHS SNPs program;
RL   Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA   Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA   Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA   Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA   Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA   Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA   Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA   Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA   Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA   Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA   Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA   Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA   Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA   Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA   Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA   McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA   Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-3.
RC   TISSUE=Brain, and Prostate;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   PROTEIN SEQUENCE OF 3-36; 48-74 AND 228-248, FUNCTION, CATALYTIC ACTIVITY,
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC   TISSUE=Liver;
RX   PubMed=8424666; DOI=10.1006/abbi.1993.1044;
RA   Maines M.D., Trakshel G.M.;
RT   "Purification and characterization of human biliverdin reductase.";
RL   Arch. Biochem. Biophys. 300:320-326(1993).
RN   [8]
RP   PROTEIN SEQUENCE OF 3-22, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP   LOCATION, AND TISSUE SPECIFICITY.
RC   TISSUE=Liver;
RX   PubMed=7929092; DOI=10.1016/s0021-9258(19)51088-2;
RA   Yamaguchi T., Komoda Y., Nakajima H.;
RT   "Biliverdin-IX alpha reductase and biliverdin-IX beta reductase from human
RT   liver. Purification and characterization.";
RL   J. Biol. Chem. 269:24343-24348(1994).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-230, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT   refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [11]
RP   INVOLVEMENT IN HBLVD.
RX   PubMed=19580635; DOI=10.1111/j.1478-3231.2009.02029.x;
RA   Gafvels M., Holmstrom P., Somell A., Sjovall F., Svensson J.O., Stahle L.,
RA   Broome U., Stal P.;
RT   "A novel mutation in the biliverdin reductase-A gene combined with liver
RT   cirrhosis results in hyperbiliverdinaemia (green jaundice).";
RL   Liver Int. 29:1116-1124(2009).
RN   [12]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-174 AND SER-178, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
RN   [13]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-248 AND LYS-253, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA   Olsen J.V., Mann M.;
RT   "Lysine acetylation targets protein complexes and co-regulates major
RT   cellular functions.";
RL   Science 325:834-840(2009).
RN   [14]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [15]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [16]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [17]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=25944712; DOI=10.1002/pmic.201400617;
RA   Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA   Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT   "N-terminome analysis of the human mitochondrial proteome.";
RL   Proteomics 15:2519-2524(2015).
RN   [18] {ECO:0007744|PDB:2H63}
RP   X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 7-296 IN COMPLEX WITH NADP.
RG   Structural genomics consortium (SGC);
RT   "Crystal structure of human biliverdin reductase A.";
RL   Submitted (FEB-2009) to the PDB data bank.
CC   -!- FUNCTION: Reduces the gamma-methene bridge of the open tetrapyrrole,
CC       biliverdin IX alpha, to bilirubin with the concomitant oxidation of a
CC       NADH or NADPH cofactor (PubMed:8631357, PubMed:8424666,
CC       PubMed:7929092). Uses the reactants NADH or NADPH depending on the pH;
CC       NADH is used at the acidic pH range (6-6.9) and NADPH at the alkaline
CC       range (8.5-8.7) (PubMed:8631357, PubMed:8424666, PubMed:7929092).
CC       NADPH, however, is the probable reactant in biological systems
CC       (PubMed:7929092). {ECO:0000269|PubMed:7929092,
CC       ECO:0000269|PubMed:8424666, ECO:0000269|PubMed:8631357}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=bilirubin IXalpha + NAD(+) = biliverdin IXalpha + H(+) + NADH;
CC         Xref=Rhea:RHEA:15797, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945, ChEBI:CHEBI:57977, ChEBI:CHEBI:57991; EC=1.3.1.24;
CC         Evidence={ECO:0000269|PubMed:7929092, ECO:0000269|PubMed:8424666,
CC         ECO:0000269|PubMed:8631357};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=bilirubin IXalpha + NADP(+) = biliverdin IXalpha + H(+) +
CC         NADPH; Xref=Rhea:RHEA:15793, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:57977, ChEBI:CHEBI:57991, ChEBI:CHEBI:58349; EC=1.3.1.24;
CC         Evidence={ECO:0000269|PubMed:7929092, ECO:0000269|PubMed:8424666,
CC         ECO:0000269|PubMed:8631357};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000269|PubMed:8631357};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000305|PubMed:8631357};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=3.2 uM for NADPH {ECO:0000269|PubMed:8631357};
CC         KM=50 uM for NADH {ECO:0000269|PubMed:8631357};
CC   -!- PATHWAY: Porphyrin-containing compound metabolism; protoheme
CC       degradation.
CC   -!- SUBUNIT: Monomer. {ECO:0000269|Ref.18}.
CC   -!- INTERACTION:
CC       P53004; Q8TBB1: LNX1; NbExp=5; IntAct=EBI-7410441, EBI-739832;
CC       P53004; P28482: MAPK1; NbExp=2; IntAct=EBI-7410441, EBI-959949;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:7929092,
CC       ECO:0000269|PubMed:8424666}.
CC   -!- TISSUE SPECIFICITY: Liver. {ECO:0000269|PubMed:7929092,
CC       ECO:0000269|PubMed:8424666}.
CC   -!- DISEASE: Hyperbiliverdinemia (HBLVD) [MIM:614156]: A condition
CC       characterized by a green discoloration of the skin, urine, serum, and
CC       other bodily fluids. It is due to increased biliverdin resulting from
CC       inefficient conversion to bilirubin. Affected individuals appear to
CC       have symptoms only in the context of obstructive cholestasis and/or
CC       liver failure. In some cases, green jaundice can resolve after
CC       resolution of obstructive cholestasis. {ECO:0000269|PubMed:19580635}.
CC       Note=The disease is caused by variants affecting the gene represented
CC       in this entry.
CC   -!- SIMILARITY: Belongs to the Gfo/Idh/MocA family. Biliverdin reductase
CC       subfamily. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/blvra/";
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DR   EMBL; U34877; AAC35588.1; -; mRNA.
DR   EMBL; X93086; CAA63635.1; -; mRNA.
DR   EMBL; AK291862; BAF84551.1; -; mRNA.
DR   EMBL; AY616754; AAT11126.1; -; Genomic_DNA.
DR   EMBL; AC005189; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC004939; AAD05025.1; -; Genomic_DNA.
DR   EMBL; AC004985; AAP21879.1; -; Genomic_DNA.
DR   EMBL; BC005902; AAH05902.1; -; mRNA.
DR   EMBL; BC008456; AAH08456.1; -; mRNA.
DR   CCDS; CCDS5472.1; -.
DR   PIR; G02066; G02066.
DR   PIR; S62624; S62624.
DR   RefSeq; NP_000703.2; NM_000712.3.
DR   RefSeq; NP_001240752.1; NM_001253823.1.
DR   RefSeq; XP_011513776.1; XM_011515474.2.
DR   RefSeq; XP_016868009.1; XM_017012520.1.
DR   PDB; 2H63; X-ray; 2.70 A; A/B/C/D=7-296.
DR   PDBsum; 2H63; -.
DR   AlphaFoldDB; P53004; -.
DR   SMR; P53004; -.
DR   BioGRID; 107113; 91.
DR   CORUM; P53004; -.
DR   DIP; DIP-42180N; -.
DR   IntAct; P53004; 27.
DR   MINT; P53004; -.
DR   STRING; 9606.ENSP00000385757; -.
DR   DrugBank; DB00157; NADH.
DR   GlyGen; P53004; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P53004; -.
DR   MetOSite; P53004; -.
DR   PhosphoSitePlus; P53004; -.
DR   SwissPalm; P53004; -.
DR   BioMuta; BLVRA; -.
DR   DMDM; 23830892; -.
DR   OGP; P53004; -.
DR   REPRODUCTION-2DPAGE; IPI00294158; -.
DR   EPD; P53004; -.
DR   jPOST; P53004; -.
DR   MassIVE; P53004; -.
DR   MaxQB; P53004; -.
DR   PaxDb; 9606-ENSP00000385757; -.
DR   PeptideAtlas; P53004; -.
DR   ProteomicsDB; 56566; -.
DR   Pumba; P53004; -.
DR   Antibodypedia; 13185; 409 antibodies from 28 providers.
DR   DNASU; 644; -.
DR   Ensembl; ENST00000265523.9; ENSP00000265523.4; ENSG00000106605.11.
DR   Ensembl; ENST00000402924.5; ENSP00000385757.1; ENSG00000106605.11.
DR   GeneID; 644; -.
DR   KEGG; hsa:644; -.
DR   MANE-Select; ENST00000265523.9; ENSP00000265523.4; NM_000712.4; NP_000703.2.
DR   UCSC; uc003tir.4; human.
DR   AGR; HGNC:1062; -.
DR   CTD; 644; -.
DR   DisGeNET; 644; -.
DR   GeneCards; BLVRA; -.
DR   HGNC; HGNC:1062; BLVRA.
DR   HPA; ENSG00000106605; Low tissue specificity.
DR   MalaCards; BLVRA; -.
DR   MIM; 109750; gene.
DR   MIM; 614156; phenotype.
DR   neXtProt; NX_P53004; -.
DR   OpenTargets; ENSG00000106605; -.
DR   Orphanet; 276405; Hyperbiliverdinemia.
DR   PharmGKB; PA25373; -.
DR   VEuPathDB; HostDB:ENSG00000106605; -.
DR   eggNOG; ENOG502QTSZ; Eukaryota.
DR   GeneTree; ENSGT00390000011072; -.
DR   HOGENOM; CLU_053157_0_0_1; -.
DR   InParanoid; P53004; -.
DR   OMA; HEGHIRQ; -.
DR   OrthoDB; 2906063at2759; -.
DR   PhylomeDB; P53004; -.
DR   TreeFam; TF342889; -.
DR   BioCyc; MetaCyc:HS02928-MONOMER; -.
DR   BRENDA; 1.3.1.24; 2681.
DR   PathwayCommons; P53004; -.
DR   Reactome; R-HSA-189483; Heme degradation.
DR   Reactome; R-HSA-9707564; Cytoprotection by HMOX1.
DR   SABIO-RK; P53004; -.
DR   SignaLink; P53004; -.
DR   SIGNOR; P53004; -.
DR   UniPathway; UPA00684; -.
DR   BioGRID-ORCS; 644; 12 hits in 1166 CRISPR screens.
DR   ChiTaRS; BLVRA; human.
DR   EvolutionaryTrace; P53004; -.
DR   GenomeRNAi; 644; -.
DR   Pharos; P53004; Tbio.
DR   PRO; PR:P53004; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; P53004; Protein.
DR   Bgee; ENSG00000106605; Expressed in monocyte and 205 other cell types or tissues.
DR   ExpressionAtlas; P53004; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0106276; F:biliberdin reductase NAD+ activity; IDA:UniProtKB.
DR   GO; GO:0004074; F:biliverdin reductase (NAD(P)+) activity; IDA:UniProtKB.
DR   GO; GO:0106277; F:biliverdin reductase (NADP+) activity; IEA:UniProtKB-EC.
DR   GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0042167; P:heme catabolic process; IDA:UniProtKB.
DR   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR   InterPro; IPR017094; Biliverdin_Rdtase_A.
DR   InterPro; IPR015249; Biliverdin_Rdtase_cat.
DR   InterPro; IPR000683; Gfo/Idh/MocA-like_OxRdtase_N.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   PANTHER; PTHR43377; BILIVERDIN REDUCTASE A; 1.
DR   PANTHER; PTHR43377:SF1; BILIVERDIN REDUCTASE A; 1.
DR   Pfam; PF09166; Biliv-reduc_cat; 1.
DR   Pfam; PF01408; GFO_IDH_MocA; 1.
DR   PIRSF; PIRSF037032; Biliverdin_reductase_A; 1.
DR   SUPFAM; SSF55347; Glyceraldehyde-3-phosphate dehydrogenase-like, C-terminal domain; 1.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR   Genevisible; P53004; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Cytoplasm; Direct protein sequencing;
KW   Metal-binding; NAD; NADP; Oxidoreductase; Phosphoprotein;
KW   Reference proteome; Zinc.
FT   PROPEP          1..2
FT                   /evidence="ECO:0000269|PubMed:7929092,
FT                   ECO:0000269|PubMed:8424666"
FT                   /id="PRO_0000010852"
FT   CHAIN           3..296
FT                   /note="Biliverdin reductase A"
FT                   /evidence="ECO:0000269|PubMed:8631357"
FT                   /id="PRO_0000010853"
FT   BINDING         16..19
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000269|Ref.18, ECO:0007744|PDB:2H63"
FT   BINDING         44..46
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000269|Ref.18, ECO:0007744|PDB:2H63"
FT   BINDING         77..80
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000269|Ref.18, ECO:0007744|PDB:2H63"
FT   BINDING         98
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000269|Ref.18, ECO:0007744|PDB:2H63"
FT   BINDING         280
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000303|PubMed:8631357"
FT   BINDING         281
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000303|PubMed:8631357"
FT   BINDING         292
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000303|PubMed:8631357"
FT   BINDING         293
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000303|PubMed:8631357"
FT   MOD_RES         174
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:19690332"
FT   MOD_RES         178
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19690332"
FT   MOD_RES         230
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         248
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:19608861"
FT   MOD_RES         253
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:19608861"
FT   VARIANT         3
FT                   /note="A -> T (in dbSNP:rs699512)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:8950184, ECO:0000269|Ref.4"
FT                   /id="VAR_019230"
FT   VARIANT         37
FT                   /note="L -> V (in dbSNP:rs17245918)"
FT                   /evidence="ECO:0000269|Ref.4"
FT                   /id="VAR_019231"
FT   VARIANT         56
FT                   /note="Q -> R (in dbSNP:rs1050916)"
FT                   /evidence="ECO:0000269|Ref.4"
FT                   /id="VAR_014851"
FT   CONFLICT        121
FT                   /note="L -> S (in Ref. 6; AAH05902)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        154..155
FT                   /note="AG -> SD (in Ref. 2; CAA63635)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        160
FT                   /note="E -> D (in Ref. 2; CAA63635)"
FT                   /evidence="ECO:0000305"
FT   STRAND          9..14
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   HELIX           18..28
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   HELIX           33..36
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   STRAND          37..43
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   STRAND          50..53
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   HELIX           59..64
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   STRAND          70..73
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   HELIX           77..89
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   STRAND          93..98
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   HELIX           104..117
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   STRAND          121..124
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   HELIX           126..129
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   HELIX           131..140
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   STRAND          145..154
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   HELIX           159..162
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   HELIX           165..168
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   HELIX           170..180
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   STRAND          182..193
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   STRAND          198..207
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   STRAND          212..219
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   STRAND          226..235
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   HELIX           250..262
FT                   /evidence="ECO:0007829|PDB:2H63"
FT   HELIX           268..290
FT                   /evidence="ECO:0007829|PDB:2H63"
SQ   SEQUENCE   296 AA;  33428 MW;  2CF2AA7F1CDDB707 CRC64;
     MNAEPERKFG VVVVGVGRAG SVRMRDLRNP HPSSAFLNLI GFVSRRELGS IDGVQQISLE
     DALSSQEVEV AYICSESSSH EDYIRQFLNA GKHVLVEYPM TLSLAAAQEL WELAEQKGKV
     LHEEHVELLM EEFAFLKKEV VGKDLLKGSL LFTAGPLEEE RFGFPAFSGI SRLTWLVSLF
     GELSLVSATL EERKEDQYMK MTVCLETEKK SPLSWIEEKG PGLKRNRYLS FHFKSGSLEN
     VPNVGVNKNI FLKDQNIFVQ KLLGQFSEKE LAAEKKRILH CLGLAEEIQK YCCSRK
//