BIEA_RAT
ID BIEA_RAT Reviewed; 295 AA.
AC P46844;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Biliverdin reductase A {ECO:0000303|PubMed:1371282};
DE Short=BVR A;
DE EC=1.3.1.24 {ECO:0000269|PubMed:8020496};
DE AltName: Full=Biliverdin-IX alpha-reductase {ECO:0000303|PubMed:12079357};
DE Flags: Precursor;
GN Name=Blvra; Synonyms=Blvr;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, AND
RP CATALYTIC ACTIVITY.
RC TISSUE=Kidney;
RX PubMed=1371282; DOI=10.1016/s0021-9258(19)50627-5;
RA Fakhrai H., Maines M.D.;
RT "Expression and characterization of a cDNA for rat kidney biliverdin
RT reductase. Evidence suggesting the liver and kidney enzymes are the same
RT transcript product.";
RL J. Biol. Chem. 267:4023-4029(1992).
RN [2]
RP PROTEIN SEQUENCE OF 119-136, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (NOV-2006) to UniProtKB.
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF CYS-73; CYS-280 AND CYS-291.
RX PubMed=8020496; DOI=10.1111/j.1432-1033.1994.tb18902.x;
RA McCoubrey W.K. Jr., Maines M.D.;
RT "Site-directed mutagenesis of cysteine residues in biliverdin reductase.
RT Roles in substrate and cofactor binding.";
RL Eur. J. Biochem. 222:597-603(1994).
RN [4]
RP CRYSTALLIZATION.
RX PubMed=10957639; DOI=10.1107/s0907444900008520;
RA Sun D., Sato M., Yoshida T., Shimizu H., Miyatake H., Adachi S., Shiro Y.,
RA Kikuchi A.;
RT "Crystallization and preliminary X-ray diffraction analysis of a rat
RT biliverdin reductase.";
RL Acta Crystallogr. D 56:1180-1182(2000).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-154, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [6] {ECO:0007744|PDB:1LC0, ECO:0007744|PDB:1LC3}
RP X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 8-291 IN COMPLEX WITH NAD, AND
RP SUBUNIT.
RX PubMed=12079357; DOI=10.1016/s0022-2836(02)00383-2;
RA Whitby F.G., Phillips J.D., Hill C.P., McCoubrey W.K. Jr., Maines M.D.;
RT "Crystal structure of a biliverdin IXalpha reductase enzyme-cofactor
RT complex.";
RL J. Mol. Biol. 319:1199-1210(2002).
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:1371282, PubMed:8020496). Uses the
CC reactants NADH or NADPH depending on the pH; NADH is used at the acidic
CC pH range (6-6.9) and NADPH at the alkaline range (8.5-8.7)
CC (PubMed:1371282, PubMed:8020496). NADPH, however, is the probable
CC reactant in biological systems (PubMed:8020496).
CC {ECO:0000269|PubMed:1371282, ECO:0000269|PubMed:8020496}.
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:1371282, ECO:0000269|PubMed:8020496};
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:1371282, ECO:0000269|PubMed:8020496};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P53004};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P53004};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.9 uM for biliverdin (at pH 6.75) {ECO:0000269|PubMed:8020496};
CC KM=3.4 uM for biliverdin (at pH 8.7) {ECO:0000269|PubMed:8020496};
CC KM=333 uM for NADH (at pH 6.75) {ECO:0000269|PubMed:8020496};
CC KM=2.9 uM for NADPH (at pH 8.7) {ECO:0000269|PubMed:8020496};
CC Note=kcat is 82.4 min(-1) at pH 6.75 (PubMed:8020496). kcat is 88.6
CC min(-1) at pH 8.7 (PubMed:8020496). {ECO:0000269|PubMed:8020496};
CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoheme
CC degradation.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:12079357}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P53004}.
CC -!- SIMILARITY: Belongs to the Gfo/Idh/MocA family. Biliverdin reductase
CC subfamily. {ECO:0000305}.
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DR EMBL; M81681; AAA40830.1; -; mRNA.
DR PIR; A42268; A42268.
DR RefSeq; NP_446302.1; NM_053850.1.
DR PDB; 1GCU; X-ray; 1.40 A; A=1-295.
DR PDB; 1LC0; X-ray; 1.20 A; A=5-295.
DR PDB; 1LC3; X-ray; 1.50 A; A=5-295.
DR PDBsum; 1GCU; -.
DR PDBsum; 1LC0; -.
DR PDBsum; 1LC3; -.
DR AlphaFoldDB; P46844; -.
DR SMR; P46844; -.
DR STRING; 10116.ENSRNOP00000015843; -.
DR iPTMnet; P46844; -.
DR PhosphoSitePlus; P46844; -.
DR jPOST; P46844; -.
DR PaxDb; P46844; -.
DR PRIDE; P46844; -.
DR GeneID; 116599; -.
DR KEGG; rno:116599; -.
DR UCSC; RGD:620721; rat.
DR CTD; 644; -.
DR RGD; 620721; Blvra.
DR eggNOG; ENOG502QTSZ; Eukaryota.
DR InParanoid; P46844; -.
DR OrthoDB; 879838at2759; -.
DR PhylomeDB; P46844; -.
DR BRENDA; 1.3.1.24; 5301.
DR Reactome; R-RNO-189483; Heme degradation.
DR Reactome; R-RNO-9707564; Cytoprotection by HMOX1.
DR SABIO-RK; P46844; -.
DR UniPathway; UPA00684; -.
DR EvolutionaryTrace; P46844; -.
DR PRO; PR:P46844; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005829; C:cytosol; ISS: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; ISO:RGD.
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 Pfam; PF09166; Biliv-reduc_cat; 1.
DR Pfam; PF01408; GFO_IDH_MocA; 1.
DR PIRSF; PIRSF037032; Biliverdin_reductase_A; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
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:1371282"
FT /id="PRO_0000010856"
FT CHAIN 3..295
FT /note="Biliverdin reductase A"
FT /id="PRO_0000010857"
FT BINDING 18..19
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12079357,
FT ECO:0007744|PDB:1LC3"
FT BINDING 76..79
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12079357,
FT ECO:0007744|PDB:1LC3"
FT BINDING 97
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12079357,
FT ECO:0007744|PDB:1LC3"
FT BINDING 167
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12079357,
FT ECO:0007744|PDB:1LC3"
FT BINDING 279
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P53004"
FT BINDING 280
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P53004"
FT BINDING 291
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P53004"
FT BINDING 292
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P53004"
FT MOD_RES 154
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 173
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P53004"
FT MOD_RES 177
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53004"
FT MOD_RES 247
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P53004"
FT MOD_RES 252
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P53004"
FT MUTAGEN 73
FT /note="C->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:8020496"
FT MUTAGEN 280
FT /note="C->A: Reduced activity."
FT /evidence="ECO:0000269|PubMed:8020496"
FT MUTAGEN 291
FT /note="C->A: Reduced activity."
FT /evidence="ECO:0000269|PubMed:8020496"
FT STRAND 8..14
FT /evidence="ECO:0007829|PDB:1LC0"
FT HELIX 18..27
FT /evidence="ECO:0007829|PDB:1LC0"
FT HELIX 30..33
FT /evidence="ECO:0007829|PDB:1LC0"
FT STRAND 36..42
FT /evidence="ECO:0007829|PDB:1LC0"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:1LC0"
FT HELIX 58..63
FT /evidence="ECO:0007829|PDB:1LC0"
FT STRAND 65..72
FT /evidence="ECO:0007829|PDB:1LC0"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:1LC0"
FT HELIX 79..88
FT /evidence="ECO:0007829|PDB:1LC0"
FT STRAND 92..97
FT /evidence="ECO:0007829|PDB:1LC0"
FT HELIX 103..115
FT /evidence="ECO:0007829|PDB:1LC0"
FT STRAND 120..123
FT /evidence="ECO:0007829|PDB:1LC0"
FT HELIX 125..128
FT /evidence="ECO:0007829|PDB:1LC0"
FT HELIX 130..139
FT /evidence="ECO:0007829|PDB:1LC0"
FT STRAND 144..154
FT /evidence="ECO:0007829|PDB:1LC0"
FT HELIX 158..161
FT /evidence="ECO:0007829|PDB:1LC0"
FT HELIX 164..167
FT /evidence="ECO:0007829|PDB:1LC0"
FT HELIX 169..179
FT /evidence="ECO:0007829|PDB:1LC0"
FT STRAND 183..192
FT /evidence="ECO:0007829|PDB:1LC0"
FT HELIX 193..195
FT /evidence="ECO:0007829|PDB:1LC0"
FT STRAND 197..205
FT /evidence="ECO:0007829|PDB:1LC0"
FT STRAND 211..218
FT /evidence="ECO:0007829|PDB:1LC0"
FT STRAND 225..234
FT /evidence="ECO:0007829|PDB:1LC0"
FT STRAND 235..237
FT /evidence="ECO:0007829|PDB:1GCU"
FT HELIX 249..261
FT /evidence="ECO:0007829|PDB:1LC0"
FT HELIX 267..290
FT /evidence="ECO:0007829|PDB:1LC0"
SQ SEQUENCE 295 AA; 33566 MW; 219C8EA96C150588 CRC64;
MDAEPKRKFG VVVVGVGRAG SVRLRDLKDP RSAAFLNLIG FVSRRELGSL DEVRQISLED
ALRSQEIDVA YICSESSSHE DYIRQFLQAG KHVLVEYPMT LSFAAAQELW ELAAQKGRVL
HEEHVELLME EFEFLRREVL GKELLKGSLR FTASPLEEER FGFPAFSGIS RLTWLVSLFG
ELSLISATLE ERKEDQYMKM TVQLETQNKG LLSWIEEKGP GLKRNRYVNF QFTSGSLEEV
PSVGVNKNIF LKDQDIFVQK LLDQVSAEDL AAEKKRIMHC LGLASDIQKL CHQKK
