BIEA_MOUSE
ID BIEA_MOUSE Reviewed; 295 AA.
AC Q9CY64; Q3T9C6; Q80WR6; Q9DD21;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Biliverdin reductase A;
DE Short=BVR A;
DE EC=1.3.1.24 {ECO:0000250|UniProtKB:P53004};
DE AltName: Full=Biliverdin-IX alpha-reductase;
DE Flags: Precursor;
GN Name=Blvra {ECO:0000312|MGI:MGI:88170};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Embryonic liver, Kidney, and Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-154, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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. Uses the reactants NADH or NADPH depending on
CC the pH; NADH is used at the acidic pH range (6-6.9) and NADPH at the
CC alkaline range (8.5-8.7). NADPH, however, is the probable reactant in
CC biological systems. {ECO:0000250|UniProtKB:P53004}.
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:0000250|UniProtKB:P53004};
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:0000250|UniProtKB:P53004};
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 -!- PATHWAY: Porphyrin-containing compound metabolism; protoheme
CC degradation.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P53004}.
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; AK002231; BAB21950.1; -; mRNA.
DR EMBL; AK010847; BAB27219.1; -; mRNA.
DR EMBL; AK172620; BAE43098.1; -; mRNA.
DR EMBL; BC052146; AAH52146.1; -; mRNA.
DR CCDS; CCDS16692.1; -.
DR RefSeq; NP_080954.4; NM_026678.4.
DR RefSeq; XP_006498634.1; XM_006498571.3.
DR RefSeq; XP_006498635.1; XM_006498572.3.
DR AlphaFoldDB; Q9CY64; -.
DR SMR; Q9CY64; -.
DR BioGRID; 225034; 4.
DR STRING; 10090.ENSMUSP00000002064; -.
DR iPTMnet; Q9CY64; -.
DR PhosphoSitePlus; Q9CY64; -.
DR SwissPalm; Q9CY64; -.
DR EPD; Q9CY64; -.
DR jPOST; Q9CY64; -.
DR MaxQB; Q9CY64; -.
DR PaxDb; Q9CY64; -.
DR PeptideAtlas; Q9CY64; -.
DR PRIDE; Q9CY64; -.
DR ProteomicsDB; 273488; -.
DR Antibodypedia; 13185; 368 antibodies from 28 providers.
DR DNASU; 109778; -.
DR Ensembl; ENSMUST00000002064; ENSMUSP00000002064; ENSMUSG00000001999.
DR GeneID; 109778; -.
DR KEGG; mmu:109778; -.
DR UCSC; uc008meq.1; mouse.
DR CTD; 644; -.
DR MGI; MGI:88170; Blvra.
DR VEuPathDB; HostDB:ENSMUSG00000001999; -.
DR eggNOG; ENOG502QTSZ; Eukaryota.
DR GeneTree; ENSGT00390000011072; -.
DR HOGENOM; CLU_053157_0_0_1; -.
DR InParanoid; Q9CY64; -.
DR OMA; ELFTPDF; -.
DR OrthoDB; 879838at2759; -.
DR PhylomeDB; Q9CY64; -.
DR TreeFam; TF342889; -.
DR BRENDA; 1.3.1.24; 3474.
DR Reactome; R-MMU-189483; Heme degradation.
DR Reactome; R-MMU-9707564; Cytoprotection by HMOX1.
DR UniPathway; UPA00684; -.
DR BioGRID-ORCS; 109778; 1 hit in 74 CRISPR screens.
DR PRO; PR:Q9CY64; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9CY64; protein.
DR Bgee; ENSMUSG00000001999; Expressed in right kidney and 255 other tissues.
DR ExpressionAtlas; Q9CY64; baseline and differential.
DR Genevisible; Q9CY64; MM.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0106276; F:biliberdin reductase NAD+ activity; ISS:UniProtKB.
DR GO; GO:0004074; F:biliverdin reductase (NAD(P)+) activity; IDA:MGI.
DR GO; GO:0106277; F:biliverdin reductase (NADP+) activity; IEA:UniProtKB-EC.
DR GO; GO:0000166; F:nucleotide binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0042167; P:heme catabolic process; ISO:MGI.
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 Acetylation; Cytoplasm; Metal-binding; NAD; NADP; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Zinc.
FT PROPEP 1..2
FT /evidence="ECO:0000250|UniProtKB:P46844"
FT /id="PRO_0000010854"
FT CHAIN 3..295
FT /note="Biliverdin reductase A"
FT /id="PRO_0000010855"
FT BINDING 18..19
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P46844"
FT BINDING 76..79
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P46844"
FT BINDING 97
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P46844"
FT BINDING 167
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P46844"
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:21183079"
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 229
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 CONFLICT 27
FT /note="L -> S (in Ref. 2; AAH52146)"
FT /evidence="ECO:0000305"
FT CONFLICT 295
FT /note="Q -> QWGGSFRYL (in Ref. 1; BAB21950)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 295 AA; 33525 MW; F2E1682BD77032A4 CRC64;
MSTEPKRKFG VVVVGVGRAG SVRIRDLKDP HSSAFLNLIG YVSRRELGSL DNVRQISLED
ALRSQEVDVA YICTESSSHE DYIRQFLQAG KHVLVEYPMA LSFAAAQELW ELAAQKGRVL
HEEHIELLME EFEFLKREVA GKELLKGSLR FTASPLEEEK FGFPAFSGIS RLTWLVSLFG
ELSLISATME NRKEDQYMKM TVQLETQNKS PLSWIEEKGP GLKRNRHISI HFKSGSLEEV
PNVGVNKNIF LKDQDIFIQK LLGQVSAEDL AAEKKRILHC LELASDIQRL CHRKQ
