BCDO2_MOUSE
ID BCDO2_MOUSE Reviewed; 532 AA.
AC Q99NF1;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Carotenoid-cleaving dioxygenase, mitochondrial {ECO:0000305|PubMed:21106934};
DE EC=1.13.11.- {ECO:0000269|PubMed:21106934};
DE EC=1.13.11.71 {ECO:0000269|PubMed:21106934};
DE AltName: Full=B-diox-II {ECO:0000303|PubMed:11278918};
DE AltName: Full=Beta,beta-carotene 9',10'-oxygenase {ECO:0000303|PubMed:11278918};
DE AltName: Full=Beta-carotene dioxygenase 2 {ECO:0000312|MGI:MGI:2177469};
GN Name=Bco2 {ECO:0000312|MGI:MGI:2177469}; Synonyms=Bcdo2;
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 [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=11278918; DOI=10.1074/jbc.m011510200;
RA Kiefer C., Hessel S., Lampert J.M., Vogt K., Lederer M.O., Breithaupt D.E.,
RA von Lintig J.;
RT "Identification and characterization of a mammalian enzyme catalyzing the
RT asymmetric oxidative cleavage of provitamin A.";
RL J. Biol. Chem. 276:14110-14116(2001).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INDUCTION BY
RP CAROTENOIDS, AND DISRUPTION PHENOTYPE.
RX PubMed=21106934; DOI=10.1096/fj.10-173906;
RA Amengual J., Lobo G.P., Golczak M., Li H.N., Klimova T., Hoppel C.L.,
RA Wyss A., Palczewski K., von Lintig J.;
RT "A mitochondrial enzyme degrades carotenoids and protects against oxidative
RT stress.";
RL FASEB J. 25:948-959(2011).
CC -!- FUNCTION: Broad specificity mitochondrial dioxygenase that mediates the
CC asymmetric oxidative cleavage of carotenoids (PubMed:11278918,
CC PubMed:21106934). Cleaves carotenes (pure hydrocarbon carotenoids) such
CC as all-trans-beta-carotene and lycopene as well as xanthophylls
CC (oxygenated carotenoids) such as zeaxanthin, lutein and beta-
CC cryptoxanthin at both the 9,10 and the 9',10' carbon-carbon double bond
CC (PubMed:11278918, PubMed:21106934). Through its function in carotenoids
CC metabolism regulates oxidative stress and the production of important
CC signaling molecules (PubMed:21106934). {ECO:0000269|PubMed:11278918,
CC ECO:0000269|PubMed:21106934}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-beta-carotene + O2 = all-trans-10'-apo-beta-
CC carotenal + beta-ionone; Xref=Rhea:RHEA:26389, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17579, ChEBI:CHEBI:32325, ChEBI:CHEBI:53153;
CC EC=1.13.11.71; Evidence={ECO:0000269|PubMed:11278918,
CC ECO:0000269|PubMed:21106934};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26390;
CC Evidence={ECO:0000269|PubMed:21106934};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-cis-lycopene + O2 = (3E,5E)-6,10-dimethylundeca-3,5,9-trien-
CC 2-one + 5-cis-10'-apo-lycopenal; Xref=Rhea:RHEA:68444,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:67207, ChEBI:CHEBI:177905,
CC ChEBI:CHEBI:177906; Evidence={ECO:0000250|UniProtKB:Q6QT07};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68445;
CC Evidence={ECO:0000250|UniProtKB:Q6QT07};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=13-cis-lycopene + O2 = (3E,5E)-6,10-dimethylundeca-3,5,9-
CC trien-2-one + 13-cis-10'-apo-lycopenal; Xref=Rhea:RHEA:68448,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:67207, ChEBI:CHEBI:177907,
CC ChEBI:CHEBI:177908; Evidence={ECO:0000250|UniProtKB:Q6QT07};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68449;
CC Evidence={ECO:0000250|UniProtKB:Q6QT07};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lutein + O2 = (3R)-3-hydroxy-10'-apo-beta-carotenal + (3R,6R)-
CC hydroxy-alpha-ionone; Xref=Rhea:RHEA:68428, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:28838, ChEBI:CHEBI:177902, ChEBI:CHEBI:177904;
CC Evidence={ECO:0000269|PubMed:21106934};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68429;
CC Evidence={ECO:0000269|PubMed:21106934};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lutein + O2 = (3R)-hydroxy-beta-ionone + (3R,6R)-3-hydroxy-
CC 10'-apo-alpha-carotenal; Xref=Rhea:RHEA:68432, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:28838, ChEBI:CHEBI:53173, ChEBI:CHEBI:177903;
CC Evidence={ECO:0000269|PubMed:21106934};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68433;
CC Evidence={ECO:0000269|PubMed:21106934};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-zeaxanthin + 2 O2 = 2 (3R)-hydroxy-beta-ionone +
CC 4,9-dimethyldodeca-2,4,6,8,10-pentaenedial; Xref=Rhea:RHEA:26393,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:27547, ChEBI:CHEBI:53171,
CC ChEBI:CHEBI:53173; Evidence={ECO:0000269|PubMed:21106934};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26394;
CC Evidence={ECO:0000305|PubMed:21106934};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-zeaxanthin + O2 = (3R)-3-hydroxy-10'-apo-beta-
CC carotenal + (3R)-hydroxy-beta-ionone; Xref=Rhea:RHEA:68104,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:27547, ChEBI:CHEBI:53173,
CC ChEBI:CHEBI:177902; Evidence={ECO:0000269|PubMed:21106934};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68105;
CC Evidence={ECO:0000305|PubMed:21106934};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-cryptoxanthin + O2 = (3R)-hydroxy-beta-ionone + all-
CC trans-10'-apo-beta-carotenal; Xref=Rhea:RHEA:68440,
CC ChEBI:CHEBI:10362, ChEBI:CHEBI:15379, ChEBI:CHEBI:53153,
CC ChEBI:CHEBI:53173; Evidence={ECO:0000269|PubMed:21106934};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68441;
CC Evidence={ECO:0000269|PubMed:21106934};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-10'-apo-beta-carotenal + O2 = 4,9-dimethyldodeca-
CC 2,4,6,8,10-pentaenedial + beta-ionone; Xref=Rhea:RHEA:68452,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32325, ChEBI:CHEBI:53153,
CC ChEBI:CHEBI:53171; Evidence={ECO:0000269|PubMed:21106934};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68453;
CC Evidence={ECO:0000269|PubMed:21106934};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-3-hydroxy-10'-apo-beta-carotenal + O2 = (3R)-hydroxy-
CC beta-ionone + 4,9-dimethyldodeca-2,4,6,8,10-pentaenedial;
CC Xref=Rhea:RHEA:68424, ChEBI:CHEBI:15379, ChEBI:CHEBI:53171,
CC ChEBI:CHEBI:53173, ChEBI:CHEBI:177902;
CC Evidence={ECO:0000269|PubMed:21106934};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68425;
CC Evidence={ECO:0000305|PubMed:21106934};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R,6R)-3-hydroxy-10'-apo-alpha-carotenal + O2 = (3R,6R)-
CC hydroxy-alpha-ionone + 4,9-dimethyldodeca-2,4,6,8,10-pentaenedial;
CC Xref=Rhea:RHEA:68436, ChEBI:CHEBI:15379, ChEBI:CHEBI:53171,
CC ChEBI:CHEBI:177903, ChEBI:CHEBI:177904;
CC Evidence={ECO:0000269|PubMed:21106934};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68437;
CC Evidence={ECO:0000269|PubMed:21106934};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000250|UniProtKB:Q6QT07};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250|UniProtKB:Q6QT07};
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:21106934}.
CC -!- TISSUE SPECIFICITY: Expressed in small intestine, liver, kidney, testis
CC and less abundantly in spleen, brain, lung, and heart.
CC {ECO:0000269|PubMed:11278918}.
CC -!- INDUCTION: Up-regulated by carotenoids. {ECO:0000269|PubMed:21106934}.
CC -!- DISRUPTION PHENOTYPE: Homozygous knockout mice lacking Bcdo2 develop
CC normally, and both females and males are fertile when raised on
CC standard diet (PubMed:21106934). On a diet supplemented with
CC xanthophylls, knockout mice accumulate derivatives of these
CC xanthophylls in all tested tissues and develop liver steatosis with
CC large lipid droplets in hepatocytes and a significantly increased
CC triacylglyceride content (PubMed:21106934). Accumulated carotenoids
CC impair mitochondrial respiration, induce ROS production and cellular
CC signaling pathways related to oxidative stress (PubMed:21106934).
CC {ECO:0000269|PubMed:21106934}.
CC -!- SIMILARITY: Belongs to the carotenoid oxygenase family. {ECO:0000305}.
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DR EMBL; AJ290392; CAC28026.1; -; mRNA.
DR CCDS; CCDS40620.1; -.
DR RefSeq; NP_573480.1; NM_133217.3.
DR RefSeq; XP_006510107.1; XM_006510044.3.
DR RefSeq; XP_006510108.1; XM_006510045.1.
DR RefSeq; XP_006510109.1; XM_006510046.3.
DR AlphaFoldDB; Q99NF1; -.
DR SMR; Q99NF1; -.
DR STRING; 10090.ENSMUSP00000112727; -.
DR PhosphoSitePlus; Q99NF1; -.
DR SwissPalm; Q99NF1; -.
DR MaxQB; Q99NF1; -.
DR PaxDb; Q99NF1; -.
DR PRIDE; Q99NF1; -.
DR ProteomicsDB; 273477; -.
DR Antibodypedia; 45628; 118 antibodies from 19 providers.
DR DNASU; 170752; -.
DR Ensembl; ENSMUST00000119103; ENSMUSP00000112727; ENSMUSG00000032066.
DR GeneID; 170752; -.
DR KEGG; mmu:170752; -.
DR UCSC; uc009pjq.1; mouse.
DR CTD; 83875; -.
DR MGI; MGI:2177469; Bco2.
DR VEuPathDB; HostDB:ENSMUSG00000032066; -.
DR eggNOG; KOG1285; Eukaryota.
DR GeneTree; ENSGT00950000182913; -.
DR HOGENOM; CLU_016472_1_1_1; -.
DR InParanoid; Q99NF1; -.
DR OMA; RAHGKVC; -.
DR OrthoDB; 895046at2759; -.
DR PhylomeDB; Q99NF1; -.
DR TreeFam; TF314019; -.
DR BRENDA; 1.13.11.71; 3474.
DR Reactome; R-MMU-975634; Retinoid metabolism and transport.
DR BioGRID-ORCS; 170752; 3 hits in 74 CRISPR screens.
DR PRO; PR:Q99NF1; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q99NF1; protein.
DR Bgee; ENSMUSG00000032066; Expressed in duodenum and 49 other tissues.
DR ExpressionAtlas; Q99NF1; baseline and differential.
DR Genevisible; Q99NF1; MM.
DR GO; GO:0005739; C:mitochondrion; IDA:BHF-UCL.
DR GO; GO:0010437; F:9,10 (9', 10')-carotenoid-cleaving dioxygenase activity; ISS:UniProtKB.
DR GO; GO:0102076; F:beta,beta-carotene-9',10'-cleaving oxygenase activity; IDA:UniProtKB.
DR GO; GO:0003834; F:beta-carotene 15,15'-dioxygenase activity; IBA:GO_Central.
DR GO; GO:0010436; F:carotenoid dioxygenase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016702; F:oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; IDA:UniProtKB.
DR GO; GO:0016121; P:carotene catabolic process; IDA:UniProtKB.
DR GO; GO:0016119; P:carotene metabolic process; IDA:UniProtKB.
DR GO; GO:0016116; P:carotenoid metabolic process; IMP:BHF-UCL.
DR GO; GO:0062172; P:lutein catabolic process; ISS:UniProtKB.
DR GO; GO:1901176; P:lycopene catabolic process; ISS:UniProtKB.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IMP:BHF-UCL.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IMP:BHF-UCL.
DR GO; GO:0042574; P:retinal metabolic process; IGI:MGI.
DR GO; GO:0042573; P:retinoic acid metabolic process; NAS:UniProtKB.
DR GO; GO:0016124; P:xanthophyll catabolic process; IDA:UniProtKB.
DR GO; GO:0016122; P:xanthophyll metabolic process; IMP:MGI.
DR GO; GO:1901826; P:zeaxanthin catabolic process; ISS:UniProtKB.
DR InterPro; IPR004294; Carotenoid_Oase.
DR PANTHER; PTHR10543; PTHR10543; 1.
DR Pfam; PF03055; RPE65; 1.
PE 1: Evidence at protein level;
KW Dioxygenase; Iron; Lipid metabolism; Metal-binding; Mitochondrion;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..532
FT /note="Carotenoid-cleaving dioxygenase, mitochondrial"
FT /id="PRO_0000143939"
FT BINDING 179
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9JJS6"
FT BINDING 239
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9JJS6"
FT BINDING 310
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9JJS6"
FT BINDING 526
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9JJS6"
SQ SEQUENCE 532 AA; 60142 MW; 7461AD5A53FE86A3 CRC64;
MLGPKQSLPC IAPLLTTAEE TLSAVSARVR GHIPEWLNGY LLRVGPGKFE FGKDRYNHWF
DGMALLHQFR MERGTVTYKS KFLQSDTYKA NSAGGRIVIS EFGTLALPDP CKSIFERFMS
RFEPPTMTDN TNVNFVQYKG DYYMSTETNF MNKVDIEMLE RTEKVDWSKF IAVNGATAHP
HYDPDGTAYN MGNSYGPRGS CYNIIRVPPK KKEPGETIHG AQVLCSIAST EKMKPSYYHS
FGMTKNYIIF VEQPVKMKLW KIITSKIRGK PFADGISWEP QYNTRFHVVD KHTGQLLPGM
YYSMPFLTYH QINAFEDQGC IVIDLCCQDD GRSLDLYQLQ NLRKAGEGLD QVYELKAKSF
PRRFVLPLDV SVDAAEGKNL SPLSYSSASA VKQGDGEIWC SPENLHHEDL EEEGGIEFPQ
INYGRFNGKK YSFFYGCGFR HLVGDSLIKV DVTNKTLRVW REEGFYPSEP VFVPVPGADE
EDSGVILSVV ITPNQSESNF LLVLDAKSFT ELGRAEVPVQ MPYGFHGTFV PI
