BCDO1_HUMAN
ID BCDO1_HUMAN Reviewed; 547 AA.
AC Q9HAY6; A0AV48; A0AV50; Q9NVH5;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Beta,beta-carotene 15,15'-dioxygenase {ECO:0000305|PubMed:11401432};
DE EC=1.13.11.63 {ECO:0000269|PubMed:11401432, ECO:0000269|PubMed:17951468, ECO:0000269|PubMed:24668807};
DE AltName: Full=Beta-carotene dioxygenase 1;
DE AltName: Full=Beta-carotene oxygenase 1 {ECO:0000312|HGNC:HGNC:13815};
GN Name=BCO1 {ECO:0000312|HGNC:HGNC:13815};
GN Synonyms=BCDO {ECO:0000312|HGNC:HGNC:13815},
GN BCDO1 {ECO:0000312|HGNC:HGNC:13815}, BCMO1 {ECO:0000312|HGNC:HGNC:13815};
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], FUNCTION, CATALYTIC ACTIVITY, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Retinal pigment epithelium;
RX PubMed=11401432; DOI=10.1006/geno.2000.6476;
RA Yan W., Jang G.-F., Haeseleer F., Esumi N., Chang J., Kerrigan M.,
RA Campochiaro M., Campochiaro P., Palczewski K., Zack D.J.;
RT "Cloning and characterization of a human beta,beta-carotene-15,15-prime
RT dioxygenase that is highly expressed in the retinal pigment epithelium.";
RL Genomics 72:193-202(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT SER-267.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-267.
RC TISSUE=Colon;
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 [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=24668807; DOI=10.1074/jbc.m114.557710;
RA dela Sena C., Riedl K.M., Narayanasamy S., Curley R.W. Jr., Schwartz S.J.,
RA Harrison E.H.;
RT "The human enzyme that converts dietary provitamin A carotenoids to vitamin
RT A is a dioxygenase.";
RL J. Biol. Chem. 289:13661-13666(2014).
RN [6]
RP VARIANT HCVAD MET-170, CHARACTERIZATION OF VARIANT HCVAD MET-170, FUNCTION,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=17951468; DOI=10.1093/jn/137.11.2346;
RA Lindqvist A., Sharvill J., Sharvill D.E., Andersson S.;
RT "Loss-of-function mutation in carotenoid 15,15'-monooxygenase identified in
RT a patient with hypercarotenemia and hypovitaminosis A.";
RL J. Nutr. 137:2346-2350(2007).
CC -!- FUNCTION: Symmetrically cleaves beta-carotene into two molecules of
CC retinal using a dioxygenase mechanism. {ECO:0000269|PubMed:11401432,
CC ECO:0000269|PubMed:17951468, ECO:0000269|PubMed:24668807}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-beta-carotene + O2 = 2 all-trans-retinal;
CC Xref=Rhea:RHEA:32887, ChEBI:CHEBI:15379, ChEBI:CHEBI:17579,
CC ChEBI:CHEBI:17898; EC=1.13.11.63;
CC Evidence={ECO:0000269|PubMed:11401432, ECO:0000269|PubMed:17951468,
CC ECO:0000269|PubMed:24668807};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32888;
CC Evidence={ECO:0000269|PubMed:17951468};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000250|UniProtKB:Q9JJS6};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250|UniProtKB:Q9JJS6};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.0 uM for all-trans-beta-carotene {ECO:0000269|PubMed:17951468};
CC Vmax=7.2 umol/min/mg enzyme for the formation of 2 all-trans-retinal
CC {ECO:0000269|PubMed:17951468};
CC Note=kcat is 0.45 min(-1) with all-trans-beta-carotene as substrate.
CC {ECO:0000269|PubMed:17951468};
CC -!- PATHWAY: Cofactor metabolism; retinol metabolism.
CC {ECO:0000269|PubMed:17951468}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9I993}.
CC -!- TISSUE SPECIFICITY: Highly expressed in retinal pigment epithelium.
CC Also expressed in kidney, testis, liver, brain, small intestine and
CC colon. {ECO:0000269|PubMed:11401432}.
CC -!- DISEASE: Hypercarotenemia and vitamin A deficiency, autosomal dominant
CC (HCVAD) [MIM:115300]: A disorder characterized by increased serum beta-
CC carotene, decreased conversion of beta-carotene to vitamin A and
CC decreased serum vitamin A. {ECO:0000269|PubMed:17951468}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the carotenoid oxygenase family. {ECO:0000305}.
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DR EMBL; AF294900; AAG15380.1; -; mRNA.
DR EMBL; AK001592; BAA91776.1; -; mRNA.
DR EMBL; CH471114; EAW95537.1; -; Genomic_DNA.
DR EMBL; BC126210; AAI26211.1; -; mRNA.
DR EMBL; BC126212; AAI26213.1; -; mRNA.
DR CCDS; CCDS10934.1; -.
DR RefSeq; NP_059125.2; NM_017429.2.
DR AlphaFoldDB; Q9HAY6; -.
DR SMR; Q9HAY6; -.
DR BioGRID; 119790; 15.
DR IntAct; Q9HAY6; 2.
DR STRING; 9606.ENSP00000258168; -.
DR DrugBank; DB06755; Beta carotene.
DR SwissLipids; SLP:000000143; -.
DR iPTMnet; Q9HAY6; -.
DR PhosphoSitePlus; Q9HAY6; -.
DR BioMuta; BCO1; -.
DR DMDM; 41688803; -.
DR jPOST; Q9HAY6; -.
DR MassIVE; Q9HAY6; -.
DR MaxQB; Q9HAY6; -.
DR PaxDb; Q9HAY6; -.
DR PeptideAtlas; Q9HAY6; -.
DR PRIDE; Q9HAY6; -.
DR ProteomicsDB; 81458; -.
DR Antibodypedia; 48219; 134 antibodies from 19 providers.
DR DNASU; 53630; -.
DR Ensembl; ENST00000258168.7; ENSP00000258168.2; ENSG00000135697.10.
DR GeneID; 53630; -.
DR KEGG; hsa:53630; -.
DR MANE-Select; ENST00000258168.7; ENSP00000258168.2; NM_017429.3; NP_059125.2.
DR UCSC; uc002fgn.2; human.
DR CTD; 53630; -.
DR DisGeNET; 53630; -.
DR GeneCards; BCO1; -.
DR HGNC; HGNC:13815; BCO1.
DR HPA; ENSG00000135697; Tissue enhanced (intestine).
DR MalaCards; BCO1; -.
DR MIM; 115300; phenotype.
DR MIM; 605748; gene.
DR neXtProt; NX_Q9HAY6; -.
DR OpenTargets; ENSG00000135697; -.
DR Orphanet; 199285; Hereditary hypercarotenemia and vitamin A deficiency.
DR PharmGKB; PA37812; -.
DR VEuPathDB; HostDB:ENSG00000135697; -.
DR eggNOG; KOG1285; Eukaryota.
DR GeneTree; ENSGT00950000182913; -.
DR HOGENOM; CLU_016472_1_1_1; -.
DR OMA; ENYIIFL; -.
DR OrthoDB; 524712at2759; -.
DR PhylomeDB; Q9HAY6; -.
DR TreeFam; TF314019; -.
DR BioCyc; MetaCyc:HS06050-MON; -.
DR BRENDA; 1.13.11.63; 2681.
DR PathwayCommons; Q9HAY6; -.
DR Reactome; R-HSA-975634; Retinoid metabolism and transport.
DR SABIO-RK; Q9HAY6; -.
DR SignaLink; Q9HAY6; -.
DR UniPathway; UPA00912; -.
DR BioGRID-ORCS; 53630; 6 hits in 1062 CRISPR screens.
DR ChiTaRS; BCO1; human.
DR GenomeRNAi; 53630; -.
DR Pharos; Q9HAY6; Tbio.
DR PRO; PR:Q9HAY6; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9HAY6; protein.
DR Bgee; ENSG00000135697; Expressed in pigmented layer of retina and 95 other tissues.
DR ExpressionAtlas; Q9HAY6; baseline and differential.
DR Genevisible; Q9HAY6; HS.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0003834; F:beta-carotene 15,15'-dioxygenase activity; IDA:UniProtKB.
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:1901810; P:beta-carotene metabolic process; IEA:Ensembl.
DR GO; GO:0016121; P:carotene catabolic process; IDA:UniProtKB.
DR GO; GO:0042574; P:retinal metabolic process; IDA:UniProtKB.
DR GO; GO:0001523; P:retinoid metabolic process; IDA:UniProtKB.
DR GO; GO:0042572; P:retinol metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0035238; P:vitamin A biosynthetic process; NAS:BHF-UCL.
DR InterPro; IPR004294; Carotenoid_Oase.
DR PANTHER; PTHR10543; PTHR10543; 1.
DR Pfam; PF03055; RPE65; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Dioxygenase; Disease variant; Iron; Lipid metabolism;
KW Metal-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..547
FT /note="Beta,beta-carotene 15,15'-dioxygenase"
FT /id="PRO_0000143933"
FT REGION 528..547
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 172
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9JJS6"
FT BINDING 237
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9JJS6"
FT BINDING 308
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9JJS6"
FT BINDING 514
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9JJS6"
FT VARIANT 170
FT /note="T -> M (in HCVAD; decreased beta-carotene 15,15'-
FT monooxygenase activity; 90% decrease compared to wild-type;
FT decreased catalytic efficiency; no effect on affinity for
FT all-trans-beta-carotene; dbSNP:rs119478057)"
FT /evidence="ECO:0000269|PubMed:17951468"
FT /id="VAR_058112"
FT VARIANT 267
FT /note="R -> S (in dbSNP:rs12934922)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3"
FT /id="VAR_048406"
FT VARIANT 379
FT /note="A -> V (in dbSNP:rs7501331)"
FT /id="VAR_048407"
FT CONFLICT 302
FT /note="D -> G (in Ref. 2; BAA91776)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 547 AA; 62637 MW; F94BC8B01D56F9CB CRC64;
MDIIFGRNRK EQLEPVRAKV TGKIPAWLQG TLLRNGPGMH TVGESRYNHW FDGLALLHSF
TIRDGEVYYR SKYLRSDTYN TNIEANRIVV SEFGTMAYPD PCKNIFSKAF SYLSHTIPDF
TDNCLINIMK CGEDFYATSE TNYIRKINPQ TLETLEKVDY RKYVAVNLAT SHPHYDEAGN
VLNMGTSIVE KGKTKYVIFK IPATVPEGKK QGKSPWKHTE VFCSIPSRSL LSPSYYHSFG
VTENYVIFLE QPFRLDILKM ATAYIRRMSW ASCLAFHREE KTYIHIIDQR TRQPVQTKFY
TDAMVVFHHV NAYEEDGCIV FDVIAYEDNS LYQLFYLANL NQDFKENSRL TSVPTLRRFA
VPLHVDKNAE VGTNLIKVAS TTATALKEED GQVYCQPEFL YEGLELPRVN YAHNGKQYRY
VFATGVQWSP IPTKIIKYDI LTKSSLKWRE DDCWPAEPLF VPAPGAKDED DGVILSAIVS
TDPQKLPFLL ILDAKSFTEL ARASVDVDMH MDLHGLFITD MDWDTKKQAA SEEQRDRASD
CHGAPLT