Q9HAY6 (BCDO1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Beta,beta-carotene 15,15'-monooxygenase
EC=1.14.99.36

Alternative name(s):
Beta-carotene dioxygenase 1

Gene names

Name:	BCMO1
Synonyms:	BCDO, BCDO1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	547 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Symmetrically cleaves beta-carotene into two molecules of retinal. The reaction proceeds in three stages, epoxidation of the 15,15'-double bond, hydration of the double bond leading to ring opening, and oxidative cleavage of the diol formed.
Catalytic activity	Beta-carotene + O2 = 2 all-trans-retinal.
Cofactor	Binds 1 Fe2+ ion per subunit By similarity.
Pathway	Cofactor metabolism; retinol metabolism.
Tissue specificity	Highly expressed in retinal pigment epithelium. Also expressed in kidney, testis, liver, brain, small intestine and colon. Ref.1
Involvement in disease	Hypercarotenemia and vitamin A deficiency, autosomal dominant (ADHVAD) [MIM:115300]: A disorder characterized by increased serum beta-carotene, decreased conversion of beta-carotene to vitamin A and decreased serum vitamin A. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5
Sequence similarities	Belongs to the carotenoid oxygenase family.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	retinal metabolic process Non-traceable author statement PubMed 15983114. Source: BHF-UCL retinol metabolic process Inferred from electronic annotation. Source: UniProtKB-UniPathway steroid metabolic process Traceable author statement. Source: Reactome vitamin A biosynthetic process Non-traceable author statement PubMed 15983114. Source: BHF-UCL
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	beta-carotene 15,15'-monooxygenase activity Inferred from direct assay Ref.1. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW monooxygenase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 547	547	Beta,beta-carotene 15,15'-monooxygenase		PRO_0000143933
Sites
	Metal binding	172	1	Iron; catalytic By similarity
	Metal binding	237	1	Iron; catalytic By similarity
	Metal binding	308	1	Iron; catalytic By similarity
	Metal binding	514	1	Iron; catalytic By similarity
Natural variations
	Natural variant	170	1	T → M in ADHVAD; has about 90% decreased enzyme activity compared to wild-type; no evidence for a dominant-negative effect; consistent with a loss-of-function mutation resulting in haploinsufficiency. Ref.5		VAR_058112
	Natural variant	267	1	R → S. Ref.3 Ref.4 Corresponds to variant rs12934922 [ dbSNP | Ensembl ].		VAR_048406
	Natural variant	379	1	A → V. Corresponds to variant rs7501331 [ dbSNP | Ensembl ].		VAR_048407
Experimental info
	Sequence conflict	302	1	D → G in BAA91776. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9HAY6 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: F94BC8B01D56F9CB	FASTA	547	62,637
	10 20 30 40 50 60 MDIIFGRNRK EQLEPVRAKV TGKIPAWLQG TLLRNGPGMH TVGESRYNHW FDGLALLHSF 70 80 90 100 110 120 TIRDGEVYYR SKYLRSDTYN TNIEANRIVV SEFGTMAYPD PCKNIFSKAF SYLSHTIPDF 130 140 150 160 170 180 TDNCLINIMK CGEDFYATSE TNYIRKINPQ TLETLEKVDY RKYVAVNLAT SHPHYDEAGN 190 200 210 220 230 240 VLNMGTSIVE KGKTKYVIFK IPATVPEGKK QGKSPWKHTE VFCSIPSRSL LSPSYYHSFG 250 260 270 280 290 300 VTENYVIFLE QPFRLDILKM ATAYIRRMSW ASCLAFHREE KTYIHIIDQR TRQPVQTKFY 310 320 330 340 350 360 TDAMVVFHHV NAYEEDGCIV FDVIAYEDNS LYQLFYLANL NQDFKENSRL TSVPTLRRFA 370 380 390 400 410 420 VPLHVDKNAE VGTNLIKVAS TTATALKEED GQVYCQPEFL YEGLELPRVN YAHNGKQYRY 430 440 450 460 470 480 VFATGVQWSP IPTKIIKYDI LTKSSLKWRE DDCWPAEPLF VPAPGAKDED DGVILSAIVS 490 500 510 520 530 540 TDPQKLPFLL ILDAKSFTEL ARASVDVDMH MDLHGLFITD MDWDTKKQAA SEEQRDRASD CHGAPLT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of a human beta,beta-carotene-15,15-prime dioxygenase that is highly expressed in the retinal pigment epithelium." Yan W., Jang G.-F., Haeseleer F., Esumi N., Chang J., Kerrigan M., Campochiaro M., Campochiaro P., Palczewski K., Zack D.J. Genomics 72:193-202(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Retinal pigment epithelium.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT SER-267.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-267. Tissue: Colon.
[5]	"Loss-of-function mutation in carotenoid 15,15'-monooxygenase identified in a patient with hypercarotenemia and hypovitaminosis A." Lindqvist A., Sharvill J., Sharvill D.E., Andersson S. J. Nutr. 137:2346-2350(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ADHVAD MET-170.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF294900 mRNA. Translation: AAG15380.1. AK001592 mRNA. Translation: BAA91776.1. CH471114 Genomic DNA. Translation: EAW95537.1. BC126210 mRNA. Translation: AAI26211.1. BC126212 mRNA. Translation: AAI26213.1.
IPI	IPI00307216.
RefSeq	NP_059125.2. NM_017429.2.
UniGene	Hs.212172.
3D structure databases
ProteinModelPortal	Q9HAY6.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9HAY6. 1 interaction.
STRING	9606.ENSP00000258168.
PTM databases
PhosphoSite	Q9HAY6.
Polymorphism databases
DMDM	41688803.
Proteomic databases
PaxDb	Q9HAY6.
PRIDE	Q9HAY6.
Protocols and materials databases
DNASU	53630.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000258168; ENSP00000258168; ENSG00000135697.
GeneID	53630.
KEGG	hsa:53630.
UCSC	uc002fgn.1. human.
Organism-specific databases
CTD	53630.
GeneCards	GC16P081272.
HGNC	HGNC:13815. BCMO1.
HPA	HPA043811.
MIM	115300. phenotype. 605748. gene.
neXtProt	NX_Q9HAY6.
Orphanet	199285. Hereditary hypercarotenemia and vitamin A deficiency.
PharmGKB	PA37812.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG3670.
HOGENOM	HOG000232156.
HOVERGEN	HBG050679.
InParanoid	Q9HAY6.
KO	K00515.
OMA	ITENYIV.
OrthoDB	EOG4G7BZ5.
PhylomeDB	Q9HAY6.
Enzyme and pathway databases
BioCyc	MetaCyc:HS06050-MONOMER.
Reactome	REACT_111217. Metabolism.
SABIO-RK	Q9HAY6.
UniPathway	UPA00912.
Gene expression databases
ArrayExpress	Q9HAY6.
Bgee	Q9HAY6.
CleanEx	HS_BCMO1.
Genevestigator	Q9HAY6.
GermOnline	ENSG00000135697. Homo sapiens.
Family and domain databases
InterPro	IPR004294. Carotenoid_Oase. [Graphical view]
PANTHER	PTHR10543. PTHR10543. 1 hit.
Pfam	PF03055. RPE65. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	BCMO1. human.
GenomeRNAi	53630.
NextBio	56108.
SOURCE	Search...

Entry information

Entry name

BCDO1_HUMAN

Accession

Primary (citable) accession number: Q9HAY6
Secondary accession number(s): A0AV48, A0AV50, Q9NVH5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 10, 2003
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.