Q9BYV7 (BCDO2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Beta,beta-carotene 9',10'-oxygenase
EC=1.13.11.71

Alternative name(s):
B-diox-II
Beta-carotene dioxygenase 2

Gene names

Name:	BCO2
Synonyms:	BCDO2

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	579 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Asymmetrically cleaves beta-carotene at the 9',10' double bond resulting in the formation of beta-apo-10'-carotenal and beta-ionone. Besides beta-carotene, lycopene is also oxidatively cleaved. The apocarotenals formed by this enzyme may be the precursors for the biosynthesis of retinoic acid or exert unknown physiological effects. Ref.7
Catalytic activity	All-trans-beta-carotene + O2 = all-trans-10'-apo-beta-carotenal + beta-ionone.
Cofactor	Binds 1 Fe2+ ion per subunit By similarity.
Subcellular location	Mitochondrion Ref.7.
Tissue specificity	Highly expressed in retinal pigment epithelium. Also expressed in stomach, small intestine, liver, testis, kidney, adrenal gland, pancreas, heart, skeletal muscle and prostate (at protein level). Ref.6
Sequence similarities	Belongs to the carotenoid oxygenase family.
Sequence caution	The sequence CAC27994.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Iron Metal-binding
Molecular function	Dioxygenase Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	carotene catabolic process Inferred from direct assay PubMed 21302131. Source: BHF-UCL carotenoid metabolic process Inferred from sequence or structural similarity Ref.7. Source: BHF-UCL regulation of mitochondrial membrane potential Inferred from sequence or structural similarity Ref.7. Source: BHF-UCL regulation of reactive oxygen species metabolic process Inferred from sequence or structural similarity Ref.7. Source: BHF-UCL retinal metabolic process Non-traceable author statement Ref.5. Source: UniProtKB retinoic acid metabolic process Non-traceable author statement Ref.5. Source: UniProtKB
Cellular_component	mitochondrion Inferred from sequence or structural similarity Ref.7. Source: BHF-UCL
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Inferred from direct assay Ref.5. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9BYV7-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9BYV7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: Missing.

Note: No experimental confirmation available.

Isoform 4 (identifier: Q9BYV7-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: Missing.
     501-506: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 579	579	Beta,beta-carotene 9',10'-oxygenase		PRO_0000143937
Sites
	Metal binding	226	1	Iron; catalytic By similarity
	Metal binding	286	1	Iron; catalytic By similarity
	Metal binding	357	1	Iron; catalytic By similarity
	Metal binding	573	1	Iron; catalytic By similarity
Natural variations
	Alternative sequence	1 – 34	34	Missing in isoform 2 and isoform 4.		VSP_008599
	Alternative sequence	501 – 506	6	Missing in isoform 4.		VSP_008600
	Natural variant	231	1	L → P. Ref.1 Ref.2 Ref.5 Corresponds to variant rs10891338 [ dbSNP | Ensembl ].		VAR_047047
	Natural variant	289	1	G → E. Corresponds to variant rs17113607 [ dbSNP | Ensembl ].		VAR_047048
	Natural variant	548	1	I → L. Ref.1 Ref.2 Ref.5 Corresponds to variant rs2217401 [ dbSNP | Ensembl ].		VAR_047049
Experimental info
	Sequence conflict	26	1	H → Y in CAC27994. Ref.5
	Sequence conflict	177	1	N → D in CAC27994. Ref.5
	Sequence conflict	258	1	K → E in CAC27994. Ref.5
	Sequence conflict	446	1	W → C in CAC27994. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 5, 2010. Version 5. Checksum: B14F54FCEC1092CE	FASTA	579	65,674
	10 20 30 40 50 60 MFFRVFLHFI RSHSATAVDF LPVMVHRLPV FKRYMGNTPQ KKAVFGQCRG LPCVAPLLTT 70 80 90 100 110 120 VEEAPRGISA RVWGHFPKWL NGSLLRIGPG KFEFGKDKYN HWFDGMALLH QFRMAKGTVT 130 140 150 160 170 180 YRSKFLQSDT YKANSAKNRI VISEFGTLAL PDPCKNVFER FMSRFELPGK AAAMTDNTNV 190 200 210 220 230 240 NYVRYKGDYY LCTETNFMNK VDIETLEKTE KVDWSKFIAV NGATAHPHYD LDGTAYNMGN 250 260 270 280 290 300 SFGPYGFSYK VIRVPPEKVD LGETIHGVQV ICSIASTEKG KPSYYHSFGM TRNYIIFIEQ 310 320 330 340 350 360 PLKMNLWKIA TSKIRGKAFS DGISWEPQCN TRFHVVEKRT GQLLPGRYYS KPFVTFHQIN 370 380 390 400 410 420 AFEDQGCVII DLCCQDNGRT LEVYQLQNLR KAGEGLDQVH NSAAKSFPRR FVLPLNVSLN 430 440 450 460 470 480 APEGDNLSPL SYTSASAVKQ ADGTIWCSHE NLHQEDLEKE GGIEFPQIYY DRFSGKKYHF 490 500 510 520 530 540 FYGCGFRHLV GDSLIKVDVV NKTLKVWRED GFYPSEPVFV PAPGTNEEDG GVILSVVITP 550 560 570 NQNESNFILV LDAKNFEELG RAEVPVQMPY GFHGTFIPI
	Isoform 2 [UniParc]. Checksum: E09F77FEBB534B65	FASTA	545	61,526
	10 20 30 40 50 60 MGNTPQKKAV FGQCRGLPCV APLLTTVEEA PRGISARVWG HFPKWLNGSL LRIGPGKFEF 70 80 90 100 110 120 GKDKYNHWFD GMALLHQFRM AKGTVTYRSK FLQSDTYKAN SAKNRIVISE FGTLALPDPC 130 140 150 160 170 180 KNVFERFMSR FELPGKAAAM TDNTNVNYVR YKGDYYLCTE TNFMNKVDIE TLEKTEKVDW 190 200 210 220 230 240 SKFIAVNGAT AHPHYDLDGT AYNMGNSFGP YGFSYKVIRV PPEKVDLGET IHGVQVICSI 250 260 270 280 290 300 ASTEKGKPSY YHSFGMTRNY IIFIEQPLKM NLWKIATSKI RGKAFSDGIS WEPQCNTRFH 310 320 330 340 350 360 VVEKRTGQLL PGRYYSKPFV TFHQINAFED QGCVIIDLCC QDNGRTLEVY QLQNLRKAGE 370 380 390 400 410 420 GLDQVHNSAA KSFPRRFVLP LNVSLNAPEG DNLSPLSYTS ASAVKQADGT IWCSHENLHQ 430 440 450 460 470 480 EDLEKEGGIE FPQIYYDRFS GKKYHFFYGC GFRHLVGDSL IKVDVVNKTL KVWREDGFYP 490 500 510 520 530 540 SEPVFVPAPG TNEEDGGVIL SVVITPNQNE SNFILVLDAK NFEELGRAEV PVQMPYGFHG TFIPI
	Isoform 4 [UniParc]. Checksum: DD12ACD19DD37669	FASTA	539	60,842
	10 20 30 40 50 60 MGNTPQKKAV FGQCRGLPCV APLLTTVEEA PRGISARVWG HFPKWLNGSL LRIGPGKFEF 70 80 90 100 110 120 GKDKYNHWFD GMALLHQFRM AKGTVTYRSK FLQSDTYKAN SAKNRIVISE FGTLALPDPC 130 140 150 160 170 180 KNVFERFMSR FELPGKAAAM TDNTNVNYVR YKGDYYLCTE TNFMNKVDIE TLEKTEKVDW 190 200 210 220 230 240 SKFIAVNGAT AHPHYDLDGT AYNMGNSFGP YGFSYKVIRV PPEKVDLGET IHGVQVICSI 250 260 270 280 290 300 ASTEKGKPSY YHSFGMTRNY IIFIEQPLKM NLWKIATSKI RGKAFSDGIS WEPQCNTRFH 310 320 330 340 350 360 VVEKRTGQLL PGRYYSKPFV TFHQINAFED QGCVIIDLCC QDNGRTLEVY QLQNLRKAGE 370 380 390 400 410 420 GLDQVHNSAA KSFPRRFVLP LNVSLNAPEG DNLSPLSYTS ASAVKQADGT IWCSHENLHQ 430 440 450 460 470 480 EDLEKEGGIE FPQIYYDRFS GKKYHFFYGC GFRHLVGDSL IKVDVVWRED GFYPSEPVFV 490 500 510 520 530 PAPGTNEEDG GVILSVVITP NQNESNFILV LDAKNFEELG RAEVPVQMPY GFHGTFIPI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"An ortholog of the human retinal pigment epithelium protein RPE65." Cunningham F.X. Jr. Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANTS PRO-231 AND LEU-548. Tissue: Uterus.
[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] (ISOFORM 4), VARIANTS PRO-231 AND LEU-548. Tissue: Placenta.
[3]	NHLBI resequencing and genotyping service (RS&G) Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Identification and characterization of a mammalian enzyme catalyzing the asymmetric oxidative cleavage of provitamin A." Kiefer C., Hessel S., Lampert J.M., Vogt K., Lederer M.O., Breithaupt D.E., von Lintig J. J. Biol. Chem. 276:14110-14116(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 17-579 (ISOFORM 1), VARIANTS PRO-231 AND LEU-548. Tissue: Liver.
[6]	"Cell type-specific expression of beta-carotene 9',10'-monooxygenase in human tissues." Lindqvist A., He Y.-G., Andersson S. J. Histochem. Cytochem. 53:1403-1412(2005) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"A mitochondrial enzyme degrades carotenoids and protects against oxidative stress." Amengual J., Lobo G.P., Golczak M., Li H.N., Klimova T., Hoppel C.L., Wyss A., Palczewski K., von Lintig J. FASEB J. 25:948-959(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF276432 mRNA. Translation: AAK69433.1. AK027801 mRNA. Translation: BAB55379.1. EF444956 Genomic DNA. Translation: ACA05952.1. AP002884 Genomic DNA. No translation available. AJ290393 mRNA. Translation: CAC27994.1. Different initiation.
IPI	IPI00472555. IPI00479961. IPI00978312.
RefSeq	NP_001032367.2. NM_001037290.2. NP_001243326.1. NM_001256397.1.
UniGene	Hs.728325.
3D structure databases
ProteinModelPortal	Q9BYV7.
SMR	Q9BYV7. Positions 57-576.
ModBase	Search...
PTM databases
PhosphoSite	Q9BYV7.
Polymorphism databases
DMDM	308153680.
Proteomic databases
PaxDb	Q9BYV7.
PRIDE	Q9BYV7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000357685; ENSP00000350314; ENSG00000197580. ENST00000393032; ENSP00000376752; ENSG00000197580. ENST00000438022; ENSP00000414843; ENSG00000197580. ENST00000526088; ENSP00000436615; ENSG00000197580. ENST00000531169; ENSP00000437053; ENSG00000197580.
GeneID	83875.
KEGG	hsa:83875.
UCSC	uc001pne.1. human. uc009yyn.3. human.
Organism-specific databases
CTD	83875.
GeneCards	GC11P112046.
HGNC	HGNC:18503. BCO2.
HPA	HPA039825. HPA040695.
MIM	611740. gene.
neXtProt	NX_Q9BYV7.
PharmGKB	PA162377424.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG3670.
HOGENOM	HOG000232156.
HOVERGEN	HBG050679.
InParanoid	Q9BYV7.
KO	K10252.
OMA	VSLNAPE.
OrthoDB	EOG45B1FD.
Enzyme and pathway databases
BioCyc	MetaCyc:G66-33846-MONOMER.
Gene expression databases
ArrayExpress	Q9BYV7.
Bgee	Q9BYV7.
CleanEx	HS_BCO2.
Genevestigator	Q9BYV7.
GermOnline	ENSG00000197580. 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	BCO2. human.
GenomeRNAi	83875.
NextBio	72911.
SOURCE	Search...

Entry information

Entry name

BCDO2_HUMAN

Accession

Primary (citable) accession number: Q9BYV7
Secondary accession number(s): B0YIX5, Q96JC8, Q96JY5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 10, 2003
Last sequence update:	October 5, 2010
Last modified:	May 1, 2013
This is version 101 of the entry and version 5 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.