ID   CP26A_HUMAN             Reviewed;         497 AA.
AC   O43174; Q5VXI0;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   16-DEC-2008, sequence version 2.
DT   03-NOV-2009, entry version 80.
DE   RecName: Full=Cytochrome P450 26A1;
DE            EC=1.14.-.-;
DE   AltName: Full=Retinoic acid-metabolizing cytochrome;
DE   AltName: Full=P450 retinoic acid-inactivating 1;
DE            Short=P450RAI;
DE            Short=hP450RAI;
DE   AltName: Full=Retinoic acid 4-hydroxylase;
GN   Name=CYP26A1; Synonyms=CYP26, P450RAI1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=97373542; PubMed=9228017; DOI=10.1074/jbc.272.30.18538;
RA   White J.A., Beckett-Jones B., Guo Y.-D., Dilworth F.J., Bonasoro J.,
RA   Jones G., Petkovich M.;
RT   "cDNA cloning of human retinoic acid-metabolizing enzyme (hP450RAI)
RT   identifies a novel family of cytochromes P450.";
RL   J. Biol. Chem. 272:18538-18541(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=98380037; PubMed=9716180;
RA   Sonneveld E., van den Brink C.E., van der Leede B.M., Schulkes R.K.,
RA   Petkovich M., van der Burg B., van der Saag P.T.;
RT   "Human retinoic acid (RA) 4-hydroxylase (CYP26) is highly specific for
RT   all-trans-RA and can be induced through RA receptors in human breast
RT   and colon carcinoma cells.";
RL   Cell Growth Differ. 9:629-637(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164054; DOI=10.1038/nature02462;
RA   Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA   Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA   Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA   Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA   Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA   Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA   Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA   Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA   Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA   Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA   Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA   Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA   Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA   Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA   Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA   Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA   Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA   Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA   Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA   Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA   Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA   Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA   Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA   Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 10.";
RL   Nature 429:375-381(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   TISSUE SPECIFICITY.
RX   MEDLINE=99045433; PubMed=9826557; DOI=10.1006/bbrc.1998.9659;
RA   Trofimova-Griffin M.E., Juchau M.R.;
RT   "Expression of cytochrome P450RAI (CYP26) in human fetal hepatic and
RT   cephalic tissues.";
RL   Biochem. Biophys. Res. Commun. 252:487-491(1998).
CC   -!- FUNCTION: Plays a key role in retinoic acid metabolism. Acts on
CC       retinoids, including all-trans-retinoic acid (RA) and its
CC       stereoisomer 9-cis-RA. Capable of both 4-hydroxylation and 18-
CC       hydroxylation. Responsible for generation of several hydroxylated
CC       forms of RA, including 4-OH-RA, 4-oxo-RA and 18-OH-RA.
CC   -!- COFACTOR: Heme group (By similarity).
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC       membrane protein. Microsome membrane; Peripheral membrane protein.
CC   -!- TISSUE SPECIFICITY: Highest levels in adult liver, heart,
CC       pituitary gland, adrenal gland, placenta and regions of the brain.
CC   -!- INDUCTION: By retinoic acid.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family.
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DR   EMBL; AF005418; AAB88881.1; -; mRNA.
DR   EMBL; AL358613; CAH72803.1; -; Genomic_DNA.
DR   EMBL; CH471066; EAW50079.1; -; Genomic_DNA.
DR   IPI; IPI00304967; -.
DR   RefSeq; NP_000774.2; -.
DR   UniGene; Hs.150595; -.
DR   HSSP; P14779; 1JPZ.
DR   STRING; O43174; -.
DR   PRIDE; O43174; -.
DR   Ensembl; ENST00000224356; ENSP00000224356; ENSG00000095596; Homo sapiens.
DR   Ensembl; ENST00000371531; ENSP00000360586; ENSG00000095596; Homo sapiens.
DR   Ensembl; ENST00000394139; ENSP00000377695; ENSG00000095596; Homo sapiens.
DR   GeneID; 1592; -.
DR   KEGG; hsa:1592; -.
DR   UCSC; uc001kil.2; human.
DR   CTD; 1592; -.
DR   GeneCards; GC10P094823; -.
DR   HGNC; HGNC:2603; CYP26A1.
DR   HPA; CAB015447; -.
DR   MIM; 602239; gene.
DR   PharmGKB; PA27098; -.
DR   HOGENOM; O43174; -.
DR   HOVERGEN; O43174; -.
DR   OMA; QRKKVIM; -.
DR   Reactome; REACT_13433; Biological oxidations.
DR   ArrayExpress; O43174; -.
DR   Bgee; O43174; -.
DR   CleanEx; HS_CYP26A1; -.
DR   Genevestigator; O43174; -.
DR   GermOnline; ENSG00000095596; Homo sapiens.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; EXP:Reactome.
DR   GO; GO:0019898; C:extrinsic to membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005792; C:microsome; IDA:UniProtKB.
DR   GO; GO:0009055; F:electron carrier activity; IEA:InterPro.
DR   GO; GO:0020037; F:heme binding; NAS:UniProtKB.
DR   GO; GO:0019825; F:oxygen binding; TAS:ProtInc.
DR   GO; GO:0008401; F:retinoic acid 4-hydroxylase activity; IDA:UniProtKB.
DR   GO; GO:0001972; F:retinoic acid binding; IDA:UniProtKB.
DR   GO; GO:0048387; P:negative regulation of retinoic acid recept...; TAS:UniProtKB.
DR   GO; GO:0055114; P:oxidation reduction; IEA:UniProtKB-KW.
DR   GO; GO:0034653; P:retinoic acid catabolic process; IDA:UniProtKB.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017973; Cyt_P450_C.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR   Gene3D; G3DSA:1.10.630.10; Cyt_P450; 1.
DR   PANTHER; PTHR19383; Cyt_P450; 1.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00465; EP450IV.
DR   PRINTS; PR00385; P450.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   1: Evidence at protein level;
KW   Complete proteome; Endoplasmic reticulum; Heme; Iron; Membrane;
KW   Metal-binding; Microsome; Monooxygenase; Oxidoreductase.
FT   CHAIN         1    497       Cytochrome P450 26A1.
FT                                /FTId=PRO_0000051980.
FT   METAL       442    442       Iron (heme axial ligand) (Potential).
FT   CONFLICT    104    105       EH -> DD (in Ref. 1; AAB88881).
SQ   SEQUENCE   497 AA;  56199 MW;  834318FA493E76D4 CRC64;
     MGLPALLASA LCTFVLPLLL FLAAIKLWDL YCVSGRDRSC ALPLPPGTMG FPFFGETLQM
     VLQRRKFLQM KRRKYGFIYK THLFGRPTVR VMGADNVRRI LLGEHRLVSV HWPASVRTIL
     GSGCLSNLHD SSHKQRKKVI MRAFSREALE CYVPVITEEV GSSLEQWLSC GERGLLVYPE
     VKRLMFRIAM RILLGCEPQL AGDGDSEQQL VEAFEEMTRN LFSLPIDVPF SGLYRGMKAR
     NLIHARIEQN IRAKICGLRA SEAGQGCKDA LQLLIEHSWE RGERLDMQAL KQSSTELLFG
     GHETTASAAT SLITYLGLYP HVLQKVREEL KSKGLLCKSN QDNKLDMEIL EQLKYIGCVI
     KETLRLNPPV PGGFRVALKT FELNGYQIPK GWNVIYSICD THDVAEIFTN KEEFNPDRFM
     LPHPEDASRF SFIPFGGGLR SCVGKEFAKI LLKIFTVELA RHCDWQLLNG PPTMKTSPTV
     YPVDNLPARF THFHGEI
//