ID   CP26A_CHICK             Reviewed;         492 AA.
AC   Q9PUB4; Q9PUG2;
DT   23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   03-AUG-2022, entry version 117.
DE   RecName: Full=Cytochrome P450 26A1;
DE            EC=1.14.13.- {ECO:0000269|PubMed:10588879};
DE   AltName: Full=Retinoic acid-degrading enzyme CYP26 {ECO:0000303|PubMed:10588879};
GN   Name=CYP26A1; Synonyms=CYP26;
OS   Gallus gallus (Chicken).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC   Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC   Phasianinae; Gallus.
OX   NCBI_TaxID=9031;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, INDUCTION, AND
RP   DEVELOPMENTAL STAGE.
RC   TISSUE=Embryonic spinal cord;
RX   PubMed=10588879; DOI=10.1006/dbio.1999.9487;
RA   Swindell E.C., Thaller C., Sockanathan S., Petkovich M., Jessell T.M.,
RA   Eichele G.;
RT   "Complementary domains of retinoic acid production and degradation in the
RT   early chick embryo.";
RL   Dev. Biol. 216:282-296(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 368-474.
RA   Martinez-Ceballos E., Burdsal C.A.;
RL   Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of
CC       all-trans retinoic acid (atRA), a signaling molecule that binds to
CC       retinoic acid receptors and regulates gene transcription
CC       (PubMed:10588879). Mechanistically, uses molecular oxygen inserting one
CC       oxygen atom into a substrate, and reducing the second into a water
CC       molecule, with two electrons provided by NADPH via cytochrome P450
CC       reductase (CPR; NADPH-ferrihemoprotein reductase). Catalyzes the
CC       hydroxylation of carbon hydrogen bonds of atRA primarily at C-4
CC       (PubMed:10588879). Has no activity toward 9-cis and 13-cis retinoic
CC       acid stereoisomers. May play a role in the oxidative metabolism of
CC       xenobiotics such as tazarotenic acid (By similarity).
CC       {ECO:0000250|UniProtKB:O43174, ECO:0000269|PubMed:10588879}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=all-trans-retinoate + O2 + reduced [NADPH--hemoprotein
CC         reductase] = all-trans-(4S)-hydroxyretinoate + H(+) + H2O + oxidized
CC         [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:51492, Rhea:RHEA-
CC         COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:35291,
CC         ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:134185;
CC         Evidence={ECO:0000269|PubMed:10588879};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51493;
CC         Evidence={ECO:0000305|PubMed:10588879};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:O43174}; Peripheral membrane protein. Microsome
CC       membrane {ECO:0000250|UniProtKB:O43174}; Peripheral membrane protein.
CC   -!- DEVELOPMENTAL STAGE: Expressed at stage 4 in the ectoderm, stage 5-7 in
CC       the nascent notochord and at stage 7 its expression decreases in the
CC       anterior part of the embryo. From stage 7-10 its expression is
CC       restricted to the dorsal folds of the neural tube and to rhombomere 2.
CC       At stage 10, it is expressed in the lateral plate endoderm and in the
CC       tail bud and by stage 11/12 it disappears in the neural tube, followed
CC       by a confined expression at stage 12 to dorsal neural tube and at stage
CC       15 an increasing expression in the ectoderm.
CC       {ECO:0000269|PubMed:10588879}.
CC   -!- INDUCTION: By retinoic acid. {ECO:0000269|PubMed:10588879}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; AF199462; AAF09250.1; -; mRNA.
DR   EMBL; AF185266; AAD56546.1; -; mRNA.
DR   RefSeq; NP_001001129.1; NM_001001129.1.
DR   AlphaFoldDB; Q9PUB4; -.
DR   SMR; Q9PUB4; -.
DR   STRING; 9031.ENSGALP00000010871; -.
DR   PaxDb; Q9PUB4; -.
DR   GeneID; 408183; -.
DR   KEGG; gga:408183; -.
DR   CTD; 1592; -.
DR   VEuPathDB; HostDB:geneid_408183; -.
DR   eggNOG; KOG0157; Eukaryota.
DR   InParanoid; Q9PUB4; -.
DR   OrthoDB; 871849at2759; -.
DR   PhylomeDB; Q9PUB4; -.
DR   PRO; PR:Q9PUB4; -.
DR   Proteomes; UP000000539; Unplaced.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0062182; F:all-trans retinoic acid 4-hydrolase activity; IEA:RHEA.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0004497; F:monooxygenase activity; IBA:GO_Central.
DR   GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR   GO; GO:0008401; F:retinoic acid 4-hydroxylase activity; IDA:UniProtKB.
DR   GO; GO:0034653; P:retinoic acid catabolic process; IDA:MGI.
DR   GO; GO:0016125; P:sterol metabolic process; IBA:GO_Central.
DR   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00465; EP450IV.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; SSF48264; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   1: Evidence at protein level;
KW   Endoplasmic reticulum; Heme; Iron; Lipid metabolism; Membrane;
KW   Metal-binding; Microsome; Monooxygenase; Oxidoreductase;
KW   Reference proteome.
FT   CHAIN           1..492
FT                   /note="Cytochrome P450 26A1"
FT                   /id="PRO_0000051982"
FT   BINDING         437
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        371
FT                   /note="I -> V (in Ref. 2; AAD56546)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        472..474
FT                   /note="GPI -> SPT (in Ref. 2; AAD56546)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   492 AA;  55265 MW;  7F28B72E75C232FB CRC64;
     MGFSALVASA LCTFLLPLLL FLAAVRLWDL YCASGRDPSC PLPLPPGTMG LPFFGETLQM
     VLQRRKFLQM KRRKYGFIYK THLFGRPTVR VMGAENVRHI LLGEHRLVSV QWPASVRTIL
     GSGCLSNLHN GQHKHRKKVI MQAFSRDALQ HYVPVIQEEV SACLAQWLGA GPCLLVYPEV
     KRLMFRIAMR ILLGFQPRQA SPDGEQQLVE AFEEMIRNLF SLPIDVPFSG LYRGLRARNI
     IHAKIEENIR AKMARKEPEG GYKDALQLLM EHTQGNGEQL NMQELKESAT ELLFGGHETT
     ASAATSLIAF LGLHHDVLQK VRKELQLKGL LSGPNQEKQL NMEFLEQLKY TGCVIKETLR
     LSPPVPGGFR IALKTLELNG YQIPKGWNVI YSICDTHDVA DLFTDKDEFN PDRFMSPSPE
     DSSRFSFIPF GGGLRSCVGK EFAKVLLKIF TVELARSCDW QLLNGPPTMK TGPIVYPVDN
     LPAKFIGFSG QI