CP26A_MOUSE
ID CP26A_MOUSE Reviewed; 497 AA.
AC O55127; Q9R1F4;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Cytochrome P450 26A1;
DE EC=1.14.13.- {ECO:0000269|PubMed:9250660, ECO:0000269|PubMed:9442090};
DE AltName: Full=Cytochrome P450RAI {ECO:0000303|PubMed:9442090};
DE AltName: Full=Retinoic acid 4-hydroxylase {ECO:0000303|PubMed:9442090};
DE AltName: Full=Retinoic acid-metabolizing cytochrome {ECO:0000303|PubMed:9442090};
GN Name=Cyp26a1 {ECO:0000312|MGI:MGI:1096359}; Synonyms=Cyp26, P450ra;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND INDUCTION.
RC STRAIN=C3H/HeJ;
RX PubMed=9250660; DOI=10.1093/emboj/16.14.4163;
RA Fujii H., Sato T., Kaneko S., Gotoh O., Fujii-Kuriyama Y., Osawa K.,
RA Kato S., Hamada H.;
RT "Metabolic inactivation of retinoic acid by a novel P450 differentially
RT expressed in developing mouse embryos.";
RL EMBO J. 16:4163-4173(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND INDUCTION.
RX PubMed=9442090; DOI=10.1074/jbc.273.4.2409;
RA Abu-Abed S.S., Beckett B.R., Chiba H., Chithalen J.V., Jones G.,
RA Metzger D., Chambon P., Petkovich M.;
RT "Mouse P450RAI (CYP26) expression and retinoic acid-inducible retinoic acid
RT metabolism in F9 cells are regulated by retinoic acid receptor gamma and
RT retinoid X receptor alpha.";
RL J. Biol. Chem. 273:2409-2415(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Tooth;
RX PubMed=11063033; DOI=10.3109/03008209809017046;
RA Paine C.T., Paine M.L., Snead M.L.;
RT "Identification of tuftelin- and amelogenin-interacting proteins using the
RT yeast two-hybrid system.";
RL Connect. Tissue Res. 38:257-267(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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).
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 Mechanistically, uses molecular oxygen inserting one oxygen atom into a
CC substrate, and reducing the second into a water molecule, with two
CC electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-
CC ferrihemoprotein reductase). Catalyzes the hydroxylation of carbon
CC hydrogen bonds of atRA primarily at C-4 and C-18 (PubMed:9250660,
CC PubMed:9442090). Has no activity toward 9-cis and 13-cis retinoic acid
CC 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:9250660,
CC ECO:0000269|PubMed:9442090}.
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:9250660, ECO:0000269|PubMed:9442090};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51493;
CC Evidence={ECO:0000305|PubMed:9250660, ECO:0000305|PubMed:9442090};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-(4S)-hydroxyretinoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = all-trans-(4S,16)-dihydroxyretinoate + H(+)
CC + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:51632, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:134185,
CC ChEBI:CHEBI:134233; Evidence={ECO:0000250|UniProtKB:O43174};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51633;
CC Evidence={ECO:0000250|UniProtKB:O43174};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinoate + O2 + reduced [NADPH--hemoprotein
CC reductase] = all-trans-18-hydroxyretinoate + H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:55856, 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:139258;
CC Evidence={ECO:0000269|PubMed:9442090};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55857;
CC Evidence={ECO:0000305|PubMed:9442090};
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 -!- INDUCTION: By retinoic acid. {ECO:0000269|PubMed:9250660,
CC ECO:0000269|PubMed:9442090}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; Y12657; CAA73206.1; -; mRNA.
DR EMBL; AF115769; AAD17217.1; -; mRNA.
DR EMBL; BC012673; AAH12673.1; -; mRNA.
DR CCDS; CCDS29780.1; -.
DR RefSeq; NP_031837.2; NM_007811.2.
DR AlphaFoldDB; O55127; -.
DR SMR; O55127; -.
DR STRING; 10090.ENSMUSP00000025946; -.
DR iPTMnet; O55127; -.
DR PhosphoSitePlus; O55127; -.
DR MaxQB; O55127; -.
DR PaxDb; O55127; -.
DR PRIDE; O55127; -.
DR ProteomicsDB; 283439; -.
DR GeneID; 13082; -.
DR KEGG; mmu:13082; -.
DR UCSC; uc008his.2; mouse.
DR CTD; 1592; -.
DR MGI; MGI:1096359; Cyp26a1.
DR eggNOG; KOG0157; Eukaryota.
DR InParanoid; O55127; -.
DR OrthoDB; 871849at2759; -.
DR PhylomeDB; O55127; -.
DR TreeFam; TF105093; -.
DR Reactome; R-MMU-211916; Vitamins.
DR Reactome; R-MMU-5365859; RA biosynthesis pathway.
DR BioGRID-ORCS; 13082; 5 hits in 78 CRISPR screens.
DR PRO; PR:O55127; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O55127; protein.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0062183; F:all-trans retinoic acid 18-hydroxylase activity; ISO:MGI.
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:0016709; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen; ISS:UniProtKB.
DR GO; GO:0008401; F:retinoic acid 4-hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0001972; F:retinoic acid binding; ISO:MGI.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IMP:MGI.
DR GO; GO:0071300; P:cellular response to retinoic acid; IEP:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; IMP:MGI.
DR GO; GO:0014032; P:neural crest cell development; IGI:MGI.
DR GO; GO:0034653; P:retinoic acid catabolic process; IDA:MGI.
DR GO; GO:0042573; P:retinoic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; IDA:MGI.
DR GO; GO:0016125; P:sterol metabolic process; IBA:GO_Central.
DR GO; GO:0006805; P:xenobiotic metabolic process; ISS:UniProtKB.
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..497
FT /note="Cytochrome P450 26A1"
FT /id="PRO_0000051981"
FT BINDING 442
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 9
FT /note="S -> T (in Ref. 3; AAD17217)"
FT /evidence="ECO:0000305"
FT CONFLICT 154
FT /note="L -> P (in Ref. 4; AAH12673)"
FT /evidence="ECO:0000305"
FT CONFLICT 356
FT /note="I -> T (in Ref. 4; AAH12673)"
FT /evidence="ECO:0000305"
FT CONFLICT 492
FT /note="Y -> H (in Ref. 4; AAH12673)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 497 AA; 56178 MW; 33B07D7C29134471 CRC64;
MGLPALLASA LCTFVLPLLL FLAALKLWDL YCVSSRDRSC ALPLPPGTMG FPFFGETLQM
VLQRRKFLQM KRRKYGFIYK THLFGRPTVR VMGADNVRRI LLGEHRLVSV HWPASVRTIL
GAGCLSNLHD SSHKQRKKVI MQAFSREALQ CYVLVIAEEV SSCLEQWLSC GERGLLVYPE
VKRLMFRIAM RILLGCEPGP AGGGEDEQQL VEAFEEMTRN LFSLPIDVPF SGLYRGVKAR
NLIHARIEEN IRAKIRRLQA TEPDGGCKDA LQLLIEHSWE RGERLDMQAL KQSSTELLFG
GHETTASAAT SLITYLGLYP HVLQKVREEI KSKGLLCKSN QDNKLDMETL EQLKYIGCVI
KETLRLNPPV PGGFRVALKT FELNGYQIPK GWNVIYSICD THDVADIFTN KEEFNPDRFI
VPHPEDASRF SFIPFGGGLR SCVGKEFAKI LLKIFTVELA RHCDWQLLNG PPTMKTSPTV
YPVDNLPARF TYFQGDI
