ID CP26A_DANRE Reviewed; 492 AA.
AC P79739;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 27-MAR-2024, entry version 119.
DE RecName: Full=Cytochrome P450 26A1;
DE EC=1.14.13.- {ECO:0000269|PubMed:8939936};
DE AltName: Full=Cytochrome P450RAI;
DE AltName: Full=Retinoic acid 4-hydroxylase {ECO:0000303|PubMed:8939936};
DE AltName: Full=Retinoic acid-metabolizing cytochrome;
GN Name=cyp26a1; Synonyms=cyp26;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND INDUCTION.
RX PubMed=8939936; DOI=10.1074/jbc.271.47.29922;
RA White J.A., Guo Y.-D., Baetz K., Beckett-Jones B., Bonasoro J., Hsu K.E.,
RA Dilworth F.J., Jones G., Petkovich M.;
RT "Identification of the retinoic acid-inducible all-trans-retinoic acid 4-
RT hydroxylase.";
RL J. Biol. Chem. 271:29922-29927(1996).
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:8939936). 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:8939936). 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:8939936}.
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:8939936};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51493;
CC Evidence={ECO:0000305|PubMed:8939936};
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:8939936}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; U68234; AAC60045.1; -; mRNA.
DR AlphaFoldDB; P79739; -.
DR SMR; P79739; -.
DR STRING; 7955.ENSDARP00000041727; -.
DR SwissLipids; SLP:000001673; -.
DR PaxDb; 7955-ENSDARP00000041727; -.
DR AGR; ZFIN:ZDB-GENE-990415-44; -.
DR ZFIN; ZDB-GENE-990415-44; cyp26a1.
DR eggNOG; KOG0157; Eukaryota.
DR InParanoid; P79739; -.
DR Reactome; R-DRE-211916; Vitamins.
DR Reactome; R-DRE-5365859; RA biosynthesis pathway.
DR PRO; PR:P79739; -.
DR Proteomes; UP000000437; Genome assembly.
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:0008401; F:retinoic acid 4-hydroxylase activity; IDA:ZFIN.
DR GO; GO:0034672; P:anterior/posterior pattern specification involved in pronephros development; IMP:ZFIN.
DR GO; GO:0055014; P:atrial cardiac muscle cell development; IGI:ZFIN.
DR GO; GO:0001568; P:blood vessel development; IMP:ZFIN.
DR GO; GO:0048854; P:brain morphogenesis; IMP:ZFIN.
DR GO; GO:0071299; P:cellular response to vitamin A; IDA:ZFIN.
DR GO; GO:0021797; P:forebrain anterior/posterior pattern specification; IGI:ZFIN.
DR GO; GO:0007507; P:heart development; IMP:ZFIN.
DR GO; GO:0030902; P:hindbrain development; IMP:ZFIN.
DR GO; GO:0003131; P:mesodermal-endodermal cell signaling; IMP:ZFIN.
DR GO; GO:0030917; P:midbrain-hindbrain boundary development; IGI:ZFIN.
DR GO; GO:0003151; P:outflow tract morphogenesis; IGI:ZFIN.
DR GO; GO:0031016; P:pancreas development; IMP:ZFIN.
DR GO; GO:0042574; P:retinal metabolic process; IMP:ZFIN.
DR GO; GO:0034653; P:retinoic acid catabolic process; IMP:ZFIN.
DR GO; GO:0042573; P:retinoic acid metabolic process; IDA:ZFIN.
DR GO; GO:0090242; P:retinoic acid receptor signaling pathway involved in somitogenesis; IMP:ZFIN.
DR GO; GO:0021661; P:rhombomere 4 morphogenesis; IMP:ZFIN.
DR GO; GO:0001756; P:somitogenesis; IMP:ZFIN.
DR GO; GO:0016125; P:sterol metabolic process; IBA:GO_Central.
DR GO; GO:0001944; P:vasculature development; IGI:ZFIN.
DR Gene3D; 1.10.630.10; Cytochrome P450; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR PANTHER; PTHR24286; CYTOCHROME P450 26; 1.
DR PANTHER; PTHR24286:SF194; CYTOCHROME P450 26A1; 1.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; Cytochrome P450; 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_0000051983"
FT BINDING 438
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:0000250"
SQ SEQUENCE 492 AA; 56281 MW; FD471435B2F30509 CRC64;
MGLYTLMVTF LCTIVLPVLL FLAAVKLWEM LMIRRVDPNC RSPLPPGTMG LPFIGETLQL
ILQRRKFLRM KRQKYGCIYK THLFGNPTVR VMGADNVRQI LLGEHKLVSV QWPASVRTIL
GSDTLSNVHG VQHKNKKKAI MRAFSRDALE HYIPVIQQEV KSAIQEWLQK DSCVLVYPEM
KKLMFRIAMR ILLGFEPEQI KTDEQELVEA FEEMIKNLFS LPIDVPFSGL YRGLRARNFI
HSKIEENIRK KIQDDDNENE QKYKDALQLL IENSRRSDEP FSLQAMKEAA TELLFGGHET
TASTATSLVM FLGLNTEVVQ KVREEVQEKV EMGMYTPGKG LSMELLDQLK YTGCVIKETL
RINPPVPGGF RVALKTFELN GYQIPKGWNV IYSICDTHDV ADVFPNKEEF QPERFMSKGL
EDGSRFNYIP FGGGSRMCVG KEFAKVLLKI FLVELTQHCN WILSNGPPTM KTGPTIYPVD
NLPTKFTSYV RN
//
