CP26A_XENLA
ID CP26A_XENLA Reviewed; 492 AA.
AC O93323;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=Cytochrome P450 26A1;
DE EC=1.14.13.- {ECO:0000250|UniProtKB:O43174};
DE AltName: Full=Retinoic acid-converting enzyme;
DE Short=RACE;
DE AltName: Full=Retinoic acid-degrading enzyme CYP26;
DE Short=xCYP26 {ECO:0000303|PubMed:9857192};
GN Name=cyp26a1; Synonyms=cyp26;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INDUCTION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=9857192; DOI=10.1093/emboj/17.24.7361;
RA Hollemann T., Chen Y., Grunz H., Pieler T.;
RT "Regionalized metabolic activity establishes boundaries of retinoic acid
RT signalling.";
RL EMBO J. 17:7361-7372(1998).
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. May regulate
CC at-RA signaling during hindbrain development (PubMed:9857192).
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. Has no activity toward 9-cis
CC and 13-cis retinoic acid stereoisomers. May play a role in the
CC oxidative metabolism of xenobiotics such as tazarotenic acid (By
CC similarity). {ECO:0000250|UniProtKB:O43174,
CC ECO:0000269|PubMed:9857192}.
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:0000250|UniProtKB:O43174};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51493;
CC Evidence={ECO:0000250|UniProtKB:O43174};
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 -!- TISSUE SPECIFICITY: Expressed primarily in ovary, brain and eyes.
CC {ECO:0000269|PubMed:9857192}.
CC -!- DEVELOPMENTAL STAGE: At the onset of gastrulation, expressed within the
CC marginal zone and in the dorsal animal hemisphere. In advanced
CC gastrulae (stage 13), detected in the prospective neuroectoderm and the
CC underlying involuted mesoderm, in an area that corresponds to the
CC prechordal plate. At stage 14, expressed in the cement gland anlage,
CC the mid-/hindbrain boundary and the auditory placodes. At tadpole
CC stages of development, most prominent in the first, second and third
CC branchial arch, in the lens epithelium and in the posterior dorsal fin,
CC as well as in the posterior wall of the tail tip.
CC {ECO:0000269|PubMed:9857192}.
CC -!- INDUCTION: By retinoic acid. {ECO:0000269|PubMed:9857192}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AF057566; AAC25158.1; -; mRNA.
DR AlphaFoldDB; O93323; -.
DR SMR; O93323; -.
DR OMA; KLWEVYM; -.
DR Proteomes; UP000186698; 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:0008401; F:retinoic acid 4-hydroxylase activity; ISS:UniProtKB.
DR GO; GO:0042573; P:retinoic acid 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 2: Evidence at transcript 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_0000051984"
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"
SQ SEQUENCE 492 AA; 55460 MW; D1D4BB7651BF2D3E CRC64;
MDLYTLLTSA LCTLALPLLL LLTAAKLWEV YCLRRKDAAC ANPLPPGTMG LPFFGETLQM
VLQRRRFLQV KRSQYGRIYK THLFGSPTVR VTGAENVRQI LMGEHKLVSV HWPASVRTIL
GAGCLSNLHD NEHKYTKKVI AQAFSREALA NYVPQMEEEV RCSVNLWLQS GPCVLVYPAI
KRMMFRIAMR LLLGCDPQRM DREQEETLLE AFEEMSRNLF SLPIDVPFSG LYRGLRARNL
IHAQIEENIK EKLQREPDEH CKDALQLLID YSRRNGEPIN LQALKESATE LLFGGHGTTA
SAATSLTSFL ALHKDVLEKV RKELETQGLL STKPEEKKEL SIEVLQQLKY TSCVIKETLR
LSPPVAGGFR VALKTFVLNG YQIPKGWNVI YSIADTHGEA DLFPDTDKFN PDRFLTPLPR
DSSRFGFIPF GGGVRCCIGK EFAKILLKVF VVELCRNCDW ELLNGSPAMT TSPIICPVDN
LPAKFKPFSS SI
