CP2J4_RAT
ID CP2J4_RAT Reviewed; 501 AA.
AC Q9QXF7;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Cytochrome P450 2J4;
DE EC=1.14.14.1 {ECO:0000269|PubMed:9143331};
DE AltName: Full=CYPIIJ4;
GN Name=CYP2J4 {ECO:0000303|PubMed:9143331};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Intestinal mucosa;
RX PubMed=9143331; DOI=10.1006/abbi.1997.9922;
RA Zhang Q.Y., Ding X., Kaminsky L.S.;
RT "CDNA cloning, heterologous expression, and characterization of rat
RT intestinal CYP2J4.";
RL Arch. Biochem. Biophys. 340:270-278(1997).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9606960; DOI=10.1006/abbi.1998.0654;
RA Zhang Q.Y., Raner G., Ding X., Dunbar D., Coon M.J., Kaminsky L.S.;
RT "Characterization of the cytochrome P450 CYP2J4: expression in rat small
RT intestine and role in retinoic acid biotransformation from retinal.";
RL Arch. Biochem. Biophys. 353:257-264(1998).
CC -!- FUNCTION: A cytochrome P450 monooxygenase that may play a major role in
CC intestinal retinoid metabolism. Catalyzes the oxidative transformation
CC of all-trans retinal and 9-cis-retinal to the corresponding active
CC forms all-trans and 9-cis retinoic acids (PubMed:9606960). Catalyzes
CC the hydroxylation of carbon-hydrogen bonds. Hydroxylates arachidonic
CC acid predominantly at the omega-1 position (PubMed:9143331).
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 hemoprotein reductase) (PubMed:9143331, PubMed:9606960).
CC {ECO:0000269|PubMed:9143331, ECO:0000269|PubMed:9606960}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein
CC reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:142491; EC=1.14.14.1;
CC Evidence={ECO:0000269|PubMed:9143331};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150;
CC Evidence={ECO:0000305|PubMed:9143331};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:39759, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:76627; Evidence={ECO:0000269|PubMed:9143331};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39760;
CC Evidence={ECO:0000305|PubMed:9143331};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinal + O2 + reduced [NADPH--hemoprotein
CC reductase] = all-trans-retinoate + 2 H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:42088, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17898, ChEBI:CHEBI:35291,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:9606960};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42089;
CC Evidence={ECO:0000305|PubMed:9606960};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=9-cis-retinal + O2 + reduced [NADPH--hemoprotein reductase] =
CC 9-cis-retinoate + 2 H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:65524, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:78273,
CC ChEBI:CHEBI:78630; Evidence={ECO:0000269|PubMed:9606960};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65525;
CC Evidence={ECO:0000305|PubMed:9606960};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P33261};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=49 uM for 9-cis-retinal {ECO:0000269|PubMed:9606960};
CC KM=54 uM for all-trans-retinal {ECO:0000269|PubMed:9606960};
CC Vmax=21 nmol/min/nmol enzyme toward 9-cis-retinal
CC {ECO:0000269|PubMed:9606960};
CC Vmax=20 nmol/min/nmol enzyme toward all-trans-retinal
CC {ECO:0000269|PubMed:9606960};
CC -!- PATHWAY: Lipid metabolism; arachidonate metabolism.
CC {ECO:0000305|PubMed:9143331}.
CC -!- PATHWAY: Cofactor metabolism; retinol metabolism.
CC {ECO:0000305|PubMed:9606960}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:9143331, ECO:0000269|PubMed:9606960}; Multi-pass
CC membrane protein {ECO:0000255}. Microsome membrane
CC {ECO:0000269|PubMed:9143331, ECO:0000269|PubMed:9606960}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in small intestinal enterocytes (at
CC protein level) (PubMed:9143331). In the intestinal crypt, expressed at
CC higher levels in the mature villous cells than in undifferentiated
CC crypt cells (at protein level) (PubMed:9143331, PubMed:9606960).
CC Expressed in liver, kidney, lung, and olfactory mucosa (at protein
CC level) (PubMed:9143331). {ECO:0000269|PubMed:9143331,
CC ECO:0000269|PubMed:9606960}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; L81170; AAF21133.1; -; mRNA.
DR AlphaFoldDB; Q9QXF7; -.
DR SMR; Q9QXF7; -.
DR SwissLipids; SLP:000001680; -.
DR UCSC; RGD:620007; rat.
DR PhylomeDB; Q9QXF7; -.
DR UniPathway; UPA00383; -.
DR UniPathway; UPA00912; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0008391; F:arachidonic acid monooxygenase activity; IDA:UniProtKB.
DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0042572; P:retinol metabolic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR008071; Cyt_P450_E_grp-I_CYP2J-like.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR01688; EP450ICYP2J.
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; Transmembrane; Transmembrane helix.
FT CHAIN 1..501
FT /note="Cytochrome P450 2J4"
FT /id="PRO_0000451769"
FT TRANSMEM 12..32
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 77..97
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 447
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|UniProtKB:P33261"
SQ SEQUENCE 501 AA; 57878 MW; E109044023024DCC CRC64;
MLATAGSLIA TIWAALHLRT LLVAALTFLL LADYFKTRRP KNYPPGPWGL PFVGNIFQLD
FGQPHLSIQP FVKKYGNIFS LNLGDITSVV ITGLPLIKET FTHIEQNILN RPLSVMQERI
TNKNGLIFSS GQTWKEQRRF ALMTLRNFGL GKKSLEQRMQ EEAHYLVEAI REEKGKPFNP
HFSINNAVSN IICSVTFGER FEYHDSRFQE MLRLLDEVMY LETTMISQLY NIFPWIMKYI
PGSHQTVFRN WEKLKLFVSS MIDDHRKDWN PEEPRDFIDA FLKEMSKYPE KTTSFNEENL
ICSTLDLFFA GTETTSTTLR WALLYMALYP EVQEKVQAEI DRVIGQKRAA SLADRESMPY
TNAVIHEVQR MGNIIPLNVP REVAMDTTLN GFHLPKGTMV LTNLTALHRD PKEWATPDVF
NPEHFLENGQ FKKRESFLPF SMGKRACLGE QLARSELFIF FTSLMQKFTF KPPTNEKLSL
KFRNGLTLSP VTHRICAVPR E
