CP4V2_RAT
ID CP4V2_RAT Reviewed; 525 AA.
AC A2RRT9;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Cytochrome P450 4V2;
DE AltName: Full=Docosahexaenoic acid omega-hydroxylase CYP4V2 {ECO:0000250|UniProtKB:Q6ZWL3};
DE EC=1.14.14.79 {ECO:0000250|UniProtKB:Q6ZWL3};
DE AltName: Full=Long-chain fatty acid omega-monooxygenase {ECO:0000250|UniProtKB:Q6ZWL3};
DE EC=1.14.14.80 {ECO:0000250|UniProtKB:Q6ZWL3};
GN Name=Cyp4v2; Synonyms=Cyp4v3;
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] {ECO:0000312|EMBL:AAI31847.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung {ECO:0000312|EMBL:AAI31847.1};
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 fatty acid
CC metabolism in the eye. Catalyzes the omega-hydroxylation of
CC polyunsaturated fatty acids (PUFAs) docosahexaenoate (DHA) and its
CC precursor eicosapentaenoate (EPA), and may contribute to the
CC homeostasis of these retinal PUFAs. Omega hydroxylates saturated fatty
CC acids such as laurate, myristate and palmitate, the catalytic
CC efficiency decreasing in the following order: myristate > laurate >
CC palmitate (C14>C12>C16). Mechanistically, uses molecular oxygen
CC inserting one oxygen atom into a substrate, and reducing the second
CC into a water molecule, with two electrons provided by NADPH via
CC cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase).
CC {ECO:0000250|UniProtKB:Q6ZWL3}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoate + O2 + reduced [NADPH--hemoprotein reductase] =
CC 12-hydroxydodecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:38947, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:18262, ChEBI:CHEBI:36204, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; Evidence={ECO:0000250|UniProtKB:Q6ZWL3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38948;
CC Evidence={ECO:0000250|UniProtKB:Q6ZWL3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + reduced [NADPH--hemoprotein reductase] + tetradecanoate =
CC 14-hydroxytetradecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:40203, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30807, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:77033; Evidence={ECO:0000250|UniProtKB:Q6ZWL3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40204;
CC Evidence={ECO:0000250|UniProtKB:Q6ZWL3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoate + O2 + reduced [NADPH--hemoprotein reductase] =
CC 16-hydroxyhexadecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:40199, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:55329, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.80;
CC Evidence={ECO:0000250|UniProtKB:Q6ZWL3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40200;
CC Evidence={ECO:0000250|UniProtKB:Q6ZWL3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 20-hydroxy-(5Z,8Z,11Z,14Z,17Z)-
CC eicosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:39791, 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:58562,
CC ChEBI:CHEBI:76639; Evidence={ECO:0000250|UniProtKB:Q6ZWL3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39792;
CC Evidence={ECO:0000250|UniProtKB:Q6ZWL3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced
CC [NADPH--hemoprotein reductase] = 22-hydroxy-(4Z,7Z,10Z,13Z,16Z,19Z)-
CC docosahexaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:40155, 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:77015,
CC ChEBI:CHEBI:77016; EC=1.14.14.79;
CC Evidence={ECO:0000250|UniProtKB:Q6ZWL3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40156;
CC Evidence={ECO:0000250|UniProtKB:Q6ZWL3};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P51869};
CC -!- ACTIVITY REGULATION: Inhibited by N-hydroxy-N'-(4-n-butyl-2-
CC methylphenyl formamidine)(HET0016) with an IC(50) of 38 nM.
CC {ECO:0000250|UniProtKB:Q6ZWL3}.
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC {ECO:0000250|UniProtKB:Q6ZWL3}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q6ZWL3}; Single-pass membrane protein
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000255}.
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DR EMBL; BC131846; AAI31847.1; -; mRNA.
DR RefSeq; NP_001129072.1; NM_001135600.1.
DR AlphaFoldDB; A2RRT9; -.
DR SMR; A2RRT9; -.
DR STRING; 10116.ENSRNOP00000019302; -.
DR PaxDb; A2RRT9; -.
DR PeptideAtlas; A2RRT9; -.
DR PRIDE; A2RRT9; -.
DR Ensembl; ENSRNOT00000019302; ENSRNOP00000019302; ENSRNOG00000042426.
DR GeneID; 266761; -.
DR KEGG; rno:266761; -.
DR CTD; 102294; -.
DR RGD; 708530; Cyp4v3.
DR eggNOG; KOG0157; Eukaryota.
DR GeneTree; ENSGT00940000157278; -.
DR HOGENOM; CLU_001570_5_1_1; -.
DR InParanoid; A2RRT9; -.
DR OMA; IFRRMKM; -.
DR OrthoDB; 1247045at2759; -.
DR PhylomeDB; A2RRT9; -.
DR TreeFam; TF105088; -.
DR Reactome; R-RNO-211976; Endogenous sterols.
DR Reactome; R-RNO-2453902; The canonical retinoid cycle in rods (twilight vision).
DR UniPathway; UPA00199; -.
DR PRO; PR:A2RRT9; -.
DR Proteomes; UP000002494; Chromosome 16.
DR Bgee; ENSRNOG00000042426; Expressed in liver and 19 other tissues.
DR Genevisible; A2RRT9; RN.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0102033; F:long-chain fatty acid omega-hydroxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0010430; P:fatty acid omega-oxidation; ISS:UniProtKB.
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; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
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; Monooxygenase; NADP; Oxidoreductase; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..525
FT /note="Cytochrome P450 4V2"
FT /id="PRO_0000311708"
FT TRANSMEM 13..33
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 329
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /note="covalent"
FT /evidence="ECO:0000250|UniProtKB:P51869"
FT BINDING 467
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:P51869"
SQ SEQUENCE 525 AA; 60580 MW; D93E3911A6B5D5BD CRC64;
MLWLWLGLSG QKLLLWGAAS AVSVAGATVL LNILQMLVSY ARKWQQMRPI PSVARAYPLV
GHALFMKPNN TEFFQQIIQY TEEFRHLPII KLWIGPVPLV ALYKAENVEV ILTSSKQIDK
SFMYKFLQPW LGLGLLTSTG SKWRARRKML TPSFHFTILE DFLDVMNEQA NILVNKLEKH
VNQEAFNCFF PITLCALDII CETAMGKNIG AQSNGDSEYV RTVYRMSDMI YRRMKMPWFW
FDLWYLMFKE GRDHKKGLKS LHTFTNNVIA ERVNARKAEQ DCIGAGRGPL PSKTKRKAFL
DLLLSVTDEE GNKLSHEDIR EEVDTFMFEG HDTTAAAINW SLYLLGSNPE VQRKVDKELD
DVFGRSHRPV TLEDLKKLKY LDCVIKETLR VFPSVPLFAR SLSEDCEVAG YKISKGTEAV
IIPYALHRDP RYFPDPEEFQ PERFFPENSQ GRHPYAYVPF SAGPRNCIGQ KFAVMEEKTI
LACILREFWI ESNQKREELG LAGDLILRPN NGIWIKLKRR HEDDP
