CP4V2_PONAB
ID CP4V2_PONAB Reviewed; 525 AA.
AC Q5RCN6;
DT 02-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 81.
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;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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:0000305}.
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DR EMBL; CR858234; CAH90471.1; -; mRNA.
DR RefSeq; NP_001125245.1; NM_001131773.1.
DR AlphaFoldDB; Q5RCN6; -.
DR SMR; Q5RCN6; -.
DR STRING; 9601.ENSPPYP00000017045; -.
DR GeneID; 100172140; -.
DR KEGG; pon:100172140; -.
DR CTD; 285440; -.
DR eggNOG; KOG0157; Eukaryota.
DR eggNOG; KOG3627; Eukaryota.
DR InParanoid; Q5RCN6; -.
DR OrthoDB; 1247045at2759; -.
DR UniPathway; UPA00199; -.
DR Proteomes; UP000001595; Unplaced.
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_0000051860"
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; 60695 MW; 65C241D69B99E396 CRC64;
MAGLWLGLVW QKLLLWGAAS AVSLAGASLV LSLLQRVASY ARKWQQMRPI PTVARAYPLV
GHALLMKRDG REFFQQIIEY TEEYRHMPLL KLWVGPVPMV ALYNAENVEV ILTSSRQIDK
SSMYKFLEPW LGLGLLTSTG NKWRSRRKML TPTFHFTILE DFLDIMNEQA NILVKKLEKH
VNQEAFNCFF YITLCALDII CETAMGKNIG AQSNDDSEYV RAVYRMSQMI FQRIKMPWLW
LDLWYLMFKE GWEHEKGLKI LHTFTNNVIA ERANEMNADE DCRGVGRGSA PSKNKRRAFL
DLLLSVTDDE GNRLSHEDIR EEVDTFMFEG HDTTAAAINW SLYLLGCNPE VQQKVDHELD
DVFGKSDRPA TVEDLKKLRY LECVIKETLR LFPSVPLFAR SVSEDCEVAG YRVLKGTEAV
IIPYALHRDP RYFPNPEEFQ PERFFPENAQ GRHPYAYVPF SAGPRNCIGQ KFAVMEEKTI
LSCILRHFWI ESNQKREELG LEGQLILRPS NGIWIKLKRR DADEP
