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MGP003587

UniProt Annotations

Entry Information
Gene Namecytochrome P450, family 4, subfamily F, polypeptide 2
Protein EntryCP4F2_HUMAN
UniProt IDP78329
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=P78329-1; Sequence=Displayed; Name=2; IsoId=P78329-2; Sequence=VSP_055578, VSP_055579, VSP_055580; Note=No experimental confirmation available.;
Biophysicochemical PropertiesKinetic parameters: KM=74.8 uM for leukotriene-B(4) {ECO:0000269|PubMed:9799565}; KM=1.7 uM for menaquinone-4 (MK-4) {ECO:0000269|PubMed:24138531}; Vmax=2.42 nmol/min/mg enzyme {ECO:0000269|PubMed:9799565}; Note=kcat is 0.067 min(-1) with menaquinone-4 (MK-4) as substrate. {ECO:0000269|PubMed:24138531};
Catalytic Activity(5Z,8Z,11Z,14Z)-icosatetraenoate + NADPH + O(2) = (5Z,8Z,11Z,14Z)-20-hydroxyicosa-5,8,11,14-tetraenoate + NADP(+) + H(2)O. {ECO:0000269|PubMed:10660572}.
Catalytic Activity(6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa- 6,8,10,14-tetraenoate + NADPH + O(2) = (6Z,8E,10E,14Z)-(5S,12R)- 5,12,20-trihydroxyicosa-6,8,10,14-tetraenoate + NADP(+) + H(2)O. {ECO:0000269|PubMed:8026587, ECO:0000269|PubMed:9799565}.
Catalytic ActivityPhylloquinone + NADPH + O(2) = omega- hydroxyphylloquinone + NADP(+) + H(2)O. {ECO:0000269|PubMed:24138531}.
CofactorName=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250|UniProtKB:P24464};
DiseaseCoumarin resistance (CMRES) [MIM:122700]: A condition characterized by partial or complete resistance to warfarin or other 4-hydroxycoumarin derivatives. These drugs are used as anti- coagulants for the prevention of thromboembolic diseases in subjects with deep vein thrombosis, atrial fibrillation, or mechanical heart valve replacement. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry. The variant Met-433 is associated with coumarin (the brand name of warfarin) resistance by increasing coumarin maintenance dose in patients on this anti-coagulant therapy. This is probably due to decreased activity of the phylloquinone omega- hydroxylase activity, leading to an increase in hepatic vitamin K levels that warfarin must antagonize (PubMed:24138531). {ECO:0000269|PubMed:18250228, ECO:0000269|PubMed:19207028, ECO:0000269|PubMed:19270263, ECO:0000269|PubMed:19297519, ECO:0000269|PubMed:20555338, ECO:0000269|PubMed:23132553, ECO:0000269|PubMed:24138531}.
FunctionOmega-hydroxylase that oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids and xenobiotics. Plays a key role in vitamin K catabolism by mediating omega-hydroxylation of vitamin K1 (phylloquinone), and menaquinone-4 (MK-4), a form of vitamin K2. Hydroxylation of phylloquinone and MK-4 probably regulates blood coagulation (PubMed:19297519, PubMed:24138531). Also shows arachidonic acid omega-hydroxylase activity in kidney, by mediating conversion of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), possibly influencing blood pressure control (PubMed:10660572, PubMed:17341693, PubMed:18574070). Also acts as a leukotriene-B(4) omega-hydroxylase by mediating conversion of leukotriene-B(4) (LTB4) to its omega-hydroxylated metabolite 20-hydroxyleukotriene- B(4) (20-OH LTB4) (PubMed:8026587, PubMed:9799565). {ECO:0000269|PubMed:10660572, ECO:0000269|PubMed:17341693, ECO:0000269|PubMed:18574070, ECO:0000269|PubMed:19297519, ECO:0000269|PubMed:24138531, ECO:0000269|PubMed:8026587, ECO:0000269|PubMed:9799565}.
InteractionP16333:NCK1; NbExp=2; IntAct=EBI-1752413, EBI-389883;
PathwayCofactor degradation; phylloquinone degradation. {ECO:0000269|PubMed:24138531}.
SimilarityBelongs to the cytochrome P450 family. {ECO:0000305}.
Subcellular LocationMicrosome membrane {ECO:0000269|PubMed:19297519, ECO:0000269|PubMed:24138531, ECO:0000269|PubMed:8026587}; Peripheral membrane protein {ECO:0000305}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:20861217}; Peripheral membrane protein {ECO:0000305}.
Tissue SpecificityLiver. Also present in kidney: specifically expressed in the S2 and S3 segments of proximal tubules in cortex and outer medulla (PubMed:10660572). {ECO:0000269|PubMed:10492403, ECO:0000269|PubMed:10660572}.
Web ResourceName=SeattleSNPs; URL="http://pga.gs.washington.edu/data/cyp4f2/";
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