CYP4F2 - Phylloquinone omega-hydroxylase CYP4F2 - human protein (Function)
 
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CYP4F2 »  Phylloquinone omega-hydroxylase CYP4F2   [ EC 1.14.13.194 ]
 
Protein also known as:  20-hydroxyeicosatetraenoic acid synthase [EC 1.14.13.-] (20-HETE synthase).
Gene name:  CYP4F2
Family name: Cytochrome P450
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
Omega-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 (PubMed19297519, PubMed24138531). 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 (PubMed10660572, PubMed17341693, PubMed18574070). 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) (PubMed8026587, PubMed9799565).  
8
  • UniProtKB
GO molecular function 
Alkane 1-monooxygenase activitydefinition[GO:0018685]  
1
  • BHF-UCL
Alpha-tocopherol omega-hydroxylase activitydefinition[GO:0052871]  
1
  • UniProtKB
Arachidonic acid epoxygenase activitydefinition[GO:0008392]  
2
  • UniProtKB
Arachidonic acid omega-hydroxylase activitydefinition[GO:0052869]  
2
  • UniProtKB
Heme bindingdefinition[GO:0020037] silver  
1
  • InterPro 2 GO
Iron ion bindingdefinition[GO:0005506] silver  
1
  • InterPro 2 GO
Leukotriene-B4 20-monooxygenase activitydefinition[GO:0050051]  
2
  • UniProtKB
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygendefinition[GO:0016709]  
2
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
1
  • IntAct
Tocotrienol omega-hydroxylase activitydefinition[GO:0052872]  
1
  • UniProtKB
Vitamin-K-epoxide reductase (warfarin-sensitive) activitydefinition[GO:0047057]  
1
  • UniProtKB
GO biological process 
Arachidonic acid metabolic processdefinition[GO:0019369]  
1
  • UniProtKB
Blood coagulationdefinition[GO:0007596]  
2
  • UniProtKB
Drug metabolic processdefinition[GO:0017144]  
2
  • UniProtKB
Epoxygenase P450 pathwaydefinition[GO:0019373]  
2
  • UniProtKB
Leukotriene B4 catabolic processdefinition[GO:0036101]  
3
  • UniProtKB
Long-chain fatty acid metabolic processdefinition[GO:0001676]  
1
  • BHF-UCL
Menaquinone catabolic processdefinition[GO:0042361]  
1
  • UniProtKB
Negative regulation of blood coagulationdefinition[GO:0030195]  
1
  • UniProtKB
Negative regulation of icosanoid secretiondefinition[GO:0032304]  
1
  • UniProtKB
Oxidation-reduction processdefinition[GO:0055114]  
3
  • UniProtKB
Phylloquinone catabolic processdefinition[GO:0042376]  
2
  • UniProtKB
  • UniPathway
Positive regulation of icosanoid secretiondefinition[GO:0032305]  
1
  • UniProtKB
Pressure natriuresisdefinition[GO:0003095]  
1
  • UniProtKB
Regulation of blood pressuredefinition[GO:0008217]  
1
  • UniProtKB
Renal water homeostasisdefinition[GO:0003091]  
1
  • UniProtKB
Sodium ion homeostasisdefinition[GO:0055078]  
1
  • UniProtKB
Very long-chain fatty acid metabolic processdefinition[GO:0000038]  
1
  • BHF-UCL
Vitamin E metabolic processdefinition[GO:0042360]  
1
  • UniProtKB
Vitamin K biosynthetic processdefinition[GO:0042371]  
1
  • UniProtKB
Vitamin K catabolic processdefinition[GO:0042377]  
2
  • UniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reactions
EC 1.14.13.30: (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.  
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  • UniProtKB
EC 1.14.13.194: Phylloquinone + NADPH + O(2) omega-hydroxyphylloquinone + NADP(+) + H(2)O.  
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  • UniProtKB
EC 1.14.13.-: (5Z,8Z,11Z,14Z)-icosatetraenoate + NADPH + O(2) (5Z,8Z,11Z,14Z)-20-hydroxyicosa-5,8,11,14-tetraenoate + NADP(+) + H(2)O.  
2
  • UniProtKB
It requires the following cofactor
 heme  
2
  • UniProtKB
 
More information is available from:
Pathways 
This protein is involved in the following pathway
Cofactor degradation; phylloquinone degradation  
2
  • UniProtKB
According to KEGG, this protein belongs to the following pathways:
Arachidonic acid metabolism  hsa00590+8529  
Metabolic pathways  hsa01100+8529  
According to Reactome, this protein belongs to the following pathways:
Eicosanoids  REACT_13645  
Fatty acids  REACT_13814  
Miscellaneous substrates  REACT_13425  
Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE)  REACT_150134  
Synthesis of Leukotrienes (LT) and Eoxins (EX)  REACT_150420  
 
More information is available from:
 

Biophysicochemical properties

Kinetic parameters
kcat is 0.067 min(-1) with menaquinone-4 (MK-4) as substrate.
KM 1.7 uM for menaquinone-4 (MK-4)
KM 74.8 uM for leukotriene-B(4)
Vmax 2.42 nmol/min/mg enzyme

Keywords

Molecular function 
Monooxygenase  definition   [KW-0503]
Oxidoreductase  definition   [KW-0560]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: CYP4F2
GenomeRNAi: 8529
PRO: PR:P78329