Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DE3GT9C)

DME Name Cytochrome P450 4F2 (CYP4F2)
Synonyms
Cytochrome P450 family 4 subfamily F member 2; Arachidonic acid omega-hydroxylase; CYP4F2; CYPIVF2; Leukotriene-B(4) 20-monooxygenase 1; Leukotriene-B(4) omega-hydroxylase 1; Phylloquinone omega-hydroxylase CYP4F2
Gene Name CYP4F2
UniProt ID
CP4F2_HUMAN
INTEDE ID
DME0025
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Gene ID
8529
EC Number EC: 1.14.13.30
Oxidoreductase
Oxygen paired donor oxidoreductase
NADH/NADPH donor oxidoreductase
EC: 1.14.13.30
Lineage Species: Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Sequence
MSQLSLSWLGLWPVAASPWLLLLLVGASWLLAHVLAWTYAFYDNCRRLRCFPQPPRRNWF
WGHQGMVNPTEEGMRVLTQLVATYPQGFKVWMGPISPLLSLCHPDIIRSVINASAAIAPK
DKFFYSFLEPWLGDGLLLSAGDKWSRHRRMLTPAFHFNILKPYMKIFNESVNIMHAKWQL
LASEGSACLDMFEHISLMTLDSLQKCVFSFDSHCQEKPSEYIAAILELSALVSKRHHEIL
LHIDFLYYLTPDGQRFRRACRLVHDFTDAVIQERRRTLPSQGVDDFLQAKAKSKTLDFID
VLLLSKDEDGKKLSDEDIRAEADTFMFEGHDTTASGLSWVLYHLAKHPEYQERCRQEVQE
LLKDREPKEIEWDDLAHLPFLTMCMKESLRLHPPVPVISRHVTQDIVLPDGRVIPKGIIC
LISVFGTHHNPAVWPDPEVYDPFRFDPENIKERSPLAFIPFSAGPRNCIGQTFAMAEMKV
VLALTLLRFRVLPDHTEPRRKPELVLRAEGGLWLRVEPLS
Function
This enzyme is involved in the metabolism of various endogenous substrates, including fatty acids, eicosanoids and vitamins. It catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of long- and very long-chain fatty acids and displays high omega-hydroxylase activity toward polyunsaturated fatty acids (PUFAs). It participates in the conversion of arachidonic acid to omega-hydroxyeicosatetraenoic acid (20-HETE) and plays a role in the oxidative inactivation of eicosanoids. In addition, it catalyzes omega-hydroxylation of 3-hydroxy fatty acids and converts monoepoxides of linoleic acid leukotoxin and isoleukotoxin to omega-hydroxylated metabolites. It also contributes to the degradation of very long-chain fatty acids (VLCFAs) by catalyzing successive omega-oxidations and chain shortening. It plays an important role in vitamin metabolism by chain shortening and catalyzes omega- hydroxylation of the phytyl chain of tocopherols (forms of vitamin E), with preference for gamma-tocopherols over alpha-tocopherols. It also can Omega-hydroxylates and inactivates phylloquinone (vitamin K1), and menaquinone-4 (MK-4, a form of vitamin K2), both acting as cofactors in blood coagulation.
KEGG Pathway
( )
( )
Reactome Pathway
Fatty acids (R-HSA-211935 )
Miscellaneous substrates (R-HSA-211958 )
Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE) (R-HSA-2142816 )
Synthesis of Leukotrienes (LT) and Eoxins (EX) (R-HSA-2142691 )
Eicosanoids (R-HSA-211979 )

Molecular Interaction Atlas (MIA) of This DME

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DME
3 Approved Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Dinoprostone DMTYOPD Medical abortion JA00.1Z Approved [1]
Fingolimod DM5JVAN Primary progressive multiple sclerosis 8A40.1 Approved [2]
Ebastine DMQRX24 Irritable bowel syndrome DD91.0 Phase 4 [3]
3 Clinical Trial Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Pafuramidine DMFKOR9 Malaria 1F40-1F45 Phase 3 [4]
Tocopherol DMBIJZ6 Phenylketonuria 5C50.0 Phase 2 [5]
GSK618334 DMJPXZ4 Drug abuse 6C4G.1Z Phase 1 [6]
1 Investigative Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Arachidonic acid DMUOQZD Discovery agent N.A. Investigative [7]

Molecular Expression Atlas (MEA) of This DME

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DME
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Acute myelocytic leukaemia 2B33.1 Bone marrow 4.69E-45 -1.57E+00 -1.86E+00
Alopecia ED70 Skin from scalp 9.26E-01 -4.25E-03 -4.96E-03
Alzheimer's disease 8A20 Entorhinal cortex 2.43E-02 2.94E-02 1.61E-01
Ankylosing spondylitis FA92.0 Pheripheral blood 6.13E-01 -5.27E-02 -3.41E-01
Aortic stenosis BB70 Calcified aortic valve 9.75E-01 -7.20E-02 -8.68E-02
Apnea 7A40 Hyperplastic tonsil 3.84E-01 -3.78E-01 -8.74E-01
Arthropathy FA00-FA5Z Peripheral blood 4.78E-02 2.38E-01 6.21E-01
Asthma CA23 Nasal and bronchial airway 1.70E-01 2.14E-02 5.91E-02
Atopic dermatitis EA80 Skin 9.67E-03 -3.47E-01 -4.75E-01
Autism 6A02 Whole blood 6.05E-01 1.86E-02 4.41E-02
Autoimmune uveitis 9A96 Peripheral monocyte 9.74E-01 -3.04E-03 -2.49E-02
Autosomal dominant monocytopenia 4B04 Whole blood 4.64E-02 -4.05E-01 -7.74E-01
Bacterial infection of gingival 1C1H Gingival tissue 2.09E-01 -4.08E-02 -1.07E-01
Batten disease 5C56.1 Whole blood 2.91E-01 1.41E-01 1.29E+00
Behcet's disease 4A62 Peripheral blood 4.26E-01 1.30E-01 6.44E-01
Bipolar disorder 6A60-6A6Z Prefrontal cortex 7.73E-01 1.06E-03 6.18E-03
Bladder cancer 2C94 Bladder tissue 1.69E-03 8.12E-01 1.80E+00
Breast cancer 2C60-2C6Z Breast tissue 5.91E-03 -6.16E-02 -1.85E-01
Cardioembolic stroke 8B11.20 Whole blood 1.19E-05 5.95E-01 1.27E+00
Cervical cancer 2C77 Cervical tissue 8.32E-01 -5.68E-02 -1.88E-01
Childhood onset rheumatic disease FA20.Z Peripheral blood 8.77E-01 1.25E-01 5.46E-02
Chronic hepatitis C 1E51.1 Whole blood 4.26E-01 4.73E-02 4.00E-01
Chronic obstructive pulmonary disease CA22 Lung tissue 7.40E-02 1.06E-01 4.35E-01
Chronic obstructive pulmonary disease CA22 Small airway epithelium 2.02E-04 2.61E-01 5.68E-01
Chronic rhinosinusitis CA0A Sinus mucosa tissue 5.92E-02 1.00E-01 1.03E+00
Colon cancer 2B90 Colon tissue 5.22E-04 -3.36E-01 -4.21E-01
Coronary artery disease BA80-BA8Z Peripheral blood 7.88E-01 -5.82E-02 -3.11E-01
Diffuse large B-cell lymphoma 2A81 Tonsil tissue 8.75E-01 4.72E-02 2.34E-01
Endometriosis GA10 Endometrium tissue 6.66E-02 1.84E-01 5.69E-01
Familial hypercholesterolemia 5C80.00 Peripheral blood 8.81E-01 2.68E-02 1.40E-01
Familial hypercholesterolemia 5C80.00 Whole blood 1.05E-08 -7.43E-01 -1.32E+00
Gastric cancer 2B72 Gastric tissue 1.17E-02 5.41E-01 3.02E+00
Glioblastopma 2A00.00 Nervous tissue 7.23E-03 -1.07E-01 -3.76E-01
Glioma 2A00.0Y-2A00.0Z Brain stem tissue 6.65E-01 1.14E-02 1.34E-01
Glioma 2A00.0Y-2A00.0Z White matter tissue 4.91E-02 -4.18E-01 -4.94E-01
Head and neck cancer 2D42 Head and neck tissue 1.81E-02 -2.35E-01 -4.27E-01
HIV-associated neurocognitive impairment 8A2Y-8A2Z White matter tissue 4.96E-01 -2.58E-02 -1.13E-01
Huntington's disease 8A01.10 Whole blood 2.79E-01 8.25E-03 4.91E-02
Idiopathic pulmonary fibrosis CB03.4 Lung tissue 1.88E-01 -7.62E-02 -1.28E-01
Immunodeficiency 4A00-4A20 Peripheral blood 8.52E-01 -2.09E-02 -2.56E-01
Influenza 1E30 Whole blood 9.24E-02 1.56E-01 1.77E+00
Interstitial cystitis GC00.3 Bladder tissue 2.46E-02 -3.39E-01 -1.42E+00
Intracranial aneurysm 8B01.0 Intracranial artery 6.78E-01 -1.03E-01 -3.85E-01
Irritable bowel syndrome DD91.0 Rectal colon tissue 8.67E-01 1.15E-01 1.26E-01
Ischemic stroke 8B11 Peripheral blood 3.71E-03 1.14E-01 6.64E-01
Juvenile idiopathic arthritis FA24 Peripheral blood 6.79E-01 1.48E-01 1.33E-01
Lateral sclerosis 8B60.4 Skin 7.39E-01 1.13E-01 4.22E-01
Lateral sclerosis 8B60.4 Cervical spinal cord 8.37E-01 2.61E-02 1.29E-01
Liver cancer 2C12.0 Liver tissue 5.20E-51 -1.55E+00 -3.79E+00
Liver failure DB99.7-DB99.8 Liver tissue 5.58E-05 -4.45E+00 -1.12E+01
Lung cancer 2C25 Lung tissue 1.39E-18 2.98E-02 1.17E-01
Lupus erythematosus 4A40 Whole blood 3.38E-02 2.15E-01 2.94E-01
Major depressive disorder 6A70-6A7Z Hippocampus 4.56E-01 5.77E-02 3.59E-01
Major depressive disorder 6A70-6A7Z Whole blood 7.79E-01 -9.28E-02 -1.99E-01
Melanoma 2C30 Skin 2.52E-04 -1.97E+00 -1.06E+00
Multiple myeloma 2A83.1 Peripheral blood 5.27E-01 -1.18E-01 -5.64E-01
Multiple myeloma 2A83.1 Bone marrow 7.40E-04 -4.31E-01 -2.29E+00
Multiple sclerosis 8A40 Plasmacytoid dendritic cells 2.36E-01 -6.45E-02 -1.81E-01
Myelodysplastic syndrome 2A36-2A3Z Bone marrow 3.51E-02 -4.11E-03 -1.16E-02
Myelofibrosis 2A20.2 Whole blood 9.41E-01 1.32E-02 5.20E-02
Myocardial infarction BA41-BA50 Peripheral blood 3.67E-03 1.02E+00 8.40E-01
Myopathy 8C70.6 Muscle tissue 2.17E-01 -4.07E-02 -2.34E-01
Neonatal sepsis KA60 Whole blood 4.03E-10 4.86E-01 8.90E-01
Neuroectodermal tumour 2A00.11 Brain stem tissue 3.09E-03 -4.41E-01 -1.25E+00
Non-alcoholic fatty liver disease DB92 Liver tissue 2.15E-02 3.80E-01 1.30E+00
Obesity related type 2 diabetes 5A11 Omental adipose tissue 7.15E-01 -8.86E-02 -4.95E-01
Olive pollen allergy CA08.00 Peripheral blood 2.64E-01 9.62E-02 5.36E-01
Oral cancer 2B6E Oral tissue 2.87E-03 -2.55E-01 -5.71E-01
Osteoarthritis FA00-FA0Z Synovial tissue 6.84E-02 -2.74E-01 -1.65E+00
Osteoporosis FB83.1 Bone marrow 1.48E-01 3.43E-02 1.63E-01
Ovarian cancer 2C73 Ovarian tissue 2.33E-01 1.08E-01 2.67E-01
Pancreatic cancer 2C10 Pancreas 6.15E-02 7.98E-02 1.82E-01
Parkinson's disease 8A00.0 Substantia nigra tissue 5.10E-01 -3.24E-02 -1.39E-01
Pediatric respiratory syncytial virus infection CA40.11 Peripheral blood 1.37E-02 2.76E-01 1.57E+00
Pituitary cancer 2D12 Pituitary tissue 1.77E-01 2.96E-01 8.55E-01
Pituitary gonadotrope tumour 2D12 Pituitary tissue 4.68E-02 1.86E-01 7.93E-01
Polycystic ovary syndrome 5A80.1 Vastus lateralis muscle 1.44E-01 -8.09E-02 -4.93E-01
Polycythemia vera 2A20.4 Whole blood 9.60E-01 -1.27E-04 -4.81E-04
Pompe disease 5C51.3 Biceps muscle 9.65E-01 -6.33E-03 -5.23E-02
Preterm birth KA21.4Z Myometrium 6.38E-01 6.47E-04 5.05E-03
Prostate cancer 2C82 Prostate 4.49E-02 -7.84E-01 -4.13E-01
Psoriasis EA90 Skin 1.56E-07 7.10E-01 8.46E-01
Rectal cancer 2B92 Rectal colon tissue 5.65E-01 -1.36E-01 -2.31E-01
Renal cancer 2C90-2C91 Kidney 3.18E-03 -2.45E+00 -1.73E+00
Retinoblastoma 2D02.2 Uvea 1.21E-02 -1.78E-01 -8.33E-01
Rheumatoid arthritis FA20 Synovial tissue 6.40E-02 -1.44E-01 -7.62E-01
Rhinovirus infection CA42.1 Nasal epithelium tissue 1.52E-01 -4.72E-02 -2.41E-01
Schizophrenia 6A20 Prefrontal cortex 4.04E-01 3.74E-02 9.88E-02
Schizophrenia 6A20 Superior temporal cortex 6.40E-01 -4.65E-02 -3.37E-01
Scleroderma 4A42.Z Whole blood 1.26E-01 2.13E-01 7.41E-01
Seizure 8A60-8A6Z Whole blood 5.20E-01 1.23E-01 2.10E-01
Sensitive skin EK0Z Skin 8.55E-01 5.69E-02 1.42E-01
Sepsis with septic shock 1G41 Whole blood 5.95E-20 5.40E-01 9.30E-01
Shwachman-Diamond syndrome 3A70.0 Bone marrow 4.51E-01 -4.26E-01 -1.03E+00
Sickle cell disease 3A51.0-3A51.3 Peripheral blood 4.70E-02 2.27E-01 9.04E-01
Simpson golabi behmel syndrome LD2C Adipose tissue 2.50E-01 -7.31E-02 -1.01E+00
Sjogren's syndrome 4A43.2 Salivary gland tissue 6.62E-01 -9.75E-02 -4.29E-01
Skin cancer 2C30-2C3Z Skin 1.33E-27 -9.03E-01 -8.35E-01
Thrombocythemia 3B63 Whole blood 9.85E-02 -1.45E-01 -5.83E-01
Thrombocytopenia 3B64 Whole blood 5.63E-01 0.00E+00 0.00E+00
Thyroid cancer 2D10 Thyroid 2.58E-04 8.29E-02 3.11E-01
Tibial muscular dystrophy 8C75 Muscle tissue 5.54E-02 -2.61E-01 -1.07E+00
Tuberous sclerosis complex LD2D.2 Perituberal tissue 7.20E-01 2.71E-02 1.80E-01
Type 2 diabetes 5A11 Liver tissue 9.92E-01 -8.06E-03 -3.20E-02
Ureter cancer 2C92 Urothelium 2.25E-01 -3.53E-02 -1.92E-01
Uterine cancer 2C78 Endometrium tissue 4.97E-04 1.67E-01 3.63E-01
Vitiligo ED63.0 Skin 8.43E-01 2.26E-01 1.54E-01
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⏷ Show the Full List of DME Expression Under 107 Diseases

References

1 Cloning and characterization of CYP4F21: a prostaglandin E2 20-hydroxylase of ram seminal vesicles. Arch Biochem Biophys. 2001 May 1;389(1):123-9.
2 CYP4F enzymes are responsible for the elimination of fingolimod (FTY720), a novel treatment of relapsing multiple sclerosis. Drug Metab Dispos. 2011 Feb;39(2):191-8.
3 cDNA cloning and expression of a novel cytochrome p450 (cyp4f12) from human small intestine. Biochem Biophys Res Commun. 2001 Feb 2;280(4):1135-41.
4 Human enteric microsomal CYP4F enzymes O-demethylate the antiparasitic prodrug pafuramidine. Drug Metab Dispos. 2007 Nov;35(11):2067-75.
5 Discovery, characterization, and significance of the cytochrome P450 omega-hydroxylase pathway of vitamin E catabolism. Ann N Y Acad Sci. 2004 Dec;1031:13-21.
6 Product information - Gilenya.
7 Role of cytochrome P450 enzymes in the bioactivation of polyunsaturated fatty acids. Biochim Biophys Acta. 2011 Jan;1814(1):210-22.