Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DEBS639)

DME Name Vitamin D(3) 25-hydroxylase (CYP27A1)
Synonyms Sterol 27-hydroxylase; Cytochrome P-450C27/25; Mitochondrial sterol 26-hydroxylase; Cytochrome P450 27; 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol 26-hydroxylase; CYP27; CYP27A1
Gene Name CYP27A1
UniProt ID
CP27A_HUMAN
INTEDE ID
DME0026
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Gene ID
1593
EC Number EC: 1.14.15.15
Oxidoreductase
Oxygen paired donor oxidoreductase
Iron-sulfur protein donor oxidoreductase
EC: 1.14.15.15
Lineage Species: Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Sequence
MAALGCARLRWALRGAGRGLCPHGARAKAAIPAALPSDKATGAPGAGPGVRRRQRSLEEI
PRLGQLRFFFQLFVQGYALQLHQLQVLYKAKYGPMWMSYLGPQMHVNLASAPLLEQVMRQ
EGKYPVRNDMELWKEHRDQHDLTYGPFTTEGHHWYQLRQALNQRLLKPAEAALYTDAFNE
VIDDFMTRLDQLRAESASGNQVSDMAQLFYYFALEAICYILFEKRIGCLQRSIPEDTVTF
VRSIGLMFQNSLYATFLPKWTRPVLPFWKRYLDGWNAIFSFGKKLIDEKLEDMEAQLQAA
GPDGIQVSGYLHFLLASGQLSPREAMGSLPELLMAGVDTTSNTLTWALYHLSKDPEIQEA
LHEEVVGVVPAGQVPQHKDFAHMPLLKAVLKETLRLYPVVPTNSRIIEKEIEVDGFLFPK
NTQFVFCHYVVSRDPTAFSEPESFQPHRWLRNSQPATPRIQHPFGSVPFGYGVRACLGRR
IAELEMQLLLARLIQKYKVVLAPETGELKSVARIVLVPNKKVGLQFLQRQC
Function
This enzyme catalyzes regio- and stereospecific hydroxylation of cholesterol and its derivatives. It hydroxylates (with R stereochemistry) the terminal methyl group of cholesterol side-chain in a three step reaction to yield at first a C26 alcohol, then a C26 aldehyde and finally a C26 acid. It plays a role in cholestanol metabolism in the cerebellum. It also hydroxylates retinal 7- ketocholesterol, a noxious oxysterol with pro-inflammatory and pro- apoptotic effects, and may play a role in its elimination from the retinal pigment epithelium. It catalyzes 25-hydroxylation of vitamin D3 that is required for its conversion to a functionally active form.
KEGG Pathway
Cholesterol metabolism (hsa04979 )
Metabolic pathways (hsa01100 )
PPAR signaling pathway (hsa03320 )
Primary bile acid biosynthesis (hsa00120 )
Reactome Pathway
Endogenous sterols (R-HSA-211976 )
Synthesis of bile acids and bile salts via 24-hydroxycholesterol (R-HSA-193775 )
Synthesis of bile acids and bile salts via 27-hydroxycholesterol (R-HSA-193807 )
Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol (R-HSA-193368 )
Defective CYP27A1 causes Cerebrotendinous xanthomatosis (CTX) (R-HSA-5578996 )

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
Doxercalciferol DM6FG1P Chronic kidney disease GB61 Approved [1]
Vitamin D DMWQUC9 N. A. N. A. Approved [2]
Alfacalcidol DM1237M Hyperparathyroidism 5A51 Phase 4 [3]
1 Clinical Trial Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
ANW-32821 DMMJOZD N. A. N. A. Phase 2 [4]

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 2.09E-04 9.38E-02 2.53E-01
Alopecia ED70 Skin from scalp 9.66E-01 3.45E-02 8.53E-02
Alzheimer's disease 8A20 Entorhinal cortex 4.39E-04 2.42E-01 4.47E-01
Ankylosing spondylitis FA92.0 Pheripheral blood 1.41E-01 6.36E-02 2.25E-01
Aortic stenosis BB70 Calcified aortic valve 3.29E-01 -2.69E-01 -5.29E-01
Apnea 7A40 Hyperplastic tonsil 3.18E-01 1.51E-02 5.66E-02
Arthropathy FA00-FA5Z Peripheral blood 1.63E-01 3.06E-01 5.42E-01
Asthma CA23 Nasal and bronchial airway 2.07E-04 -2.67E-01 -4.75E-01
Atopic dermatitis EA80 Skin 1.58E-01 2.13E-01 8.49E-01
Autism 6A02 Whole blood 2.63E-01 1.63E-02 3.93E-02
Autoimmune uveitis 9A96 Peripheral monocyte 9.72E-02 4.45E-01 7.08E-01
Autosomal dominant monocytopenia 4B04 Whole blood 2.31E-01 1.07E-01 1.43E-01
Bacterial infection of gingival 1C1H Gingival tissue 1.18E-01 5.57E-02 2.52E-01
Batten disease 5C56.1 Whole blood 6.09E-01 4.28E-01 6.54E-01
Behcet's disease 4A62 Peripheral blood 9.66E-01 -1.71E-01 -4.19E-01
Bipolar disorder 6A60-6A6Z Prefrontal cortex 6.54E-01 2.10E-02 8.19E-02
Bladder cancer 2C94 Bladder tissue 6.46E-04 -9.96E-01 -2.75E+00
Breast cancer 2C60-2C6Z Breast tissue 4.07E-05 -1.29E-01 -3.61E-01
Cardioembolic stroke 8B11.20 Whole blood 9.02E-02 1.18E-01 1.21E-01
Cervical cancer 2C77 Cervical tissue 1.42E-02 -1.44E-01 -6.13E-01
Childhood onset rheumatic disease FA20.Z Peripheral blood 3.90E-01 1.17E-01 1.98E-01
Chronic hepatitis C 1E51.1 Whole blood 8.05E-01 -1.69E-01 -6.33E-01
Chronic obstructive pulmonary disease CA22 Lung tissue 8.66E-01 -4.53E-02 -1.02E-01
Chronic obstructive pulmonary disease CA22 Small airway epithelium 1.92E-03 2.08E-01 4.43E-01
Chronic rhinosinusitis CA0A Sinus mucosa tissue 5.28E-02 -8.13E-02 -3.16E-01
Colon cancer 2B90 Colon tissue 7.30E-35 -5.96E-01 -1.45E+00
Coronary artery disease BA80-BA8Z Peripheral blood 7.08E-01 -5.53E-02 -3.27E-01
Diffuse large B-cell lymphoma 2A81 Tonsil tissue 7.22E-01 -1.73E-02 -7.39E-02
Endometriosis GA10 Endometrium tissue 9.01E-01 1.09E-01 1.86E-01
Familial hypercholesterolemia 5C80.00 Peripheral blood 2.55E-01 -1.10E-01 -4.66E-01
Familial hypercholesterolemia 5C80.00 Whole blood 4.37E-03 4.90E-01 1.02E+00
Gastric cancer 2B72 Gastric tissue 2.08E-01 5.27E-01 9.75E-01
Glioblastopma 2A00.00 Nervous tissue 5.44E-02 1.21E-01 1.84E-01
Glioma 2A00.0Y-2A00.0Z Brain stem tissue 1.07E-07 -9.79E-01 -1.51E+01
Glioma 2A00.0Y-2A00.0Z White matter tissue 9.26E-01 -1.74E-01 -1.90E-01
Head and neck cancer 2D42 Head and neck tissue 1.61E-06 -3.59E-01 -8.52E-01
HIV-associated neurocognitive impairment 8A2Y-8A2Z White matter tissue 2.38E-01 3.07E-01 4.13E-01
Huntington's disease 8A01.10 Whole blood 6.02E-02 4.78E-01 8.78E-01
Idiopathic pulmonary fibrosis CB03.4 Lung tissue 6.24E-03 5.39E-01 1.66E+00
Immunodeficiency 4A00-4A20 Peripheral blood 8.35E-01 -2.84E-02 -2.62E-01
Influenza 1E30 Whole blood 2.57E-01 -6.00E-02 -2.97E-01
Interstitial cystitis GC00.3 Bladder tissue 1.44E-04 -8.16E-01 -6.14E+00
Intracranial aneurysm 8B01.0 Intracranial artery 3.63E-03 8.38E-01 2.60E+00
Irritable bowel syndrome DD91.0 Rectal colon tissue 3.12E-02 -3.12E-01 -5.63E-01
Ischemic stroke 8B11 Peripheral blood 1.26E-01 -1.85E-01 -4.13E-01
Juvenile idiopathic arthritis FA24 Peripheral blood 9.24E-02 -1.97E-01 -2.32E-01
Lateral sclerosis 8B60.4 Skin 8.84E-01 -2.81E-03 -7.23E-03
Lateral sclerosis 8B60.4 Cervical spinal cord 8.36E-02 2.85E-01 1.39E+00
Liver cancer 2C12.0 Liver tissue 2.50E-13 -4.93E-01 -1.02E+00
Liver failure DB99.7-DB99.8 Liver tissue 8.06E-04 -1.79E+00 -3.71E+00
Lung cancer 2C25 Lung tissue 1.86E-65 -9.89E-01 -1.86E+00
Lupus erythematosus 4A40 Whole blood 3.27E-01 1.23E-01 2.23E-01
Major depressive disorder 6A70-6A7Z Hippocampus 5.51E-01 5.29E-02 2.30E-01
Major depressive disorder 6A70-6A7Z Whole blood 5.21E-01 -3.80E-02 -6.05E-02
Melanoma 2C30 Skin 4.33E-01 2.22E-01 2.73E-01
Multiple myeloma 2A83.1 Peripheral blood 1.64E-01 1.19E-01 6.72E-01
Multiple myeloma 2A83.1 Bone marrow 3.55E-03 5.53E-01 1.59E+00
Multiple sclerosis 8A40 Plasmacytoid dendritic cells 4.51E-01 1.41E-01 3.76E-01
Myelodysplastic syndrome 2A36-2A3Z Bone marrow 5.14E-02 1.30E-01 5.30E-01
Myelofibrosis 2A20.2 Whole blood 1.60E-01 -1.16E-01 -5.78E-01
Myocardial infarction BA41-BA50 Peripheral blood 2.37E-03 8.34E-01 6.45E-01
Myopathy 8C70.6 Muscle tissue 4.43E-01 -8.11E-02 -7.48E-01
Neonatal sepsis KA60 Whole blood 9.66E-01 -1.36E-01 -2.47E-01
Neuroectodermal tumour 2A00.11 Brain stem tissue 3.15E-14 -1.38E+00 -7.77E+00
Non-alcoholic fatty liver disease DB92 Liver tissue 7.88E-01 9.81E-02 1.89E-01
Obesity related type 2 diabetes 5A11 Omental adipose tissue 3.77E-01 4.59E-03 1.83E-02
Olive pollen allergy CA08.00 Peripheral blood 3.14E-01 5.90E-01 6.80E-01
Oral cancer 2B6E Oral tissue 3.99E-10 -6.47E-01 -1.86E+00
Osteoarthritis FA00-FA0Z Synovial tissue 9.00E-01 1.85E-01 3.16E-01
Osteoporosis FB83.1 Bone marrow 9.81E-01 8.80E-02 4.82E-01
Ovarian cancer 2C73 Ovarian tissue 9.24E-05 -6.81E-01 -2.30E+00
Pancreatic cancer 2C10 Pancreas 1.26E-01 2.51E-01 5.59E-01
Parkinson's disease 8A00.0 Substantia nigra tissue 5.81E-03 3.82E-01 1.32E+00
Pediatric respiratory syncytial virus infection CA40.11 Peripheral blood 6.43E-01 1.07E-02 3.27E-02
Pituitary cancer 2D12 Pituitary tissue 5.70E-01 3.94E-01 2.37E+00
Pituitary gonadotrope tumour 2D12 Pituitary tissue 1.82E-03 4.01E-01 2.14E+00
Polycystic ovary syndrome 5A80.1 Vastus lateralis muscle 2.10E-02 9.44E-02 6.91E-01
Polycythemia vera 2A20.4 Whole blood 1.91E-01 7.77E-02 3.63E-01
Pompe disease 5C51.3 Biceps muscle 2.04E-01 3.23E-01 1.92E+00
Preterm birth KA21.4Z Myometrium 3.10E-02 -4.25E-01 -1.53E+00
Prostate cancer 2C82 Prostate 2.63E-08 -1.47E+00 -1.99E+00
Psoriasis EA90 Skin 1.09E-34 -6.10E-01 -1.84E+00
Rectal cancer 2B92 Rectal colon tissue 6.07E-04 -8.19E-01 -2.91E+00
Renal cancer 2C90-2C91 Kidney 9.35E-01 -1.32E-01 -2.67E-01
Retinoblastoma 2D02.2 Uvea 2.42E-10 1.93E+00 1.02E+01
Rheumatoid arthritis FA20 Synovial tissue 9.77E-06 5.91E-01 3.13E+00
Rhinovirus infection CA42.1 Nasal epithelium tissue 5.54E-02 -9.45E-02 -4.74E-01
Schizophrenia 6A20 Prefrontal cortex 1.87E-03 1.99E-01 4.12E-01
Schizophrenia 6A20 Superior temporal cortex 8.35E-02 -1.81E-01 -7.50E-01
Scleroderma 4A42.Z Whole blood 1.16E-01 -2.45E-01 -7.83E-01
Seizure 8A60-8A6Z Whole blood 8.02E-01 -7.01E-02 -1.28E-01
Sensitive skin EK0Z Skin 4.01E-01 9.70E-02 7.04E-01
Sepsis with septic shock 1G41 Whole blood 2.35E-02 -2.03E-01 -4.64E-01
Shwachman-Diamond syndrome 3A70.0 Bone marrow 3.45E-01 1.94E-02 1.17E-01
Sickle cell disease 3A51.0-3A51.3 Peripheral blood 2.97E-02 -1.33E-01 -6.23E-01
Simpson golabi behmel syndrome LD2C Adipose tissue 9.84E-01 -1.45E-01 -1.57E-01
Sjogren's syndrome 4A43.2 Salivary gland tissue 5.72E-01 -1.11E-01 -3.62E-01
Skin cancer 2C30-2C3Z Skin 1.79E-09 4.80E-01 1.04E+00
Thrombocythemia 3B63 Whole blood 1.02E-01 2.40E-01 1.12E+00
Thrombocytopenia 3B64 Whole blood 4.43E-01 3.62E-01 7.56E-01
Thyroid cancer 2D10 Thyroid 8.78E-03 1.23E-01 3.23E-01
Tibial muscular dystrophy 8C75 Muscle tissue 3.07E-01 1.08E-01 4.31E-01
Tuberous sclerosis complex LD2D.2 Perituberal tissue 6.17E-02 8.86E-01 2.34E+00
Type 2 diabetes 5A11 Liver tissue 2.59E-02 -2.64E-01 -1.34E+00
Ureter cancer 2C92 Urothelium 6.34E-01 -3.96E-02 -1.14E-01
Uterine cancer 2C78 Endometrium tissue 3.15E-14 -3.62E-01 -6.49E-01
Vitiligo ED63.0 Skin 7.07E-02 -2.30E-01 -6.23E-01
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⏷ Show the Full List of DME Expression Under 107 Diseases

References

1 Efficacy and safety of oral doxercalciferol in the management of secondary hyperparathyroidism in chronic kidney disease stage 4. Indian J Nephrol. 2013 Jul;23(4):271-5.
2 Chemoprevention of prostate cancer by cholecalciferol (vitamin D3): 25-hydroxylase (CYP27A1) in human prostate epithelial cells. Clin Exp Metastasis. 2005;22(3):265-73.
3 Kidney microsomal 25- and 1alpha-hydroxylase in vitamin D metabolism: catalytic properties, molecular cloning, cellular localization and expression during development. Biochim Biophys Acta. 2002 Feb 28;1580(2-3):133-44.
4 Cholesterol-metabolizing cytochromes P450. Drug Metab Dispos. 2006 Apr;34(4):513-20.