Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DEWSHL5)

• DME Name: Vitamin B12 methionine synthase (MTR)
• Synonyms: Methionine synthase; Vitamin-B12 dependent methionine synthase; 5-methyltetrahydrofolate--homocysteine methyltransferase; MS; MTR
• Gene Name: MTR
• UniProt ID: METH_HUMAN
• INTEDE ID: DME0153
• Gene ID: 4548
• EC Number:
  EC: 2.1.1.13
  Transferase
  Methylase
  Methyltransferase
  EC: 2.1.1.13
• Lineage:
  Species: Homo sapiens
  Kingdom: Metazoa
  Phylum: Chordata
  Class: Mammalia
  Order: Primates
  Family: Hominidae
  Genus: Homo
  Species: Homo sapiens
• Sequence:
  MSPALQDLSQPEGLKKTLRDEINAILQKRIMVLDGGMGTMIQREKLNEEHFRGQEFKDHA
  RPLKGNNDILSITQPDVIYQIHKEYLLAGADIIETNTFSSTSIAQADYGLEHLAYRMNMC
  SAGVARKAAEEVTLQTGIKRFVAGALGPTNKTLSVSPSVERPDYRNITFDELVEAYQEQA
  KGLLDGGVDILLIETIFDTANAKAALFALQNLFEEKYAPRPIFISGTIVDKSGRTLSGQT
  GEGFVISVSHGEPLCIGLNCALGAAEMRPFIEIIGKCTTAYVLCYPNAGLPNTFGDYDET
  PSMMAKHLKDFAMDGLVNIVGGCCGSTPDHIREIAEAVKNCKPRVPPATAFEGHMLLSGL
  EPFRIGPYTNFVNIGERCNVAGSRKFAKLIMAGNYEEALCVAKVQVEMGAQVLDVNMDDG
  MLDGPSAMTRFCNLIASEPDIAKVPLCIDSSNFAVIEAGLKCCQGKCIVNSISLKEGEDD
  FLEKARKIKKYGAAMVVMAFDEEGQATETDTKIRVCTRAYHLLVKKLGFNPNDIIFDPNI
  LTIGTGMEEHNLYAINFIHATKVIKETLPGARISGGLSNLSFSFRGMEAIREAMHGVFLY
  HAIKSGMDMGIVNAGNLPVYDDIHKELLQLCEDLIWNKDPEATEKLLRYAQTQGTGGKKV
  IQTDEWRNGPVEERLEYALVKGIEKHIIEDTEEARLNQKKYPRPLNIIEGPLMNGMKIVG
  DLFGAGKMFLPQVIKSARVMKKAVGHLIPFMEKEREETRVLNGTVEEEDPYQGTIVLATV
  KGDVHDIGKNIVGVVLGCNNFRVIDLGVMTPCDKILKAALDHKADIIGLSGLITPSLDEM
  IFVAKEMERLAIRIPLLIGGATTSKTHTAVKIAPRYSAPVIHVLDASKSVVVCSQLLDEN
  LKDEYFEEIMEEYEDIRQDHYESLKERRYLPLSQARKSGFQMDWLSEPHPVKPTFIGTQV
  FEDYDLQKLVDYIDWKPFFDVWQLRGKYPNRGFPKIFNDKTVGGEARKVYDDAHNMLNTL
  ISQKKLRARGVVGFWPAQSIQDDIHLYAEAAVPQAAEPIATFYGLRQQAEKDSASTEPYY
  CLSDFIAPLHSGIRDYLGLFAVACFGVEELSKAYEDDGDDYSSIMVKALGDRLAEAFAEE
  LHERVRRELWAYCGSEQLDVADLRRLRYKGIRPAPGYPSQPDHTEKLTMWRLADIEQSTG
  IRLTESLAMAPASAVSGLYFSNLKSKYFAVGKISKDQVEDYALRKNISVAEVEKWLGPIL
  GYDTD
• Function: This enzyme catalyzes the transfer of a methyl group from methyl- cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine. Subsequently, remethylates the cofactor using methyltetrahydrofolate.
• KEGG Pathway:
  Biosynthesis of amino acids (hsa01230)
  Cysteine and methionine metabolism (hsa00270)
  Metabolic pathways (hsa01100)
  One carbon pool by folate (hsa00670)
  Selenocompound metabolism (hsa00450)
• Reactome Pathway:
  Defective MTR causes methylmalonic aciduria and homocystinuria type cblG (R-HSA-3359469)
  Defective MTRR causes methylmalonic aciduria and homocystinuria type cblE (R-HSA-3359467)
  Methylation (R-HSA-156581)
  Sulfur amino acid metabolism (R-HSA-1614635)
  Cobalamin (Cbl, vitamin B12) transport and metabolism (R-HSA-196741)

Molecular Interaction Atlas (MIA) of This DME

2 Approved Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[1]
Levomefolic acid	DMUV5JB	N. A.	N. A.	Approved	[2]

Molecular Expression Atlas (MEA) of This DME

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2B33.1	Bone marrow	6.02E-05	-3.37E-01	-6.10E-01
Alopecia	ED70	Skin from scalp	1.84E-07	3.64E-01	1.47E+00
Alzheimer's disease	8A20	Entorhinal cortex	2.00E-01	2.53E-02	8.34E-02
Ankylosing spondylitis	FA92.0	Pheripheral blood	4.77E-01	2.50E-02	1.03E-01
Aortic stenosis	BB70	Calcified aortic valve	6.72E-01	-3.34E-01	-1.75E-01
Apnea	7A40	Hyperplastic tonsil	6.14E-01	1.29E-01	1.83E-01
Arthropathy	FA00-FA5Z	Peripheral blood	1.07E-01	-1.53E-01	-5.68E-01
Asthma	CA23	Nasal and bronchial airway	1.90E-02	2.59E-02	3.19E-02
Atopic dermatitis	EA80	Skin	2.55E-04	-1.86E-01	-7.58E-01
Autism	6A02	Whole blood	1.16E-02	2.67E-01	7.18E-01
Autoimmune uveitis	9A96	Peripheral monocyte	1.49E-01	5.30E-01	1.85E+00
Autosomal dominant monocytopenia	4B04	Whole blood	6.58E-01	-1.13E-01	-2.40E-01
Bacterial infection of gingival	1C1H	Gingival tissue	3.59E-02	-9.69E-03	-3.22E-02
Batten disease	5C56.1	Whole blood	6.28E-01	-4.84E-04	-3.99E-03
Behcet's disease	4A62	Peripheral blood	8.32E-01	1.69E-03	6.57E-03
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	3.31E-01	-6.69E-03	-2.50E-02
Bladder cancer	2C94	Bladder tissue	3.47E-08	-8.11E-01	-5.36E+00
Breast cancer	2C60-2C6Z	Breast tissue	4.91E-04	1.42E-01	2.31E-01
Cardioembolic stroke	8B11.20	Whole blood	1.01E-06	-4.67E-01	-1.54E+00
Cervical cancer	2C77	Cervical tissue	9.94E-03	3.12E-01	5.82E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	8.43E-01	-1.67E-01	-1.25E-01
Chronic hepatitis C	1E51.1	Whole blood	9.20E-01	8.00E-03	4.32E-02
Chronic obstructive pulmonary disease	CA22	Lung tissue	3.36E-03	-1.47E-01	-6.14E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	1.05E-02	-2.45E-01	-7.85E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	5.53E-03	-3.37E-01	-1.33E+00
Colon cancer	2B90	Colon tissue	1.40E-46	5.33E-01	1.48E+00
Coronary artery disease	BA80-BA8Z	Peripheral blood	7.93E-01	-1.29E-01	-9.41E-02
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	2.13E-01	1.68E-01	3.62E-01
Endometriosis	GA10	Endometrium tissue	5.20E-01	-5.94E-02	-1.06E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	9.84E-02	1.19E-01	9.02E-01
Familial hypercholesterolemia	5C80.00	Whole blood	4.50E-06	4.32E-01	1.22E+00
Gastric cancer	2B72	Gastric tissue	2.17E-01	-3.52E-01	-1.24E+00
Glioblastopma	2A00.00	Nervous tissue	5.71E-36	4.58E-01	9.32E-01
Glioma	2A00.0Y-2A00.0Z	Brain stem tissue	2.38E-01	7.04E-01	1.61E+00
Glioma	2A00.0Y-2A00.0Z	White matter tissue	3.77E-01	-4.84E-02	-1.56E-01
Head and neck cancer	2D42	Head and neck tissue	7.12E-05	1.43E-01	4.32E-01
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	5.62E-02	2.07E-01	3.92E-01
Huntington's disease	8A01.10	Whole blood	2.02E-01	-1.41E-01	-4.89E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	5.58E-01	1.67E-01	7.10E-01
Immunodeficiency	4A00-4A20	Peripheral blood	5.84E-02	-1.42E-01	-8.82E-01
Influenza	1E30	Whole blood	4.93E-02	-1.03E+00	-2.10E+00
Interstitial cystitis	GC00.3	Bladder tissue	9.03E-02	-1.84E-01	-1.20E+00
Intracranial aneurysm	8B01.0	Intracranial artery	6.96E-03	-5.78E-01	-1.74E+00
Irritable bowel syndrome	DD91.0	Rectal colon tissue	1.54E-03	1.40E-01	6.59E-01
Ischemic stroke	8B11	Peripheral blood	4.96E-01	-1.09E-01	-3.16E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	1.71E-01	-6.85E-02	-1.52E-01
Lateral sclerosis	8B60.4	Skin	1.55E-01	-2.19E-01	-1.16E+00
Lateral sclerosis	8B60.4	Cervical spinal cord	4.67E-01	2.11E-01	4.62E-01
Liver cancer	2C12.0	Liver tissue	4.85E-17	1.13E+00	2.17E+00
Liver failure	DB99.7-DB99.8	Liver tissue	1.15E-01	2.89E-01	8.93E-01
Lung cancer	2C25	Lung tissue	1.03E-01	-9.00E-02	-2.96E-01
Lupus erythematosus	4A40	Whole blood	1.41E-13	-4.38E-01	-9.63E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	8.01E-01	-4.41E-02	-1.63E-01
Major depressive disorder	6A70-6A7Z	Whole blood	1.74E-01	-3.31E-02	-7.84E-02
Melanoma	2C30	Skin	3.55E-01	-2.10E-01	-3.61E-01
Multiple myeloma	2A83.1	Peripheral blood	3.99E-01	-1.00E-01	-4.76E-01
Multiple myeloma	2A83.1	Bone marrow	9.93E-04	3.59E-01	1.62E+00
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	2.04E-01	-1.62E-01	-5.04E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	2.22E-04	4.35E-01	7.09E-01
Myelofibrosis	2A20.2	Whole blood	4.33E-01	-1.90E-01	-7.81E-01
Myocardial infarction	BA41-BA50	Peripheral blood	1.54E-03	-2.25E-01	-4.56E-01
Myopathy	8C70.6	Muscle tissue	1.53E-03	-1.73E-01	-1.55E+00
Neonatal sepsis	KA60	Whole blood	1.93E-17	-7.38E-01	-1.52E+00
Neuroectodermal tumour	2A00.11	Brain stem tissue	1.93E-04	7.68E-01	1.59E+00
Non-alcoholic fatty liver disease	DB92	Liver tissue	8.47E-01	1.61E-01	5.51E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	4.02E-01	9.16E-02	1.96E-01
Olive pollen allergy	CA08.00	Peripheral blood	7.54E-02	-7.26E-01	-1.62E+00
Oral cancer	2B6E	Oral tissue	4.07E-05	7.02E-01	9.84E-01
Osteoarthritis	FA00-FA0Z	Synovial tissue	3.99E-01	-1.71E-01	-4.50E-01
Osteoporosis	FB83.1	Bone marrow	5.65E-01	-1.92E-01	-7.10E-01
Ovarian cancer	2C73	Ovarian tissue	2.97E-01	-5.79E-02	-8.50E-02
Pancreatic cancer	2C10	Pancreas	7.00E-01	-1.80E-01	-3.90E-01
Parkinson's disease	8A00.0	Substantia nigra tissue	4.56E-01	-1.14E-01	-3.31E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	3.84E-02	-8.80E-02	-4.53E-01
Pituitary cancer	2D12	Pituitary tissue	5.08E-02	4.81E-01	1.75E+00
Pituitary gonadotrope tumour	2D12	Pituitary tissue	1.94E-03	5.85E-01	1.78E+00
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	3.21E-01	1.39E-02	6.72E-02
Polycythemia vera	2A20.4	Whole blood	4.30E-05	-3.04E-01	-1.24E+00
Pompe disease	5C51.3	Biceps muscle	3.38E-02	-2.03E-01	-1.11E+00
Preterm birth	KA21.4Z	Myometrium	2.85E-02	2.50E-01	1.33E+00
Prostate cancer	2C82	Prostate	2.86E-01	-3.17E-02	-5.56E-02
Psoriasis	EA90	Skin	1.36E-05	-1.52E-01	-5.70E-01
Rectal cancer	2B92	Rectal colon tissue	2.63E-03	5.62E-01	1.96E+00
Renal cancer	2C90-2C91	Kidney	3.28E-01	2.58E-02	1.67E-01
Retinoblastoma	2D02.2	Uvea	5.53E-10	1.27E+00	5.82E+00
Rheumatoid arthritis	FA20	Synovial tissue	1.02E-02	-6.76E-01	-1.64E+00
Rhinovirus infection	CA42.1	Nasal epithelium tissue	5.78E-01	1.85E-02	9.67E-02
Schizophrenia	6A20	Prefrontal cortex	8.26E-01	1.20E-01	2.12E-01
Schizophrenia	6A20	Superior temporal cortex	7.03E-01	-7.56E-02	-4.15E-01
Scleroderma	4A42.Z	Whole blood	2.52E-04	-2.97E-01	-1.66E+00
Seizure	8A60-8A6Z	Whole blood	3.75E-01	-1.22E-01	-2.90E-01
Sensitive skin	EK0Z	Skin	2.21E-01	4.40E-03	3.58E-02
Sepsis with septic shock	1G41	Whole blood	5.33E-55	-9.62E-01	-1.97E+00
Shwachman-Diamond syndrome	3A70.0	Bone marrow	5.49E-01	-5.07E-01	-1.01E+00
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	8.15E-01	-2.27E-01	-4.06E-01
Simpson golabi behmel syndrome	LD2C	Adipose tissue	7.71E-01	1.35E-01	1.88E-01
Sjogren's syndrome	4A43.2	Salivary gland tissue	3.17E-01	2.61E-01	4.75E-01
Skin cancer	2C30-2C3Z	Skin	8.29E-02	2.24E-01	6.10E-01
Thrombocythemia	3B63	Whole blood	2.56E-01	-1.53E-01	-6.09E-01
Thrombocytopenia	3B64	Whole blood	3.91E-01	-4.83E-01	-4.20E-01
Thyroid cancer	2D10	Thyroid	5.51E-05	-1.74E-01	-5.85E-01
Tibial muscular dystrophy	8C75	Muscle tissue	2.04E-03	-4.86E-01	-1.74E+00
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	3.44E-02	3.01E-01	1.54E+00
Type 2 diabetes	5A11	Liver tissue	3.82E-01	8.28E-02	1.58E-01
Ureter cancer	2C92	Urothelium	5.02E-01	-4.22E-02	-2.43E-01
Uterine cancer	2C78	Endometrium tissue	6.62E-01	-1.95E-01	-2.32E-01
Vitiligo	ED63.0	Skin	3.74E-01	6.00E-02	4.10E-01

The Drug Therapeutic Target (DTT) Role of This DME

• DME DTT Name: Methionine synthase (MTR) DTT Info
• DME DTT Type: Literature-reported

References

• [1] Metabolic derangement of methionine and folate metabolism in mice deficient in methionine synthase reductase. Mol Genet Metab. 2007 May;91(1):85-97.
• [2] Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 2010 Aug;49(8):535-48.