Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DE6NIY9)

DME Name Methionine synthase reductase (MTRR)
Synonyms Methionine synthase cob(II)alamin reductase (methylating); NADPH-dependent diflavin oxidoreductase; MSR; MTRR
Gene Name MTRR
UniProt ID
MTRR_HUMAN
INTEDE ID
DME0431
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Gene ID
4552
EC Number EC: 1.16.1.8
Oxidoreductase
Metal ion oxidoreductase
NAD/NADP acceptor oxidoreductase
EC: 1.16.1.8
Lineage Species: Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Sequence
MRRFLLLYATQQGQAKAIAEEICEQAVVHGFSADLHCISESDKYDLKTETAPLVVVVSTT
GTGDPPDTARKFVKEIQNQTLPVDFFAHLRYGLLGLGDSEYTYFCNGGKIIDKRLQELGA
RHFYDTGHADDCVGLELVVEPWIAGLWPALRKHFRSSRGQEEISGALPVASPASSRTDLV
KSELLHIESQVELLRFDDSGRKDSEVLKQNAVNSNQSNVVIEDFESSLTRSVPPLSQASL
NIPGLPPEYLQVHLQESLGQEESQVSVTSADPVFQVPISKAVQLTTNDAIKTTLLVELDI
SNTDFSYQPGDAFSVICPNSDSEVQSLLQRLQLEDKREHCVLLKIKADTKKKGATLPQHI
PAGCSLQFIFTWCLEIRAIPKKAFLRALVDYTSDSAEKRRLQELCSKQGAADYSRFVRDA
CACLLDLLLAFPSCQPPLSLLLEHLPKLQPRPYSCASSSLFHPGKLHFVFNIVEFLSTAT
TEVLRKGVCTGWLALLVASVLQPNIHASHEDSGKALAPKISISPRTTNSFHLPDDPSIPI
IMVGPGTGIAPFIGFLQHREKLQEQHPDGNFGAMWLFFGCRHKDRDYLFRKELRHFLKHG
ILTHLKVSFSRDAPVGEEEAPAKYVQDNIQLHGQQVARILLQENGHIYVCGDAKNMAKDV
HDALVQIISKEVGVEKLEAMKTLATLKEEKRYLQDIWS
Function
This enzyme is involved in the reductive regeneration of cob(I)alamin (vitamin B12) cofactor required for the maintenance of methionine synthase in a functional state. It is necessary for utilization of methylgroups from the folate cycle, thereby affecting transgenerational epigenetic inheritance. Folate pathway donates methyl groups necessary for cellular methylation and affects different pathways such as DNA methylation, possibly explaining the transgenerational epigenetic inheritance effects.
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

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
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [1]
Folic Acid DMEMBJC Colorectal carcinoma Approved [2]
Menadione DMSJDTY Vitamin K deficiency 5B59 Approved [1]
2 Investigative Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Dichloroindophenol DMAEI51 N. A. N. A. Investigative [1]
Ferricyanide DM1TH08 N. A. N. A. Investigative [1]
Experimental Enzyme Kinetic Data of Drugs
Drug Name Indication Highest Status Kinetic Data REF
Doxorubicin Acute myelogenous leukaemia [2A41] Approved Km = 0.0286 microM [1]
Menadione Vitamin K deficiency [5B59] Approved Km = 0.0177 microM [1]

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 5.39E-19 3.95E-01 1.11E+00
Alopecia ED70 Skin from scalp 2.50E-01 1.88E-02 6.06E-02
Alzheimer's disease 8A20 Entorhinal cortex 1.53E-02 9.36E-02 2.94E-01
Ankylosing spondylitis FA92.0 Pheripheral blood 9.91E-01 -1.84E-01 -7.69E-01
Aortic stenosis BB70 Calcified aortic valve 7.61E-01 -1.67E-01 -1.92E-01
Apnea 7A40 Hyperplastic tonsil 4.05E-01 5.02E-02 8.34E-02
Arthropathy FA00-FA5Z Peripheral blood 1.53E-01 -2.51E-01 -6.98E-01
Asthma CA23 Nasal and bronchial airway 9.28E-06 9.96E-02 1.86E-01
Atopic dermatitis EA80 Skin 6.80E-03 -2.74E-01 -1.21E+00
Autism 6A02 Whole blood 9.38E-01 -4.09E-03 -1.33E-02
Autoimmune uveitis 9A96 Peripheral monocyte 4.24E-02 6.04E-02 1.74E-01
Autosomal dominant monocytopenia 4B04 Whole blood 1.54E-03 1.09E+00 2.83E+00
Bacterial infection of gingival 1C1H Gingival tissue 4.26E-07 2.80E-01 9.49E-01
Batten disease 5C56.1 Whole blood 2.08E-01 -2.36E-01 -1.29E+00
Behcet's disease 4A62 Peripheral blood 8.96E-01 -1.75E-01 -8.17E-01
Bipolar disorder 6A60-6A6Z Prefrontal cortex 3.26E-01 2.42E-02 1.44E-01
Bladder cancer 2C94 Bladder tissue 1.79E-04 -4.07E-01 -2.47E+00
Breast cancer 2C60-2C6Z Breast tissue 2.27E-14 1.29E-01 3.40E-01
Cardioembolic stroke 8B11.20 Whole blood 5.91E-01 1.46E-01 4.40E-01
Cervical cancer 2C77 Cervical tissue 2.74E-03 1.50E-01 5.78E-01
Childhood onset rheumatic disease FA20.Z Peripheral blood 3.71E-01 -6.69E-02 -5.15E-02
Chronic hepatitis C 1E51.1 Whole blood 6.25E-01 -3.34E-02 -1.04E-01
Chronic obstructive pulmonary disease CA22 Lung tissue 5.82E-01 -5.77E-02 -1.82E-01
Chronic obstructive pulmonary disease CA22 Small airway epithelium 5.80E-01 1.38E-02 4.74E-02
Chronic rhinosinusitis CA0A Sinus mucosa tissue 1.45E-01 -1.53E-01 -7.85E-01
Colon cancer 2B90 Colon tissue 2.29E-10 1.53E-01 5.65E-01
Coronary artery disease BA80-BA8Z Peripheral blood 6.18E-01 2.21E-01 2.49E-01
Diffuse large B-cell lymphoma 2A81 Tonsil tissue 2.81E-01 1.28E-01 1.95E-01
Endometriosis GA10 Endometrium tissue 1.95E-01 2.42E-01 5.23E-01
Familial hypercholesterolemia 5C80.00 Peripheral blood 6.06E-01 8.43E-03 5.76E-02
Familial hypercholesterolemia 5C80.00 Whole blood 1.93E-02 1.91E-01 7.12E-01
Gastric cancer 2B72 Gastric tissue 4.23E-01 4.62E-01 8.89E-01
Glioblastopma 2A00.00 Nervous tissue 1.14E-09 -1.68E-01 -4.30E-01
Glioma 2A00.0Y-2A00.0Z Brain stem tissue 8.11E-01 -1.94E-01 -2.14E-01
Glioma 2A00.0Y-2A00.0Z White matter tissue 3.93E-03 4.40E-01 1.57E+00
Head and neck cancer 2D42 Head and neck tissue 9.14E-08 2.30E-01 6.96E-01
HIV-associated neurocognitive impairment 8A2Y-8A2Z White matter tissue 8.38E-01 -3.36E-02 -1.73E-01
Huntington's disease 8A01.10 Whole blood 4.55E-01 -9.11E-02 -3.46E-01
Idiopathic pulmonary fibrosis CB03.4 Lung tissue 7.22E-03 -4.90E-01 -2.21E+00
Immunodeficiency 4A00-4A20 Peripheral blood 2.31E-01 9.09E-02 5.48E-01
Influenza 1E30 Whole blood 5.24E-04 -1.40E+00 -5.80E+00
Interstitial cystitis GC00.3 Bladder tissue 3.53E-01 6.01E-02 3.39E-01
Intracranial aneurysm 8B01.0 Intracranial artery 1.73E-02 -4.05E-01 -1.39E+00
Irritable bowel syndrome DD91.0 Rectal colon tissue 8.71E-01 4.32E-02 2.18E-01
Ischemic stroke 8B11 Peripheral blood 2.86E-01 -5.80E-03 -2.63E-02
Juvenile idiopathic arthritis FA24 Peripheral blood 5.94E-02 -1.27E-02 -2.75E-02
Lateral sclerosis 8B60.4 Skin 2.97E-01 1.67E-01 5.06E-01
Lateral sclerosis 8B60.4 Cervical spinal cord 1.71E-01 -2.11E-01 -7.74E-01
Liver cancer 2C12.0 Liver tissue 2.22E-01 -5.75E-02 -1.09E-01
Liver failure DB99.7-DB99.8 Liver tissue 9.80E-07 -1.09E+00 -5.95E+00
Lung cancer 2C25 Lung tissue 9.48E-29 -4.49E-01 -1.45E+00
Lupus erythematosus 4A40 Whole blood 2.13E-01 -3.09E-02 -6.67E-02
Major depressive disorder 6A70-6A7Z Hippocampus 5.75E-01 -4.45E-03 -2.58E-02
Major depressive disorder 6A70-6A7Z Whole blood 2.84E-01 -1.05E-02 -2.45E-02
Melanoma 2C30 Skin 8.01E-01 -6.39E-03 -1.40E-02
Multiple myeloma 2A83.1 Peripheral blood 4.23E-01 3.67E-03 2.72E-02
Multiple myeloma 2A83.1 Bone marrow 1.08E-05 9.91E-01 4.04E+00
Multiple sclerosis 8A40 Plasmacytoid dendritic cells 7.36E-01 1.48E-02 5.20E-02
Myelodysplastic syndrome 2A36-2A3Z Bone marrow 1.01E-02 1.46E-01 4.08E-01
Myelofibrosis 2A20.2 Whole blood 9.75E-01 1.13E-01 4.64E-01
Myocardial infarction BA41-BA50 Peripheral blood 1.09E-02 -3.99E-01 -7.26E-01
Myopathy 8C70.6 Muscle tissue 3.09E-01 -1.40E-01 -5.50E-01
Neonatal sepsis KA60 Whole blood 5.72E-08 4.59E-01 9.94E-01
Neuroectodermal tumour 2A00.11 Brain stem tissue 7.84E-01 2.35E-02 5.53E-02
Non-alcoholic fatty liver disease DB92 Liver tissue 2.28E-02 5.85E-01 1.97E+00
Obesity related type 2 diabetes 5A11 Omental adipose tissue 4.19E-01 -2.82E-02 -9.18E-02
Olive pollen allergy CA08.00 Peripheral blood 3.29E-01 -4.51E-01 -9.80E-01
Oral cancer 2B6E Oral tissue 1.11E-04 5.30E-01 8.80E-01
Osteoarthritis FA00-FA0Z Synovial tissue 2.04E-01 -1.56E-01 -3.51E-01
Osteoporosis FB83.1 Bone marrow 1.25E-02 -5.73E-01 -2.39E+00
Ovarian cancer 2C73 Ovarian tissue 5.09E-02 3.28E-01 7.65E-01
Pancreatic cancer 2C10 Pancreas 5.36E-01 -1.44E-01 -3.76E-01
Parkinson's disease 8A00.0 Substantia nigra tissue 3.17E-02 2.76E-01 8.24E-01
Pediatric respiratory syncytial virus infection CA40.11 Peripheral blood 8.51E-02 1.63E-01 8.88E-01
Pituitary cancer 2D12 Pituitary tissue 3.27E-01 -1.58E-01 -3.59E-01
Pituitary gonadotrope tumour 2D12 Pituitary tissue 3.00E-01 -1.52E-01 -5.38E-01
Polycystic ovary syndrome 5A80.1 Vastus lateralis muscle 2.92E-01 -8.23E-02 -4.12E-01
Polycythemia vera 2A20.4 Whole blood 4.90E-01 5.49E-02 2.18E-01
Pompe disease 5C51.3 Biceps muscle 5.85E-04 -3.61E-01 -2.50E+00
Preterm birth KA21.4Z Myometrium 9.13E-01 6.66E-02 1.15E-01
Prostate cancer 2C82 Prostate 4.99E-01 2.43E-01 4.68E-01
Psoriasis EA90 Skin 1.25E-13 2.56E-01 1.04E+00
Rectal cancer 2B92 Rectal colon tissue 1.54E-02 2.72E-01 1.36E+00
Renal cancer 2C90-2C91 Kidney 6.10E-01 2.22E-01 5.71E-01
Retinoblastoma 2D02.2 Uvea 3.04E-01 1.59E-01 8.03E-01
Rheumatoid arthritis FA20 Synovial tissue 3.12E-01 -3.21E-01 -4.98E-01
Rhinovirus infection CA42.1 Nasal epithelium tissue 5.17E-01 -5.00E-02 -3.53E-01
Schizophrenia 6A20 Prefrontal cortex 1.88E-01 -1.92E-02 -5.59E-02
Schizophrenia 6A20 Superior temporal cortex 2.92E-01 -3.75E-02 -1.72E-01
Scleroderma 4A42.Z Whole blood 5.53E-10 -4.79E-01 -4.30E+00
Seizure 8A60-8A6Z Whole blood 5.80E-01 1.52E-01 4.64E-01
Sensitive skin EK0Z Skin 5.86E-02 2.36E-01 1.58E+00
Sepsis with septic shock 1G41 Whole blood 1.55E-02 1.48E-02 4.72E-02
Shwachman-Diamond syndrome 3A70.0 Bone marrow 9.16E-01 4.47E-02 1.30E-01
Sickle cell disease 3A51.0-3A51.3 Peripheral blood 6.59E-02 -1.18E-01 -2.32E-01
Simpson golabi behmel syndrome LD2C Adipose tissue 5.20E-02 -4.05E-01 -2.58E+00
Sjogren's syndrome 4A43.2 Salivary gland tissue 2.59E-01 2.33E-01 9.90E-01
Skin cancer 2C30-2C3Z Skin 1.56E-04 1.34E-01 4.66E-01
Thrombocythemia 3B63 Whole blood 1.38E-01 2.14E-02 8.01E-02
Thrombocytopenia 3B64 Whole blood 5.94E-01 -6.17E-01 -8.32E-01
Thyroid cancer 2D10 Thyroid 5.15E-01 -2.33E-02 -9.82E-02
Tibial muscular dystrophy 8C75 Muscle tissue 1.05E-04 -6.05E-01 -1.29E+00
Tuberous sclerosis complex LD2D.2 Perituberal tissue 2.18E-01 -2.45E-01 -1.06E+00
Type 2 diabetes 5A11 Liver tissue 5.06E-01 3.22E-03 9.53E-03
Ureter cancer 2C92 Urothelium 6.05E-02 1.10E-01 6.37E-01
Uterine cancer 2C78 Endometrium tissue 1.56E-23 4.43E-01 1.02E+00
Vitiligo ED63.0 Skin 8.42E-03 1.54E-01 1.62E+00
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⏷ Show the Full List of DME Expression Under 107 Diseases

References

1 Differences in the efficiency of reductive activation of methionine synthase and exogenous electron acceptors between the common polymorphic variants of human methionine synthase reductase. Biochemistry. 2002 Nov 12;41(45):13378-85.
2 Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome in China. J Zhejiang Univ Sci B. 2008 Feb;9(2):93-9.