Details of Drug-Metabolizing Enzyme (DME)

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

DME Name Glutamate-cysteine ligase regulatory (GCLM)
Synonyms
Glutamate--cysteine ligase modifier subunit; Glutamate--cysteine ligase regulatory subunit; Gamma-ECS regulatory subunit; Gamma-glutamylcysteine synthetase regulatory subunit; GCLM; GCS light chain; GLCLR
Gene Name GCLM
UniProt ID
GSH0_HUMAN
INTEDE ID
DME0486
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Gene ID
2730
EC Number EC: 6.3.2.2
Ligase
Carbon-nitrogen ligase
Peptide synthase
EC: 6.3.2.2
Lineage Species: Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Sequence
MGTDSRAAKALLARARTLHLQTGNLLNWGRLRKKCPSTHSEELHDCIQKTLNEWSSQINP
DLVREFPDVLECTVSHAVEKINPDEREEMKVSAKLFIVESNSSSSTRSAVDMACSVLGVA
QLDSVIIASPPIEDGVNLSLEHLQPYWEELENLVQSKKIVAIGTSDLDKTQLEQLYQWAQ
VKPNSNQVNLASCCVMPPDLTAFAKQFDIQLLTHNDPKELLSEASFQEALQESIPDIQAH
EWVPLWLLRYSVIVKSRGIIKSKGYILQAKRRGS
Function
This enzyme is the first rate limiting enzyme of glutathione synthesis. The enzyme consists of two subunits, a heavy catalytic subuit and a light regulatory subunit. Gamma glutamylcysteine synthetase deficiency has been implicated in some forms of hemolytic anemia.
KEGG Pathway
Cysteine and methionine metabolism (hsa00270 )
Ferroptosis (hsa04216 )
Glutathione metabolism (hsa00480 )
Metabolic pathways (hsa01100 )
Reactome Pathway
Glutathione synthesis and recycling (R-HSA-174403 )
Defective GCLC causes Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency (HAGGSD) (R-HSA-5578999 )

Molecular Interaction Atlas (MIA) of This DME

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DME
1 Clinical Trial Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
L-cysteine DMCMOS8 Amyloidosis 5D00 Clinical trial [4]
Experimental Enzyme Kinetic Data of Drugs
Drug Name Indication Highest Status Kinetic Data REF
L-cysteine Amyloidosis [5D00] Clinical trial Km = 0.1 microM [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 1.11E-32 -1.53E+00 -1.60E+00
Alopecia ED70 Skin from scalp 3.55E-05 -3.14E-01 -9.91E-01
Alzheimer's disease 8A20 Entorhinal cortex 6.78E-01 -1.29E-03 -4.18E-03
Ankylosing spondylitis FA92.0 Pheripheral blood 3.79E-01 2.00E-02 4.05E-02
Aortic stenosis BB70 Calcified aortic valve 5.80E-01 4.55E-01 8.42E-01
Apnea 7A40 Hyperplastic tonsil 4.70E-01 -2.04E-01 -2.10E-01
Arthropathy FA00-FA5Z Peripheral blood 3.10E-01 -3.39E-01 -9.14E-01
Asthma CA23 Nasal and bronchial airway 1.08E-04 2.86E-01 2.97E-01
Atopic dermatitis EA80 Skin 2.50E-03 4.30E-01 1.18E+00
Autism 6A02 Whole blood 2.53E-02 8.05E-02 2.05E-01
Autoimmune uveitis 9A96 Peripheral monocyte 2.72E-01 3.47E-01 8.49E-01
Autosomal dominant monocytopenia 4B04 Whole blood 8.42E-02 9.20E-01 1.02E+00
Bacterial infection of gingival 1C1H Gingival tissue 6.22E-01 3.80E-02 4.91E-02
Batten disease 5C56.1 Whole blood 2.34E-01 -1.29E-02 -4.15E-02
Behcet's disease 4A62 Peripheral blood 7.28E-01 1.53E-02 3.46E-02
Bipolar disorder 6A60-6A6Z Prefrontal cortex 5.89E-01 2.95E-02 8.82E-02
Bladder cancer 2C94 Bladder tissue 7.32E-01 -1.17E-02 -1.91E-02
Breast cancer 2C60-2C6Z Breast tissue 1.52E-04 -1.85E-01 -2.51E-01
Cardioembolic stroke 8B11.20 Whole blood 2.81E-01 6.88E-02 2.55E-01
Cervical cancer 2C77 Cervical tissue 7.92E-03 2.66E-01 3.11E-01
Childhood onset rheumatic disease FA20.Z Peripheral blood 5.07E-01 1.79E-01 2.82E-01
Chronic hepatitis C 1E51.1 Whole blood 2.17E-01 -1.20E-01 -2.92E-01
Chronic obstructive pulmonary disease CA22 Lung tissue 3.63E-01 -9.27E-02 -1.37E-01
Chronic obstructive pulmonary disease CA22 Small airway epithelium 4.14E-03 3.76E-01 5.55E-01
Chronic rhinosinusitis CA0A Sinus mucosa tissue 3.46E-01 -7.56E-01 -8.34E-01
Colon cancer 2B90 Colon tissue 1.53E-07 2.53E-01 4.45E-01
Coronary artery disease BA80-BA8Z Peripheral blood 3.84E-01 4.15E-01 8.04E-01
Diffuse large B-cell lymphoma 2A81 Tonsil tissue 5.27E-01 5.15E-01 7.24E-01
Endometriosis GA10 Endometrium tissue 6.99E-02 3.46E-01 4.28E-01
Familial hypercholesterolemia 5C80.00 Peripheral blood 9.40E-01 1.99E-01 6.02E-01
Familial hypercholesterolemia 5C80.00 Whole blood 7.86E-01 2.68E-02 5.78E-02
Gastric cancer 2B72 Gastric tissue 1.95E-01 6.52E-01 5.38E-01
Glioblastopma 2A00.00 Nervous tissue 2.75E-25 5.18E-01 7.87E-01
Glioma 2A00.0Y-2A00.0Z Brain stem tissue 5.40E-01 -4.69E-01 -6.69E-01
Glioma 2A00.0Y-2A00.0Z White matter tissue 9.23E-01 -2.01E-02 -3.12E-02
Head and neck cancer 2D42 Head and neck tissue 1.37E-01 -3.73E-01 -3.80E-01
HIV-associated neurocognitive impairment 8A2Y-8A2Z White matter tissue 9.36E-01 2.12E-01 3.09E-01
Huntington's disease 8A01.10 Whole blood 3.42E-01 6.10E-02 1.52E-01
Idiopathic pulmonary fibrosis CB03.4 Lung tissue 1.30E-01 -6.91E-01 -6.64E-01
Immunodeficiency 4A00-4A20 Peripheral blood 1.08E-01 -2.06E-01 -9.87E-01
Influenza 1E30 Whole blood 7.31E-01 -1.44E-01 -4.64E-01
Interstitial cystitis GC00.3 Bladder tissue 7.49E-01 1.82E-02 4.35E-02
Intracranial aneurysm 8B01.0 Intracranial artery 2.33E-01 3.64E-01 3.50E-01
Irritable bowel syndrome DD91.0 Rectal colon tissue 4.42E-01 9.85E-02 2.47E-01
Ischemic stroke 8B11 Peripheral blood 5.42E-01 -7.60E-02 -1.90E-01
Juvenile idiopathic arthritis FA24 Peripheral blood 1.87E-01 7.53E-02 2.02E-01
Lateral sclerosis 8B60.4 Skin 3.38E-01 -1.64E-01 -3.60E-01
Lateral sclerosis 8B60.4 Cervical spinal cord 5.32E-01 -3.00E-01 -2.72E-01
Liver cancer 2C12.0 Liver tissue 3.71E-01 -2.09E-01 -2.22E-01
Liver failure DB99.7-DB99.8 Liver tissue 3.24E-01 -2.57E-01 -4.59E-01
Lung cancer 2C25 Lung tissue 1.71E-21 3.54E-01 6.80E-01
Lupus erythematosus 4A40 Whole blood 9.55E-02 1.25E-01 1.84E-01
Major depressive disorder 6A70-6A7Z Hippocampus 2.91E-01 8.07E-02 2.39E-01
Major depressive disorder 6A70-6A7Z Whole blood 4.69E-01 -3.70E-02 -7.93E-02
Melanoma 2C30 Skin 1.14E-02 -9.99E-01 -9.12E-01
Multiple myeloma 2A83.1 Peripheral blood 6.96E-01 -5.44E-02 -1.37E-01
Multiple myeloma 2A83.1 Bone marrow 1.72E-01 4.46E-02 1.30E-01
Multiple sclerosis 8A40 Plasmacytoid dendritic cells 4.35E-01 -1.45E-01 -2.99E-01
Myelodysplastic syndrome 2A36-2A3Z Bone marrow 1.00E-04 2.11E-01 3.98E-01
Myelofibrosis 2A20.2 Whole blood 3.45E-03 1.65E+00 3.60E+00
Myocardial infarction BA41-BA50 Peripheral blood 1.63E-03 -3.55E-01 -6.04E-01
Myopathy 8C70.6 Muscle tissue 1.25E-01 -2.13E-01 -3.04E-01
Neonatal sepsis KA60 Whole blood 1.59E-35 1.24E+00 2.91E+00
Neuroectodermal tumour 2A00.11 Brain stem tissue 4.02E-05 1.02E+00 1.98E+00
Non-alcoholic fatty liver disease DB92 Liver tissue 2.08E-01 7.31E-01 8.18E-01
Obesity related type 2 diabetes 5A11 Omental adipose tissue 7.73E-01 -4.37E-01 -4.55E-01
Olive pollen allergy CA08.00 Peripheral blood 3.38E-01 -4.70E-01 -1.10E+00
Oral cancer 2B6E Oral tissue 1.20E-03 7.91E-01 7.07E-01
Osteoarthritis FA00-FA0Z Synovial tissue 9.00E-01 -2.17E-01 -1.07E-01
Osteoporosis FB83.1 Bone marrow 4.47E-01 -6.34E-01 -8.07E-01
Ovarian cancer 2C73 Ovarian tissue 1.55E-01 6.08E-01 4.83E-01
Pancreatic cancer 2C10 Pancreas 2.86E-01 5.04E-01 5.93E-01
Parkinson's disease 8A00.0 Substantia nigra tissue 2.94E-01 -1.69E-01 -2.17E-01
Pediatric respiratory syncytial virus infection CA40.11 Peripheral blood 1.73E-02 1.87E-01 3.49E-01
Pituitary cancer 2D12 Pituitary tissue 4.76E-02 3.98E-01 7.67E-01
Pituitary gonadotrope tumour 2D12 Pituitary tissue 3.12E-01 1.00E-01 1.85E-01
Polycystic ovary syndrome 5A80.1 Vastus lateralis muscle 7.36E-01 8.27E-02 1.53E-01
Polycythemia vera 2A20.4 Whole blood 7.84E-09 6.76E-01 1.52E+00
Pompe disease 5C51.3 Biceps muscle 9.84E-01 -1.04E-02 -3.82E-02
Preterm birth KA21.4Z Myometrium 2.48E-01 2.53E-01 7.17E-01
Prostate cancer 2C82 Prostate 3.45E-01 4.10E-01 3.95E-01
Psoriasis EA90 Skin 6.34E-01 -4.40E-03 -6.20E-03
Rectal cancer 2B92 Rectal colon tissue 8.46E-02 7.11E-01 1.03E+00
Renal cancer 2C90-2C91 Kidney 8.70E-04 1.90E+00 1.89E+00
Retinoblastoma 2D02.2 Uvea 3.85E-04 1.01E+00 3.40E+00
Rheumatoid arthritis FA20 Synovial tissue 8.92E-01 -3.44E-01 -3.02E-01
Rhinovirus infection CA42.1 Nasal epithelium tissue 8.77E-01 9.90E-02 2.33E-01
Schizophrenia 6A20 Prefrontal cortex 6.94E-01 -1.02E-01 -1.53E-01
Schizophrenia 6A20 Superior temporal cortex 8.08E-01 5.08E-02 2.15E-01
Scleroderma 4A42.Z Whole blood 1.18E-02 -8.52E-01 -1.57E+00
Seizure 8A60-8A6Z Whole blood 3.79E-02 3.11E-01 6.41E-01
Sensitive skin EK0Z Skin 4.39E-01 -3.29E-01 -1.32E+00
Sepsis with septic shock 1G41 Whole blood 1.67E-116 1.54E+00 3.39E+00
Shwachman-Diamond syndrome 3A70.0 Bone marrow 2.97E-02 5.38E-01 1.69E+00
Sickle cell disease 3A51.0-3A51.3 Peripheral blood 2.52E-02 6.62E-01 7.96E-01
Simpson golabi behmel syndrome LD2C Adipose tissue 2.52E-01 8.93E-01 1.68E+00
Sjogren's syndrome 4A43.2 Salivary gland tissue 3.11E-01 7.35E-01 1.31E+00
Skin cancer 2C30-2C3Z Skin 3.46E-01 -1.03E-02 -1.40E-02
Thrombocythemia 3B63 Whole blood 6.45E-07 7.47E-01 1.63E+00
Thrombocytopenia 3B64 Whole blood 5.60E-01 -2.26E-01 -2.06E-01
Thyroid cancer 2D10 Thyroid 4.41E-04 -2.89E-01 -4.97E-01
Tibial muscular dystrophy 8C75 Muscle tissue 4.25E-01 2.06E-01 4.55E-01
Tuberous sclerosis complex LD2D.2 Perituberal tissue 5.01E-02 -4.89E-01 -1.81E+00
Type 2 diabetes 5A11 Liver tissue 4.36E-01 3.52E-01 6.46E-01
Ureter cancer 2C92 Urothelium 8.91E-02 2.43E-02 1.67E-01
Uterine cancer 2C78 Endometrium tissue 4.69E-35 1.19E+00 1.54E+00
Vitiligo ED63.0 Skin 5.27E-01 -3.07E-01 -8.08E-01
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⏷ Show the Full List of DME Expression Under 107 Diseases

The Drug Therapeutic Target (DTT) Role of This DME

DME DTT Name Glutamate--cysteine ligase modifier (GCLM) DTT Info
DME DTT Type Literature-reported
3 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Buthionine sulfoximine DMJ46CB Malaria 1F40-1F45 Investigative [1]
Cystamine DMS5DHY Discovery agent N.A. Investigative [2]
N-Formylmethionine DM7GBDX Discovery agent N.A. Investigative [3]

References

1 Novel molecular targets for antimalarial chemotherapy. Int J Antimicrob Agents. 2007 Jul;30(1):4-10.
2 The gamma-glutamylcysteine synthetase of Onchocerca volvulus. Mol Biochem Parasitol. 2000 Dec;111(2):243-51.
3 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
4 The enzymes of glutathione synthesis: gamma-glutamylcysteine synthetase. Adv Enzymol Relat Areas Mol Biol. 1999;73:209-67, xii.