Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DESYL1F)

DME Name Glutamate-cysteine ligase catalytic (GCLC)
Synonyms Gamma-glutamylcysteine synthetase; Glutamate--cysteine ligase catalytic subunit; Gamma-ECS; GCLC; GCS heavy chain; GLCL; GLCLC
Gene Name GCLC
UniProt ID
GSH1_HUMAN
INTEDE ID
DME0485
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Gene ID
2729
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
MGLLSQGSPLSWEETKRHADHVRRHGILQFLHIYHAVKDRHKDVLKWGDEVEYMLVSFDH
ENKKVRLVLSGEKVLETLQEKGERTNPNHPTLWRPEYGSYMIEGTPGQPYGGTMSEFNTV
EANMRKRRKEATSILEENQALCTITSFPRLGCPGFTLPEVKPNPVEGGASKSLFFPDEAI
NKHPRFSTLTRNIRHRRGEKVVINVPIFKDKNTPSPFIETFTEDDEASRASKPDHIYMDA
MGFGMGNCCLQVTFQACSISEARYLYDQLATICPIVMALSAASPFYRGYVSDIDCRWGVI
SASVDDRTREERGLEPLKNNNYRISKSRYDSIDSYLSKCGEKYNDIDLTIDKEIYEQLLQ
EGIDHLLAQHVAHLFIRDPLTLFEEKIHLDDANESDHFENIQSTNWQTMRFKPPPPNSDI
GWRVEFRPMEVQLTDFENSAYVVFVVLLTRVILSYKLDFLIPLSKVDENMKVAQKRDAVL
QGMFYFRKDICKGGNAVVDGCGKAQNSTELAAEEYTLMSIDTIINGKEGVFPGLIPILNS
YLENMEVDVDTRCSILNYLKLIKKRASGELMTVARWMREFIANHPDYKQDSVITDEMNYS
LILKCNQIANELCECPELLGSAFRKVKYSGSKTDSSN
Function This enzyme is the first rate limiting enzyme of glutathione synthesis. The enzyme consists of two subunits, a heavy catalytic subunit and a light regulatory subunit.
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 [1]
Experimental Enzyme Kinetic Data of Drugs
Drug Name Indication Highest Status Kinetic Data REF
L-cysteine Amyloidosis [5D00] Clinical trial Km = 0.1 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 1.32E-09 -5.98E-01 -8.35E-01
Alopecia ED70 Skin from scalp 1.83E-06 -2.91E-01 -1.19E+00
Alzheimer's disease 8A20 Entorhinal cortex 6.26E-01 -2.58E-03 -7.03E-03
Ankylosing spondylitis FA92.0 Pheripheral blood 6.33E-01 -3.75E-02 -1.36E-01
Aortic stenosis BB70 Calcified aortic valve 6.67E-01 -3.25E-01 -4.13E-01
Apnea 7A40 Hyperplastic tonsil 5.08E-03 -1.26E+00 -1.73E+00
Arthropathy FA00-FA5Z Peripheral blood 6.67E-01 -3.76E-02 -1.22E-01
Asthma CA23 Nasal and bronchial airway 1.06E-01 1.11E-01 1.17E-01
Atopic dermatitis EA80 Skin 1.17E-02 -2.62E-01 -1.03E+00
Autism 6A02 Whole blood 7.23E-01 -4.33E-02 -1.35E-01
Autoimmune uveitis 9A96 Peripheral monocyte 1.27E-01 -1.27E-01 -3.68E-01
Autosomal dominant monocytopenia 4B04 Whole blood 5.96E-01 1.46E-01 3.66E-01
Bacterial infection of gingival 1C1H Gingival tissue 2.72E-01 8.27E-02 1.94E-01
Batten disease 5C56.1 Whole blood 9.10E-01 -1.20E-01 -7.10E-01
Behcet's disease 4A62 Peripheral blood 9.07E-01 -6.93E-02 -2.06E-01
Bipolar disorder 6A60-6A6Z Prefrontal cortex 9.09E-01 7.96E-03 3.85E-02
Bladder cancer 2C94 Bladder tissue 3.62E-05 -1.13E+00 -2.54E+00
Breast cancer 2C60-2C6Z Breast tissue 2.47E-10 -4.14E-01 -4.73E-01
Cardioembolic stroke 8B11.20 Whole blood 1.16E-06 4.22E-01 1.75E+00
Cervical cancer 2C77 Cervical tissue 3.39E-01 -1.72E-03 -3.68E-03
Childhood onset rheumatic disease FA20.Z Peripheral blood 9.41E-01 2.32E-02 2.53E-02
Chronic hepatitis C 1E51.1 Whole blood 7.08E-01 3.47E-02 1.20E-01
Chronic obstructive pulmonary disease CA22 Lung tissue 8.34E-01 -3.04E-03 -1.02E-02
Chronic obstructive pulmonary disease CA22 Small airway epithelium 3.53E-01 -3.05E-02 -5.86E-02
Chronic rhinosinusitis CA0A Sinus mucosa tissue 3.17E-02 -1.28E+00 -1.04E+00
Colon cancer 2B90 Colon tissue 5.14E-02 3.02E-02 9.45E-02
Coronary artery disease BA80-BA8Z Peripheral blood 1.77E-02 1.42E-01 2.13E+00
Diffuse large B-cell lymphoma 2A81 Tonsil tissue 6.53E-01 6.86E-02 8.94E-02
Endometriosis GA10 Endometrium tissue 3.41E-02 -3.34E-01 -3.27E-01
Familial hypercholesterolemia 5C80.00 Peripheral blood 6.05E-01 -4.56E-02 -1.41E-01
Familial hypercholesterolemia 5C80.00 Whole blood 1.83E-01 3.31E-01 7.26E-01
Gastric cancer 2B72 Gastric tissue 9.76E-01 -4.44E-02 -7.20E-02
Glioblastopma 2A00.00 Nervous tissue 1.72E-08 2.04E-01 4.14E-01
Glioma 2A00.0Y-2A00.0Z Brain stem tissue 6.25E-01 -1.96E-01 -7.64E-01
Glioma 2A00.0Y-2A00.0Z White matter tissue 5.57E-05 -1.01E+00 -2.02E+00
Head and neck cancer 2D42 Head and neck tissue 8.76E-05 -1.61E-01 -1.18E-01
HIV-associated neurocognitive impairment 8A2Y-8A2Z White matter tissue 7.04E-01 9.66E-02 1.54E-01
Huntington's disease 8A01.10 Whole blood 4.38E-01 -2.91E-01 -8.85E-01
Idiopathic pulmonary fibrosis CB03.4 Lung tissue 6.32E-01 2.11E-01 4.79E-01
Immunodeficiency 4A00-4A20 Peripheral blood 9.68E-02 -1.02E-01 -9.54E-01
Influenza 1E30 Whole blood 6.20E-03 -6.93E-01 -4.41E+00
Interstitial cystitis GC00.3 Bladder tissue 1.48E-04 -1.84E+00 -4.41E+00
Intracranial aneurysm 8B01.0 Intracranial artery 3.37E-02 3.36E-01 5.37E-01
Irritable bowel syndrome DD91.0 Rectal colon tissue 6.71E-01 1.65E-02 6.52E-02
Ischemic stroke 8B11 Peripheral blood 4.46E-01 1.89E-02 8.05E-02
Juvenile idiopathic arthritis FA24 Peripheral blood 1.24E-02 4.89E-02 1.21E-01
Lateral sclerosis 8B60.4 Skin 9.34E-01 1.45E-01 3.75E-01
Lateral sclerosis 8B60.4 Cervical spinal cord 5.58E-02 -8.08E-01 -8.92E-01
Liver cancer 2C12.0 Liver tissue 2.03E-06 -4.17E-01 -7.65E-01
Liver failure DB99.7-DB99.8 Liver tissue 4.64E-04 -1.02E+00 -2.87E+00
Lung cancer 2C25 Lung tissue 6.97E-77 1.02E+00 2.21E+00
Lupus erythematosus 4A40 Whole blood 3.22E-02 -1.28E-01 -3.42E-01
Major depressive disorder 6A70-6A7Z Hippocampus 6.23E-01 -1.86E-02 -9.27E-02
Major depressive disorder 6A70-6A7Z Whole blood 7.02E-01 2.11E-02 5.30E-02
Melanoma 2C30 Skin 1.24E-04 -3.51E-01 -9.54E-01
Multiple myeloma 2A83.1 Peripheral blood 4.18E-01 -1.37E-01 -2.76E-01
Multiple myeloma 2A83.1 Bone marrow 7.76E-03 5.00E-01 1.44E+00
Multiple sclerosis 8A40 Plasmacytoid dendritic cells 1.06E-01 -6.50E-01 -1.33E+00
Myelodysplastic syndrome 2A36-2A3Z Bone marrow 3.95E-05 2.22E-01 7.90E-01
Myelofibrosis 2A20.2 Whole blood 1.60E-02 1.26E+00 4.33E+00
Myocardial infarction BA41-BA50 Peripheral blood 1.42E-02 -5.22E-02 -7.28E-02
Myopathy 8C70.6 Muscle tissue 6.65E-02 7.82E-02 3.17E-01
Neonatal sepsis KA60 Whole blood 5.49E-02 4.79E-02 7.17E-02
Neuroectodermal tumour 2A00.11 Brain stem tissue 8.72E-02 5.14E-01 9.53E-01
Non-alcoholic fatty liver disease DB92 Liver tissue 3.12E-02 1.34E-01 4.90E-01
Obesity related type 2 diabetes 5A11 Omental adipose tissue 8.32E-01 1.41E-01 2.22E-01
Olive pollen allergy CA08.00 Peripheral blood 4.01E-01 8.41E-01 6.74E-01
Oral cancer 2B6E Oral tissue 1.43E-01 3.26E-01 2.38E-01
Osteoarthritis FA00-FA0Z Synovial tissue 7.71E-01 -7.84E-02 -1.18E-01
Osteoporosis FB83.1 Bone marrow 1.38E-01 -1.58E-01 -3.58E-01
Ovarian cancer 2C73 Ovarian tissue 5.60E-01 7.02E-01 5.17E-01
Pancreatic cancer 2C10 Pancreas 9.00E-01 -1.84E-01 -2.68E-01
Parkinson's disease 8A00.0 Substantia nigra tissue 7.72E-01 4.55E-03 1.06E-02
Pediatric respiratory syncytial virus infection CA40.11 Peripheral blood 1.49E-02 5.56E-02 2.55E-01
Pituitary cancer 2D12 Pituitary tissue 9.26E-09 1.30E+00 3.32E+00
Pituitary gonadotrope tumour 2D12 Pituitary tissue 1.21E-07 1.99E+00 4.15E+00
Polycystic ovary syndrome 5A80.1 Vastus lateralis muscle 4.91E-01 3.82E-02 1.61E-01
Polycythemia vera 2A20.4 Whole blood 5.97E-02 8.43E-02 2.81E-01
Pompe disease 5C51.3 Biceps muscle 8.44E-03 5.15E-01 1.41E+00
Preterm birth KA21.4Z Myometrium 4.63E-01 3.56E-01 5.02E-01
Prostate cancer 2C82 Prostate 2.43E-06 -3.79E-01 -7.61E-01
Psoriasis EA90 Skin 1.40E-02 1.24E-01 3.02E-01
Rectal cancer 2B92 Rectal colon tissue 1.49E-01 1.27E-01 5.26E-01
Renal cancer 2C90-2C91 Kidney 1.05E-03 6.27E-01 1.21E+00
Retinoblastoma 2D02.2 Uvea 7.43E-04 7.74E-01 3.77E+00
Rheumatoid arthritis FA20 Synovial tissue 5.86E-01 -9.54E-02 -1.38E-01
Rhinovirus infection CA42.1 Nasal epithelium tissue 7.46E-03 -1.74E-01 -5.34E-01
Schizophrenia 6A20 Prefrontal cortex 1.62E-01 -9.03E-02 -2.32E-01
Schizophrenia 6A20 Superior temporal cortex 7.85E-02 -1.17E-01 -5.16E-01
Scleroderma 4A42.Z Whole blood 9.14E-01 4.97E-02 1.61E-01
Seizure 8A60-8A6Z Whole blood 2.70E-02 -1.79E-01 -2.62E-01
Sensitive skin EK0Z Skin 3.64E-01 -1.93E-03 -1.97E-02
Sepsis with septic shock 1G41 Whole blood 2.70E-01 -2.71E-01 -5.63E-01
Shwachman-Diamond syndrome 3A70.0 Bone marrow 7.37E-03 8.32E-01 2.92E+00
Sickle cell disease 3A51.0-3A51.3 Peripheral blood 1.95E-02 -3.11E-01 -4.76E-01
Simpson golabi behmel syndrome LD2C Adipose tissue 4.32E-01 -8.82E-02 -2.74E-01
Sjogren's syndrome 4A43.2 Salivary gland tissue 4.94E-05 8.82E-01 7.04E+00
Skin cancer 2C30-2C3Z Skin 2.40E-19 -3.11E-01 -8.53E-01
Thrombocythemia 3B63 Whole blood 5.07E-02 -1.61E-01 -5.54E-01
Thrombocytopenia 3B64 Whole blood 1.91E-01 -1.19E+00 -1.04E+00
Thyroid cancer 2D10 Thyroid 2.07E-06 -3.63E-01 -1.03E+00
Tibial muscular dystrophy 8C75 Muscle tissue 8.21E-01 -9.82E-02 -3.37E-01
Tuberous sclerosis complex LD2D.2 Perituberal tissue 7.26E-01 -1.53E-01 -1.87E+00
Type 2 diabetes 5A11 Liver tissue 4.35E-02 1.91E-01 6.69E-01
Ureter cancer 2C92 Urothelium 6.95E-01 1.22E-01 2.06E-01
Uterine cancer 2C78 Endometrium tissue 1.72E-01 -8.61E-02 -7.51E-02
Vitiligo ED63.0 Skin 7.66E-01 6.63E-03 3.72E-02
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⏷ Show the Full List of DME Expression Under 107 Diseases

References

1 The enzymes of glutathione synthesis: gamma-glutamylcysteine synthetase. Adv Enzymol Relat Areas Mol Biol. 1999;73:209-67, xii.