Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10488)
Regulator Name Glutathione hydrolase 1 proenzyme (GGT1)
Synonyms
GGT; Gamma-glutamyltransferase 1; Gamma-glutamyltranspeptidase 1; Leukotriene-C4 hydrolase; CD_antigen=CD224
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Gene Name GGT1
Gene ID 2678
Regulator Type Protein coding
Uniprot ID P19440
Sequence
MKKKLVVLGLLAVVLVLVIVGLCLWLPSASKEPDNHVYTRAAVAADAKQCSKIGRDALRD
GGSAVDAAIAALLCVGLMNAHSMGIGGGLFLTIYNSTTRKAEVINAREVAPRLAFATMFN
SSEQSQKGGLSVAVPGEIRGYELAHQRHGRLPWARLFQPSIQLARQGFPVGKGLAAALEN
KRTVIEQQPVLCEVFCRDRKVLREGERLTLPQLADTYETLAIEGAQAFYNGSLTAQIVKD
IQAAGGIVTAEDLNNYRAELIEHPLNISLGDVVLYMPSAPLSGPVLALILNILKGYNFSR
ESVESPEQKGLTYHRIVEAFRFAYAKRTLLGDPKFVDVTEVVRNMTSEFFAAQLRAQISD
DTTHPISYYKPEFYTPDDGGTAHLSVVAEDGSAVSATSTINLYFGSKVRSPVSGILFNNE
MDDFSSPSITNEFGVPPSPANFIQPGKQPLSSMCPTIMVGQDGQVRMVVGAAGGTQITTA
TALAIIYNLWFGYDVKRAVEEPRLHNQLLPNVTTVERNIDQAVTAALETRHHHTQIASTF
IAVVQAIVRTAGGWAAASDSRKGGEPAGY

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Family Gamma-glutamyltransferase family
Function
Cleaves the gamma-glutamyl bond of extracellular glutathione (gamma-Glu-Cys-Gly), glutathione conjugates (such as maresin conjugate (13R)-S-glutathionyl-(14S)-hydroxy-(4Z,7Z,9E,11E,16Z,19Z)- docosahexaenoate, MCTR1) and other gamma-glutamyl compounds (such as leukotriene C4, LTC4). The metabolism of glutathione by GGT1 releases free glutamate and the dipeptide cysteinyl-glycine, which is hydrolyzed to cysteine and glycine by dipeptidases. In the presence of high concentrations of dipeptides and some amino acids, can also catalyze a transpeptidation reaction, transferring the gamma-glutamyl moiety to an acceptor amino acid to form a new gamma-glutamyl compound. Contributes to cysteine homeostasis, glutathione homeostasis and in the conversion of the leukotriene LTC4 to LTD4.; [Isoform 3]: Seems to be inactive.

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HGNC ID
HGNC:4250
KEGG ID hsa:2678
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
GGT1 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Browse Drug
Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
 Target Info 
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Oesophageal cancer ICD-11: 2B70
 Disease Info 
Responsed Drug Oridonin Investigative
 Drug Info 
Pathway Response Glutathione metabolism hsa00480
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 TE-1 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_1759
Response regulation The levels of intracellular iron, malondialdehyde, and reactive oxygen species after oridonin (Ori) treatment, while interfering with the effects of Ori with ferroptosis inhibitor, demonstrating that Ori's inhibition of TE1( esophageal cancer cell) cell proliferation is associated with ferroptosis. Ori can inhibit the gamma-glutamyl cycle by inhibiting the activity of GGT1 and binding to cysteine, thereby inducing ferroptosis to exert anti-cancer activity. Eventually, the value of intracellular GSH/GSSG was reduced, and the enzymatic activity of the glutathione peroxidase 4 (GPX4) was significantly decreased.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Oesophageal cancer ICD-11: 2B70
 Disease Info 
Responsed Drug Oridonin Investigative
 Drug Info 
Pathway Response Glutathione metabolism hsa00480
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 TE-1 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_1759
Response regulation The levels of intracellular iron, malondialdehyde, and reactive oxygen species after oridonin (Ori) treatment, while interfering with the effects of Ori with ferroptosis inhibitor, demonstrating that Ori's inhibition of TE1(esophageal cancer cell) cell proliferation is associated with ferroptosis. Ori can inhibit the gamma-glutamyl cycle by inhibiting the activity of GGT1 and binding to cysteine, thereby inducing ferroptosis to exert anti-cancer activity. Eventually, the value of intracellular GSH/GSSG was reduced, and the enzymatic activity of the glutathione peroxidase 4 (GPX4) was significantly decreased.
Oesophageal cancer [ICD-11: 2B70]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Glutathione hydrolase 1 proenzyme (GGT1) Protein coding
 Regulator Info 
Responsed Drug Oridonin Investigative
 Drug Info 
Pathway Response Glutathione metabolism hsa00480
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 TE-1 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_1759
Response regulation The levels of intracellular iron, malondialdehyde, and reactive oxygen species after oridonin (Ori) treatment, while interfering with the effects of Ori with ferroptosis inhibitor, demonstrating that Ori's inhibition of TE1( esophageal cancer cell) cell proliferation is associated with ferroptosis. Ori can inhibit the gamma-glutamyl cycle by inhibiting the activity of GGT1 and binding to cysteine, thereby inducing ferroptosis to exert anti-cancer activity. Eventually, the value of intracellular GSH/GSSG was reduced, and the enzymatic activity of the glutathione peroxidase 4 (GPX4) was significantly decreased.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Glutathione hydrolase 1 proenzyme (GGT1) Protein coding
 Regulator Info 
Responsed Drug Oridonin Investigative
 Drug Info 
Pathway Response Glutathione metabolism hsa00480
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 TE-1 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_1759
Response regulation The levels of intracellular iron, malondialdehyde, and reactive oxygen species after oridonin (Ori) treatment, while interfering with the effects of Ori with ferroptosis inhibitor, demonstrating that Ori's inhibition of TE1(esophageal cancer cell) cell proliferation is associated with ferroptosis. Ori can inhibit the gamma-glutamyl cycle by inhibiting the activity of GGT1 and binding to cysteine, thereby inducing ferroptosis to exert anti-cancer activity. Eventually, the value of intracellular GSH/GSSG was reduced, and the enzymatic activity of the glutathione peroxidase 4 (GPX4) was significantly decreased.
Oridonin [Investigative]
 Drug Info 
In total 2 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Phospholipid hydroperoxide glutathione peroxidase (GPX4) Suppressor
 Target Info 
Responsed Disease Oesophageal cancer ICD-11: 2B70
 Disease Info 
Pathway Response Glutathione metabolism hsa00480
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 TE-1 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_1759
Response regulation The levels of intracellular iron, malondialdehyde, and reactive oxygen species after oridonin (Ori) treatment, while interfering with the effects of Ori with ferroptosis inhibitor, demonstrating that Ori's inhibition of TE1( esophageal cancer cell) cell proliferation is associated with ferroptosis. Ori can inhibit the gamma-glutamyl cycle by inhibiting the activity of GGT1 and binding to cysteine, thereby inducing ferroptosis to exert anti-cancer activity. Eventually, the value of intracellular GSH/GSSG was reduced, and the enzymatic activity of the glutathione peroxidase 4 (GPX4) was significantly decreased.
Experiment 2 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Phospholipid hydroperoxide glutathione peroxidase (GPX4) Suppressor
 Target Info 
Responsed Disease Oesophageal cancer ICD-11: 2B70
 Disease Info 
Pathway Response Glutathione metabolism hsa00480
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 TE-1 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_1759
Response regulation The levels of intracellular iron, malondialdehyde, and reactive oxygen species after oridonin (Ori) treatment, while interfering with the effects of Ori with ferroptosis inhibitor, demonstrating that Ori's inhibition of TE1(esophageal cancer cell) cell proliferation is associated with ferroptosis. Ori can inhibit the gamma-glutamyl cycle by inhibiting the activity of GGT1 and binding to cysteine, thereby inducing ferroptosis to exert anti-cancer activity. Eventually, the value of intracellular GSH/GSSG was reduced, and the enzymatic activity of the glutathione peroxidase 4 (GPX4) was significantly decreased.
References
Ref 1 Oridonin induces ferroptosis by inhibiting gamma-glutamyl cycle in TE1 cells. Phytother Res. 2021 Jan;35(1):494-503. doi: 10.1002/ptr.6829. Epub 2020 Aug 31.