General Information of the Ferroptosis Target (ID: TAR10024)
Target Name GTP cyclohydrolase 1 (GCH1)
Synonyms
GTP cyclohydrolase I
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Gene Name GCH1
Sequence
MEKGPVRAPAEKPRGARCSNGFPERDPPRPGPSRPAEKPPRPEAKSAQPADGWKGERPRS
EEDNELNLPNLAAAYSSILSSLGENPQRQGLLKTPWRAASAMQFFTKGYQETISDVLNDA
IFDEDHDEMVIVKDIDMFSMCEHHLVPFVGKVHIGYLPNKQVLGLSKLARIVEIYSRRLQ
VQERLTKQIAVAITEALRPAGVGVVVEATHMCMVMRGVQKMNSKTVTSTMLGVFREDPKT
REEFLTLIRS

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Family GTP cyclohydrolase I family
Function
Positively regulates nitric oxide synthesis in umbilical vein endothelial cells (HUVECs). May be involved in dopamine synthesis. May modify pain sensitivity and persistence. Isoform GCH-1 is the functional enzyme, the potential function of the enzymatically inactive isoforms remains unknown.

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Gene ID 2643
Uniprot ID
P30793
Target Type Driver Suppressor Marker
Mechanism Diagram Click to View the Original Diagram
Tissue Relative Abundances of This Target
Full List of Regulator(s) of This Ferroptosis Target and Corresponding Disease/Drug Response(s)
GCH1 can be involved in and affect the ferroptosis by the following regulators, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulting from the regulation of certain regulators.
Browse Regulator related Disease
Paired mesoderm homeobox protein 2 (PRRX2)
Glioblastoma [ICD-11: 2A00]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [1]
Regulator for Ferroptosis Suppressor
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
GSC51 (WHO grade IV specimens)
GSC52 (WHO grade IV specimens)
GSC53 (WHO grade IV specimens)
GSC55 (WHO grade IV specimens)
GSC56 (WHO grade IV specimens)
GSC58 (WHO grade IV specimens)
In Vivo Model
Five-week-old female BALB/c nude mice were purchased from Shanghai Jihui Laboratory Animal Care Co., Ltd (Shanghai, China). All mice were bred in the Laboratory Animal Center of Shanghai Tenth Peoples Hospital under specific pathogen-free conditions. The animal experiments were performed by the Animal Care Committee of Shanghai Tenth Peoples Hospital. Briefly, each group contains five mice, and 5 x 104 GSCs were injected orthotopically into the mouse brain at 2 mm lateral and 2 mm anterior to the bregma with a stereotaxic apparatus. Then the survival time of each mouse was calculated, and the tumor volume was calculated according to the formula: V = (D x d2) / 2, where D represents the longest diameter and d represents the shortest diameter.

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Response Description CircLRFN5 can be used as a potential Glioblastoma biomarker and become a target for molecular therapies or ferroptosis-dependent therapy in GBM. Mechanistically, circLRFN5 binds to PRRX2 protein and promotes its degradation via a ubiquitin-mediated proteasomal pathway. PRRX2 can transcriptionally upregulate GCH1 expression in GSCs, which is a ferroptosis suppressor via generating the antioxidant tetrahydrobiopterin (BH4).
CircLRFN5 (circRNA)
Glioblastoma [ICD-11: 2A00]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [1]
Regulator for Ferroptosis Driver
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
GSC51 (WHO grade IV specimens)
GSC52 (WHO grade IV specimens)
GSC53 (WHO grade IV specimens)
GSC55 (WHO grade IV specimens)
GSC56 (WHO grade IV specimens)
GSC58 (WHO grade IV specimens)
In Vivo Model
Five-week-old female BALB/c nude mice were purchased from Shanghai Jihui Laboratory Animal Care Co., Ltd (Shanghai, China). All mice were bred in the Laboratory Animal Center of Shanghai Tenth Peoples Hospital under specific pathogen-free conditions. The animal experiments were performed by the Animal Care Committee of Shanghai Tenth Peoples Hospital. Briefly, each group contains five mice, and 5 x 104 GSCs were injected orthotopically into the mouse brain at 2 mm lateral and 2 mm anterior to the bregma with a stereotaxic apparatus. Then the survival time of each mouse was calculated, and the tumor volume was calculated according to the formula: V = (D x d2) / 2, where D represents the longest diameter and d represents the shortest diameter.

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Response Description CircLRFN5 can be used as a potential Glioblastoma biomarker and become a target for molecular therapies or ferroptosis-dependent therapy in GBM. Mechanistically, circLRFN5 binds to PRRX2 protein and promotes its degradation via a ubiquitin-mediated proteasomal pathway. PRRX2 can transcriptionally upregulate GCH1 expression in GSCs, which is a ferroptosis suppressor via generating the antioxidant tetrahydrobiopterin (BH4).
References
Ref 1 Correction: CircLRFN5 inhibits the progression of glioblastoma via PRRX2/GCH1 mediated ferroptosis. J Exp Clin Cancer Res. 2022 Nov 10;41(1):320. doi: 10.1186/s13046-022-02527-7.