Ferroptosis Target Information
General Information of the Ferroptosis Target (ID: TAR10005)
Target Name | Fatty acid CoA ligase Acsl3 (ACSL3) | ||||
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Synonyms |
Arachidonate--CoA ligase; Long-chain acyl-CoA synthetase 3; Long-chain-fatty-acid--CoA ligase 3; Medium-chain acyl-CoA ligase Acsl3
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Gene Name | ACSL3 | ||||
Sequence |
MNNHVSSKPSTMKLKHTINPILLYFIHFLISLYTILTYIPFYFFSESRQEKSNRIKAKPV
NSKPDSAYRSVNSLDGLASVLYPGCDTLDKVFTYAKNKFKNKRLLGTREVLNEEDEVQPN GKIFKKVILGQYNWLSYEDVFVRAFNFGNGLQMLGQKPKTNIAIFCETRAEWMIAAQACF MYNFQLVTLYATLGGPAIVHALNETEVTNIITSKELLQTKLKDIVSLVPRLRHIITVDGK PPTWSEFPKGIIVHTMAAVEALGAKASMENQPHSKPLPSDIAVIMYTSGSTGLPKGVMIS HSNIIAGITGMAERIPELGEEDVYIGYLPLAHVLELSAELVCLSHGCRIGYSSPQTLADQ SSKIKKGSKGDTSMLKPTLMAAVPEIMDRIYKNVMNKVSEMSSFQRNLFILAYNYKMEQI SKGRNTPLCDSFVFRKVRSLLGGNIRLLLCGGAPLSATTQRFMNICFCCPVGQGYGLTES AGAGTISEVWDYNTGRVGAPLVCCEIKLKNWEEGGYFNTDKPHPRGEILIGGQSVTMGYY KNEAKTKADFFEDENGQRWLCTGDIGEFEPDGCLKIIDRKKDLVKLQAGEYVSLGKVEAA LKNLPLVDNICAYANSYHSYVIGFVVPNQKELTELARKKGLKGTWEELCNSCEMENEVLK VLSEAAISASLEKFEIPVKIRLSPEPWTPETGLVTDAFKLKRKELKTHYQADIERMYGRK Click to Show/Hide
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Family | ATP-dependent AMP-binding enzyme family | ||||
Function |
Acyl-CoA synthetases (ACSL) activates long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta- oxidation. Required for the incorporation of fatty acids into phosphatidylcholine, the major phospholipid located on the surface of VLDL (very low density lipoproteins). Has mainly an anabolic role in energy metabolism. Mediates hepatic lipogenesis. Preferentially uses myristate, laurate, arachidonate and eicosapentaenoate as substrates. Both isoforms exhibit the same level of activity.
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Gene ID | 2181 | ||||
Uniprot ID | |||||
Target Type | Driver Suppressor Marker | ||||
Mechanism Diagram | Click to View the Original Diagram | ||||
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Tissue Relative Abundances of This Target
Full List of Regulator(s) of This Ferroptosis Target and Corresponding Disease/Drug Response(s)
ACSL3 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
Browse Regulator related Drug
Perilipin-2 (PLIN2)
Gastric cancer [ICD-11: 2B72]
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 | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Apoptosis | hsa04210 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell proliferation | |||||
In Vitro Model |
SGC-7901 cells | Gastric carcinoma | Homo sapiens | CVCL_0520 | |
MGC-803 cells | Gastric mucinous adenocarcinoma | Homo sapiens | CVCL_5334 | ||
In Vivo Model |
SGC7901 cell line transfected with OvPLIN2, ShPLIN2 and Control were injected subcutaneously into the nude mice (BALB/c nu/nu, female, 5 weeks old, Beijing Huafukang Biotechnology Co. Ltd. China) which were anaesthetized with 1% Sodium pentobarbital. The long diameter a and short diameter b of mouse tumor and the weights were measured every 4-5 days, and the relative tumor volumes (RTV) were calculated according to formula 0.5 x a x b x b.
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Response Description | Overexpression and knockdown of PLIN2 augmented the proliferation and apoptosis of gastric carcinoma cell lines SGC7901 and MGC803, respectively. PLIN2 modulated Ferroptosis pathway through regulating transcription factors-PRDM11 and IPO7:ACSL3 was a critical gene involved in abnormal lipid metabolism, ALOX15 facilitated apoptosis and necrosis. | ||||
Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3)
Lung cancer [ICD-11: 2C25]
In total 1 item(s) under this disease | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator | [2] | ||||
Regulator for Ferroptosis | Suppressor | ||||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
BEAS-2B cells | Normal | Homo sapiens | CVCL_0168 | |
NCI-H1299 cells | Lung large cell carcinoma | Homo sapiens | CVCL_0060 | ||
SW1990 cells | Pancreatic adenocarcinoma | Homo sapiens | CVCL_1723 | ||
HCT 116 cells | Colon carcinoma | Homo sapiens | CVCL_0291 | ||
In Vivo Model |
Igf2bp3-/- mice were generated by Cyagen Biosciences (Guangzhou,China). Mettl3-/- mice were obtained as described in our previous study. H1299 cells with or without IGF2BP3 overexpression were digested and adjusted to a density of 5 x 106 cells/200 uL. Next, 200 uL of cells were injected into the right armpit of each 4-6-week-old athymic nude mouse (Jiesijie, Shanghai, China). The weight and tumor size of nude mice were measured. Each group contained five mice. After 2 weeks, mice were injected daily with dimethyl sulfoxide (DMSO, Beyotime Biotechnology, Shanghai, China) with or without imidazole ketone erastin (IKE, 50 mg/kg, MedChemExpress, Monmouth, NJ, USA) or rigosertib (RIG, 250 mg/kg, Selleck, Houston, TX, USA).
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Response Description | After IGF2BP3 overexpression, expression levels and mRNA stabilities of these anti-ferroptotic factors were successfully sustained. Notably, significant correlations between SLC3A2, ACSL3, and IGF2BP3 were revealed in clinical Lung adenocarcinoma specimens, further establishing the essential role of IGF2BP3 in desensitizing ferroptosis. Inducing ferroptosis has been gradually accepted as an alternative strategy to treat tumors. | ||||
Unspecific Regulator
Cerebral ischemia [ICD-11: 8B10]
In total 1 item(s) under this disease | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator | [3] | ||||
Responsed Drug | Baicalein | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
HT22 cells | Normal | Mus musculus | CVCL_0321 | |
In Vivo Model |
The mice (23-25 g, 8-10 weeks old) were subjected to transientmiddle cerebral artery occlusion (tMCAO) to induce cerebral ischemia as previously described protocol . Briefly, mice were anesthetized with intraperitoneal injection of pentobarbital sodium (60 mg/kg) and subcutaneous injection of meloxicam (10mg/kg) during tMCAO operation. Monofilament with a silicon coating on the tip and a diameter of 0.12 mm (A5-122, Beijing Cinontech Co. Ltd., China) was inserted into the ICA from CCA to occlude the middle cerebral artery (MCA) for 1.5 h. The suture was then removed to restore blood flow for another 22.5 h reperfusion. Sham control mice were subjected to similar surgical operations without MCA occlusion. Specifically, the monofilament was inserted only 5 mm above the carotid bifurcation and withdrew immediately in the Sham group.
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Response Description | Baicalein inhibited the ferroptosis by regulating on the expression levels of GPX4, ACSL4 and ACSL3 in OGD/R cells, tMCAO mice and RSL3-stimulated HT22 cells. Our findings demonstrated that baicalein reversed the cerebral ischemia-reperfusion injury via anti-ferroptosis, which was regulated by GPX4/ACSL4/ACSL3 axis. | ||||
Unspecific Regulator
Baicalein
[Investigative]
In total 1 item(s) under this drug | |||||
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator | [3] | ||||
Responsed Disease | Cerebral ischemia [ICD-11: 8B10] | ||||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | HT22 cells | Normal | Mus musculus | CVCL_0321 | |
In Vivo Model |
The mice (23-25 g, 8-10 weeks old) were subjected to transientmiddle cerebral artery occlusion (tMCAO) to induce cerebral ischemia as previously described protocol . Briefly, mice were anesthetized with intraperitoneal injection of pentobarbital sodium (60 mg/kg) and subcutaneous injection of meloxicam (10mg/kg) during tMCAO operation. Monofilament with a silicon coating on the tip and a diameter of 0.12 mm (A5-122, Beijing Cinontech Co. Ltd., China) was inserted into the ICA from CCA to occlude the middle cerebral artery (MCA) for 1.5 h. The suture was then removed to restore blood flow for another 22.5 h reperfusion. Sham control mice were subjected to similar surgical operations without MCA occlusion. Specifically, the monofilament was inserted only 5 mm above the carotid bifurcation and withdrew immediately in the Sham group.
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Response Description | Baicalein inhibited the ferroptosis by regulating on the expression levels of GPX4, ACSL4 and ACSL3 in OGD/R cells, tMCAO mice and RSL3-stimulated HT22 cells. Our findings demonstrated that baicalein reversed the cerebral ischemia-reperfusion injury via anti-ferroptosis, which was regulated by GPX4/ACSL4/ACSL3 axis. | ||||
References