General Information of the Ferroptosis Regulator (ID: REG10298)
Regulator Name Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2)
Gene Name ACSF2
Gene ID 80221
Regulator Type Protein coding
Uniprot ID Q96CM8
Sequence
MAVYVGMLRLGRLCAGSSGVLGARAALSRSWQEARLQGVRFLSSREVDRMVSTPIGGLSY
VQGCTKKHLNSKTVGQCLETTAQRVPEREALVVLHEDVRLTFAQLKEEVDKAASGLLSIG
LCKGDRLGMWGPNSYAWVLMQLATAQAGIILVSVNPAYQAMELEYVLKKVGCKALVFPKQ
FKTQQYYNVLKQICPEVENAQPGALKSQRLPDLTTVISVDAPLPGTLLLDEVVAAGSTRQ
HLDQLQYNQQFLSCHDPINIQFTSGTTGSPKGATLSHYNIVNNSNILGERLKLHEKTPEQ
LRMILPNPLYHCLGSVAGTMMCLMYGATLILASPIFNGKKALEAISRERGTFLYGTPTMF
VDILNQPDFSSYDISTMCGGVIAGSPAPPELIRAIINKINMKDLVVAYGTTENSPVTFAH
FPEDTVEQKAESVGRIMPHTEARIMNMEAGTLAKLNTPGELCIRGYCVMLGYWGEPQKTE
EAVDQDKWYWTGDVATMNEQGFCKIVGRSKDMIIRGGENIYPAELEDFFHTHPKVQEVQV
VGVKDDRMGEEICACIRLKDGEETTVEEIKAFCKGKISHFKIPKYIVFVTNYPLTISGKI
QKFKLREQMERHLNL

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Family ATP-dependent AMP-binding enzyme family
Function
Acyl-CoA synthases catalyze the initial reaction in fatty acid metabolism, by forming a thioester with CoA. Has some preference toward medium-chain substrates. Plays a role in adipocyte differentiation.

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HGNC ID
HGNC:26101
KEGG ID hsa:80221
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
ACSF2 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).
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Unspecific Target [Unspecific Target]
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Breast cancer ICD-11: 2C60
Responsed Drug Etoposide Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
MCF-10A cells Normal Homo sapiens CVCL_0598
MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
Response regulation The combined treatment of etoposide and erastin synergistically induced oxidative stress and lipid peroxidation, while suppressing glutathione peroxidase activity in breast cancer cells. More importantly, the combination treatment synergistically increased iron accumulation, which was associated with altered expression of IREB2/FPN1. Additionally, ferroptosis-regulating proteins ACSF2 and GPX4 were altered more potently by the combination treatment, compared to untreated cells and erastin treatment alone (p<0.05).
Experiment 2 Reporting the Ferroptosis Target of This Regulator [2]
Responsed Disease Ulcerative colitis ICD-11: DD71
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
IEC-6 cells Normal Rattus norvegicus CVCL_0343
In Vivo Model
C57BL/6 mice were randomly divided into two groups: control group (n = 7) and DSS group (n = 7). Mice in the DSS group were given 3.0% (w/v) dextran sulfate sodium (DSS, molecular weight, 36-50 kDa; MP Biomedicals, UK) in the drinking water for 7 days. Mice in the control group were fed with normal drinking water throughout the experimental period.

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Response regulation Ferroptosis is closely associated with the development of ulcerative colitis (UC), and the ferroptosis-related gene ACSF2 can be used as a potential biomarker for the diagnosis and treatment of UC.
Breast cancer [ICD-11: 2C60]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2) Protein coding
Responsed Drug Etoposide Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
MCF-10A cells Normal Homo sapiens CVCL_0598
MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
Response regulation The combined treatment of etoposide and erastin synergistically induced oxidative stress and lipid peroxidation, while suppressing glutathione peroxidase activity in breast cancer cells. More importantly, the combination treatment synergistically increased iron accumulation, which was associated with altered expression of IREB2/FPN1. Additionally, ferroptosis-regulating proteins ACSF2 and GPX4 were altered more potently by the combination treatment, compared to untreated cells and erastin treatment alone (p<0.05).
Ulcerative colitis [ICD-11: DD71]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Medium-chain acyl-CoA ligase ACSF2, mitochondrial (ACSF2) Protein coding
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
IEC-6 cells Normal Rattus norvegicus CVCL_0343
In Vivo Model
C57BL/6 mice were randomly divided into two groups: control group (n = 7) and DSS group (n = 7). Mice in the DSS group were given 3.0% (w/v) dextran sulfate sodium (DSS, molecular weight, 36-50 kDa; MP Biomedicals, UK) in the drinking water for 7 days. Mice in the control group were fed with normal drinking water throughout the experimental period.

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Response regulation Ferroptosis is closely associated with the development of ulcerative colitis (UC), and the ferroptosis-related gene ACSF2 can be used as a potential biomarker for the diagnosis and treatment of UC.
Etoposide [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Unspecific Target
Responsed Disease Breast cancer ICD-11: 2C60
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
MCF-10A cells Normal Homo sapiens CVCL_0598
MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
Response regulation The combined treatment of etoposide and erastin synergistically induced oxidative stress and lipid peroxidation, while suppressing glutathione peroxidase activity in breast cancer cells. More importantly, the combination treatment synergistically increased iron accumulation, which was associated with altered expression of IREB2/FPN1. Additionally, ferroptosis-regulating proteins ACSF2 and GPX4 were altered more potently by the combination treatment, compared to untreated cells and erastin treatment alone (p<0.05).
References
Ref 1 Etoposide in combination with erastin synergistically altered iron homeostasis and induced ferroptotic cell death through regulating IREB2/FPN1 expression in estrogen receptor positive-breast cancer cells. Life Sci. 2023 Jan 1;312:121222. doi: 10.1016/j.lfs.2022.121222. Epub 2022 Nov 25.
Ref 2 ACSF2-mediated ferroptosis is involved in ulcerative colitis. Life Sci. 2023 Jan 15;313:121272. doi: 10.1016/j.lfs.2022.121272. Epub 2022 Dec 9.