Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10052)
Regulator Name Acyl-CoA 6-desaturase (FADS2)
Synonyms
Delta(6) fatty acid desaturase; Fatty acid desaturase 2
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Gene Name FADS2
Gene ID 9415
Regulator Type Protein coding
Uniprot ID O95864
Sequence
MGKGGNQGEGAAEREVSVPTFSWEEIQKHNLRTDRWLVIDRKVYNITKWSIQHPGGQRVI
GHYAGEDATDAFRAFHPDLEFVGKFLKPLLIGELAPEEPSQDHGKNSKITEDFRALRKTA
EDMNLFKTNHVFFLLLLAHIIALESIAWFTVFYFGNGWIPTLITAFVLATSQAQAGWLQH
DYGHLSVYRKPKWNHLVHKFVIGHLKGASANWWNHRHFQHHAKPNIFHKDPDVNMLHVFV
LGEWQPIEYGKKKLKYLPYNHQHEYFFLIGPPLLIPMYFQYQIIMTMIVHKNWVDLAWAV
SYYIRFFITYIPFYGILGALLFLNFIRFLESHWFVWVTQMNHIVMEIDQEAYRDWFSSQL
TATCNVEQSFFNDWFSGHLNFQIEHHLFPTMPRHNLHKIAPLVKSLCAKHGIEYQEKPLL
RALLDIIRSLKKSGKLWLDAYLHK

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Family Fatty acid desaturase type 1 family
Function
Involved in the biosynthesis of highly unsaturated fatty acids (HUFA) from the essential polyunsaturated fatty acids (PUFA) linoleic acid (LA) (18:2n-6) and alpha-linolenic acid (ALA) (18:3n-3) precursors, acting as a fatty acyl-coenzyme A (CoA) desaturase that introduces a cis double bond at carbon 6 of the fatty acyl chain. Catalyzes the first and rate limiting step in this pathway which is the desaturation of LA (18:2n-6) and ALA (18:3n-3) into gamma-linoleate (GLA) (18:3n-6) and stearidonate (18:4n-3), respectively. Subsequently, in the biosynthetic pathway of HUFA n- 3 series, it desaturates tetracosapentaenoate (24:5n-3) to tetracosahexaenoate (24:6n-3), which is then converted to docosahexaenoate (DHA)(22:6n-3), an important lipid for nervous system function. Desaturates hexadecanate (palmitate) to produce 6Z-hexadecenoate (sapienate), a fatty acid unique to humans and major component of human sebum, that has been implicated in the development of acne and may have potent antibacterial activity. It can also desaturate (11E)-octadecenoate (trans- vaccenoate, the predominant trans fatty acid in human milk) at carbon 6 generating (6Z,11E)-octadecadienoate. In addition to Delta-6 activity, this enzyme exhibits Delta-8 activity with slight biases toward n-3 fatty acyl-CoA substrates.

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HGNC ID
HGNC:3575
KEGG ID hsa:9415
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
FADS2 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
Unspecific Target [Unspecific Target]
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Chronic hepatitis C ICD-11: 1E51
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 Huh-7.5 cells Hepatocellular carcinoma Homo sapiens CVCL_7927
HEK293 FT cells Normal Homo sapiens CVCL_6911
PH5CH8 cells Normal Homo sapiens CVCL_VL00
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
In Vivo Model
Chimeric mice were purchased from PhoenixBio Co. (Hiroshima, Japan). The chimeric mice were generated by transplanting human primary hepatocytes into severe combined immunodeficient mice (3-week-old male) carrying the urokinase plasminogen activator transgene under control of an albumin promoter (Alb-uPA).

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Response regulation Inhibiting FADS2 markedly enhances hepatitis C virus (HCV) replication, whereas the ferroptosis-inducing compound erastin alters conformation of the HCV replicase and sensitizes it to direct-acting antiviral agents targeting the viral protease. Collectively, these data establish FADS2 as an important pro-ferroptotic factor that also restricts HCV replication.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [2]
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 MRC-5 cells Normal Homo sapiens CVCL_0440
HBE1 cells Normal Homo sapiens CVCL_0287
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H358 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
NCI-H522 cells Non-small cell lung carcinoma Homo sapiens CVCL_1567
PC-9 cells Lung adenocarcinoma Homo sapiens CVCL_B260
95C cells Lung giant cell carcinoma Homo sapiens CVCL_7109
95D cells Lung giant cell carcinoma Homo sapiens CVCL_7110
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
SCID Mice (Hunan SJA Laboratory Animal Co.Ltd.) were injected with A549 (1 x 106 cells/mouse) or H358 (2 x 106 cells/mouse) cells via mammary fat pad (10 mice/group). Mice with A549 or H358 cells were imaged from dorsal and ventral views every three days.

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Response regulation LSH (HELLS) is involved in ferroptosis and is a potential therapeutic target in cancer because of its crucial role in ferroptosis. LSH functioned as an oncogene in lung cancer in vitro and in vivo. And LSH promotes the lipid metabolic genes, including SCD1 and FADS2.
Chronic hepatitis C [ICD-11: 1E51]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Acyl-CoA 6-desaturase (FADS2) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 Huh-7.5 cells Hepatocellular carcinoma Homo sapiens CVCL_7927
HEK293 FT cells Normal Homo sapiens CVCL_6911
PH5CH8 cells Normal Homo sapiens CVCL_VL00
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
In Vivo Model
Chimeric mice were purchased from PhoenixBio Co. (Hiroshima, Japan). The chimeric mice were generated by transplanting human primary hepatocytes into severe combined immunodeficient mice (3-week-old male) carrying the urokinase plasminogen activator transgene under control of an albumin promoter (Alb-uPA).

    Click to Show/Hide
Response regulation Inhibiting FADS2 markedly enhances hepatitis C virus (HCV) replication, whereas the ferroptosis-inducing compound erastin alters conformation of the HCV replicase and sensitizes it to direct-acting antiviral agents targeting the viral protease. Collectively, these data establish FADS2 as an important pro-ferroptotic factor that also restricts HCV replication.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Acyl-CoA 6-desaturase (FADS2) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 MRC-5 cells Normal Homo sapiens CVCL_0440
HBE1 cells Normal Homo sapiens CVCL_0287
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H358 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
NCI-H522 cells Non-small cell lung carcinoma Homo sapiens CVCL_1567
PC-9 cells Lung adenocarcinoma Homo sapiens CVCL_B260
95C cells Lung giant cell carcinoma Homo sapiens CVCL_7109
95D cells Lung giant cell carcinoma Homo sapiens CVCL_7110
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
SCID Mice (Hunan SJA Laboratory Animal Co.Ltd.) were injected with A549 (1 x 106 cells/mouse) or H358 (2 x 106 cells/mouse) cells via mammary fat pad (10 mice/group). Mice with A549 or H358 cells were imaged from dorsal and ventral views every three days.

    Click to Show/Hide
Response regulation LSH (HELLS) is involved in ferroptosis and is a potential therapeutic target in cancer because of its crucial role in ferroptosis. LSH functioned as an oncogene in lung cancer in vitro and in vivo. And LSH promotes the lipid metabolic genes, including SCD1 and FADS2.
References
Ref 1 FADS2-dependent fatty acid desaturation dictates cellular sensitivity to ferroptosis and permissiveness for hepatitis C virus replication. Cell Chem Biol. 2022 May 19;29(5):799-810.e4. doi: 10.1016/j.chembiol.2021.07.022. Epub 2021 Sep 13.
Ref 2 EGLN1/c-Myc Induced Lymphoid-Specific Helicase Inhibits Ferroptosis through Lipid Metabolic Gene Expression Changes. Theranostics. 2017 Jul 23;7(13):3293-3305. doi: 10.7150/thno.19988. eCollection 2017.