Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10409)
Regulator Name Long-chain fatty acid transport protein 5 (SLC27A5)
Synonyms
ACSB; ACSVL6; FACVL3; FATP5; Bile acid-CoA ligase; Bile acyl-CoA synthetase; Cholate--CoA ligase; Fatty-acid-coenzyme A ligase, very long-chain 3; Long-chain-fatty-acid--CoA ligase; Solute carrier family 27 member 5; Very long-chain acyl-CoA synthetase homolog 2 {|, |}; Very long-chain acyl-CoA synthetase-related protein
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Gene Name SLC27A5
Gene ID 10998
Regulator Type Protein coding
Uniprot ID Q9Y2P5
Sequence
MGVRQQLALLLLLLLLLWGLGQPVWPVAVALTLRWLLGDPTCCVLLGLAMLARPWLGPWV
PHGLSLAAAALALTLLPARLPPGLRWLPADVIFLAKILHLGLKIRGCLSRQPPDTFVDAF
ERRARAQPGRALLVWTGPGAGSVTFGELDARACQAAWALKAELGDPASLCAGEPTALLVL
ASQAVPALCMWLGLAKLGCPTAWINPHGRGMPLAHSVLSSGARVLVVDPDLRESLEEILP
KLQAENIRCFYLSHTSPTPGVGALGAALDAAPSHPVPADLRAGITWRSPALFIYTSGTTG
LPKPAILTHERVLQMSKMLSLSGATADDVVYTVLPLYHVMGLVVGILGCLDLGATCVLAP
KFSTSCFWDDCRQHGVTVILYVGELLRYLCNIPQQPEDRTHTVRLAMGNGLRADVWETFQ
QRFGPIRIWEVYGSTEGNMGLVNYVGRCGALGKMSCLLRMLSPFELVQFDMEAAEPVRDN
QGFCIPVGLGEPGLLLTKVVSQQPFVGYRGPRELSERKLVRNVRQSGDVYYNTGDVLAMD
REGFLYFRDRLGDTFRWKGENVSTHEVEGVLSQVDFLQQVNVYGVCVPGCEGKVGMAAVQ
LAPGQTFDGEKLYQHVRAWLPAYATPHFIRIQDAMEVTSTFKLMKTRLVREGFNVGIVVD
PLFVLDNRAQSFRPLTAEMYQAVCEGTWRL

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Family ATP-dependent AMP-binding enzyme family
Function
May mediate the import of long-chain fatty acids (LCFA) by facilitating their transport across cell membranes. Also catalyzes the ATP-dependent formation of fatty acyl-CoA using LCFA and very-long-chain fatty acids (VLCFA) as substrates. Mainly functions as a bile acyl-CoA synthetase catalyzing the activation of bile acids via ATP-dependent formation of bile acid CoA thioesters which is necessary for their subsequent conjugation with glycine or taurine. Both primary bile acids (cholic acid and chenodeoxycholic acid) and secondary bile acids (deoxycholic acid and lithocholic acid) are the principal substrates. In vitro, activates 3-alpha,7-alpha,12-alpha- trihydroxy-5-beta-cholestanate ((25R)-3alpha,7alpha,12alpha-trihydroxy- 5beta-cholestan-26-oate or THCA), the C27 precursor of cholic acid deriving from the de novo synthesis from cholesterol. Plays an important role in hepatic fatty acid uptake and bile acid reconjugation and recycling but not in de novo synthesis of bile acids (By similarity).

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HGNC ID
HGNC:10999
KEGG ID hsa:10998
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
SLC27A5 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
Nuclear factor erythroid 2-related factor 2 (NFE2L2) [Suppressor; Marker]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
PLC/PRF/5 cells Hepatocellular carcinoma Homo sapiens CVCL_0485
SK-HEP-1 cells Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
In Vivo Model
Age-matched male BALB/c nude mice (4-6 weeks old) were used for the orthotopic mouse model. Cohorts of mice were randomized into different treatment groups. 4 x 106 tumor cells were suspended in a 50 ul PBS/Matrigel (356234, BD Biosciences) mixture (1:1 (v/v) ratio) for each group of mice and injected into the left liver lobes by surgical implantation.

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Response regulation The combination of sorafenib and carmustine (BCNU), a selective inhibitor of GSR, remarkably hamper tumor growth by enhancing ferroptotic cell death in vivo. SLC27A5 serves as a suppressor in sorafenib resistance and promotes sorafenib-triggered ferroptosis via restraining the NRF2/GSR pathway in hepatocellular carcinoma, providing a potential therapeutic strategy for overcoming sorafenib resistance.
Hepatocellular carcinoma [ICD-11: 2C12]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Long-chain fatty acid transport protein 5 (SLC27A5) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
PLC/PRF/5 cells Hepatocellular carcinoma Homo sapiens CVCL_0485
SK-HEP-1 cells Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
In Vivo Model
Age-matched male BALB/c nude mice (4-6 weeks old) were used for the orthotopic mouse model. Cohorts of mice were randomized into different treatment groups. 4 x 106 tumor cells were suspended in a 50 ul PBS/Matrigel (356234, BD Biosciences) mixture (1:1 (v/v) ratio) for each group of mice and injected into the left liver lobes by surgical implantation.

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Response regulation The combination of sorafenib and carmustine (BCNU), a selective inhibitor of GSR, remarkably hamper tumor growth by enhancing ferroptotic cell death in vivo. SLC27A5 serves as a suppressor in sorafenib resistance and promotes sorafenib-triggered ferroptosis via restraining the NRF2/GSR pathway in hepatocellular carcinoma, providing a potential therapeutic strategy for overcoming sorafenib resistance.
References
Ref 1 SLC27A5 promotes sorafenib-induced ferroptosis in hepatocellular carcinoma by downregulating glutathione reductase. Cell Death Dis. 2023 Jan 12;14(1):22. doi: 10.1038/s41419-023-05558-w.