General Information of the Ferroptosis Regulator (ID: REG10347)
Regulator Name Protein lifeguard 4 (TMBIM4)
Synonyms
GAAP, LFG4; Golgi anti-apoptotic protein; Protein S1R; Transmembrane BAX inhibitor motif-containing protein 4; Z-protein
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Gene Name TMBIM4
Gene ID 51643
Regulator Type Protein coding
Uniprot ID Q9HC24
Sequence
MADPDPRYPRSSIEDDFNYGSSVASATVHIRMAFLRKVYSILSLQVLLTTVTSTVFLYFE
SVRTFVHESPALILLFALGSLGLIFALILNRHKYPLNLYLLFGFTLLEALTVAVVVTFYD
VYIILQAFILTTTVFFGLTVYTLQSKKDFSKFGAGLFALLWILCLSGFLKFFFYSEIMEL
VLAAAGALLFCGFIIYDTHSLMHKLSPEEYVLAAISLYLDIINLFLHLLRFLEAVNKK

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Family BI1 family. LFG subfamily
Function
Anti-apoptotic protein which can inhibit apoptosis induced by intrinsic and extrinsic apoptotic stimuli. Can modulate both capacitative Ca2+ entry and inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release.

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HGNC ID
HGNC:24257
KEGG ID hsa:51643
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
TMBIM4 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
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Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
Responsed Drug Sorafenib Investigative
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
SMMC-7721 cells Endocervical adenocarcinoma Homo sapiens CVCL_0534
PLC/PRF/5 cells Hepatocellular carcinoma Homo sapiens CVCL_0485
In Vivo Model
To generate murine subcutaneous tumours, 1 x 107 control shRNA or S1R-knockdown Huh7 cells in 200 uL of PBS were injected subcutaneously to the right of the dorsal midline. At day seven, the mice were randomly divided into groups and treated with sorafenib (10 mg/kg/intraperitoneal injection (i.p.), once every other day) for 2 weeks. On day 28, tumours were removed.

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Response regulation S1R (TMBIM4) protects hepatocellular carcinoma cells against sorafenib and subsequent ferroptosis. Inhibition of S1R by RNAi and antagonists markedly increased the anticancer activity of sorafenib by modulating the expression of GPX4, iron metabolism and ROS.
Hepatocellular carcinoma [ICD-11: 2C12]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Protein lifeguard 4 (TMBIM4) Protein coding
Responsed Drug Sorafenib Investigative
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
SMMC-7721 cells Endocervical adenocarcinoma Homo sapiens CVCL_0534
PLC/PRF/5 cells Hepatocellular carcinoma Homo sapiens CVCL_0485
In Vivo Model
To generate murine subcutaneous tumours, 1 x 107 control shRNA or S1R-knockdown Huh7 cells in 200 uL of PBS were injected subcutaneously to the right of the dorsal midline. At day seven, the mice were randomly divided into groups and treated with sorafenib (10 mg/kg/intraperitoneal injection (i.p.), once every other day) for 2 weeks. On day 28, tumours were removed.

    Click to Show/Hide
Response regulation S1R (TMBIM4) protects hepatocellular carcinoma cells against sorafenib and subsequent ferroptosis. Inhibition of S1R by RNAi and antagonists markedly increased the anticancer activity of sorafenib by modulating the expression of GPX4, iron metabolism and ROS.
Sorafenib [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Suppressor
Response Target Phospholipid hydroperoxide glutathione peroxidase (GPX4) Suppressor
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
SMMC-7721 cells Endocervical adenocarcinoma Homo sapiens CVCL_0534
PLC/PRF/5 cells Hepatocellular carcinoma Homo sapiens CVCL_0485
In Vivo Model
To generate murine subcutaneous tumours, 1 x 107 control shRNA or S1R-knockdown Huh7 cells in 200 uL of PBS were injected subcutaneously to the right of the dorsal midline. At day seven, the mice were randomly divided into groups and treated with sorafenib (10 mg/kg/intraperitoneal injection (i.p.), once every other day) for 2 weeks. On day 28, tumours were removed.

    Click to Show/Hide
Response regulation S1R (TMBIM4) protects hepatocellular carcinoma cells against sorafenib and subsequent ferroptosis. Inhibition of S1R by RNAi and antagonists markedly increased the anticancer activity of sorafenib by modulating the expression of GPX4, iron metabolism and ROS.
References
Ref 1 Sigma-1 receptor protects against ferroptosis in hepatocellular carcinoma cells. J Cell Mol Med. 2019 Nov;23(11):7349-7359. doi: 10.1111/jcmm.14594. Epub 2019 Sep 10.