Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10026)
Regulator Name E3 ubiquitin-protein ligase RNF113A (RNF113A)
Synonyms
RNF113, ZNF183 ; Cwc24 homolog
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Gene Name RNF113A
Gene ID 7737
Regulator Type Protein coding
Uniprot ID O15541
Sequence
MAEQLSPGKAVDQVCTFLFKKPGRKGAAGRRKRPACDPEPGESGSSSDEGCTVVRPEKKR
VTHNPMIQKTRDSGKQKAAYGDLSSEEEEENEPESLGVVYKSTRSAKPVGPEDMGATAVY
ELDTEKERDAQAIFERSQKIQEELRGKEDDKIYRGINNYQKYMKPKDTSMGNASSGMVRK
GPIRAPEHLRATVRWDYQPDICKDYKETGFCGFGDSCKFLHDRSDYKHGWQIERELDEGR
YGVYEDENYEVGSDDEEIPFKCFICRQSFQNPVVTKCRHYFCESCALQHFRTTPRCYVCD
QQTNGVFNPAKELIAKLEKHRATGEGGASDLPEDPDEDAIPIT

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Function
Required for pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre- mRNAs (Probable). E3 ubiquitin-protein ligase that catalyzes the transfer of ubiquitin onto target proteins. Catalyzes polyubiquitination of SNRNP200/BRR2 with non-canonical 'Lys-63'-linked polyubiquitin chains. Plays a role in DNA repair via its role in the synthesis of 'Lys-63'- linked polyubiquitin chains that recruit ALKBH3 and the ASCC complex to sites of DNA damage by alkylating agents. Ubiquitinates CXCR4, leading to its degradation, and thereby contributes to the termination of CXCR4 signaling.

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HGNC ID
HGNC:12974
KEGG ID hsa:7737
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
RNF113A 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
Diamine acetyltransferase 1 (SAT1) [Driver]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Driver
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model
 A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1975 cells Lung adenocarcinoma Homo sapiens CVCL_1511
HEK293 cells Normal Homo sapiens CVCL_0045
PCS-201-012 (Human normal dermal fibroblasts)
In Vivo Model
Five millions of control or RNF113A-depleted Cisplatin-resistant A549 cells were transplanted into immunodeficient NOD/SCID 8 weeks old mice. Tumors were grown up to 0.1-0.2 mm3 and mice were then treated with Cisplatin (1 mg/kg) six times every 3 days. Seven mice were used per experimental conditions. No randomization of mice was used.

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Response regulation RNF113A, whose loss-of-function causes the X-linked trichothiodystrophy, is overexpressed in lung cancer and protects from Cisplatin-dependent cell death. RNF113A deficiency triggers cell death upon DNA damage through multiple mechanisms, including apoptosis via the destabilization of the prosurvival protein MCL-1, ferroptosis due to enhanced SAT1 expression, and increased production of ROS due to altered Noxa1 expression.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator E3 ubiquitin-protein ligase RNF113A (RNF113A) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model
 A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1975 cells Lung adenocarcinoma Homo sapiens CVCL_1511
HEK293 cells Normal Homo sapiens CVCL_0045
PCS-201-012 (Human normal dermal fibroblasts)
In Vivo Model
Five millions of control or RNF113A-depleted Cisplatin-resistant A549 cells were transplanted into immunodeficient NOD/SCID 8 weeks old mice. Tumors were grown up to 0.1-0.2 mm3 and mice were then treated with Cisplatin (1 mg/kg) six times every 3 days. Seven mice were used per experimental conditions. No randomization of mice was used.

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Response regulation RNF113A, whose loss-of-function causes the X-linked trichothiodystrophy, is overexpressed in lung cancer and protects from Cisplatin-dependent cell death. RNF113A deficiency triggers cell death upon DNA damage through multiple mechanisms, including apoptosis via the destabilization of the prosurvival protein MCL-1, ferroptosis due to enhanced SAT1 expression, and increased production of ROS due to altered Noxa1 expression.
References
Ref 1 The X-linked trichothiodystrophy-causing gene RNF113A links the spliceosome to cell survival upon DNA damage. Nat Commun. 2020 Mar 9;11(1):1270. doi: 10.1038/s41467-020-15003-7.