Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10324)
Regulator Name Kelch domain-containing protein 3
Synonyms
Testis intracellular mediator protein
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Gene ID 116138
Regulator Type Protein coding
Uniprot ID Q9BQ90
Sequence
MLRWTVHLEGGPRRVNHAAVAVGHRVYSFGGYCSGEDYETLRQIDVHIFNAVSLRWTKLP
PVKSAIRGQAPVVPYMRYGHSTVLIDDTVLLWGGRNDTEGACNVLYAFDVNTHKWFTPRV
SGTVPGARDGHSACVLGKIMYIFGGYEQQADCFSNDIHKLDTSTMTWTLICTKGSPARWR
DFHSATMLGSHMYVFGGRADRFGPFHSNNEIYCNRIRVFDTRTEAWLDCPPTPVLPEGRR
SHSAFGYNGELYIFGGYNARLNRHFHDLWKFNPVSFTWKKIEPKGKGPCPRRRQCCCIVG
DKIVLFGGTSPSPEEGLGDEFDLIDHSDLHILDFSPSLKTLCKLAVIQYNLDQSCLPHDI
RWELNAMTTNSNISRPIVSSHG

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Function
Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms. The CRL2(KLHDC3) complex specifically recognizes proteins with a glycine (Gly) at the C-terminus, leading to their ubiquitination and degradation: recognizes the C-terminal -Arg-(Xaa)n-Arg-Gly, -Arg- (Xaa)n-Lys-Gly, and -Arg-(Xaa)n-Gln-Gly degrons. The CRL2(KLHDC3) complex mediates ubiquitination and degradation of truncated SELENOV and SEPHS2 selenoproteins produced by failed UGA/Sec decoding, which end with a glycine. May be involved in meiotic recombination process.

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HGNC ID
HGNC:20704
KEGG ID hsa:116138
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
Kelch domain-containing protein 3 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
Cystine/glutamate transporter (SLC7A11) [Driver; Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Ovarian cancer ICD-11: 2C73
 Disease Info 
Pathway Response Ubiquitin mediated proteolysis hsa04120
Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell growth
In Vitro Model
 HEK-293T cells Normal Homo sapiens CVCL_0063
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
SK-OV-3 cells Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
OVCAR-3 cells Ovarian serous adenocarcinoma Homo sapiens CVCL_0465
SJSA-1 cells Osteosarcoma Homo sapiens CVCL_1697
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
CT26 cells Colon adenocarcinoma Mus musculus CVCL_7254
L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
HCCLM3 cells Adult hepatocellular carcinoma Homo sapiens CVCL_6832
In Vivo Model
4-6-week-old female BALB/c nu/nu mice obtained from SLAC Laboratory Animal Co., Ltd. were bred and maintained in our institutional pathogen-free mouse facilities. Ovarian tumors were established by subcutaneously injecting 5 x 106 SKOV3 cells in 100 ul of PBS buffer into the right flank of 6-week-old nude mice (four mice for each group). At the end of 3 weeks, mice were killed and in vivo solid tumors were dissected and weighed.

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Response regulation KLHDC3 expression is elevated in ovarian cancer. KLHDC3 suppresses ferroptosis in vitro and supports tumor growth in vivo by relieving p14ARF-mediated suppression of SLC7A11 transcription.
Ovarian cancer [ICD-11: 2C73]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Kelch domain-containing protein 3 Protein coding
 Regulator Info 
Pathway Response Ubiquitin mediated proteolysis hsa04120
Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell growth
In Vitro Model
 HEK-293T cells Normal Homo sapiens CVCL_0063
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
SK-OV-3 cells Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
OVCAR-3 cells Ovarian serous adenocarcinoma Homo sapiens CVCL_0465
SJSA-1 cells Osteosarcoma Homo sapiens CVCL_1697
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
CT26 cells Colon adenocarcinoma Mus musculus CVCL_7254
L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
HCCLM3 cells Adult hepatocellular carcinoma Homo sapiens CVCL_6832
In Vivo Model
4-6-week-old female BALB/c nu/nu mice obtained from SLAC Laboratory Animal Co., Ltd. were bred and maintained in our institutional pathogen-free mouse facilities. Ovarian tumors were established by subcutaneously injecting 5 x 106 SKOV3 cells in 100 ul of PBS buffer into the right flank of 6-week-old nude mice (four mice for each group). At the end of 3 weeks, mice were killed and in vivo solid tumors were dissected and weighed.

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Response regulation KLHDC3 expression is elevated in ovarian cancer. KLHDC3 suppresses ferroptosis in vitro and supports tumor growth in vivo by relieving p14ARF-mediated suppression of SLC7A11 transcription.
References
Ref 1 CRL2-KLHDC3 E3 ubiquitin ligase complex suppresses ferroptosis through promoting p14(ARF) degradation. Cell Death Differ. 2022 Apr;29(4):758-771. doi: 10.1038/s41418-021-00890-0. Epub 2021 Nov 6.