Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10042)
Regulator Name Lysine-specific demethylase 4A (KDM4A)
Synonyms
JHDM3A, JMJD2, JMJD2A, KIAA0677; JmjC domain-containing histone demethylation protein 3A; Jumonji domain-containing protein 2A; [histone H3]-trimethyl-L-lysine(36) demethylase 4A
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Gene Name KDM4A
Gene ID 9682
Regulator Type Protein coding
Uniprot ID O75164
Sequence
MASESETLNPSARIMTFYPTMEEFRNFSRYIAYIESQGAHRAGLAKVVPPKEWKPRASYD
DIDDLVIPAPIQQLVTGQSGLFTQYNIQKKAMTVREFRKIANSDKYCTPRYSEFEELERK
YWKNLTFNPPIYGADVNGTLYEKHVDEWNIGRLRTILDLVEKESGITIEGVNTPYLYFGM
WKTSFAWHTEDMDLYSINYLHFGEPKSWYSVPPEHGKRLERLAKGFFPGSAQSCEAFLRH
KMTLISPLMLKKYGIPFDKVTQEAGEFMITFPYGYHAGFNHGFNCAESTNFATRRWIEYG
KQAVLCSCRKDMVKISMDVFVRKFQPERYKLWKAGKDNTVIDHTLPTPEAAEFLKESELP
PRAGNEEECPEEDMEGVEDGEEGDLKTSLAKHRIGTKRHRVCLEIPQEVSQSELFPKEDL
SSEQYEMTECPAALAPVRPTHSSVRQVEDGLTFPDYSDSTEVKFEELKNVKLEEEDEEEE
QAAAALDLSVNPASVGGRLVFSGSKKKSSSSLGSGSSRDSISSDSETSEPLSCRAQGQTG
VLTVHSYAKGDGRVTVGEPCTRKKGSAARSFSERELAEVADEYMFSLEENKKSKGRRQPL
SKLPRHHPLVLQECVSDDETSEQLTPEEEAEETEAWAKPLSQLWQNRPPNFEAEKEFNET
MAQQAPHCAVCMIFQTYHQVEFGGFNQNCGNASDLAPQKQRTKPLIPEMCFTSTGCSTDI
NLSTPYLEEDGTSILVSCKKCSVRVHASCYGVPPAKASEDWMCSRCSANALEEDCCLCSL
RGGALQRANDDRWVHVSCAVAILEARFVNIAERSPVDVSKIPLPRFKLKCIFCKKRRKRT
AGCCVQCSHGRCPTAFHVSCAQAAGVMMQPDDWPFVVFITCFRHKIPNLERAKGALQSIT
AGQKVISKHKNGRFYQCEVVRLTTETFYEVNFDDGSFSDNLYPEDIVSQDCLQFGPPAEG
EVVQVRWTDGQVYGAKFVASHPIQMYQVEFEDGSQLVVKRDDVYTLDEELPKRVKSRLSV
ASDMRFNEIFTEKEVKQEKKRQRVINSRYREDYIEPALYRAIME

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Family JHDM3 histone demethylase family
Function
Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys- 4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. Participates in transcriptional repression of ASCL2 and E2F-responsive promoters via the recruitment of histone deacetylases and NCOR1, respectively.

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HGNC ID
HGNC:22978
KEGG ID hsa:9682
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
KDM4A 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 Osteosarcoma ICD-11: 2B51
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell metastasis
In Vitro Model
 143B cells Osteosarcoma Homo sapiens CVCL_2270
HOS cells Osteosarcoma Homo sapiens CVCL_0312
In Vivo Model
For the xenograft mouse model, 1 x 106 OS 143B cells in 100 uL PBS were subcutaneously injected with 1 x 106 OS cells. For the OS lung metastasis model and in vivo imaging, 1 x 106 143B cells in 10 uL PBS were injected orthotopically into the medullary cavity of the tibia of mice. For bioluminescent imaging, we used 143B cells stably expressing luciferase, and the luciferase substrate D-Luciferin (Selleck, China) was retro-orbitally injected before imaging on days 7 and 21.

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Response regulation KDM4A regulates SLC7A11 transcription and osteosarcoma cell ferroptosis by controlling H3K9me3 demethylation in the promoter region of SLC7A11. The findings suggestes that KDM4A activity may be a potential therapeutic target for future OS treatment.
Osteosarcoma [ICD-11: 2B51]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Lysine-specific demethylase 4A (KDM4A) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell metastasis
In Vitro Model
 143B cells Osteosarcoma Homo sapiens CVCL_2270
HOS cells Osteosarcoma Homo sapiens CVCL_0312
In Vivo Model
For the xenograft mouse model, 1 x 106 OS 143B cells in 100 uL PBS were subcutaneously injected with 1 x 106 OS cells. For the OS lung metastasis model and in vivo imaging, 1 x 106 143B cells in 10 uL PBS were injected orthotopically into the medullary cavity of the tibia of mice. For bioluminescent imaging, we used 143B cells stably expressing luciferase, and the luciferase substrate D-Luciferin (Selleck, China) was retro-orbitally injected before imaging on days 7 and 21.

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Response regulation KDM4A regulates SLC7A11 transcription and osteosarcoma cell ferroptosis by controlling H3K9me3 demethylation in the promoter region of SLC7A11. The findings suggestes that KDM4A activity may be a potential therapeutic target for future OS treatment.
References
Ref 1 KDM4A-mediated histone demethylation of SLC7A11 inhibits cell ferroptosis in osteosarcoma. Biochem Biophys Res Commun. 2021 Apr 23;550:77-83. doi: 10.1016/j.bbrc.2021.02.137. Epub 2021 Mar 6.