General Information of the Ferroptosis Regulator (ID: REG10128)
Regulator Name Lysine-specific demethylase 5A (KDM5A)
Synonyms
Histone demethylase JARID1A; Jumonji/ARID domain-containing protein 1A; Retinoblastoma-binding protein 2; [histone H3]-trimethyl-L-lysine(4) demethylase 5A
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Gene Name KDM5A
Gene ID 5927
Regulator Type Protein coding
Uniprot ID P29375
Sequence
MAGVGPGGYAAEFVPPPECPVFEPSWEEFTDPLSFIGRIRPLAEKTGICKIRPPKDWQPP
FACEVKSFRFTPRVQRLNELEAMTRVRLDFLDQLAKFWELQGSTLKIPVVERKILDLYAL
SKIVASKGGFEMVTKEKKWSKVGSRLGYLPGKGTGSLLKSHYERILYPYELFQSGVSLMG
VQMPNLDLKEKVEPEVLSTDTQTSPEPGTRMNILPKRTRRVKTQSESGDVSRNTELKKLQ
IFGAGPKVVGLAMGTKDKEDEVTRRRKVTNRSDAFNMQMRQRKGTLSVNFVDLYVCMFCG
RGNNEDKLLLCDGCDDSYHTFCLIPPLPDVPKGDWRCPKCVAEECSKPREAFGFEQAVRE
YTLQSFGEMADNFKSDYFNMPVHMVPTELVEKEFWRLVSSIEEDVIVEYGADISSKDFGS
GFPVKDGRRKILPEEEEYALSGWNLNNMPVLEQSVLAHINVDISGMKVPWLYVGMCFSSF
CWHIEDHWSYSINYLHWGEPKTWYGVPSHAAEQLEEVMRELAPELFESQPDLLHQLVTIM
NPNVLMEHGVPVYRTNQCAGEFVVTFPRAYHSGFNQGYNFAEAVNFCTADWLPIGRQCVN
HYRRLRRHCVFSHEELIFKMAADPECLDVGLAAMVCKELTLMTEEETRLRESVVQMGVLM
SEEEVFELVPDDERQCSACRTTCFLSALTCSCNPERLVCLYHPTDLCPCPMQKKCLRYRY
PLEDLPSLLYGVKVRAQSYDTWVSRVTEALSANFNHKKDLIELRVMLEDAEDRKYPENDL
FRKLRDAVKEAETCASVAQLLLSKKQKHRQSPDSGRTRTKLTVEELKAFVQQLFSLPCVI
SQARQVKNLLDDVEEFHERAQEAMMDETPDSSKLQMLIDMGSSLYVELPELPRLKQELQQ
ARWLDEVRLTLSDPQQVTLDVMKKLIDSGVGLAPHHAVEKAMAELQELLTVSERWEEKAK
VCLQARPRHSVASLESIVNEAKNIPAFLPNVLSLKEALQKAREWTAKVEAIQSGSNYAYL
EQLESLSAKGRPIPVRLEALPQVESQVAAARAWRERTGRTFLKKNSSHTLLQVLSPRTDI
GVYGSGKNRRKKVKELIEKEKEKDLDLEPLSDLEEGLEETRDTAMVVAVFKEREQKEIEA
MHSLRAANLAKMTMVDRIEEVKFCICRKTASGFMLQCELCKDWFHNSCVPLPKSSSQKKG
SSWQAKEVKFLCPLCMRSRRPRLETILSLLVSLQKLPVRLPEGEALQCLTERAMSWQDRA
RQALATDELSSALAKLSVLSQRMVEQAAREKTEKIISAELQKAAANPDLQGHLPSFQQSA
FNRVVSSVSSSPRQTMDYDDEETDSDEDIRETYGYDMKDTASVKSSSSLEPNLFCDEEIP
IKSEEVVTHMWTAPSFCAEHAYSSASKSCSQGSSTPRKQPRKSPLVPRSLEPPVLELSPG
AKAQLEELMMVGDLLEVSLDETQHIWRILQATHPPSEDRFLHIMEDDSMEEKPLKVKGKD
SSEKKRKRKLEKVEQLFGEGKQKSKELKKMDKPRKKKLKLGADKSKELNKLAKKLAKEEE
RKKKKEKAAAAKVELVKESTEKKREKKVLDIPSKYDWSGAEESDDENAVCAAQNCQRPCK
DKVDWVQCDGGCDEWFHQVCVGVSPEMAENEDYICINCAKKQGPVSPGPAPPPSFIMSYK
LPMEDLKETS

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Family JARID1 histone demethylase family
Function
Histone demethylase that specifically demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. Regulates specific gene transcription through DNA-binding on 5'-CCGCCC-3' motif. May stimulate transcription mediated by nuclear receptors. Involved in transcriptional regulation of Hox proteins during cell differentiation. May participate in transcriptional repression of cytokines such as CXCL12. Plays a role in the regulation of the circadian rhythm and in maintaining the normal periodicity of the circadian clock. In a histone demethylase-independent manner, acts as a coactivator of the CLOCK-BMAL1-mediated transcriptional activation of PER1/2 and other clock-controlled genes and increases histone acetylation at PER1/2 promoters by inhibiting the activity of HDAC1. Seems to act as a transcriptional corepressor for some genes such as MT1F and to favor the proliferation of cancer cells.

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HGNC ID
HGNC:9886
KEGG ID hsa:5927
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
KDM5A 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
Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Head neck squamous cell carcinoma ICD-11: 2D60
Pathway Response Glutamate metabolism hsa00250
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
In Vitro Model
NH-3 cells Tongue squamous cell carcinoma Homo sapiens CVCL_8126
HN4 cells Clear cell renal cell carcinoma Homo sapiens CVCL_IS30
In Vivo Model
Six-week-old athymic BALB/c male nude mice (nu/nu) were purchased from OrientBio (Seoul, Republic of Korea). HN4 parental cells with transfection of vector control or shGPX4 were subcutaneously injected into the bilateral flank of nude mice. The same was performed in HN4 erPCC with transfection of control vector or shGPX4. Each group included six mice. In other experiments, HN4 parental cells with transfection of control vector or shMPC1 were injected to nude mice in the same way above. HN4 parental cells and erPCC without target gene silencing were also injected into nude mice. Each group included six mice. From the day when gross nodules were detected in tumor implants, mice were subjected to different treatments: vehicle or sulfasalazine (250 mg/kg daily per intraperitoneal route).

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Response regulation The regulation of a KDM5A-MPC1 axis contributes to promoting ferroptosis susceptibility in head and neck cancer (HNC) cells, which might be recommended as a promising combination therapy in combating drug-tolerant persister cancer cells.
Head neck squamous cell carcinoma [ICD-11: 2D60]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Lysine-specific demethylase 5A (KDM5A) Protein coding
Pathway Response Glutamate metabolism hsa00250
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
In Vitro Model
NH-3 cells Tongue squamous cell carcinoma Homo sapiens CVCL_8126
HN4 cells Clear cell renal cell carcinoma Homo sapiens CVCL_IS30
In Vivo Model
Six-week-old athymic BALB/c male nude mice (nu/nu) were purchased from OrientBio (Seoul, Republic of Korea). HN4 parental cells with transfection of vector control or shGPX4 were subcutaneously injected into the bilateral flank of nude mice. The same was performed in HN4 erPCC with transfection of control vector or shGPX4. Each group included six mice. In other experiments, HN4 parental cells with transfection of control vector or shMPC1 were injected to nude mice in the same way above. HN4 parental cells and erPCC without target gene silencing were also injected into nude mice. Each group included six mice. From the day when gross nodules were detected in tumor implants, mice were subjected to different treatments: vehicle or sulfasalazine (250 mg/kg daily per intraperitoneal route).

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Response regulation The regulation of a KDM5A-MPC1 axis contributes to promoting ferroptosis susceptibility in head and neck cancer (HNC) cells, which might be recommended as a promising combination therapy in combating drug-tolerant persister cancer cells.
References
Ref 1 Mitochondrial pyruvate carrier 1 regulates ferroptosis in drug-tolerant persister head and neck cancer cells via epithelial-mesenchymal transition. Cancer Lett. 2021 Jun 1;507:40-54. doi: 10.1016/j.canlet.2021.03.013. Epub 2021 Mar 16.