Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10033)
Regulator Name Lysine-specific histone demethylase 1A (KDM1A)
Synonyms
BRAF35-HDAC complex protein BHC110; Flavin-containing amine oxidase domain-containing protein 2; [histone H3]-dimethyl-L-lysine(4) FAD-dependent demethylase 1A
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Gene Name KDM1A
Gene ID 23028
Regulator Type Protein coding
Uniprot ID O60341
Sequence
MLSGKKAAAAAAAAAAAATGTEAGPGTAGGSENGSEVAAQPAGLSGPAEVGPGAVGERTP
RKKEPPRASPPGGLAEPPGSAGPQAGPTVVPGSATPMETGIAETPEGRRTSRRKRAKVEY
REMDESLANLSEDEYYSEEERNAKAEKEKKLPPPPPQAPPEEENESEPEEPSGVEGAAFQ
SRLPHDRMTSQEAACFPDIISGPQQTQKVFLFIRNRTLQLWLDNPKIQLTFEATLQQLEA
PYNSDTVLVHRVHSYLERHGLINFGIYKRIKPLPTKKTGKVIIIGSGVSGLAAARQLQSF
GMDVTLLEARDRVGGRVATFRKGNYVADLGAMVVTGLGGNPMAVVSKQVNMELAKIKQKC
PLYEANGQAVPKEKDEMVEQEFNRLLEATSYLSHQLDFNVLNNKPVSLGQALEVVIQLQE
KHVKDEQIEHWKKIVKTQEELKELLNKMVNLKEKIKELHQQYKEASEVKPPRDITAEFLV
KSKHRDLTALCKEYDELAETQGKLEEKLQELEANPPSDVYLSSRDRQILDWHFANLEFAN
ATPLSTLSLKHWDQDDDFEFTGSHLTVRNGYSCVPVALAEGLDIKLNTAVRQVRYTASGC
EVIAVNTRSTSQTFIYKCDAVLCTLPLGVLKQQPPAVQFVPPLPEWKTSAVQRMGFGNLN
KVVLCFDRVFWDPSVNLFGHVGSTTASRGELFLFWNLYKAPILLALVAGEAAGIMENISD
DVIVGRCLAILKGIFGSSAVPQPKETVVSRWRADPWARGSYSYVAAGSSGNDYDLMAQPI
TPGPSIPGAPQPIPRLFFAGEHTIRNYPATVHGALLSGLREAGRIADQFLGAMYTLPRQA
TPGVPAQQSPSM

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Family Flavin monoamine oxidase family
Function
Histone demethylase that can demethylate both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me. May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity. Also acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in AR-containing complexes, which mediates phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A. Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation. Demethylates and stabilizes the DNA methylase DNMT1. Demethylates methylated 'Lys-42' and methylated 'Lys-117' of SOX2. Required for gastrulation during embryogenesis. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Effector of SNAI1-mediated transcription repression of E-cadherin/CDH1, CDN7 and KRT8. Required for the maintenance of the silenced state of the SNAI1 target genes E-cadherin/CDH1 and CDN7.

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HGNC ID
HGNC:29079
KEGG ID hsa:23028
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
KDM1A 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
NADPH oxidase 4 (NOX4) [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 Ischemia/reperfusion injury ICD-11: DB98
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HK-2 cells Normal Homo sapiens CVCL_0302
In Vivo Model
Adult male C57BL6 (C57) mice (8-12 weeks, 20-25 g) were purchased from the Animal Experiment Center of Wuhan University. All 64 mice were randomly divided into various groups by different treatments (n = 8). In sham group, after the right kidney excised, the left renal pedicles were without any treatment. In IRI group, the pedicle of the left kidney was clamped for 30 min followed by various reperfusion periods (6, 12, 24 h). To study the effects of LSD1, TCP (MedChemExpress) was injected intraperitoneally at different doses (2.5, 5, 10 mg/kg) before IRI model establishment, once a day for 1 week. TCP powder was dissolved in dimethyl sulfoxide (DMSO). In the vehicle control group, equal amount of DMSO was injected intraperitoneally.

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Response regulation LSD1 (KDM1A) inhibition blocked ferroptosis and oxidative stress caused by renal IRI through the TLR4/NOX4 pathway, indicating that LSD1 could be a potential therapeutic target for renal ischaemia reperfusion injury (IRI).
Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
H157 cells Oral cavity Squamous cell carcinoma Homo sapiens CVCL_2458
NCI-H358 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
Response regulation Knockdown of KDM1A inhibited the level of c-Myc and increased the concentration of malondialdehyde (MDA) and irons in human lung cancer cells H1299 and A549. Downregulation of c-Myc could facilitate KDM1A knockdown-mediated ferroptosis.
Ischemia/reperfusion injury [ICD-11: DB98]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Lysine-specific histone demethylase 1A (KDM1A) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HK-2 cells Normal Homo sapiens CVCL_0302
In Vivo Model
Adult male C57BL6 (C57) mice (8-12 weeks, 20-25 g) were purchased from the Animal Experiment Center of Wuhan University. All 64 mice were randomly divided into various groups by different treatments (n = 8). In sham group, after the right kidney excised, the left renal pedicles were without any treatment. In IRI group, the pedicle of the left kidney was clamped for 30 min followed by various reperfusion periods (6, 12, 24 h). To study the effects of LSD1, TCP (MedChemExpress) was injected intraperitoneally at different doses (2.5, 5, 10 mg/kg) before IRI model establishment, once a day for 1 week. TCP powder was dissolved in dimethyl sulfoxide (DMSO). In the vehicle control group, equal amount of DMSO was injected intraperitoneally.

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Response regulation LSD1 (KDM1A) inhibition blocked ferroptosis and oxidative stress caused by renal IRI through the TLR4/NOX4 pathway, indicating that LSD1 could be a potential therapeutic target for renal ischaemia reperfusion injury (IRI).
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Lysine-specific histone demethylase 1A (KDM1A) Protein coding
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
H157 cells Oral cavity Squamous cell carcinoma Homo sapiens CVCL_2458
NCI-H358 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
Response regulation Knockdown of KDM1A inhibited the level of c-Myc and increased the concentration of malondialdehyde (MDA) and irons in human lung cancer cells H1299 and A549. Downregulation of c-Myc could facilitate KDM1A knockdown-mediated ferroptosis.
References
Ref 1 Lysine-specific demethylase 1 aggravated oxidative stress and ferroptosis induced by renal ischemia and reperfusion injury through activation of TLR4/NOX4 pathway in mice. J Cell Mol Med. 2022 Aug;26(15):4254-4267. doi: 10.1111/jcmm.17444. Epub 2022 Jun 30.
Ref 2 Aberrant expression of KDM1A inhibits ferroptosis of lung cancer cells through up-regulating c-Myc. Sci Rep. 2022 Nov 10;12(1):19168. doi: 10.1038/s41598-022-23699-4.