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Details on Person UniProt:O60341 KDM1A
| Class:Id | ReferenceGeneProduct:144053 |
|---|---|
| _chainChangeLog | chain:1-852 added on Sat February 7 2015 |
| _displayName | UniProt:O60341 KDM1A |
| _timestamp | 2026-02-20 22:00:24 |
| chain | chain:1-852 |
| checksum | A61CEDE51E4E0C1D |
| comment | 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 (PubMed:15620353, PubMed:15811342, PubMed:16079794, PubMed:16079795, PubMed:16140033, PubMed:16223729, PubMed:27292636). Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed (PubMed:15620353, PubMed:15811342, PubMed:16079794, PubMed:21300290, PubMed:26214369). Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) (PubMed:15620353, PubMed:20389281, PubMed:21300290, PubMed:23721412). 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 (PubMed:16079794, PubMed:16140033, PubMed:16885027, PubMed:21300290, PubMed:23721412). 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 (PubMed:16079795). 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 (PubMed:29691401). Demethylates methylated 'Lys-42' and methylated 'Lys-117' of SOX2 (PubMed:29358331). 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 (PubMed:16079794, PubMed:16140033). Facilitates epithelial-to-mesenchymal transition by acting as an effector of SNAI1-mediated transcription repression of epithelial markers E-cadherin/CDH1, CDN7 and KRT8 (PubMed:20562920, PubMed:27292636). Required for the maintenance of the silenced state of the SNAI1 target genes E-cadherin/CDH1 and CDN7 (PubMed:20389281). Required for the repression of GIPR expression (PubMed:34655521, PubMed:34906447).FUNCTION Neuron-specific histone demethylase that demethylates mono- and dimethylated 'Lys-20' of histone H4 (H4K20me1 and H4K20me2), a chromatin repressive mark (PubMed:26214369). This demethylation is crucial for the initiation and elongation of neuronal activity-regulated genes, required for spatial learning and memory (By similarity). Mediates H3K9me2 demethylation through cooperation with the supervillin protein (SVIL), and this H3K9 demethylase activity is essential for regulating gene expression during neuronal differentiation (PubMed:25684206).FUNCTION Neuron-specific histone demethylase that demethylates mono- and dimethylated 'Lys-20' of histone H4 (H4K20me1 and H4K20me2), a chromatin repressive mark (PubMed:26214369). This demethylation is crucial for the initiation and elongation of neuronal activity-regulated genes, required for spatial learning and memory (By similarity). Mediates H3K9me2 demethylation through cooperation with the supervillin protein (SVIL), and this H3K9 demethylase activity is essential for regulating gene expression during neuronal differentiation (PubMed:25684206).CATALYTIC ACTIVITY N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + 2 A + 2 H2O = L-lysyl(4)-[histone H3] + 2 formaldehyde + 2 AH2CATALYTIC ACTIVITY N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + A + H2O = N(6)-methyl-L-lysyl(4)-[histone H3] + formaldehyde + AH2CATALYTIC ACTIVITY N(6)-methyl-L-lysyl(4)-[histone H3] + A + H2O = L-lysyl(4)-[histone H3] + formaldehyde + AH2CATALYTIC ACTIVITY N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + 2 2-oxoglutarate + 2 O2 = L-lysyl(9)-[histone H3] + 2 formaldehyde + 2 succinate + 2 CO2CATALYTIC ACTIVITY N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + 2-oxoglutarate + O2 = N(6)-methyl-L-lysyl(9)-[histone H3] + formaldehyde + succinate + CO2CATALYTIC ACTIVITY N(6)-methyl-L-lysyl(9)-[histone H3] + 2-oxoglutarate + O2 = L-lysyl(9)-[histone H3] + formaldehyde + succinate + CO2CATALYTIC ACTIVITY N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + 2 A + 2 H2O = L-lysyl(4)-[histone H3] + 2 formaldehyde + 2 AH2CATALYTIC ACTIVITY N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + A + H2O = N(6)-methyl-L-lysyl(4)-[histone H3] + formaldehyde + AH2CATALYTIC ACTIVITY N(6)-methyl-L-lysyl(4)-[histone H3] + A + H2O = L-lysyl(4)-[histone H3] + formaldehyde + AH2CATALYTIC ACTIVITY N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + 2 A + 2 H2O = L-lysyl(4)-[histone H3] + 2 formaldehyde + 2 AH2CATALYTIC ACTIVITY N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + A + H2O = N(6)-methyl-L-lysyl(4)-[histone H3] + formaldehyde + AH2CATALYTIC ACTIVITY N(6)-methyl-L-lysyl(4)-[histone H3] + A + H2O = L-lysyl(4)-[histone H3] + formaldehyde + AH2CATALYTIC ACTIVITY N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + 2 A + 2 H2O = L-lysyl(4)-[histone H3] + 2 formaldehyde + 2 AH2CATALYTIC ACTIVITY N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + A + H2O = N(6)-methyl-L-lysyl(4)-[histone H3] + formaldehyde + AH2CATALYTIC ACTIVITY N(6)-methyl-L-lysyl(4)-[histone H3] + A + H2O = L-lysyl(4)-[histone H3] + formaldehyde + AH2CATALYTIC ACTIVITY N(6),N(6)-dimethyl-L-lysyl(20)-[histone H4] + 2-oxoglutarate + O2 = N(6)-methyl-L-lysyl(20)-[histone H4] + formaldehyde + succinate + CO2CATALYTIC ACTIVITY N(6)-methyl-L-lysyl(20)-[histone H4] + 2-oxoglutarate + O2 = L-lysyl(20)-[histone H4] + formaldehyde + succinate + CO2CATALYTIC ACTIVITY N(6),N(6)-dimethyl-L-lysyl(20)-[histone H4] + 2-oxoglutarate + O2 = N(6)-methyl-L-lysyl(20)-[histone H4] + formaldehyde + succinate + CO2CATALYTIC ACTIVITY N(6)-methyl-L-lysyl(20)-[histone H4] + 2-oxoglutarate + O2 = L-lysyl(20)-[histone H4] + formaldehyde + succinate + CO2CATALYTIC ACTIVITY N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + 2 2-oxoglutarate + 2 O2 = L-lysyl(9)-[histone H3] + 2 formaldehyde + 2 succinate + 2 CO2CATALYTIC ACTIVITY N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + 2-oxoglutarate + O2 = N(6)-methyl-L-lysyl(9)-[histone H3] + formaldehyde + succinate + CO2CATALYTIC ACTIVITY N(6)-methyl-L-lysyl(9)-[histone H3] + 2-oxoglutarate + O2 = L-lysyl(9)-[histone H3] + formaldehyde + succinate + CO2CATALYTIC ACTIVITY N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + 2 2-oxoglutarate + 2 O2 = L-lysyl(9)-[histone H3] + 2 formaldehyde + 2 succinate + 2 CO2CATALYTIC ACTIVITY N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + 2-oxoglutarate + O2 = N(6)-methyl-L-lysyl(9)-[histone H3] + formaldehyde + succinate + CO2CATALYTIC ACTIVITY N(6)-methyl-L-lysyl(9)-[histone H3] + 2-oxoglutarate + O2 = L-lysyl(9)-[histone H3] + formaldehyde + succinate + CO2COFACTOR The N-terminal sequences of INSM1 and SNAI1 compete with histone H3 for the same binding site and thereby inhibit histone demethylation (in vitro).BIOPHYSICOCHEMICAL PROPERTIES kcat is 7.35 sec(-1) with H3 monomethyl-K4 as substrate when part of a complex with RCOR1 (at 25 degrees Celsius).BIOPHYSICOCHEMICAL PROPERTIES kcat is 5.47 sec(-1) with H3 monomethyl-K4 as substrate when part of a complex with RCOR1 (at 25 degrees Celsius).BIOPHYSICOCHEMICAL PROPERTIES kcat is 9.4 sec(-1) with H3 monomethyl-K4 as substrate when part of a complex with RCOR1 (at 25 degrees Celsius).BIOPHYSICOCHEMICAL PROPERTIES kcat is 5.19 sec(-1) with H3 monomethyl-K4 as substrate when part of a complex with RCOR1 (at 25 degrees Celsius).SUBUNIT Component of a histone demethylase complex with RCOR1 (PubMed:16885027, PubMed:20389281, PubMed:21300290, PubMed:23721412). Component of a RCOR/GFI/KDM1A/HDAC complex (PubMed:11102443, PubMed:12032298). Component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B, KDM1A, RCOR1 and PHF21A. The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I (PubMed:12493763, PubMed:16140033, PubMed:16885027). In the complex, RCOR1/CoREST strongly enhances the demethylase activity and protects it from the proteasome while PHF21A/BHC80 inhibits the demethylase activity (PubMed:16079794, PubMed:16956976). Interacts with INSM1 (via N-terminus) (PubMed:23721412). Interacts with the androgen receptor (AR) (PubMed:16079795). Interacts directly with GFI1 and GFI1B (By similarity). Interacts with SNAI1 (via SNAG domain) (PubMed:20389281, PubMed:20562920, PubMed:21300290, PubMed:23721412). Interacts (via AOD/Tower domain) with JADE2 (via C-terminus) (PubMed:25018020). Interacts with ESRRB; co-occupies the core set of ESRRB targets (By similarity). Interacts with SAMD1 (via WH domain); the interaction modulates KDM1A function (PubMed:33980486). Interacts with RBPJ (PubMed:29030483). Interacts with L3MBTL3 (PubMed:29030483). Interacts with ZMYND8 (PubMed:25593309). Interacts with FLAD1; which promotes KDM1A holoenzyme formation (PubMed:25954742).SUBUNIT Component of a histone demethylase complex with RCOR1. Forms a complex with SVIL, which functions to demethylate histone H3 at Lys-9 (H3K9me2) (PubMed:25684206).SUBUNIT Component of a histone demethylase complex with RCOR1.SUBUNIT Component of a histone demethylase complex with RCOR1 (PubMed:20164337). Forms a complex with SVIL, which functions to demethylate histone H3 at Lys-9 (H3K9me2) (PubMed:25684206).INTERACTION Associates with chromatin.ALTERNATIVE PRODUCTS Exon E8a-retaining LSD1 splice variant is restricted to neuronal lineage.TISSUE SPECIFICITY Ubiquitously expressed.TISSUE SPECIFICITY Expressed in brain and testis.TISSUE SPECIFICITY Expressed exclusively in brain tissues.INDUCTION Down-regulated during neural differentiation in neuroblastoma cancer.DOMAIN The SWIRM domain may act as an anchor site for a histone tail.PTM Acetylated by KAT8 in epithelial but not in mesenchymal cells, thereby regulating the epithelial-to-mesenchymal transition (PubMed:27292636). Acetylation by KAT8 reduces KDM1A association with nucleosomes, thereby decreasing histone H3 demethylation, leading to transcription activation of target genes (PubMed:27292636).PTM Polyubiquitinated by JADE2; which leads to its proteasomal degradation (PubMed:25018020). Deubiquitinated by USP38; preventing it from degradation by the 26S proteasome (PubMed:30497519).PTM Phosphorylation at Thr-371 reduces interaction with corepressors, including HDAC1/2 and CoREST, thereby converting isoform 4 from a transient dominant-negative repressor of neuronal differentiation into an active isoform that promotes neural morphogenesis and maturation.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the flavin monoamine oxidase family.CAUTION Was previously reported to interact with ASXL1. However, this publication has been retracted.CAUTION Conflicting results exist regarding the H3K4 demethylase activity of the neuron-specific isoforms (LSD1+8a). One study PubMed:20164337 reports that this isoform retains H3K4 demethylase activity. In contrast, PubMed:25684206. argues that the neuron-specific isoform is reprogrammed (via cofactors such as SVIL and others) to preferentially target H3K9me2, showing little to no H3K4me1/2 demethylase activity. The discrepancies appear to come from differences in assay type, complex composition, substrates (peptides vs nucleosomes), cofactors, post-translational states.SEQUENCE CAUTION Extended N-terminus. |
| created | [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 |
| description | recommendedName: fullName evidence="46"Lysine-specific histone demethylase 1A ecNumber evidence="31"1.14.11.- ecNumber evidence="11 29"1.14.11.65 ecNumber evidence="8 9 18 31"1.14.99.66 alternativeName: BRAF35-HDAC complex protein BHC110 alternativeName: Flavin-containing amine oxidase domain-containing protein 2 alternativeName: [histone H3]-dimethyl-L-lysine(4) FAD-dependent demethylase 1A |
| geneName | KDM1A AOF2 BHC110 KDM1 KIAA0601 LSD1 |
| identifier | O60341 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Alternative splicing Chromatin regulator Chromosome Coiled coil Cushing syndrome Developmental protein Direct protein sequencing Disease variant FAD Flavoprotein Isopeptide bond Nucleus Oxidoreductase Phosphoprotein Proteomics identification Reference proteome Repressor Transcription Transcription regulation Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | KDM1A |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8994887] ENSEMBL:ENSG00000004487 KDM1A [Homo sapiens] |
| secondaryIdentifier | KDM1A_HUMAN A8MWP9 Q5TH94 Q5TH95 Q86VT7 Q8IXK4 Q8NDP6 Q8TAZ3 Q96AW4 |
| sequenceLength | 852 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:144054] UniProt:O60341-2 KDM1A [Homo sapiens] [ReferenceIsoform:401684] UniProt:O60341-1 KDM1A [Homo sapiens] [ReferenceIsoform:9983160] Unknown:O60341-3 KDM1A [Homo sapiens] [ReferenceIsoform:9983161] Unknown:O60341-4 KDM1A [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:996769] KDM1A [nucleoplasm] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:O60341 KDM1A (144053)
