{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"O60341","secondaryAccessions":["A8MWP9","Q5TH94","Q5TH95","Q86VT7","Q8IXK4","Q8NDP6","Q8TAZ3","Q96AW4"],"uniProtkbId":"KDM1A_HUMAN","entryAudit":{"firstPublicDate":"2004-08-16","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2004-08-16","entryVersion":236,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Lysine-specific histone demethylase 1A"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26214369"}],"value":"1.14.11.-"},{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16079795"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25684206"}],"value":"1.14.11.65"},{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15620353"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15811342"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20164337"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26214369"}],"value":"1.14.99.66"}]},"alternativeNames":[{"fullName":{"value":"BRAF35-HDAC complex protein BHC110"}},{"fullName":{"value":"Flavin-containing amine oxidase domain-containing protein 2"}},{"fullName":{"value":"[histone H3]-dimethyl-L-lysine(4) FAD-dependent demethylase 1A"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:29079"}],"value":"KDM1A"},"synonyms":[{"value":"AOF2"},{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:29079"}],"value":"BHC110"},{"value":"KDM1"},{"value":"KIAA0601"},{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"15620353"}],"value":"LSD1"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12032298"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15620353"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15811342"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16079794"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16079795"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16140033"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16223729"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16885027"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16956976"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17805299"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20228790"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20389281"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20562920"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21300290"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23721412"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26214369"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27292636"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29358331"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29691401"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34655521"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34906447"}],"value":"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)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q6ZQ88"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25684206"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26214369"}],"value":"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)"}],"commentType":"FUNCTION","molecule":"Isoform 2"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q6ZQ88"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25684206"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26214369"}],"value":"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)"}],"commentType":"FUNCTION","molecule":"Isoform 4"},{"commentType":"CATALYTIC ACTIVITY","molecule":"Isoform 1","reaction":{"name":"N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + 2 A + 2 H2O = L-lysyl(4)-[histone H3] + 2 formaldehyde + 2 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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)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20164337"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25684206"}],"value":"Component of a histone demethylase complex with RCOR1. 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