KDM1A
entrez
23028
canonical
uniprot
O60341
canonical
ensembl
ENSG00000004487
resolver
ensp
ENSP00000349049
resolver
ensp
ENSP00000383042
resolver
ensp
ENSP00000473297
resolver
ensp
ENSP00000509257
resolver
ensp
ENSP00000509679
resolver
ensp
ENSP00000544719
resolver
ensp
ENSP00000644464
resolver
ensp
ENSP00000681758
resolver
ensp
ENSP00000681764
resolver
enst
ENST00000465864
resolver
enst
ENST00000685102
resolver
enst
ENST00000691682
resolver
genesymbol
KDM1A
resolver
genesymbol_syn
AOF2
resolver
genesymbol_syn
BHC110
resolver
genesymbol_syn
KDM1
resolver
genesymbol_syn
KIAA0601
resolver
genesymbol_syn
LSD1
resolver
hgnc
HGNC:29079
resolver
uniprot
A0A8I5KSH0
resolver
uniprot
A0A8I5KXU4
resolver
uniprot
A8MWP9
resolver
uniprot
Q5TH94
resolver
uniprot
Q5TH95
resolver
uniprot
Q86VT7
resolver
uniprot
Q8IXK4
resolver
uniprot
Q8NDP6
resolver
uniprot
Q8TAZ3
resolver
uniprot
Q96AW4
resolver
uniprot
R4GMQ1
resolver
uniprot_entry
A0A8I5KSH0_HUMAN
resolver
uniprot_entry
A0A8I5KXU4_HUMAN
resolver
uniprot_entry
KDM1A_HUMAN
resolver
uniprot_entry
R4GMQ1_HUMAN
resolver
uniprot_sec
A8MWP9
resolver
uniprot_sec
Q5TH94
resolver
uniprot_sec
Q5TH95
resolver
uniprot_sec
Q86VT7
resolver
uniprot_sec
Q8IXK4
resolver
uniprot_sec
Q8NDP6
resolver
uniprot_sec
Q8TAZ3
resolver
uniprot_sec
Q96AW4
resolver
activity_regulation
ACTIVITY REGULATION: The N-terminal sequences of INSM1 and SNAI1 compete with histone H3 for the same binding site and thereby inhibit histone demethylation (in vitro). {ECO:0000269|PubMed:21300290, ECO:0000269|PubMed:23721412}.
uniprot
proteins
amino_acid_sequence
MLSGKKAAAAAAAAAAAATGTEAGPGTAGGSENGSEVAAQPAGLSGPAEVGPGAVGERTPRKKEPPRASPPGGLAEPPGSAGPQAGPTVVPGSATPMETGIAETPEGRRTSRRKRAKVEYREMDESLANLSEDEYYSEEERNAKAEKEKKLPPPPPQAPPEEENESEPEEPSGVEGAAFQSRLPHDRMTSQEAACFPDIISGPQQTQKVFLFIRNRTLQLWLDNPKIQLTFEATLQQLEAPYNSDTVLVHRVHSYLERHGLINFGIYKRIKPLPTKKTGKVIIIGSGVSGLAAARQLQSFGMDVTLLEARDRVGGRVATFRKGNYVADLGAMVVTGLGGNPMAVVSKQVNMELAKIKQKCPLYEANGQAVPKEKDEMVEQEFNRLLEATSYLSHQLDFNVLNNKPVSLGQALEVVIQLQEKHVKDEQIEHWKKIVKTQEELKELLNKMVNLKEKIKELHQQYKEASEVKPPRDITAEFLVKSKHRDLTALCKEYDELAETQGKLEEKLQELEANPPSDVYLSSRDRQILDWHFANLEFANATPLSTLSLKHWDQDDDFEFTGSHLTVRNGYSCVPVALAEGLDIKLNTAVRQVRYTASGCEVIAVNTRSTSQTFIYKCDAVLCTLPLGVLKQQPPAVQFVPPLPEWKTSAVQRMGFGNLNKVVLCFDRVFWDPSVNLFGHVGSTTASRGELFLFWNLYKAPILLALVAGEAAGIMENISDDVIVGRCLAILKGIFGSSAVPQPKETVVSRWRADPWARGSYSYVAAGSSGNDYDLMAQPITPGPSIPGAPQPIPRLFFAGEHTIRNYPATVHGALLSGLREAGRIADQFLGAMYTLPRQATPGVPAQQSPSM
uniprot
proteins
disease_involvement
DISEASE: Cleft palate, psychomotor retardation, and distinctive facial features (CPRF) [MIM:616728]: A syndrome characterized by cleft palate, developmental delay, psychomotor retardation, and facial dysmorphic features including a prominent forehead, slightly arched eyebrows, elongated palpebral fissures, a wide nasal bridge, thin lips, and widely spaced teeth. Cleft palate is a congenital fissure of the soft and/or hard palate, due to faulty fusion. {ECO:0000269|PubMed:23020937, ECO:0000269|PubMed:24838796, ECO:0000269|PubMed:26656649}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: ACTH-independent macronodular adrenal hyperplasia 3 (AIMAH3) [MIM:620990]: A form of macronodular adrenal hyperplasia, a rare adrenal defect characterized by multiple, bilateral, non-pigmented, benign, adrenocortical nodules. It results in excessive production of cortisol leading to ACTH-independent Cushing syndrome. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. AIMAH3 affected individuals have low fasting cortisol and ACTH, but excess cortisol is secreted after eating. {ECO:0000269|PubMed:34655521, ECO:0000269|PubMed:34906447}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
1.14.11.-
uniprot
proteins
ec_number
1.14.11.65
uniprot
proteins
ec_number
1.14.99.66
uniprot
proteins
function
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). {ECO:0000269|PubMed:12032298, ECO:0000269|PubMed:15620353, ECO:0000269|PubMed:15811342, ECO:0000269|PubMed:16079794, ECO:0000269|PubMed:16079795, ECO:0000269|PubMed:16140033, ECO:0000269|PubMed:16223729, ECO:0000269|PubMed:16885027, ECO:0000269|PubMed:16956976, ECO:0000269|PubMed:17805299, ECO:0000269|PubMed:20228790, ECO:0000269|PubMed:20389281, ECO:0000269|PubMed:20562920, ECO:0000269|PubMed:21300290, ECO:0000269|PubMed:23721412, ECO:0000269|PubMed:26214369, ECO:0000269|PubMed:27292636, ECO:0000269|PubMed:29358331, ECO:0000269|PubMed:29691401, ECO:0000269|PubMed:34655521, ECO:0000269|PubMed:34906447}.; FUNCTION: [Isoform 2]: 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). {ECO:0000250|UniProtKB:Q6ZQ88, ECO:0000269|PubMed:25684206, ECO:0000269|PubMed:26214369}.; FUNCTION: [Isoform 4]: 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). {ECO:0000250|UniProtKB:Q6ZQ88, ECO:0000269|PubMed:25684206, ECO:0000269|PubMed:26214369}.
uniprot
proteins
mass_dalton
92903
uniprot
proteins
mutagenesis
MUTAGEN 432..436; /note="KKIVK->QQIVQ: Mimics acetylation; preventing association with chromatin."; /evidence="ECO:0000269|PubMed:27292636"; MUTAGEN 432..436; /note="KKIVK->RRIVR: Abolished acetylation by KAT8, promoting association with chromatin."; /evidence="ECO:0000269|PubMed:27292636"; MUTAGEN 503; /note="K->R: Loss of polyubiquitination."; /evidence="ECO:0000269|PubMed:25018020"; MUTAGEN 535; /note="N->A: Strongly reduces demethylase activity."; /evidence="ECO:0000269|PubMed:16956976"; MUTAGEN 564; /note="H->A: Strongly reduces demethylase activity."; /evidence="ECO:0000269|PubMed:16956976"; MUTAGEN 661; /note="K->A: Abolishes histone demethylase activity."; /evidence="ECO:0000269|PubMed:16079794"; MUTAGEN 761; /note="Y->A: Strongly reduces demethylase activity."; /evidence="ECO:0000269|PubMed:16956976"; MUTAGEN O60341-2:685; /note="K->A: Abolishes histone H4K20 demethylase activity."; /evidence="ECO:0000269|PubMed:26214369
uniprot
proteins
post_translational_modification
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). {ECO:0000269|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). {ECO:0000269|PubMed:25018020, ECO:0000269|PubMed:30497519}.; PTM: [Isoform 4]: 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. {ECO:0000269|PubMed:24111946}.
uniprot
proteins
protein_family
Flavin monoamine oxidase family
uniprot
proteins
pubmed
11102443
uniprot
proteins
pubmed
12032298
uniprot
proteins
pubmed
12493763
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15620353
uniprot
proteins
pubmed
15811342
uniprot
proteins
pubmed
16079794
uniprot
proteins
pubmed
16079795
uniprot
proteins
pubmed
16140033
uniprot
proteins
pubmed
16223729
uniprot
proteins
pubmed
16531230
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
16885027
uniprot
proteins
pubmed
16956976
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17805299
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19880879
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20164337
uniprot
proteins
pubmed
20228790
uniprot
proteins
pubmed
20389281
uniprot
proteins
pubmed
20562920
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21300290
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
23020937
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23721412
uniprot
proteins
pubmed
24111946
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24838796
uniprot
proteins
pubmed
25018020
uniprot
proteins
pubmed
25593309
uniprot
proteins
pubmed
25684206
uniprot
proteins
pubmed
25750265
uniprot
proteins
pubmed
25954742
uniprot
proteins
pubmed
26214369
uniprot
proteins
pubmed
26656649
uniprot
proteins
pubmed
27292636
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
29030483
uniprot
proteins
pubmed
29358331
uniprot
proteins
pubmed
29691401
uniprot
proteins
pubmed
30497519
uniprot
proteins
pubmed
33980486
uniprot
proteins
pubmed
34655521
uniprot
proteins
pubmed
34906447
uniprot
proteins
pubmed
9628581
uniprot
proteins
sequence_length
852
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11102443, ECO:0000269|PubMed:16079795, ECO:0000269|PubMed:20389281, ECO:0000269|PubMed:33980486}. Chromosome {ECO:0000269|PubMed:16079795, ECO:0000269|PubMed:20228790, ECO:0000269|PubMed:27292636, ECO:0000269|PubMed:33980486}. Note=Associates with chromatin. {ECO:0000269|PubMed:16079795, ECO:0000269|PubMed:20228790, ECO:0000269|PubMed:27292636, ECO:0000269|PubMed:33980486}.
uniprot
proteins