KDM1A - Lysine-specific histone demethylase 1A - human protein (Function)
 
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KDM1A »  Lysine-specific histone demethylase 1A
 
Gene name:  KDM1A
Entry whose protein(s) existence is based on evidence at protein level
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1 137 2
GENE REF ISO

Function

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Overview 
Histone demethylase that demethylates 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 (ANDR)-dependent transcription, by being recruited to ANDR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in ANDR-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. 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.  
6
  • CuratedUniProtKB
GO molecular function 
Androgen receptor bindingdefinition[GO:0050681]  
1
  • IDAUniProtKB
Chromatin bindingdefinition[GO:0003682]  
2
  • IDAUniProtKB
Demethylase activitydefinition[GO:0032451]  
1
  • IMPBHF-UCL
Enzyme bindingdefinition[GO:0019899]  
1
  • IPIBHF-UCL
Flavin adenine dinucleotide bindingdefinition[GO:0050660]  
1
  • IDAUniProtKB
Histone demethylase activitydefinition[GO:0032452]  
1
  • IDABHF-UCL
Histone demethylase activity (H3-dimethyl-K4 specific)definition[GO:0034648]  
1
  • IDAUniProtKB
Histone demethylase activity (H3-K4 specific)definition[GO:0032453]  
1
  • IDAUniProtKB
Histone demethylase activity (H3-K9 specific)definition[GO:0032454]  
2
  • IDAUniProtKB
Ligand-dependent nuclear receptor transcription coactivator activitydefinition[GO:0030374]  
1
  • IMPUniProtKB
MRF bindingdefinition[GO:0043426]  
1
  • IDABHF-UCL
Oxidoreductase activitydefinition[GO:0016491]  
1
  • IDAUniProtKB
P53 bindingdefinition[GO:0002039]  
1
  • IPIBHF-UCL
Protein bindingdefinition[GO:0005515]  
13
  • IPIIntAct
  • IPIUniProtKB
  • IPIBHF-UCL
RNA polymerase II transcription factor bindingdefinition[GO:0001085] silver  
  • IEAOrtholog Compara
Sequence-specific DNA binding transcription factor activitydefinition[GO:0003700] silver  
  • IEAOrtholog Compara
Transcription factor bindingdefinition[GO:0008134]  
1
  • IDABHF-UCL
Transcription regulatory region DNA bindingdefinition[GO:0044212]  
  • ISSOrtholog Curator
GO biological process 
Cell proliferationdefinition[GO:0008283] silver  
  • IEAOrtholog Compara
Granulocyte differentiationdefinition[GO:0030851] silver  
  • IEAOrtholog Compara
Histone H3-K4 demethylationdefinition[GO:0034720]  
2
  • IDAUniProtKB
Histone H3-K9 demethylationdefinition[GO:0033169]  
2
  • IDAUniProtKB
In utero embryonic developmentdefinition[GO:0001701] silver  
  • IEAOrtholog Compara
Muscle cell developmentdefinition[GO:0055001]  
1
  • ISSBHF-UCL
Negative regulation of DNA bindingdefinition[GO:0043392]  
1
  • ICBHF-UCL
Negative regulation of DNA damage response, signal transduction by p53 class mediatordefinition[GO:0043518]  
1
  • IMPBHF-UCL
Negative regulation of histone H3-K4 methylationdefinition[GO:0051572] silver  
  • IEAOrtholog Compara
Negative regulation of histone H3-K9 methylationdefinition[GO:0051573] silver  
  • IEAOrtholog Compara
Negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediatordefinition[GO:1902166]  
1
  • IMPBHF-UCL
Negative regulation of protein bindingdefinition[GO:0032091]  
1
  • IMPBHF-UCL
Negative regulation of sequence-specific DNA binding transcription factor activitydefinition[GO:0043433]  
2
  • IDABHF-UCL
Negative regulation of transcription from RNA polymerase II promoterdefinition[GO:0000122]  
1
  • IMPBHF-UCL
  • ISSOrtholog Curator
Negative regulation of transcription, DNA-templateddefinition[GO:0045892]  
1
  • IDABHF-UCL
Oxidation-reduction processdefinition[GO:0055114]  
  • IEAUniProtKB KW
Pituitary gland developmentdefinition[GO:0021983] silver  
  • IEAOrtholog Compara
Positive regulation of erythrocyte differentiationdefinition[GO:0045648] silver  
  • IEAOrtholog Compara
Positive regulation of hormone biosynthetic processdefinition[GO:0046886] silver  
  • IEAOrtholog Compara
Positive regulation of megakaryocyte differentiationdefinition[GO:0045654] silver  
  • IEAOrtholog Compara
Positive regulation of neural precursor cell proliferationdefinition[GO:2000179] silver  
  • IEAOrtholog Compara
Positive regulation of sequence-specific DNA binding transcription factor activitydefinition[GO:0051091]  
1
  • IDABHF-UCL
Positive regulation of stem cell proliferationdefinition[GO:2000648] silver  
  • IEAOrtholog Compara
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
1
  • IDABHF-UCL
Protein demethylationdefinition[GO:0006482]  
1
  • IMPBHF-UCL
Regulation of primitive erythrocyte differentiationdefinition[GO:0010725] silver  
  • IEAOrtholog Compara
Regulation of transcription from RNA polymerase II promoterdefinition[GO:0006357]  
1
  • IMPUniProtKB
Transcription, DNA-templateddefinition[GO:0006351]  
  • IEAUniProtKB KW
Enzymatic activity 
It requires the following cofactor
FAD.  
2
  • CuratedUniProtKB
Pathways 
According to Reactome, this protein belongs to the following pathway:
Factors involved in megakaryocyte development and platelet production  REACT_24970  
 

Biophysicochemical properties

Kinetic parameters
KM 3.0 uM for H3 monomethyl-K4
KM 4.2 uM for H3 dimethyl-K4
KM 17.5 uM for monomethyl-K4-acetyl-K9
KM 3.9 uM for H3 monomethyl-K4-monomethyl-K9

Keywords

Biological process 
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Chromatin regulator  definition   [KW-0156]
Developmental protein  definition   [KW-0217]
Oxidoreductase  definition   [KW-0560]
Repressor  definition   [KW-0678]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GenomeRNAi: 23028
PRO: PR:O60341
Chemistry
GuidetoPHARMACOLOGY: 2669