Tchem KDM1A Lysine-specific histone demethylase 1A

Protein Summary

Description

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. This gene encodes a nuclear protein containing a SWIRM domain, a FAD-binding motif, and an amine oxidase domain. This protein is a component of several histone deacetylase complexes, though it silences genes by functioning as a histone demethylase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

Uniprot Accession IDs

• O60341
• A8MWP9
• Q5TH94
• Q5TH95
• Q86VT7
• Q8IXK4
• Q8NDP6
• Q8TAZ3
• Q96AW4

Gene Name

• KDM1A

Ensembl ID

• ENST00000356634
• ENSP00000349049
• ENSG00000004487
• ENST00000400181
• ENSP00000383042

Symbol

• AOF2
• KDM1
• KIAA0601
• LSD1
• AOF2
• CPRF
• KDM1
• LSD1
• BHC110

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
molecular function	1
protein complex	1
disease perturbation	0.97
transcription factor binding site profile	0.94

Protein Classes

PANTHER Classes

Protein / Transferase / Methyltransferase / Dna Methyltransferase / Lysine-specific Histone Demethylase 1a

Protein / Oxidoreductase / Oxidase / Lysine-specific Histone Demethylase 1a

Protein / Nucleic Acid Binding / Dna Binding Protein / Dna Methyltransferase / Lysine-specific Histone Demethylase 1a

DTO Classes

Protein / Epigenetic Regulator / Eraser / Lysine Demethylase / Lysine-specific Demethylase / Lysine-specific Histone Demethylase 1a

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1068.12   (req: < 5)

Gene RIFs: 337   (req: <= 3)

Antibodies: 619   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1068.12   (req: >= 5)

Gene RIFs: 337   (req: > 3)

Antibodies: 619   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 49

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 692

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0