Molecular Target Synopsis
Domains and Structures
Drugs and Clinical Candidates
Ligand Efficiency Plot
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
Germline Genetics

KDM1A (O60341) - Overview - Molecular Target Synopsis


KDM1A, Lysine-specific histone demethylase 1A
Enzyme Classification 1.-.-.-
UniProt O60341

Also Known as KDM1A_HUMAN, KDM1A, AOF2, KDM1, KIAA0601, LSD1

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. Component of a RCOR/GFI/KDM1A/HDAC complex (PubMed:12032298, PubMed:11102443). Interacts directly with GFI1 and GFI1B. Interacts with INSM1 (By similarity). 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 the androgen receptor (AR) (PubMed:16079795). Interacts with SNAI1 (via SNAG domain) (PubMed:20562920). Interacts (via AOD/Tower domain) with JADE2 (via C-terminus) (PubMed:25018020). Interacts with ESRRB; co-occupes the core set of ESRRB targets.

Inspect Structure
See all 3D Structures for KDM1A

Isoforms / Transcripts (Protein Coding)

Sub-cellular localization

UniProt: KDM1A is active in the following subcellular-locations: nucleus.
GO terms: KDM1A is active in the following subcellular-locations: DNA repair complex, nuclear chromatin, nuclear chromosome, nucleoplasm, nucleus, protein-containing complex, transcription factor complex.

GO terms

Gene Copy Number Variation

In COSMIC - Cell Lines Project KDM1A has gain in 1 cell-lines, loss in 0 cell-lines and no signal in 1004 cell-lines. (see details)

Gene Expression

In NCI60, the highest expressing cell lines are:

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: EFO-27, MKN-1, NCI-H847

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, HSMM, NHLF

(see details)

3D Structures

For KDM1A there are:
60 structures (61 chains) solved
57 are solved in complex with at least one small molecule ligand

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry

KDM1A has been screened with 854 compounds (1436 bioactivities), 246 compounds have bioactivities that show binding affinity of <= 500nM (272 bioactivities). (see details)