KDM1A Recombinant Protein

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]

Function: 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. Ref.5 Ref.8 Ref.12 Ref.15 Ref.23 Ref.24

Cofactor: FAD. Ref.8 Ref.9

Subunit structure: Component of a RCOR/GFI/KDM1A/HDAC complex. Interacts directly with GFI1 and GFI1B

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. In the complex, RCOR1/CoREST strongly enhances the demethylase activity and protects it from the proteasome while PHF21A/BHC80 inhibits the demethylase activity. Interacts with the androgen receptor (AR). Interacts with ASXL1. Interacts with SNAI1 (via SNAG domain). Ref.5 Ref.6 Ref.7 Ref.10 Ref.11 Ref.12 Ref.22 Ref.24

Subcellular location: Nucleus Ref.6 Ref.12.

Tissue specificity: Ubiquitously expressed. Ref.12

Domain: The SWIRM domain may act as an anchor site for a histone tail. Ref.30

Sequence similarities: Belongs to the flavin monoamine oxidase family.Contains 1 SWIRM domain.

Biophysicochemical propertiesKinetic parameters:KM=3.0 µM for H3 monomethyl-K4 Ref.13KM=4.2 µM for H3 dimethyl-K4KM=3.9 µM for H3 monomethyl-K4-monomethyl-K9KM=17.5 µM for monomethyl-K4-acetyl-K9

Sequence caution: The sequence BAA25527.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.