LSD1/AOF2 (KDM1A) Antibody – Mouse Monoclonal

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]

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. Component of a RCOR/GFI/KDM1A/HDAC complex. Interacts directly with GFI1 and GFI1B. 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. Ubiquitously expressed. Belongs to the flavin monoamine oxidase family. 2 isoforms of the human protein are produced by alternative splicing.

Protein type: Transcription factor; Nuclear receptor co-regulator; Demethylase; EC 1.-.-.-; Oxidoreductase

Chromosomal Location of Human Ortholog: 1p36.12

Cellular Component: nuclear chromatin; nuclear chromosome, telomeric region; nucleoplasm; nucleus; protein complex; transcription factor complex

Molecular Function: androgen receptor binding; chromatin binding; demethylase activity; enzyme binding; FAD binding; histone demethylase activity; histone demethylase activity (H3-K4 specific); histone demethylase activity (H3-K9 specific); ligand-dependent nuclear receptor transcription coactivator activity; MRF binding; oxidoreductase activity; p53 binding; protein binding; telomeric DNA binding; transcription factor activity; transcription factor binding

Biological Process: blood coagulation; cell proliferation; establishment and/or maintenance of chromatin architecture; granulocyte differentiation; histone H3-K9 demethylation; in utero embryonic development; muscle cell development; negative regulation of DNA binding; negative regulation of DNA damage response, signal transduction by p53 class mediator; negative regulation of histone H3-K4 methylation; negative regulation of histone H3-K9 methylation; negative regulation of protein binding; negative regulation of transcription factor activity; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription, DNA-dependent; pituitary gland development; positive regulation of erythrocyte differentiation; positive regulation of histone ubiquitination; positive regulation of hormone biosynthetic process; positive regulation of megakaryocyte differentiation; positive regulation of transcription factor activity; positive regulation of transcription from RNA polymerase II promoter; protein amino acid demethylation; regulation of transcription from RNA polymerase II promoter; small GTPase mediated signal transduction; transcription, DNA-dependent