KDM1A

Not to be confused with LSD or Lysergic acid diethylamide.

Lysine (K)-specific demethylase 1A
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2COM, 2DW4, 2EJR, 2H94, 2HKO, 2IW5, 2L3D, 2UXN, 2UXX, 2V1D, 2X0L, 2XAF, 2XAG, 2XAH, 2XAJ, 2XAQ, 2XAS, 2Y48, 2Z3Y, 2Z5U, 3ABT, 3ABU, 3ZMS, 3ZMT, 3ZMU, 3ZMV, 3ZMZ, 3ZN0, 3ZN1, 4BAY, 4CZZ, 4KUM, 4UV8, 4UV9, 4UVA, 4UVB, 4UVC, 4UXN
Identifiers
Symbols	KDM1A ; AOF2; BHC110; KDM1; LSD1
External IDs	OMIM: 609132 HomoloGene: 32240 GeneCards: KDM1A Gene
Gene ontology Molecular function • RNA polymerase II transcription factor binding • p53 binding • chromatin binding • transcription factor activity, sequence-specific DNA binding • protein binding • transcription factor binding • oxidoreductase activity • enzyme binding • ligand-dependent nuclear receptor transcription coactivator activity • demethylase activity • histone demethylase activity • histone demethylase activity (H3-K4 specific) • histone demethylase activity (H3-K9 specific) • histone demethylase activity (H3-dimethyl-K4 specific) • MRF binding • transcription regulatory region DNA binding • flavin adenine dinucleotide binding • androgen receptor binding Cellular component • nuclear chromatin • nucleus • nucleoplasm • transcription factor complex Biological process • negative regulation of transcription from RNA polymerase II promoter • in utero embryonic development • chromatin organization • transcription, DNA-templated • regulation of transcription from RNA polymerase II promoter • protein demethylation • small GTPase mediated signal transduction • blood coagulation • cell proliferation • regulation of primitive erythrocyte differentiation • pituitary gland development • granulocyte differentiation • negative regulation of protein binding • histone H3-K9 demethylation • histone H3-K4 demethylation • negative regulation of DNA binding • negative regulation of sequence-specific DNA binding transcription factor activity • negative regulation of DNA damage response, signal transduction by p53 class mediator • positive regulation of erythrocyte differentiation • positive regulation of megakaryocyte differentiation • negative regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • positive regulation of hormone biosynthetic process • positive regulation of sequence-specific DNA binding transcription factor activity • negative regulation of histone H3-K4 methylation • negative regulation of histone H3-K9 methylation • muscle cell development • oxidation-reduction process • negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator • positive regulation of neural precursor cell proliferation • positive regulation of stem cell proliferation Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	23028	99982
Ensembl	ENSG00000004487	ENSMUSG00000036940
UniProt	O60341	Q6ZQ88
RefSeq (mRNA)	NM_001009999	NM_133872
RefSeq (protein)	NP_001009999	NP_598633
Location (UCSC)	Chr 1: 23.02 – 23.08 Mb	Chr 4: 136.55 – 136.6 Mb
PubMed search	[1]	[2]

Lysine-specific histone demethylase 1A (KDM1A) also known as lysine (K)-specific demethylase 1A (LSD1) is a protein in humans that is encoded by the KDM1A gene. LSD1 is a flavin-dependent monoamine oxidase, which can demethylate mono- and di-methylated lysines, specifically histone 3, lysines 4 and 9 (H3K4 and H3K9). This enzyme can have roles critical in embryogenesis and tissue-specific differentiation, as well as oocyte growth. KDM1A was the first demethylase to be discovered and thus it has been studied most extensively.

Structure

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.

Function

LSD1 (lysine-specific demethylase 1), also known as KDM1, is the first of several protein lysine demethylases discovered. Through a FAD-dependent oxidative reaction, LSD1 specifically removes histone H3K4me2 to H3K4me1 or H3K4me0. When forming a complex with androgen receptor (and possibly other nuclear hormone receptors), LSD1 changes its substrates to H3K9me2. It's now known LSD1 complex mediates a coordinated histone modification switch through enzymatic activities as well as histone modification readers in the complex.

Interactions

KDM1A has many different binding partners, which may be necessary for its demethylation activity.

Clinical significance

Deletion of the gene for KDM1A can have effects on the growth and differentiation of embryonic stem cells and can lead to embryonic lethality in knockout mice, who do not produce the KDM1A gene product KDM1A is also thought to play a role in cancer, as poorer outcomes can be correlated with higher expression of this gene. Therefore, the inhibition of KDM1A may be a possible treatment for cancer.

Mutations

De novo mutations to KDM1A have been reported in two patients, both with severe developmental delays believed to be attributable in part to the mutations. Both mutations were missense substitutions. One of the affected families has created a public website in order to identify further cases.

See also

• Histone methylation

External links

• lysine specific demethylase 1, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.