ENSG00000004487 | KDM1A
lysine (K)-specific demethylase 1A [Source:HGNC Symbol;Acc:29079]
Coord C1 exon
Coord A exon
Coord C2 exon
3' ss Seq
3' ss Score
5' ss Seq
5' ss Score
Seq C1 exon
Seq A exon
Seq C2 exon
Vast-tools module Information
Alternative protein isoforms (Ref)
Show PDB structure
C1=0.000 A=0.000 C2=0.111
Domain overlap (PROSITE):
Domain overlap (PFAM):
Suggestions for RT-PCR validation
There are 6 annotated functions for this event
(Review). LSD1-n appears to be important for neurite morphogenesis, synaptogenesis, and proper transcriptional response to neuronal depolarization.
(Review). The biochemical function of the LSD1-n isoform has been debated. The first study reporting this isoform found that LSD1-n acts like the canonical protein to remove H3K4 mono- or di- methylation marks (H3K4me1/2) from a histone peptide with similar efficiency (Zibetti et al., 2010). This first study also carried out X-ray crystallography on the histone-interacting segment of LSD1-n and did not find an altered structure compared to the canonical isoform. An- other study found that LSD1-n associates with a nuclear factor, Svil, which changes its substrate specificity from H3K4me1/2 to H3K9me1/ 2, a repressive histone modification (Laurent et al., 2015). A third group reported that LSD1-n demethylates H4K20me1/2, another mark associated with transcriptionally-repressed regions (Wang et al., 2015). These conflicting data suggest that other unknown regulatory proteins, genomic contexts, or timing in neuron maturation may, in concert, determine the substrate specificity of LSD1-n. The threonine at position 369 of LSD1-n, which is located within the microexon, can be phos- phorylated, leading to conformational changes and disassembly of the LSD1/CoREST complex (Toffolo et al., 2014. Thus, the LSD1 microexon might control dynamics of complex assembly instead of, or in addition to, modulating substrate specificity.
LSD1+8a, does not have the intrinsic capability to demethylate H3K4me2. Instead, LSD1+8a mediates H3K9me2 demethylation in collaboration with supervillin (SVIL). LSD1+8a knockdown increases H3K9me2, but not H3K4me2, levels at its target promoters and compromises neuronal differentiation.
Inclusion confers a new substrate specificity, targeting histone H4 Lys20 methylation, both in vitro and in vivo. Selective genetic ablation of LSD1n (mouse MIC KO) led to deficits in spatial learning and memory, revealing the functional importance of LSD1n in neuronal activity-regulated transcription that is necessary for long-term memory formation
LSD1 isoforms (with and without MmuEX0025260) display in vitro a comparable demethylase activity, yet the inclusion of the sole exon E8a (i.e. MmuEX0025260 reduces LSD1 repressor activity on a reporter gene. The knockdown of neurospecific variants in cortical neurons resulting in the inhibition of neurite maturation, whereas overexpression of the same variants enhances it. Instead, perturbation of LSD1 isoforms that are devoid of the neurospecific exon elicits no morphogenic effect.