KDM1A
GeneName
KDM1A
Summary
KDM1A, also known as LSD1 or LSD-1, is a 93 kDa flavin-dependent histone demethylase that plays a vital role in epigenetic regulation. It is predominantly localised in the nucleus and is associated with various protein complexes, including histone methyltransferase complexes and transcription regulator complexes. KDM1A is involved in chromatin binding and has the ability to demethylate histones, specifically H3K4 and H3K9, thereby influencing gene expression. Additionally, it participates in DNA repair processes and interacts with several transcription factors, including p53 and nuclear androgen receptors, contributing to the regulation of diverse biological pathways such as cellular responses to stress and development processes in the cerebral cortex and muscle cells.
Importance
KDM1A is relevant to: - Epigenetic modifications and gene expression regulation, impacting cellular differentiation and development. - Cancer research, particularly in the context of its role in regulating p53-mediated pathways and apoptosis. - Neurodevelopmental studies, given its involvement in neuron maturation and neural precursor cell proliferation. - DNA repair mechanisms, contributing to genomic stability and response to DNA damage. - Metabolic processes, including the regulation of guanine metabolism and thermogenesis.
Top Products
For researchers investigating KDM1A, we recommend two excellent primary antibodies that cater to a variety of applications. The first is the well-cited polyclonal antibody, Anti-KDM1/LSD1 antibody - Nuclear Marker (ab17721), which has garnered 253 citations, highlighting its reliability in Western blotting (WB) and immunocytochemistry (ICC). This antibody has also been validated in knockout models, ensuring its effectiveness in specific experimental contexts.In addition, we offer the recombinant antibody, Anti-KDM1/LSD1 antibody [EPR6825] - Nuclear Marker and ChIP Grade (ab129195). This versatile product is suitable for a broader range of applications, including WB, chromatin immunoprecipitation (ChIP), immunohistochemistry (IHC), ICC, immunoprecipitation (IP), and flow cytometry (FC). With 49 citations, it is gaining traction in the research community and is also validated in knockout models, making it an excellent choice for those seeking consistency and performance in their experiments.
Abcam Product Citation Summary
The data indicates that KDM1A is primarily studied in human cells, particularly in the context of cancer, gene regulation, and epigenetic mechanisms. Various applications such as Western blotting and immunohistochemistry are frequently employed to investigate its role in different biological processes, including breast cancer and hepatic cell regulation. Additionally, studies involving mouse models also contribute to understanding KDM1A's function.
Abcam Product Citation Table
Domain
The SWIRM domain may act as an anchor site for a histone tail.
Function
Histone demethylase that can demethylate both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context (PubMed:15620353, PubMed:15811342, PubMed:16079794, PubMed:16079795, PubMed:16140033, PubMed:16223729, PubMed:27292636). Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed (PubMed:15620353, PubMed:15811342, PubMed:16079794, PubMed:21300290, PubMed:26214369). Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) (PubMed:15620353, PubMed:20389281, PubMed:21300290, PubMed:23721412). 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 (PubMed:16079794, PubMed:16140033, PubMed:16885027, PubMed:21300290, PubMed:23721412). Also acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in AR-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 (PubMed:16079795). 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 (PubMed:29691401). Demethylates methylated 'Lys-42' and methylated 'Lys-117' of SOX2 (PubMed:29358331). 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 (PubMed:16079794, PubMed:16140033). Facilitates epithelial-to-mesenchymal transition by acting as an effector of SNAI1-mediated transcription repression of epithelial markers E-cadherin/CDH1, CDN7 and KRT8 (PubMed:20562920, PubMed:27292636). Required for the maintenance of the silenced state of the SNAI1 target genes E-cadherin/CDH1 and CDN7 (PubMed:20389281). Required for the repression of GIPR expression (PubMed:34655521, PubMed:34906447).
Isoform 2
Neuron-specific histone demethylase that demethylates mono- and dimethylated 'Lys-20' of histone H4 (H4K20me1 and H4K20me2), a chromatin repressive mark (PubMed:26214369). This demethylation is crucial for the initiation and elongation of neuronal activity-regulated genes, required for spatial learning and memory (By similarity). Mediates H3K9me2 demethylation through cooperation with the supervillin protein (SVIL), and this H3K9 demethylase activity is essential for regulating gene expression during neuronal differentiation (PubMed:25684206).
Isoform 4
Neuron-specific histone demethylase that demethylates mono- and dimethylated 'Lys-20' of histone H4 (H4K20me1 and H4K20me2), a chromatin repressive mark (PubMed:26214369). This demethylation is crucial for the initiation and elongation of neuronal activity-regulated genes, required for spatial learning and memory (By similarity). Mediates H3K9me2 demethylation through cooperation with the supervillin protein (SVIL), and this H3K9 demethylase activity is essential for regulating gene expression during neuronal differentiation (PubMed:25684206).
Involvement in disease
Cleft palate, psychomotor retardation, and distinctive facial features
CPRF
A syndrome characterized by cleft palate, developmental delay, psychomotor retardation, and facial dysmorphic features including a prominent forehead, slightly arched eyebrows, elongated palpebral fissures, a wide nasal bridge, thin lips, and widely spaced teeth. Cleft palate is a congenital fissure of the soft and/or hard palate, due to faulty fusion.
None
The disease is caused by variants affecting the gene represented in this entry.
ACTH-independent macronodular adrenal hyperplasia 3
AIMAH3
A form of macronodular adrenal hyperplasia, a rare adrenal defect characterized by multiple, bilateral, non-pigmented, benign, adrenocortical nodules. It results in excessive production of cortisol leading to ACTH-independent Cushing syndrome. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. AIMAH3 affected individuals have low fasting cortisol and ACTH, but excess cortisol is secreted after eating.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Acetylated by KAT8 in epithelial but not in mesenchymal cells, thereby regulating the epithelial-to-mesenchymal transition (PubMed:27292636). Acetylation by KAT8 reduces KDM1A association with nucleosomes, thereby decreasing histone H3 demethylation, leading to transcription activation of target genes (PubMed:27292636).
Polyubiquitinated by JADE2; which leads to its proteasomal degradation (PubMed:25018020). Deubiquitinated by USP38; preventing it from degradation by the 26S proteasome (PubMed:30497519).
Isoform 4
Phosphorylation at Thr-371 reduces interaction with corepressors, including HDAC1/2 and CoREST, thereby converting isoform 4 from a transient dominant-negative repressor of neuronal differentiation into an active isoform that promotes neural morphogenesis and maturation.
Sequence Similarities
Belongs to the flavin monoamine oxidase family.
Tissue Specificity
Ubiquitously expressed.
Isoform 2
Expressed in brain and testis.
Isoform 4
Expressed exclusively in brain tissues.
Cellular localization
- Nucleus
- Chromosome
- Associates with chromatin.
Alternative names
AOF2, BHC110, KDM1, KIAA0601, LSD1, KDM1A, Lysine-specific histone demethylase 1A, BRAF35-HDAC complex protein BHC110, Flavin-containing amine oxidase domain-containing protein 2, [histone H3]-dimethyl-L-lysine(4) FAD-dependent demethylase 1A