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FLASH GENE
Symbol KDM1A contributors: mct - updated : 14-03-2018
HGNC name lysine (K)-specific demethylase 1A
HGNC id 29079
Location 1p36.12      Physical location : 23.345.940 - 23.410.184
Synonym name
  • amine oxidase (flavin containing) domain 2
  • lysine-specific demethylase 1
  • lysine (K)-specific demethylase 1
  • FAD-binding protein BRAF35-HDAC complex, 110 kDa subunit
  • BRAF35-HDAC complex protein BHC110
  • flavin-containing amine oxidase domain-containing protein 2
    • Synonym symbol(s) BHC110, KIAA0601, LSD1, AOF2, KDM1, RP1-184J9.1
    EC.number 1.-.-.-.
    DNA
    TYPE functioning gene
    STRUCTURE 64.24 kb     21 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 splicing 3125 95 876 - 2009 19124609
    isoform a
    19 splicing 3053 92 852 - 2009 19124609
  • lacking two alternate in-frame exons compared to variant 1
  • isoform b
    • - splicing - - - in neurons 2015 26214369
  • acquires a new substrate specificity, targeting histone H4 Lys20 methylation
  • functional importance of LSD1n in neuronal activity-regulated transcription that is necessary for long-term memory formation
    		•
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  highly
     mouthtongue  moderately
    Nervousbrain   moderately
    Reproductivefemale systemuteruscervix moderately
     female systembreastmammary gland highly Homo sapiens
     male systemprostate  moderately Homo sapiens
     male systemtestis  highly Homo sapiens
    Respiratoryrespiratory tractlarynx  predominantly
    Urinarybladder   highly
    Visualeye   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductivespermatogonia Homo sapiens
    cell lineage
    cell lines prostate tumour
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal one-third of KDM1A contains a SWIRM (Swi3p, Rsc8p and Moira) domain that is commonly found in chromatin-remodelling complexes with unknown functions , and NLS motif within the N-terminal flexible domain is critical for its nuclear localization via interaction with importin alpha proteins
  • a FAD-binding motif
  • likely containing a histone H3 secondary specificity element on the enzyme surface that contributes significantly to its recognition of substrates and products
  • C-terminal amine oxidase domain required for HDM activity and transcription repression is not essential for KDM1 to interact with TAL1
    • mono polymer complex
    HOMOLOGY
    interspecies ortholog to murine Aof2
    intraspecies homolog to amine oxidase
    Homologene
    FAMILY
  • flavin monoamine oxidase family
  • FIG1 subfamily
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    text co-localized with the androgen receptor in normal human prostate and prostate tumour
    basic FUNCTION
  • functioning as a histone demethylase and transcriptional corepressor
  • demethylating Lys-4 of histone H3, a specific tag for epigenetic transcriptional activation
  • demethylating both mono- and tri-methylted Lys-4 of histone H3
  • may play a role in the repression of neuronal genes
  • stimulating androgen-receptor-dependent transcription
  • converting oxygen to hydrogen peroxide (might use alternative electron acceptors
  • KDM1A-mediated histone demethylation is regulated dynamically
  • may collaborate to generate a repressive chromatin environment
  • recognizes a large segment of the H3 tail through a deep, negatively charged pocket at the active site and possibly a shallow groove on its surface
  • PHF21A and KDM1A depend reciprocally on one another to associate with chromatin
  • essential for maintaining global DNA methylation in embryonic stem cells
  • may negatively regulate TAL1-mediated transcription and the dynamic regulation of TAL1-associated KDM1/HDAC1 complex may determine the onset of erythroid differentiation programs
  • may be involved in leukemogenesis by repressing E2A/HEB activity through its interaction with TAL1
  • chromatin-associated protein, effector of SUMO-dependent changes in chromatin structure and gene expression
  • key regulator of neural stem cell proliferation
  • recruited by nuclear receptor NR2E1 to the promoters of NR2E1 targets genes to repress their expression
  • required for ESCO1-mediated transcriptional repression
  • with ZFPM1, co-occupy chromatin sites in genes known to be regulated by GATA1
  • acts to maintain a permissive state of the chromatin in this promoter by opposing the action of a H3K9 methyltransferase
  • KDM1A and SETDB1 exhibit opposite effects in adipogenesis
  • regulates the expression and appropriate timing of key developmental regulators, as part of the KDM1A/RCOR1/HDAC complex, during early embryonic development
  • in myoblast cell differentiation, activates myogenic transcription factors
  • plays a role in skeletal muscle differentiation in association with two major transcription factors on the target myogenic promoters
  • essential in skeletal muscle differentiation by modulating epigenetic marks on MEF2- and MYOD- dependent promoters
  • its overexpression is implicated in human carcinogenesis
  • has a role in maintaining the silencing of several developmental genes in human embryonic stem cells by regulating the critical balance between H3K4 and H3K27 methylation at their regulatory regions
  • contributes to changes in chromatin that are critical to the differentiation of embryonic stem cells (ESCs)
  • may be required for ESCs to silence the ESC gene expression program completely
  • KDM1A and HDAC1 specify repressive chromatin marks in proinflammatory cytokines and classical complement pathway genes
  • novel role for LSD1 in suppressing immune responses
  • MYEF2 is bound in undifferentiated cells and is lost upon differentiation, whereas KDM1A is bound in differentiated cells
  • cell cycle-dependent association and dissociation of KDM1A with chromatin mediates short-time-scale gene expression changes during embryonic stem cell cycle progression
  • regulates gene expression by demethylating chromatin
  • KDM5B and KDM1A, co-regulate H3K4 methylation at active promoters but they retain distinct roles in demethylating gene body regions and bivalent genes
  • is a key component of the molecular circadian oscillator, which plays a pivotal role in rhythmicity and phase resetting of the circadian clock
  • is a key regulator of OXPHOS and metabolic adaptation in white adipose tissue (WAT)
  • plays a role in regulating lipogenic gene expression, suggesting KDM1A as a potential target for treating dysregulation of lipid metabolism
  • dual functions as a major regulator of AR transcriptional activity
  • is required for neuronal progenitor cell (NPC) maintenance during cortical development
  • involvement of KDM1A in ATN1 expression and neuronal progenitor cell (NPC) maintenance
  • is a master controller of gene transcription in spermatogonia and is required for spermatogonial stem cells (SSCs) and progenitor maintenance and differentiation
  • FAD-dependent enzyme that catalyzes the oxidative demethylation of histone H3K4me1/2 and H3K9me1/2 repressing and activating transcription, respectively
  • is sequestered into a distinct nuclear space that might restrict a histone-modifying function to a narrow developmental time window and/or range of odorant receptor (OR) gene targets
  • KDM1A can downregulate DACT1 expression through histone deacetylation and therefore suppress the proliferation and migration of cervical cancer cells
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS electron transport
    PATHWAY
    metabolism
    signaling
    a component
  • part of a histone deacetylase complex containing HDAC1, HDAC2, RCOR1, ZNF261, ZNF198, KIAA0182 and GTF2I
  • component of several histone deacetylase complexes
  • part of AOF2-RCOR1 complex
  • formation of a SNAI1–KDM1A–RCOR1 ternary complex critical for the stability and function of these proteins
  • KDM1A/RCOR1/HDAC complex, playing a role during early embryonic development
  • KDM1A is associated with RCOR2 in the KDM1A–RCOR2 corepressor complex
  • KDM1A–NuRD complexes present at active promoters in ESCs are essential for normal differentiation, when the active enhancers must be silenced
    • INTERACTION
    DNA
    RNA
    small molecule cofactor,
  • FAD
    • protein
  • androgen receptor
  • associated with HDAC1/2
  • interacting with RCOR1 (endows AOF2 with the ability to demethylate nucleosomal substrates and that it protects AOS2 from proteasomal degradation)
  • demethylates and stabilizes DNMT1, thus providing a previously unknown mechanistic link between the histone and DNA methylation systems
  • binding to PRDM1 through its proline-rich domain (PRDM1 binding to its target sites is accompanied by KDM1 binding to those same sites and KDM1 binding correlates with histone modifications of accessible chromatin)
  • interacted with SNAI1 (SNAG domain of SNAI1 and the amine oxidase domain of KDM1A were required for their mutual interaction)
  • interacting with PELP1, and this interactions have an essential role in histone methyl modifications at ESR1 target genes
  • interactions between KDM1A and PPP1R12A, a known regulator of RB1 phosphorylation (KDM1A silencing increased PPP1R12A protein levels, decreasing the steady state level of phosphorylated RB1)
  • folate-binding protein, and histone demethylase
  • SIRT1 and KDM1A interact directly and play conserved and concerted roles in H4K16 deacetylation and H3K4 demethylation to repress genes regulated by the Notch signaling pathway
  • functions as a transcription coactivator of ESR1 and androgen receptor (AR)
  • regulates synergistically with HDAC1 the expression of proinflammatory cytokines and genes of the classical complement pathway
  • interplay between HMG20B and HMG20A controls the activity of the KDM1A–RCOR2 complex during neuronal differentiation
  • RUNX1 interacts with two novel protein partners, KDM1A and MYEF2, in erythroid cells
  • potential role of KDM1A in regulating S100A7 expression
  • KDM1A functions as a corepressor when associated with RBPJ-repressor complex and as a NOTCH1 coactivator upon NOTCH1 activation
  • CACUL1 associated with histone demethylase KDM1A and suppressed KDM1A-enhanced ESR1 activity
  • PROX1 interacts with KDM1A to recruit the repressive KDM1A/NuRD complex to CYP7A1 promoter and co-represses transcription through epigenetic mechanisms
  • KDM1A/RCOR1 histone demethylase complex interacts with BCL11A and is required for full developmental silencing of gamma-globin genes in adult erythroid cells
  • SFMBT1 regulates transcription in somatic cells and during spermatogenesis through the formation of a stable complex with KDM1A and RCOR1
  • USP28 interacted with and stabilized KDM1A via deubiquitination
  • KDM1A cooperates with EP300 to facilitate ESR1 protein acetylation and target gene activation upon estrogen stimulation
  • actions of RCOR2 and RCOR3, in regulating KDM1A enzymatic activity and biological function in hematopoietic cells
  • KDM1A is a novel histone-modifying enzyme in the orchestrated regulation mediated by NR1H4 and small heterodimer partner that reduces hepatic Bile acids (BAs) levels and protects the liver against BA toxicity
  • plays a role in regulating SREBF1-mediated gene expression
  • KDM1A/RCOR1 interacts with extranucleosomal DNA when it productively engages its nucleosome substrate
  • KDM1A, RNF168 and TP53BP1 interacted with each other directly
  • KDM1A mediates erythroid differentiation, via epigenetic modification of the GATA2 locus
  • KDM1A-dependent shutdown of ETV2 gene expression may be a significant event required for hemangioblasts to initiate hematopoietic differentiation
  • KDM1A interacts with ZNF516 to Promote UCP1 transcription and brown fat program
  • association of the multifunctional RNA-binding protein SFPQ to KDM1A during the development of the cerebral cortex
  • in the absence of NOTCH intracellular domain (NOTCH ICD), RBPJ recruits L3MBTL3 and the histone demethylase KDM1A (also known as LSD1) to the enhancers of Notch target genes, leading to H3K4me2 demethylation and to transcriptional repression
  • CACUL1 tightly regulates PPARG signaling through the mutual opposition between SIRT1 and KDM1A, providing insight into its potential use for anti-obesity treatment
  • STIP1 acts as a scaffold promoting the interaction between KDM1A and GSK3B
  • KDM1A was found to negatively regulate DACT1 through histone deacetylation
  • OTUB2 may serve as a vital driver in Gastric cancer tumorigenesis by enhancing KDM1A-mediated stem cell-like properties
    • cell & other
    REGULATION
    induced by interleukin 4
    Other regulation of its activity by its associated factors
    NR2E1 is critical for the KDM1A inhibitor effect
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    in embryonic stem (ES) cells induces progressive loss of DNA methylation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS