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FLASH GENE
Symbol KDM3A contributors: mct - updated : 01-09-2016
HGNC name lysine (K)-specific demethylase 3A
HGNC id 20815
Location 2p11.2      Physical location : 86.668.270 - 86.719.838
Synonym name
  • testis-specific protein A
  • jumonji C domain-containing histone demethylase 2A
  • jumonji domain containing 1A
  • Synonym symbol(s) TSGA, KIAA0742, JMJD1, JHDM2A, DKFZp686A24246, DKFZp686P07111, JHMD2A, JMJD1A
    EC.number 1.14.11.-
    DNA
    TYPE functioning gene
    STRUCTURE 51.49 kb     26 Exon(s)
    regulatory sequence Promoter
    Binding site   HRE
    text structure a single pivotal hypoxia responsive element (HRE) in the promoter
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    26 - 4907 147.21 1321 - 2008 18984585
    26 - 4638 147.21 1321 - 2008 18984585
    EXPRESSION
    Rna function embryonic stem cells, pancreatic islets, diffuse gastric cancer cells
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Endocrineparathyroid   predominantly
    Nervousbrain   highly
    Reproductivefemale systemovary  highly
     male systemtestis  predominantly Homo sapiens
    Respiratorylung   highly
     respiratory tractlarynx  highly
     respiratory tracttrachea  highly
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductivespermatocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a C6-type zinc finger domain
  • one transcription factor jumonji, jmjC motif
  • a zinc finger required for its enzymatic activity
  • HOMOLOGY
    interspecies ortholog to murine Jmjd1a (91.7pc)
    Homologene
    FAMILY
  • JHDM2 histone demethylase family
  • CATEGORY enzyme , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    text
  • predominantly, but not exclusively, a nuclear protein
  • basic FUNCTION
  • specifically demethylating Lys-9 of histone H3, thereby playing a central role in histone code
  • preferentially demethylating mono- and dimethylated H3 Lys-9 residue, with a preference for dimethylated residue, while it has weak or no activity on trimethylated H3 Lys-9
  • involved in hormone-dependent transcriptional activation, by participating to recruitment to androgen-receptor target genes, resulting in H3 Lys-9 demethylation and transcriptional activation
  • may play a role in the ontogeny of white blood cells
  • may be playing a key role in maintenance of embryonic stem cell self-renewal and is a direct target of POU5F1 signaling
  • exhibits hormone-dependent recruitment to androgen-receptor target genes, resulting in H3K9 demethylation and transcriptional activation
  • histone H3K9 demethylase implicated in the nuclear hormone receptor-based transcriptional regulation
  • regulating the expression of ADM and GDF15 under hypoxia by decreasing promoter histone methylation
  • plays a role in regulating fat metabolic gene expression in muscle and brown fat tissue
  • KMD3A-controlled epigenetic histone modifications are crucial for Crem-regulated gene expression and spermatogenesis
  • mainly located around blood vessels which indicated that KDM3A is involved tumor angiogenesis
  • elevated expression of KDM3A plays a critical role in the growth of cancer cells
  • importance of a single amino acid in KDM3A implicated in the catalytic activity towards H3K9me1/2 that is not conserved in JMJD1C
  • is a new, miR-regulated, tumor promoter in Ewing Sarcoma
  • is required for male fertility, sex determination, and metabolic homeostasis through its nuclear role in chromatin remodeling
  • KDM3A, KDM3B meditated H3K9 demethylation has critical roles for early embryogenesis and embryonic stem cells (ESCs) maintenance
  • CELLULAR PROCESS nucleotide, chromatin organization, methylation
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding
    RNA
    small molecule metal binding, cofactor,
  • Zn2+
  • Fe2+ (one ion per subunit)
  • alpha-ketoglutarate
  • protein
  • interacts with the androgen receptor (AR) and facilitates transcriptional activation in response to androgens
  • activates transcription of the HOXA1 gene through demethylating histone H3 at lysine 9 di-methylation by binding to its promoter region
  • KDM3A is recruited to the SLC2A3 locus in an HIF1-dependent manner and demethylates H3K9me2 so as to upregulate its expression
  • multifunctional HSP90 client protein that participates directly in the regulation of cytoskeletal components
  • is a novel epigenetic regulator that modulates hepatic stellate cells activation and liver fibrosis through targeting PPARG gene expression
  • positive role of PHF8 in hypoxia signaling extended to hypoxia-induced neuroendocrine differentiation (NED), wherein PHF8 cooperates with KDM3A to regulate the expression of NED genes
  • KDM1A, KDM1B preferentially target H3K9 demethylation of gene-dense regions of chromosomes, thereby establishing an H3K9 hypomethylation state in euchromatin
  • cell & other
    REGULATION
    induced by hypoxia and HIF (induce transcription of the JMJD1A and JMJD2B genes leading to increased protein expression)
    Other regulated in an oxygen-dependent manner
    positively regulated by the embryonic stem cell transcription factor POU5F1 (Loh 2007)
    hypoxic regulation by HIF1A acts as a signal amplifier to facilitate hypoxic gene expression and ultimately enhancing tumor growth
    its specific phosphorylation determines target gene expression in response to heat shock
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in renal cancer cells that have lost the von Hippel Lindau tumor suppressor protein VHL and therefore display a deregulated expression of hypoxia-inducible factor
    tumoral     --over  
    in Ewing Sarcoma
    tumoral     --over  
    in human bladder carcinomas
    tumoral     --over  
    in renal cell carcinoma
    constitutional     --over  
    significantly increased in smooth muscle cells upon hypoxia treatment
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
  • loss of KDM3A is sufficient to reduce tumor growth
  • ANIMAL & CELL MODELS
  • Jhdm2a-deficient mice exhibit post-meitoic chromatin condensation defects and JHDM2A directly binds to and controls the expression of transition nuclear protein Tnp1 and protamine genes, suggesting that JHDM2A is essential for spermatogenesis