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FLASH GENE
Symbol DMRT2 contributors: np/mct - updated : 29-03-2020
HGNC name doublesex and mab-3 related transcription factor 2
HGNC id 2935
Corresponding disease
SRA2 46,XY gonadal dysgenesis, complete or partial , with 9p24 deletion
Location 9p24.3      Physical location : 1.050.345 - 1.057.553
Synonym name
  • terra (telomeric repeat containing RNA)-like protein
  • doublesex-like 2 protein
    • Synonym symbol(s) DSXL-2, DSXL2, TERRAL, TERRA
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    STRUCTURE 54.32 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure
  • differential regulation of TERRA promoters by DNA methylation, and likely two types of DMRT2 promoters, only one of which is regulated by DNA methylation
  • chromosome-specific subtelomeric sequences at its 5 prime end
  • long tracts of UUAGGG-repeats toward the 3 prime end
    • MAPPING cloned Y linked N status confirmed
    Map pter - D9S1779 - D9S1858 - DMRT1 - DMRT3 - DMRT2 - D9S129 - cen
    RNA
    TRANSCRIPTS type messenger
    text
  • six alternatively spliced isoforms, with two isoforms starting from intron2, lacking the DM domain, maybe corresponding to a bicistronic transcript
  • variants 1 and 3 encode the same isoform
    • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 splicing 2922 24.3 226 - 2019 31350341
    4 splicing 2428 62 561 - 2019 31350341
    6 splicing 2383 24.3 226 - 2019 31350341
    5 splicing 2506 24.3 226 - 2019 31350341
    4 splicing 943 24.3 226 - 2019 31350341
    3 splicing 2220 - 387 - 2019 31350341
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivemale systemtestis   
    Respiratorylung   lowly
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    Text expressed in the dermomyotome of developing vertebrate somites
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal DNA binding domain (DM)
  • a proline and serine-rich region
    • HOMOLOGY
    interspecies homolog to Drosophila double sex
    homolog to C.elegans MAB-3 related transcription factor 1
    intraspecies paralog to DMRT1 and DMRT3
    Homologene
    FAMILY
  • DMRT family
    • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    text colocalization with telomeric chromatin
    basic FUNCTION
  • involved in somitogenesis
  • essential function for DMRT2 in somite development
  • acts as a potent competitive inhibitor for telomeric DNA in addition to exerting an uncompetitive mode of inhibition
  • may be involved in telomerase regulation by the telomere substrate
  • may regulate telomerase at chromosome ends
  • may be released from the telomere, and bind and inhibit telomere-proximal telomerase molecules and prevent their access to the chromosomal end
  • promotes POT1 binding to telomeric single-stranded DNA by removing HNRNPA1
  • HNRNPA1, DMRT2 and POT1 act in concert to displace RPA1 from telomeric single-stranded DNA after DNA replication, and promote telomere capping to preserve genomic integrity
  • inhibits RPA1 displacement in early S phase, and its decline in late S phase may provide a window for RPA1 displacement
  • implicated in the regulation of telomere length and heterochromatin formation
  • functions as an epigenomic modulator in trans and as an essential regulator of telomeres in cis
  • ATF7 and DMRT2 play key roles in paternal stress-induced telomere shortening in the offspring
    • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    PAX3/DMRT2/MYF5 regulatory cascade operating in stem cells of the epaxial dermomyotome to initiate skeletal muscle formation
    a component
    INTERACTION
    DNA binding
    RNA
    small molecule metal binding,
  • Zn2+
    • protein
  • telomerase ligand and natural direct inhibitor of human telomerase
  • potent inhibitor of the RPA1 displacing activity of HNRNPA1)
  • knockdown of MORF4L2, a component of the NuA4 histone acetyltransferase complex, reduced DMRT2 levels both globally and for telomere-bound DMRT2
  • direct and essential function of HSF1 in the transcriptional activation of DMRT2 and in telomere protection upon stress
  • subtelomeric CTCF facilitates telomeric DNA replication by promoting DMRT2 transcription
  • ARNTL plays a direct role in telomere homeostasis by regulating rhythms in DMRT2 and heterochromatin
  • DMRT2 can lead to the enrichment of CBX5 at telomeres to maintain heterochromatin
  • at telomeres, DMRT2 competes with telomeric DNA for ATRX binding, suppresses ATRX localization, and ensures telomeric stability
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) SRA2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    mutations in DMRT2 are likely associated with a different (novel) subtype of SCD mainly characterized by severe rib anomalies but lacking clear segmentation defects of the vertebral bodies
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Dmrt2 knock-out mice exhibit severe rib and vertebral defects