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FLASH GENE
Symbol DACH1 contributors: mct/npt/pgu - updated : 07-03-2017
HGNC name dachshund homolog (Drosophila)
HGNC id 2663
Location 13q21.33      Physical location : 72.012.097 - 72.441.330
Synonym name dachshund homolog 1
Synonym symbol(s) DACH, FLJ10138
DNA
TYPE functioning gene
STRUCTURE 429.23 kb     11 Exon(s)
MAPPING cloned Y linked N status confirmed
Map cen - ESD - RB1 - HTR2A - D13S26 - DACH1 - EDNRB - DCT - PCCA PCCA - qter
RNA
TRANSCRIPTS type messenger
text abundant and smaller transcripts (4.8kb/4.6kb/4.1kb)
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
11 splicing 5246 - 708 - 2008 18467491
8 splicing 4802 - 560 - 2008 18467491
  • lacking three consecutive coding exons
  • same reading frame
  • 7 splicing 4640 - 506 - 2008 18467491
  • lacking three consecutive coding exons
  • same reading frame
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveliver    
    Endocrineplacenta    
    Lymphoid/Immunespleen   highly
    Nervousbraindiencephalonepithalamuspineal gland 
    Reproductivefemale systemuterus  highly
    Respiratorylung    
    Urinarykidney    
    Visualeye   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoietic    
    Lymphoid    
    Muscularstriatumskeletal  
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, pregnancy
    Text placenta, posterieur rombomeres
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a Dachbox N (DD1) in the N terminus, and a conserved dachshund domain (DS), which interacts with the nuclear co-repressor (NCoR) to repress gene expression
  • an alpha helical coiled-coil zipper domain, beginning in dachbox C (DD2) in C terminal, showing similarity to the ski family of genes
  • secondary structure forms an alpha/beta structure containing a DNA-binding motif similar to that found in the winged helix/Forkhead subgroup of DNA-binding proteins
    HOMOLOGY
    interspecies homolog to Drosophila dachshund
    homolog to murine INS and genital eminence
    homolog to murine Dach 1
    intraspecies homolog to two possible human DACH (Xq21 and 8p)
    Homologene
    FAMILY
  • Ski gene family , helix-turn-helix family
  • CATEGORY transcription factor , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • involved in eye development
  • recruited in the context of local chromatin to conduct transcriptional regulatory functions
  • inhibit c-Jun transactivation through recruitment of HDAC1 and HDAC3 to the domain of c-Jun
  • cell fate determination factor that inhibits cyclin D1 and breast tumor growth
  • inhibits oncogene-induced breast cancer cellular migration and invasion through suppression of interleukin-8
  • plays an important role in negative regulation of TNFSF11 gene expression in marrow stromal/preosteoblast cells in the bone microenvironment
  • important role in tumorigenesis, in particular, breast, prostate and ovarian cancer
  • selectively inhibited FOXM1-mediated contact-independent growth and occupancy in the context of local chromatin
  • competes as a DNA binding–specific transcription factor to attenuate signaling by the Forkhead family of transcription factors
  • distinctive tumor suppressor, which does not only suppress growth of tumor cells but also regulates FGF2-mediated tumor-initiating activity of glioma cells
  • its expression repressed growth of glioma cells
  • regulates retinal cell fate determination
  • role of DACH1 as a cell cycle regulator in myeloid cells
  • having a role as a tumor suppressor in breast cancer by regulating cell cycle progression and stem cell reprogramming factors
  • opposite roles of DACH1 associated with the regulation of the cell cycle machinery and expression of reprogramming factors in myeloid cells
  • is a novel coactivator of HOXA9 and has an oncogenic effect in hematopoietic malignancy
  • key signaling pathway for kidney development
  • zona glomerulosa selective gene in the human adrenal, activating TGFB1 signaling and suppressing aldosterone secretion
  • DACH1-mediated corepression in hepatocytes emerges as an important link between obesity and insulin resistance
  • chromosome-associated protein that regulates cellular differentiation throughout development
  • potential role for DACH1 in the development of human chronic glomerulopathy
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • with EYA1, mediated by CREBBP (regulating precursor cell proliferation and survival during organogenesis)
  • suppress tumor formation through transcriptional repression of FGF2
  • DACH1 has a stronger transcription-promoting activity with HOXA9 than does PBX2 with HOXA9
  • CEBPA and/or GATA1 directly suppress the expression of DACH1 through binding to the promoter region
  • DACH1 expression regulates the pancreatic cancer cell apoptosis through interacting with BCL2 signaling axis, whereas it controls cell migration and invasion via epithelial-mesenchymal transition (EMT) process
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in breast cancer is associated with poor prognosis (DACH1 expression functions as an endogenous inhibitor of ESR1 function
    tumoral     --low  
    might be involved in endometrial cancer progression
    tumoral   deletion    
    homozygously deleted in glioblastoma
    constitutional     --low  
    leads to hereditary renal hypodysplasia
    tumoral     --low  
    in human renal carcinoma tissue
    Susceptibility
    Variant & Polymorphism
    Candidate gene developmental disorders affecting the limbs, kidneys, eyes, ears and other sites of DACH expression, branchiooculofacial syndrome, Fraser syndrome
    Marker
  • is a potential marker of disease progression and severity for glomerular diseases
  • novel molecular marker of Renal cell carcinoma (RCC) and it attributed to the malignant behavior of renal cancer cells
  • Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    potential therapeutic insight into breast cancer
    cancerdigestivecolon
    DACH1 loss of function has important therapeutic implications for targeted therapies of colorectal cancer
    cancerurinary 
    re-activation of DACH1 may represent a potential therapeutic strategy
    ANIMAL & CELL MODELS
    Dach 1 knock out mouse