Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol TWIST1 contributors: mct/pgu - updated : 02-07-2010
HGNC name twist homolog 1 (Drosophila)
HGNC id 12428
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Hearing/Equilibriumear    
Respiratoryrespiratory tractlarynx   
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectiveadipose  highly
Connectivebone   
cells
SystemCellPubmedSpeciesStageRna symbol
 chondrocyte
not specificadipocyte
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo, fetal, pregnancy
Text placenta, head and limb buds, skin, mesodermal and neural crest cells
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a basic DNA binding structure
  • two putative NLS motifs and these NLS sequences are potentially functional
  • a C terminal basic helix-loop-helix (HLH) domain with a stretch of glycine, GGC repeat, and anti-osteogenic C-terminus, the TWIST Box, which binds and inhibits RUNX2 transactivation
  • mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies homolog to murine Dermo1
    intraspecies homolog to TAL2
    Homologene
    FAMILY
  • BHLH family of transcription factors
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • involved in osteoblast differentiation and maturation
  • interacting with the histone acetyltransferase domain of PCAF and EP300 and inhibiting their acetyltransferase
  • activities
  • regulator of embryonic morphogenesis and playing an essential role in metastasis by promoting an epithelial-mesenchymal transition
  • required for the dorsoventral patterning and for maintenance of the overlying apical ectodermal ridge
  • promotes survival and accumulation of fibroblasts by shaping their responsiveness to growth factor stimulation, and can promote pathogenic accumulation of fibroblasts in fibrotic lung disease
  • mediators of mesodermal tissue development and contribute to correct patterning of the skeleton
  • potential mediator of mesenchymal stromal/stem cells self-renewal and lineage commitment in postnatal skeletal tissues by exerting their effects on genes involved in the early stages of bone development
  • regulator of epithelial-mesenchymal transition(EMT)in lung fibrosis
  • may play a role in inflammation of white adipose tissue because it can regulate the expression and secretion of inflammatory adipokines via direct transcriptional effects in white adipocytes
  • may be a positive regulator of fatty acid oxidation in human white adipocytes
  • TWIST1 and BMI1 act cooperatively to repress expression of both E-cadherin and CDKN2A
  • directly activates BMI1 transcription by binding to the E-box in intron 1 of the BMI1 gene
  • TWIST1 and BMI1 are mutually essential to induce EMT and promote tumour-initiating capability in cancer cells
  • TWIST1 and SNAI2 act together to promote epithelial mesenchymal transition and tumor metastasis
  • master osteogenic regulator, and regulator in giant cell tumor of bone
  • CELLULAR PROCESS cell life, antiapoptosis
    nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    text antiapoptotic role in calvarial osteoblasts
    PATHWAY
    metabolism
    signaling
    a component
  • heterodimerizing with E12 protein
  • heterodimering with partner BHLH proteins and with HAND2 (coexpressed in distinct regions of the developing limb)
  • linked with SNAIL and TCF3 during embryonic development
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with RUNX1 in osteoblasts
  • binding to FGFR2 promoter and interacting with RUNX2
  • overexpression of WDR5 in the perichondrium promotes chondrocyte differentiation by modulating the expression of TWIST1 and FGF18
  • regulating with MSX2 the expression of EFNA4
  • interaction of TWIST1 with a novel protein candidate TCF4
  • direct regulation of BMI1 by TWIST1, and the functional interdependence between TWIST1 and BMI1, involved in promoting EMT and the tumour-initiating capability of head and neck cancer cells
  • SNAI1 controls ZEB1 expression at multiple levels and acts cooperatively with TWIST1 in the ZEB1 gene transcription induction
  • SETD8 acts as a dual epigenetic modifier on the promoters of the TWIST1 target genes CDH1 and CDH2 via its H4K20 monomethylation activity
  • TWIST1 regulation of IFNG depends on complex formation with RUNX3
  • cell & other
    REGULATION
    activated by thrombin (is required for thrombin-induced angiogenesis as measured by endothelial cell migration)
    induced by hypoxia (its expression in cancer cells is enhanced by hypoxia in a HEPAS1-dependent manner)
    ASSOCIATED DISORDERS
    corresponding disease(s) ACS3 , BGS2 , ISCC , DEL7P21 , CRS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    in breast carcinoma, gastric and lung cancer with metastasis
    tumoral     --over  
    in gliomas and promotes invasion
    tumoral     --low  
    by hypermethylation is observed frequently in colorectal tumors
    tumoral     --over  
    associated with unfavorable outcomes in patients with colorectal cancer
    tumoral somatic mutation      
    in giant cell tumor of bone, leading to inappropriate TWIST1 downregulation of RUNX2, arrested osteoblastic differentiation, and the maintenance of an immature and neoplastic phenotype (
    Susceptibility to breast cancer in women with Saethre-Chotzen syndrome
    Variant & Polymorphism
    Candidate gene DNA methylation markers of Gastric cancer (GC), which may serve as useful markers that may identify a distinct subset of GC
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • HIF-1alpha- and TWIST-null mice show similarities in their phenotypes