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FLASH GENE
Symbol TGIF1 contributors: mct/ - updated : 29-03-2019
HGNC name TGFB-induced factor homeobox 1
HGNC id 11776
Corresponding disease
DEL18P chromosome 18p complete or partial deletions
HPE4 holoprosencephaly 4
Location 18p11.31      Physical location : 3.412.071 - 3.458.404
Synonym name
  • TGFB-induced factor (TALE family homeobox)
  • 5'-TG-3'-interacting factor 1
  • homeobox protein TGIF1
  • TALE homeobox TG-interacting factor
  • transforming growth factor-beta-induced factor
  • Synonym symbol(s) TGIF, MGC39747, MGC5066, TALE, HPE4, FLJ97178
    DNA
    TYPE functioning gene
    STRUCTURE 46.34 kb     4 Exon(s)
    MAPPING cloned Y linked   status provisional
    Map pter - D18S45 - D18S552 - TGIF1 - D18S1132 - D18S62 - D18S471 - D18S1163 - PTPRM - D18S464 - D18S1158 - D18S482 - cen
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 2076 43 401 - 2018 29355528
    3 - 1474 - 286 - 2018 29355528
  • overexpressed in oral squamous cell carcinoma
  • 4 - 1508 - 272 - 2018 29355528
    3 - 1618 - 272 - 2018 29355528
    3 - 1382 - 252 - 2018 29355528
  • underexpresed in oral squamous cell carcinoma
  • 3 - 1469 - 252 - 2018 29355528
    3 - 1369 - 252 - 2018 29355528
    4 - 1540 - 252 - 2018 29355528
  • its expression was correlated with lower cellular differentiation, positive blood vascular invasion, advanced pathologic stage, and positive vascular lymphatic invasion of oral squamous cell carcinoma (OSCC)
  • 3 - 1530 - 275 - 2018 29355528
    4 - 1887 - 272 - 2018 29355528
    4 - 1553 - 252 - 2018 29355528
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus    
    Endocrinepancreas    
    Reproductivemale systemprostate   
    Respiratorylung    
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    Lymphoid    
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticprogenitor cell Homo sapiens
    Lymphoid/Immunelymphocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text brain
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • helix-turn-helix, DNA binding domain
  • TALE (three AA loop extension between helices) three-amino acid loop extension (TALE) type of homeodomain (HD)
  • HOMOLOGY
    interspecies homolog to murine Tgif
    Homologene
    FAMILY
  • TALE/TGIF homeobox family
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • down regulator of RXRA activities
  • SMAD2 (MADH2) binding protein and transcriptional corepressor
  • has an important role myelopoiesis and may regulate the balance between proliferation and differentiation
  • playing a key role in regulating retinoic acid signaling, and is essential to properly pattern the forebrain
  • its function is required for gastrulation, and provide the first clear evidence that Tgifs limit the transcriptional response to Nodal signaling during early embryogenesis
  • TGIF1, TGIF2 function is required for gastrulation, and provide the first clear evidence that Tgifs limit the transcriptional response to NODAL signaling during early embryogenesis
  • represses gene expression by interaction with general corepressors, and can be recruited to target genes by transforming growth factor beta (TGFB) activated Smads, or by the retinoid X receptor (RXR)
  • can regulate nuclear receptor complexes, in addition to those containing retinoic acid receptors
  • plays a role in radiation-induced normal tissue injury
  • promotes the endothelial cell inflammatory response after exposure to radiation or TNF
  • new role for TGIF1 as a proinflammatory molecule
  • is a transcriptional repressor that can modulate retinoic acid and transforming growth factor beta signaling pathways
  • regulates quiescence and self-renewal of hematopoietic stem cells
  • is a new player in human cholesterol metabolism
  • promoted the growth and migration of nonsmall cell lung cancer (NSCLC) cells
  • TGIF1, TGIF2 are transcriptional repressors that inhibit the transcriptional response to TGFB1 signaling, and can repress gene expression by direct binding to DNA
  • TGIF1, TGIF2 regulate axial patterning and reduced TGIF function sensitizes embryos to the effects of retinoic acid
  • regulates endothelial cells (ECs) function and the expression of angiogenic molecules
  • TGIF1, TGIF2 regulate ciliogenesis and EVI5L mediates likely at least part of this effect
  • TGIF1, TGIF2 play an important role in regulating basic energy metabolism in normal cells, and this function of Tgifs is amplified in some cancers
  • is a novel regulator of bone remodeling and an essential component of the PTH anabolic action
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    text physiological development of forebrain and establishing of ventral midline structure (NODAL pathway)
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • corepressor of MADH2 (SMAD2)
  • linking the NODAL pathway
  • CTBP, MADH3
  • interacts with NR1H3 and can repress transcription from a synthetic reporter activated by NR1H3
  • interacting with FBXW7 (TGIF1 is targeted for degradation by FBXW7 in a phosphorylation-dependent manner)
  • TGIF overexpression downregulates SOX3 promoter activity and decreases endogenous SOX3 protein expression in both uninduced and retinoic acid (RA)-induced NT2/D1 cells
  • TGIF1 plays a role in TNF- and radiation-induced inflammation, suggesting that it could be a target in limiting this event in the vascular compartment
  • TGIF1 is an RXRA transcriptional co-repressor and represses RXRA-dependent transcriptional responses
  • TGIF1 functioning as an important repressor of SOAT2
  • ZIC2-binding to the cis-regulatory element near the TGIF1 promoter may be involved in the mechanism underlying forebrain development and incidences of holoprosencephaly (HPE)
  • TGIF1 and TGIF2 regulate the TGFB1/NODAL signaling pathway and sonic hedgehog (SHH) signaling independently
  • multifunctional protein that represses TGFB1-activated transcription by interacting with SMAD2-SMAD4 complexes
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) HPE4 , DEL18P
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification    
    in esophageal squamous cell carcinoma
    tumoral     --over  
    in esophageal squamous cell carcinoma
    constitutional        
    impairs osteoblast differentiation and activity, leading to a reduced bone formation
    constitutional germinal mutation     loss of function
    in both TGIF1 and TGIF2 result in a failure of gastrulation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerlung 
    TGIF1 might be a therapeutic target for nonsmall cell lung cancer (NSCLC)
    ANIMAL & CELL MODELS
  • depletion of Tgif1 in mice increased the hepatic Soat2 expression and resulted in higher hepatic lipid accumulation and plasma cholesterol levels
  • Tgif1 mutation in mouse contributes to HPE pathogenesis and provide evidence that this is due to disruption of the Shh pathway