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FLASH GENE
Symbol TBX3 contributors: mct - updated : 28-09-2016
HGNC name T-box 3
HGNC id 11602
Corresponding disease
UMS ulnar mammary syndrome
Location 12q24.21      Physical location : 115.108.058 - 115.121.969
Synonym name
  • T-box transcription factor TBX3
  • bladder cancer related protein XHL
  • T-box protein 3
  • Synonym symbol(s) XHL, TBX3-ISO
    DNA
    TYPE functioning gene
    STRUCTURE 13.91 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (CAAT box)
    Binding site   transcription factor
    text structure
  • a Sp1 element and two CCAAT boxes to be essential for basal TBX3 promoter activity ( these sites are necessary for efficient basal transcription in genes which lack TATA boxes or an Initiator which we show to be the case for TBX3)
  • MAPPING cloned Y linked N status confirmed
    Physical map
    OAS2 12q24.2 2'-5'-oligoadenylate synthetase 2, 69/71kDa DTX1 12q24.1 deltex homolog 1 (Drosophila) RASAL1 12q23-q24 RAS protein activator like 1 (GAP1 like) LOC387885 12 LOC387885 DDX54 12q24.21 DEAD (Asp-Glu-Ala-Asp) box polypeptide 54 FLJ14827 12q24.21 hypothetical protein FLJ14827 LOC115811 12q24.21 hypothetical protein BC013151 TPCN1 12q24.21 two pore segment channel 1 FLJ22233 LOC196463 12q24.21 hypothetical protein LOC196463 SDS 12q24.1 serine dehydratase SDS-RS1 12q24.21 serine dehydratase related sequence 1 LHX5 12q24.31-q24.32 LIM homeobox protein 5 KIAA0682 12q23.3-q24.2 LIM homeobox protein 5 TBX5 12q24.1 T-box 5 LOC387886 12 LOC387886 LOC390361 12 similar to microtubule-associated proteins 1A/1B light chain 3 LOC386654 12q24.1-q24.2 OSTF1 pseudogene TBX3 12q24.1 T-box 3 (ulnar mammary syndrome) LOC387887 12 LOC387887 KIAA1025
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 4754 77.4 723 - 2011 21856288
  • essential roles of TBX3 and TBX3+2a in pluripotency maintaining (PMID: 24472544)
  • 8 - 4814 - 743 - 2011 21856288
  • TBX3 + 2a
  • additional exon, several splice sites
  • incorporating 20 aas within the T-box DNA-binding domain
  • could directly interact with NANOG (PMID: 24472544)
  • essential roles of TBX3 and TBX3+2a in pluripotency maintaining
  • EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheartconducting system    Homo sapiens
    Reproductivefemale systembreast    Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text in the developing conduction system in heart (
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a large N terminal DNA binding domain (T-box)
  • a C terminal transactivation/repression domain RD1
  • mono polymer homomer , dimer
    HOMOLOGY
    interspecies homolog to murine T-box gene Tbx3 (T,brachyury)
    homolog to Drosophila optomotor-blind gene (omb)
    Homologene
    FAMILY
  • T box family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus,chromatin/chromosome
    intracellular,nucleus,nucleolus
    text
  • TBX3 is present in primary cilia where it colocalizes with GLI3
  • is predominantly localized to the nucleus of S-phase cells
  • basic FUNCTION
  • involved in optic lobe formation, in specification of post limb mesoderm and in setting up the dorso/ventral limb axis
  • controls the sinoatrial node gene program and imposes pacemaker function on the atria
  • plays an important role on osteogenic differentiation and proliferation of human mesenchymal stem cell derived from adipose tissue
  • required for the molecular specification of the atrioventricular bundle and bundle branches and for the development of the ventricular septum and outflow tract
  • having an indirect role in second heart field deployment
  • potent inhibitor of senescence repressing CDKN2A
  • directly repress the expression of E-cadherin, a keratinocyte-melanoma adhesion molecule whose loss is required for the acquisition of an invasive phenotype in melanoma
  • as TBX2 may play a dual role during the radial to vertical growth phase transition by both inhibiting senescence via repression of CDKN1A expression, and enhancing melanoma invasiveness by decreasing E-cadherin level
  • plays a crucial role in controlling hepatoblast proliferation and cell-fate determination by suppressing CDKN2A expression and thereby promoting liver organogenesis
  • may function by recruiting HDACs to the T-box binding site in the promoter region
  • regulates pluripotency-associated and reprogramming factors, in addition to sharing many common downstream regulatory targets with POU5F1, SOX2, NANOG and SMAD1
  • mediates limb, mammary gland and heart development (
  • functions as inhibiting senescence and thereby promoting cell proliferation and immortalization
  • its function is important for the proliferation and specification of cells and tissues critical for development
  • is required for the functional development, maturation, and homeostasis of the conduction system in a highly dosage-sensitive manner
  • transcriptional repressor that is required for the development of the heart, limbs, and mammary glands
  • plays distinct roles in regulating self-renewal and differentiation in hESCs
  • plays a critical role in the developing heart in a dose-dependent manner
  • may play an important role as a reciprocal switch between substrate dependent cell proliferation and tumour invasion
  • TBX3 acts as an anti-apoptotic factor in mesangial cell (MC) and may be involved in the mechanism by which TGFB1 induces glomerulosclerosis and tubular fibrosis during the progression of nephropathies
  • is involved in lineage specification in several tissues during embryonic development
  • is important for the generation of hormone-sensing cells
  • plays important roles in development, stem cells, nuclear reprogramming, and cancer
  • is critical for the formation of, among other structures, the heart, limbs and mammary glands
  • is likely required for cells to transit through S-phase and that this function may be linked to its role as a pro-proliferative factor
  • TBX3 controls digit number upstream of SHH-dependent (posterior mesenchyme) and SHH-independent, cilium-based (anterior mesenchyme) Hedgehog pathway function
  • is essential in development and has emerged as an important player in the oncogenic process
  • is not only required for development of posterior forelimb bones (ulna and digits 4 and 5), but also for a subset of posterior muscles (lateral triceps and brachialis) and their bone eminence attachment sites
  • represses BMP4 expression, and maintains eye field neural progenitors in a multipotent state, then, in combination with PAX6 determines eye field cells to form retina
  • TBX2, TBX3, TBX4, TBX5 and three members of TBX1 (TBX1, TBX15, TBX18), Brachyury (T) and Eomes (TBR2) are expressed in the developing limb
  • TBX18 and other members of the T-box gene family, namely, TBX1, TBX2, TBX3, and TBX20, play additional roles in development and homeostasis of other components of the excretory system
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    text regulation
    PATHWAY
    metabolism
    signaling
    a component
  • pairing with TBX5
  • INTERACTION
    DNA binding through T-box
    RNA
    small molecule
    protein
  • binding to TBX5
  • interacts with HDAC1, 2, and 3 via two distinct binding sites
  • SOX4 is an interacting partner of TBX3
  • plays an important role in osteoclastogenesis at least in part by regulating CSF1-dependent expression of JDP2
  • DPPA3 is a direct downstream target of TBX3
  • CDKN1A repression by TBX3 is biologically significant and required for TBX3-induced cell proliferation of chondrosarcoma cells
  • TBX3 represses BMP4 transcription and is required in the eye field for both neural induction and normal eye formation
  • cell & other
    REGULATION
    activated by retinoic acid (RA) (RA activates endogenous TBX3 expression, which is mediated by an RA-receptor complex directly binding and activating the TBX3 promoter)
    Other TGFB1 regulates TBX3 gene expression in mesangial cell
    ASSOCIATED DISORDERS
    corresponding disease(s) UMS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in many cancers and in melanoma
    tumoral     --over  
    in malignant cells of primary breast cancer tissues
    constitutional     --low  
    affects multiple signaling pathways regulating second heart field proliferation and outflow tract morphogenesis, including fibroblast growth factor signaling, leading to a failure of normal heart tube extension and consequent atrioventricular and ventriculoarterial alignment defects
    tumoral     --over  
    contribute to metastasis in breast cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene may serve as a biomarker for breast cancer and have significant applications in both breast cancer diagnosis and treatment
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Ectopic expression of Tbx3 in mice revealed that Tbx3 represses the atrial phenotype and imposes the pacemaker phenotype on the atria and the mice displayed arrhythmias and developed functional ectopic pacemakers
  • arrhythmias in Tbx3-deficient embryos are accompanied by disrupted expression of multiple ion channels despite preserved expression of previously described conduction system markers
  • Tbx3-deficient embryos developed outflow tract malformations and ventricular septal defects
  • mice lacking Tbx3 develop severe outflow tract defects, including connection of both the aorta and pulmonary trunk with the right ventricle, in addition to aortic arch artery anomalies and abnormal communication between the right atrium and left ventricle