Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Tbx3. (This text reflects annotations as of Wednesday, January 23, 2013.)

---

Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This protein is a transcriptional repressor and is thought to play a role in the anterior/posterior axis of the tetrapod forelimb. Mutations in this gene cause ulnar-mammary syndrome, affecting limb, apocrine gland, tooth, hair, and genital development. Alternative splicing of this gene results in three transcript variants encoding different isoforms; however, the full length nature of one variant has not been determined. [provided by RefSeq, Jul 2008]

---

Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Tbx3
  • participates in the following biological processes:
    • cell aging ^[3]
    • mammary placode formation ^[4]
    • negative regulation of transcription, DNA-dependent ^[3]
    • specification of organ position ^[4]
  • performs the following molecular functions:
    • sequence-specific DNA binding transcription factor activity ^[7]
  • is located in the following cellular components:
    • nucleus ^{[6, 9, 12]}
• Researchers have inferred, based on physical interactions, that the gene product of Tbx3
  • performs the following molecular functions:
    • RNA polymerase II activating transcription factor binding ^[11]
    • RNA polymerase II transcription factor binding ^[11]
  • is located in the following cellular components:
    • transcription factor complex ^[2]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Tbx3
  • participates in the following biological processes:
    • atrioventricular bundle cell differentiation ^[1]
    • blood vessel development ^[5]
    • branching involved in mammary gland duct morphogenesis ^[8]
    • cardiac muscle cell differentiation ^[10]
    • cardiac muscle cell fate commitment ^[1]
    • heart looping ^{[9, 13]}
    • heart morphogenesis ^[7]
    • in utero embryonic development ^[7]
    • limb morphogenesis ^[5]
    • limbic system development ^[7]
    • mammary gland development ^{[5, 7, 8]}
    • negative regulation of epithelial cell differentiation ^[14]
    • negative regulation of transcription, DNA-dependent ^[7]
    • outflow tract morphogenesis ^[9]
    • positive regulation of stem cell proliferation ^[14]
    • positive regulation of transcription, DNA-dependent ^[7]
    • regulation of cell proliferation ^[13]
    • sinoatrial node cell development ^[15]
    • stem cell maintenance ^[14]
    • ventricular septum morphogenesis ^[1]
• Researchers have inferred, based on genetic interactions, that the gene product of Tbx3
  • participates in the following biological processes:
    • mammary placode formation based on interactions with Tbx2 ^[8]
    • palate development based on interactions with Tbx2 ^[16]

---

Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Tbx3:
  • participates in the following biological processes:
    • anterior/posterior axis specification, embryo
    • cell aging
    • embryonic digit morphogenesis
    • embryonic forelimb morphogenesis
    • female genitalia development
    • follicle-stimulating hormone secretion
    • forelimb morphogenesis
    • luteinizing hormone secretion
    • male genitalia development
    • mammary gland development
    • mesoderm morphogenesis
    • negative regulation of apoptotic process
    • negative regulation of myoblast differentiation
    • negative regulation of transcription from RNA polymerase II promoter
    • negative regulation of transcription, DNA-dependent
    • organ morphogenesis
    • positive regulation of cell cycle
    • positive regulation of cell proliferation
    • skeletal system development
  • performs the following molecular functions:
    • sequence-specific DNA binding
  • is located in the following cellular components:
    • nucleus

---

Summary text based on GO annotations supported by structural data

• Tbx3 encodes a protein or proteins that contain the following InterPro domains: p53-like transcription factor, DNA-binding, Transcription factor, Brachyury, Transcription factor, T-box, Transcription factor, T-box, conserved site, Transcription factor, T-box, region of unknown function, indicating that the gene product:
  • participates in the following biological processes:
    • regulation of transcription, DNA-dependent

---

Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Tbx3 indicates that it:
  • participates in the following biological processes:
    • multicellular organismal development
    • regulation of transcription, DNA-dependent
    • transcription, DNA-dependent
  • performs the following molecular functions:
    • DNA binding

---

References

1. Bakker ML et al. (2008) Transcription factor Tbx3 is required for the specification of the atrioventricular conduction system. Circ Res, 102:1340-9. (PubMed:18467625)
2. Boogerd KJ et al. (2008) Msx1 and Msx2 are functional interacting partners of T-box factors in the regulation of Connexin43. Cardiovasc Res, 78:485-93. (PubMed:18285513)
3. Brummelkamp TR et al. (2002) TBX-3, the gene mutated in Ulnar-Mammary Syndrome, is a negative regulator of p19ARF and inhibits senescence. J Biol Chem, 277:6567-72. (PubMed:11748239)
4. Cho KW et al. (2006) Molecular interactions between Tbx3 and Bmp4 and a model for dorsoventral positioning of mammary gland development. Proc Natl Acad Sci U S A, 103:16788-93. (PubMed:17071745)
5. Davenport TG et al. (2003) Mammary gland, limb and yolk sac defects in mice lacking Tbx3, the gene mutated in human ulnar mammary syndrome. Development, 130:2263-73. (PubMed:12668638)
6. Eriksson KS et al. (2009) T-box 3 is expressed in the adult mouse hypothalamus and medulla. Brain Res, 1302:233-9. (PubMed:19765559)
7. Hoogaars WM et al. (2007) Tbx3 controls the sinoatrial node gene program and imposes pacemaker function on the atria. Genes Dev, 21:1098-112. (PubMed:17473172)
8. Jerome-Majewska LA et al. (2005) Tbx3, the ulnar-mammary syndrome gene, and Tbx2 interact in mammary gland development through a p19Arf/p53-independent pathway. Dev Dyn, 234:922-33. (PubMed:16222716)
9. Mesbah K et al. (2008) Tbx3 is required for outflow tract development. Circ Res, 103:743-50. (PubMed:18723448)
10. Mommersteeg MT et al. (2007) Molecular pathway for the localized formation of the sinoatrial node. Circ Res, 100:354-62. (PubMed:17234970)
11. Pereira LA et al. (2011) Brachyury and related Tbx proteins interact with the Mixl1 homeodomain protein and negatively regulate Mixl1 transcriptional activity. PLoS One, 6:e28394. (PubMed:22164283)
12. Pontecorvi M et al. (2008) Expression of Tbx2 and Tbx3 in the developing hypothalamic-pituitary axis. Gene Expr Patterns, 8:411-7. (PubMed:18534921)
13. Ribeiro I et al. (2007) Tbx2 and Tbx3 regulate the dynamics of cell proliferation during heart remodeling. PLoS ONE, 2:e398. (PubMed:17460765)
14. Suzuki A et al. (2008) Tbx3 controls the fate of hepatic progenitor cells in liver development by suppressing p19ARF expression. Development, 135:1589-95. (PubMed:18356246)
15. Wiese C et al. (2009) Formation of the sinus node head and differentiation of sinus node myocardium are independently regulated by Tbx18 and Tbx3. Circ Res, 104:388-97. (PubMed:19096026)
16. Zirzow S et al. (2009) Expression and requirement of T-box transcription factors Tbx2 and Tbx3 during secondary palate development in the mouse. Dev Biol, 336:145-55. (PubMed:19769959)

---

---

Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

---