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Gene Ontology Classifications
NK2 homeobox 1

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

GO curators for mouse genes have assigned the following annotations to the gene product of Nkx2-1. (This text reflects annotations as of Tuesday, May 26, 2015.) MGI curation of this mouse gene is considered complete, including annotations derived from the biomedical literature as of May 2, 2014. If you know of any additional information regarding this mouse gene please let us know. Please supply mouse gene symbol and a PubMed ID.
Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein initially identified as a thyroid-specific transcription factor. The encoded protein binds to the thyroglobulin promoter and regulates the expression of thyroid-specific genes but has also been shown to regulate the expression of genes involved in morphogenesis. Mutations and deletions in this gene are associated with benign hereditary chorea, choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress, and may be associated with thyroid cancer. Multiple transcript variants encoding different isoforms have been found for this gene. This gene shares the symbol/alias 'TTF1' with another gene, transcription termination factor 1, which plays a role in ribosomal gene transcription. [provided by RefSeq, Feb 2014]
Summary text based on GO annotations supported by experimental evidence in mouse
Summary text based on GO annotations supported by experimental evidence in other organisms
Summary text for additional MGI annotations
  1. Amendola E et al. (2005) A mouse model demonstrates a multigenic origin of congenital hypothyroidism. Endocrinology, 146:5038-47. (PubMed:16150900)
  2. Amendola E et al. (2010) A locus on mouse chromosome 2 is involved in susceptibility to congenital hypothyroidism and contains an essential gene expressed in thyroid. Endocrinology, 151:1948-58. (PubMed:20160132)
  3. Benlhabib H et al. (2011) Epigenetic regulation of surfactant protein A gene (SP-A) expression in fetal lung reveals a critical role for Suv39h methyltransferases during development and hypoxia. Mol Cell Biol, 31:1949-58. (PubMed:21402781)
  4. Bruno MD et al. (1995) Lung cell-specific expression of the murine surfactant protein A (SP-A) gene is mediated by interactions between the SP-A promoter and thyroid transcription factor-1 [published erratum appears in J Biol Chem 1995 Jul 7;270(27):16482] J Biol Chem, 270:6531-6. (PubMed:7896788)
  5. Butt SJ et al. (2008) The requirement of Nkx2-1 in the temporal specification of cortical interneuron subtypes. Neuron, 59:722-32. (PubMed:18786356)
  6. Cheng A et al. (2007) Telomere protection mechanisms change during neurogenesis and neuronal maturation: newly generated neurons are hypersensitive to telomere and DNA damage. J Neurosci, 27:3722-33. (PubMed:17409236)
  7. Corbin JG et al. (2003) Combinatorial function of the homeodomain proteins Nkx2.1 and Gsh2 in ventral telencephalic patterning. Development, 130:4895-906. (PubMed:12930780)
  8. Dave V et al. (2006) Calcineurin/Nfat signaling is required for perinatal lung maturation and function. J Clin Invest, 116:2597-609. (PubMed:16998587)
  9. DeFelice M et al. (2003) TTF-1 phosphorylation is required for peripheral lung morphogenesis, perinatal survival, and tissue-specific gene expression. J Biol Chem, 278:35574-83. (PubMed:12829717)
  10. Di Palma T et al. (2009) TAZ is a coactivator for Pax8 and TTF-1, two transcription factors involved in thyroid differentiation. Exp Cell Res, 315:162-75. (PubMed:19010321)
  11. Du T et al. (2008) NKX2.1 specifies cortical interneuron fate by activating Lhx6. Development, 135:1559-67. (PubMed:18339674)
  12. Flandin P et al. (2010) The progenitor zone of the ventral medial ganglionic eminence requires Nkx2-1 to generate most of the globus pallidus but few neocortical interneurons. J Neurosci, 30:2812-23. (PubMed:20181579)
  13. Kimura S et al. (1996) The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary. Genes Dev, 10:60-9. (PubMed:8557195)
  14. Kusakabe T et al. (2006) Thyroid-specific enhancer-binding protein/NKX2.1 is required for the maintenance of ordered architecture and function of the differentiated thyroid. Mol Endocrinol, 20:1796-809. (PubMed:16601074)
  15. Liu C et al. (2002) GATA-6 and Thyroid Transcription Factor-1 Directly Interact and Regulate Surfactant Protein-C Gene Expression. J Biol Chem, 277:4519-25. (PubMed:11733512)
  16. Marin O et al. (2002) Patterning of the basal telencephalon and hypothalamus is essential for guidance of cortical projections. Development, 129:761-73. (PubMed:11830575)
  17. Mastronardi C et al. (2006) Deletion of the Ttf1 gene in differentiated neurons disrupts female reproduction without impairing basal ganglia function. J Neurosci, 26:13167-79. (PubMed:17182767)
  18. Matagne V et al. (2012) Thyroid transcription factor 1, a homeodomain containing transcription factor, contributes to regulating periodic oscillations in GnRH gene expression. J Neuroendocrinol, 24:916-29. (PubMed:22356123)
  19. Meeus L et al. (2004) Characterization of a novel loss of function mutation of PAX8 in a familial case of congenital hypothyroidism with in-place, normal-sized thyroid. J Clin Endocrinol Metab, 89:4285-91. (PubMed:15356023)
  20. Miller LA et al. (2001) Immunolocalization of sonic hedgehog (Shh) in developing mouse lung. J Histochem Cytochem, 49:1593-604. (PubMed:11724907)
  21. Minoo P et al. (1999) Defects in tracheoesophageal and lung morphogenesis in Nkx2.1(-/-) mouse embryos. Dev Biol, 209:60-71. (PubMed:10208743)
  22. Nery S et al. (2003) Dlx2 progenitor migration in wild type and Nkx2.1 mutant telencephalon. Cereb Cortex, 13:895-903. (PubMed:12902388)
  23. Nery S et al. (2001) Sonic hedgehog contributes to oligodendrocyte specification in the mammalian forebrain. Development, 128:527-40. (PubMed:11171336)
  24. Nobrega-Pereira S et al. (2008) Postmitotic Nkx2-1 controls the migration of telencephalic interneurons by direct repression of guidance receptors. Neuron, 59:733-45. (PubMed:18786357)
  25. Pakarinen P et al. (2002) Pituitary hormones are not required for sexual differentiation of male mice: phenotype of the T/ebp/Nkx2.1 null mutant mice. Endocrinology, 143:4477-82. (PubMed:12399445)
  26. Park KS et al. (2004) TAZ interacts with TTF-1 and regulates expression of surfactant protein-C. J Biol Chem, 279:17384-90. (PubMed:14970209)
  27. Park KS et al. (2007) SPDEF regulates goblet cell hyperplasia in the airway epithelium. J Clin Invest, 117:978-88. (PubMed:17347682)
  28. Parlato R et al. (2004) An integrated regulatory network controlling survival and migration in thyroid organogenesis. Dev Biol, 276:464-75. (PubMed:15581879)
  29. Pelizzoli R et al. (2008) TTF-1/NKX2.1 up-regulates the in vivo transcription of nestin. Int J Dev Biol, 52:55-62. (PubMed:18033672)
  30. Pleasure SJ et al. (2000) Cell migration from the ganglionic eminences is required for the development of hippocampal GABAergic interneurons. Neuron, 28:727-40. (PubMed:11163262)
  31. Pohlenz J et al. (2002) Partial deficiency of thyroid transcription factor 1 produces predominantly neurological defects in humans and mice. J Clin Invest, 109:469-73. (PubMed:11854318)
  32. Que J et al. (2007) Multiple dose-dependent roles for Sox2 in the patterning and differentiation of anterior foregut endoderm. Development, 134:2521-31. (PubMed:17522155)
  33. Reynolds PR et al. (2005) Temporal-spatial expression and transcriptional regulation of alpha7 nicotinic acetylcholine receptor by thyroid transcription factor-1 and early growth response factor-1 during murine lung development. J Biol Chem, 280:32548-54. (PubMed:16033766)
  34. Serls AE et al. (2005) Different thresholds of fibroblast growth factors pattern the ventral foregut into liver and lung. Development, 132:35-47. (PubMed:15576401)
  35. Sussel L et al. (1999) Loss of Nkx2.1 homeobox gene function results in a ventral to dorsal molecular respecification within the basal telencephalon: evidence for a transformation of the pallidum into the striatum. Development, 126:3359-70. (PubMed:10393115)
  36. Takuma N et al. (1998) Formation of Rathke's pouch requires dual induction from the diencephalon. Development, 125:4835-40. (PubMed:9806931)
  37. Tekki-Kessaris N et al. (2001) Hedgehog-dependent oligodendrocyte lineage specification in the telencephalon. Development, 128:2545-54. (PubMed:11493571)
  38. Tian J et al. (2006) Loss of Nkx2.8 deregulates progenitor cells in the large airways and leads to dysplasia. Cancer Res, 66:10399-407. (PubMed:17079460)
  39. Tian Y et al. (2011) Regulation of lung endoderm progenitor cell behavior by miR302/367. Development, 138:1235-45. (PubMed:21350014)
  40. Tomita T et al. (2008) CAATT/enhancer-binding proteins alpha and delta interact with NKX2-1 to synergistically activate mouse secretoglobin 3A2 gene expression. J Biol Chem, 283:25617-27. (PubMed:18632661)
  41. Varma S et al. (2012) The transcription factors Grainyhead-like 2 and NK2-homeobox 1 form a regulatory loop that coordinates lung epithelial cell morphogenesis and differentiation. J Biol Chem, 287:37282-95. (PubMed:22955271)
  42. Weidenfeld J et al. (2002) The WNT7b promoter is regulated by TTF-1, GATA6, and Foxa2 in lung epithelium. J Biol Chem, 277:21061-70. (PubMed:11914369)
  43. Xu Q et al. (2004) Origins of cortical interneuron subtypes. J Neurosci, 24:2612-22. (PubMed:15028753)
  44. Yin Z et al. (2006) Hop functions downstream of Nkx2.1 and GATA6 to mediate HDAC-dependent negative regulation of pulmonary gene expression. Am J Physiol Lung Cell Mol Physiol, 291:L191-9. (PubMed:16510470)
  45. Yuan B et al. (2000) Inhibition of distal lung morphogenesis in Nkx2.1(-/-) embryos. Dev Dyn, 217:180-90. (PubMed:10706142)
  46. Zhang Y et al. (2007) GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo. Development, 134:189-98. (PubMed:17164424)
  47. Zhou L et al. (1996) Thyroid transcription factor-1, hepatocyte nuclear factor-3beta, surfactant protein B, C, and Clara cell secretory protein in developing mouse lung. J Histochem Cytochem, 44:1183-93. (PubMed:8813084)

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Gene Ontology Evidence Code Abbreviations:

  EXP Inferred from experiment
  IAS Inferred from ancestral sequence
  IBA Inferred from biological aspect of ancestor
  IBD Inferred from biological aspect of descendant
  IC Inferred by curator
  IDA Inferred from direct assay
  IEA Inferred from electronic annotation
  IGI Inferred from genetic interaction
  IKR Inferred from key residues
  IMP Inferred from mutant phenotype
  IMR Inferred from missing residues
  IPI Inferred from physical interaction
  IRD Inferred from rapid divergence
  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


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