Homeobox protein Nkx-2.1

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• core promoter binding Source: CAFA <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "Structural and functional properties of the N transcriptional activation domain of thyroid transcription factor-1: similarities with the acidic activation domains."
    Tell G., Perrone L., Fabbro D., Pellizzari L., Pucillo C., De Felice M., Acquaviva R., Formisano S., Damante G.
    Biochem. J. 329:395-403(1998) [PubMed] [Europe PMC] [Abstract]
• DNA binding Source: RGD <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • Ref.1

    "Thyroid nuclear factor 1 (TTF-1) contains a homeodomain and displays a novel DNA binding specificity."
    Guazzi S., Price M., de Felice M., Damante G., Mattei M.-G., di Lauro R.
    EMBO J. 9:3631-3639(1990) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
• DNA-binding transcription activator activity, RNA polymerase II-specific Source: NTNU_SB
• DNA-binding transcription factor activity Source: MGIInferred from direct assayⁱ
  • "Expression and function of B7-1 and B7-2 in hapten-induced contact sensitivity."
    Reiser H., Schneeberger E.E.
    Eur. J. Immunol. 26:880-885(1996) [PubMed] [Europe PMC] [Abstract]
• DNA-binding transcription factor activity, RNA polymerase II-specific Source: RGDInferred from sequence orthologyⁱ
  • "TTF-1/NKX2.1 up-regulates the in vivo transcription of nestin."
    Pelizzoli R., Tacchetti C., Luzzi P., Strangio A., Bellese G., Zappia E., Guazzi S.
    Int. J. Dev. Biol. 52:55-62(2008) [PubMed] [Europe PMC] [Abstract]
  • "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."
    Bruno M.D., Bohinski R.J., Huelsman K.M., Whitsett J.A., Korfhagen T.R.
    J. Biol. Chem. 270:6531-6536(1995) [PubMed] [Europe PMC] [Abstract]
• enzyme binding Source: RGDInferred from sequence orthologyⁱ
  • "A high-confidence interaction map identifies SIRT1 as a mediator of acetylation of USP22 and the SAGA coactivator complex."
    Armour S.M., Bennett E.J., Braun C.R., Zhang X.Y., McMahon S.B., Gygi S.P., Harper J.W., Sinclair D.A.
    Mol. Cell. Biol. 33:1487-1502(2013) [PubMed] [Europe PMC] [Abstract]
• intronic transcription regulatory region DNA binding Source: RGDInferred from sequence orthologyⁱ
  • "Kras(G12D) and Nkx2-1 haploinsufficiency induce mucinous adenocarcinoma of the lung."
    Maeda Y., Tsuchiya T., Hao H., Tompkins D.H., Xu Y., Mucenski M.L., Du L., Keiser A.R., Fukazawa T., Naomoto Y., Nagayasu T., Whitsett J.A.
    J. Clin. Invest. 122:4388-4400(2012) [PubMed] [Europe PMC] [Abstract]
• intronic transcription regulatory region sequence-specific DNA binding Source: UniProtKB
• protein homodimerization activity Source: CAFAInferred from mutant phenotypeⁱ
  • "Structural and functional properties of the N transcriptional activation domain of thyroid transcription factor-1: similarities with the acidic activation domains."
    Tell G., Perrone L., Fabbro D., Pellizzari L., Pucillo C., De Felice M., Acquaviva R., Formisano S., Damante G.
    Biochem. J. 329:395-403(1998) [PubMed] [Europe PMC] [Abstract]
• RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: UniProtKB
• RNA polymerase II regulatory region DNA binding Source: RGDInferred from sequence orthologyⁱ
  • "Kras(G12D) and Nkx2-1 haploinsufficiency induce mucinous adenocarcinoma of the lung."
    Maeda Y., Tsuchiya T., Hao H., Tompkins D.H., Xu Y., Mucenski M.L., Du L., Keiser A.R., Fukazawa T., Naomoto Y., Nagayasu T., Whitsett J.A.
    J. Clin. Invest. 122:4388-4400(2012) [PubMed] [Europe PMC] [Abstract]
• RNA polymerase II regulatory region sequence-specific DNA binding Source: NTNU_SBInferred from direct assayⁱ
  • Ref.1

    "Thyroid nuclear factor 1 (TTF-1) contains a homeodomain and displays a novel DNA binding specificity."
    Guazzi S., Price M., de Felice M., Damante G., Mattei M.-G., di Lauro R.
    EMBO J. 9:3631-3639(1990) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
• sequence-specific DNA binding Source: RGDInferred from direct assayⁱ
  • "Conformational stability and DNA binding energetics of the rat thyroid transcription factor 1 homeodomain."
    Del Vecchio P., Carullo P., Barone G., Pagano B., Graziano G., Iannetti A., Acquaviva R., Leonardi A., Formisano S.
    Proteins 70:748-760(2008) [PubMed] [Europe PMC] [Abstract]
• TBP-class protein binding Source: CAFA <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • "Structural and functional properties of the N transcriptional activation domain of thyroid transcription factor-1: similarities with the acidic activation domains."
    Tell G., Perrone L., Fabbro D., Pellizzari L., Pucillo C., De Felice M., Acquaviva R., Formisano S., Damante G.
    Biochem. J. 329:395-403(1998) [PubMed] [Europe PMC] [Abstract]
• transcription regulatory region DNA binding Source: RGDInferred from sequence orthologyⁱ
  • "NKX2.1 regulates transcription of the gene for human bone morphogenetic protein-4 in lung epithelial cells."
    Zhu N.L., Li C., Xiao J., Minoo P.
    Gene 327:25-36(2004) [PubMed] [Europe PMC] [Abstract]
  • "Functional study of the human thyroid peroxidase gene promoter."
    Abramowicz M.J., Vassart G., Christophe D.
    Eur. J. Biochem. 203:467-473(1992) [PubMed] [Europe PMC] [Abstract]
  • "CAATT/enhancer-binding proteins alpha and delta interact with NKX2-1 to synergistically activate mouse secretoglobin 3A2 gene expression."
    Tomita T., Kido T., Kurotani R., Iemura S., Sterneck E., Natsume T., Vinson C., Kimura S.
    J. Biol. Chem. 283:25617-25627(2008) [PubMed] [Europe PMC] [Abstract]
  • "A germline mutation (A339V) in thyroid transcription factor-1 (TITF-1/NKX2.1) in patients with multinodular goiter and papillary thyroid carcinoma."
    Ngan E.S., Lang B.H., Liu T., Shum C.K., So M.T., Lau D.K., Leon T.Y., Cherny S.S., Tsai S.Y., Lo C.Y., Khoo U.S., Tam P.K., Garcia-Barcelo M.M.
    J. Natl. Cancer Inst. 101:162-175(2009) [PubMed] [Europe PMC] [Abstract]
  • "Upstream enhancer activity in the human surfactant protein B gene is mediated by thyroid transcription factor 1."
    Yan C., Sever Z., Whitsett J.A.
    J. Biol. Chem. 270:24852-24857(1995) [PubMed] [Europe PMC] [Abstract]

GO - Biological processⁱ

• anatomical structure formation involved in morphogenesis Source: RGDInferred from sequence orthologyⁱ
  • "Multiple dose-dependent roles for Sox2 in the patterning and differentiation of anterior foregut endoderm."
    Que J., Okubo T., Goldenring J.R., Nam K.T., Kurotani R., Morrisey E.E., Taranova O., Pevny L.H., Hogan B.L.
    Development 134:2521-2531(2007) [PubMed] [Europe PMC] [Abstract]
• animal organ morphogenesis Source: RGDInferred from sequence orthologyⁱ
  • "The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary."
    Kimura S., Hara Y., Pineau T., Fernandez-Salguero P., Fox C.H., Ward J.M., Gonzalez F.J.
    Genes Dev. 10:60-69(1996) [PubMed] [Europe PMC] [Abstract]
• axon guidance Source: RGDInferred from sequence orthologyⁱ
  • "Patterning of the basal telencephalon and hypothalamus is essential for guidance of cortical projections."
    Marin O., Baker J., Puelles L., Rubenstein J.L.
    Development 129:761-773(2002) [PubMed] [Europe PMC] [Abstract]
• brain development Source: RGDInferred from sequence orthologyⁱ
  • "Mutations in TITF-1 are associated with benign hereditary chorea."
    Breedveld G.J., van Dongen J.W.F., Danesino C., Guala A., Percy A.K., Dure L.S., Harper P., Lazarou L.P., van der Linde H., Joosse M., Grueters A., MacDonald M.E., de Vries B.B.A., Arts W.F.M., Oostra B.A., Krude H., Heutink P.
    Hum. Mol. Genet. 11:971-979(2002) [PubMed] [Europe PMC] [Abstract]
  • "Combinatorial function of the homeodomain proteins Nkx2.1 and Gsh2 in ventral telencephalic patterning."
    Corbin J.G., Rutlin M., Gaiano N., Fishell G.
    Development 130:4895-4906(2003) [PubMed] [Europe PMC] [Abstract]
  • "The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary."
    Kimura S., Hara Y., Pineau T., Fernandez-Salguero P., Fox C.H., Ward J.M., Gonzalez F.J.
    Genes Dev. 10:60-69(1996) [PubMed] [Europe PMC] [Abstract]
• cell differentiation Source: GO_Central <p>Inferred from Biological aspect of Ancestor</p> <p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#iba">GO evidence code guide</a></p> Inferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• cellular response to leptin stimulus Source: RGD <p>Inferred from Expression Pattern</p> <p>Covers cases where the annotation is inferred from the timing or location of expression of a gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#iep">GO evidence code guide</a></p> Inferred from expression patternⁱ
  • "Leptin promotes fetal lung maturity and upregulates SP-A expression in pulmonary alveoli type-II epithelial cells involving TTF-1 activation."
    Chen H., Zhang J.P., Huang H., Wang Z.H., Cheng R., Cai W.B.
    PLoS ONE 8:e69297-e69297(2013) [PubMed] [Europe PMC] [Abstract]
• cerebral cortex cell migration Source: RGDInferred from sequence orthologyⁱ
  • "Postmitotic Nkx2-1 controls the migration of telencephalic interneurons by direct repression of guidance receptors."
    Nobrega-Pereira S., Kessaris N., Du T., Kimura S., Anderson S.A., Marin O.
    Neuron 59:733-745(2008) [PubMed] [Europe PMC] [Abstract]
• cerebral cortex GABAergic interneuron differentiation Source: RGDInferred from sequence orthologyⁱ
  • "Origins of cortical interneuron subtypes."
    Xu Q., Cobos I., De La Cruz E., Rubenstein J.L., Anderson S.A.
    J. Neurosci. 24:2612-2622(2004) [PubMed] [Europe PMC] [Abstract]
  • "The requirement of Nkx2-1 in the temporal specification of cortical interneuron subtypes."
    Butt S.J., Sousa V.H., Fuccillo M.V., Hjerling-Leffler J., Miyoshi G., Kimura S., Fishell G.
    Neuron 59:722-732(2008) [PubMed] [Europe PMC] [Abstract]
• cerebral cortex neuron differentiation Source: RGDInferred from sequence orthologyⁱ
  • "NKX2.1 specifies cortical interneuron fate by activating Lhx6."
    Du T., Xu Q., Ocbina P.J., Anderson S.A.
    Development 135:1559-1567(2008) [PubMed] [Europe PMC] [Abstract]
• circadian rhythm Source: UniProtKBInferred from expression patternⁱ
  • Ref.4

    "Thyroid transcription factor 1, a homeodomain containing transcription factor, contributes to regulating periodic oscillations in GnRH gene expression."
    Matagne V., Kim J.G., Ryu B.J., Hur M.K., Kim M.S., Kim K., Park B.S., Damante G., Smiley G., Lee B.J., Ojeda S.R.
    J. Neuroendocrinol. 24:916-929(2012) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INDUCTION.
• club cell differentiation Source: RGDInferred from sequence orthologyⁱ
  • "GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo."
    Zhang Y., Rath N., Hannenhalli S., Wang Z., Cappola T., Kimura S., Atochina-Vasserman E., Lu M.M., Beers M.F., Morrisey E.E.
    Development 134:189-198(2007) [PubMed] [Europe PMC] [Abstract]
• developmental induction Source: RGDInferred from sequence orthologyⁱ
  • "Formation of Rathke's pouch requires dual induction from the diencephalon."
    Takuma N., Sheng H.Z., Furuta Y., Ward J.M., Sharma K., Hogan B.L., Pfaff S.L., Westphal H., Kimura S., Mahon K.A.
    Development 125:4835-4840(1998) [PubMed] [Europe PMC] [Abstract]
• development of primary female sexual characteristics Source: RGDInferred from expression patternⁱ
  • "TTF-1, a homeodomain gene required for diencephalic morphogenesis, is postnatally expressed in the neuroendocrine brain in a developmentally regulated and cell-specific fashion."
    Lee B.J., Cho G.J., Norgren R.B. Jr., Junier M.P., Hill D.F., Tapia V., Costa M.E., Ojeda S.R.
    Mol. Cell. Neurosci. 17:107-126(2001) [PubMed] [Europe PMC] [Abstract]
• embryonic lung development Source: RGDInferred from expression patternⁱ
  • "Leptin promotes fetal lung maturity and upregulates SP-A expression in pulmonary alveoli type-II epithelial cells involving TTF-1 activation."
    Chen H., Zhang J.P., Huang H., Wang Z.H., Cheng R., Cai W.B.
    PLoS ONE 8:e69297-e69297(2013) [PubMed] [Europe PMC] [Abstract]
• endoderm development Source: RGDInferred from sequence orthologyⁱ
  • "Defects in tracheoesophageal and lung morphogenesis in Nkx2.1(-/-) mouse embryos."
    Minoo P., Su G., Drum H., Bringas P., Kimura S.
    Dev. Biol. 209:60-71(1999) [PubMed] [Europe PMC] [Abstract]
  • "The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary."
    Kimura S., Hara Y., Pineau T., Fernandez-Salguero P., Fox C.H., Ward J.M., Gonzalez F.J.
    Genes Dev. 10:60-69(1996) [PubMed] [Europe PMC] [Abstract]
• epithelial tube branching involved in lung morphogenesis Source: RGDInferred from sequence orthologyⁱ
  • "Expression of thyroid transcription factor-1(TTF-1) in fetal and neonatal human lung."
    Stahlman M.T., Gray M.E., Whitsett J.A.
    J. Histochem. Cytochem. 44:673-678(1996) [PubMed] [Europe PMC] [Abstract]
• feeding behavior Source: RGDInferred from mutant phenotypeⁱ
  • "TTF-1, a homeodomain-containing transcription factor, regulates feeding behavior in the rat hypothalamus."
    Kim J.G., Nam-Goong I.S., Yun C.H., Jeong J.K., Kim E.S., Park J.J., Lee Y.C., Kim Y.I., Lee B.J.
    Biochem. Biophys. Res. Commun. 349:969-975(2006) [PubMed] [Europe PMC] [Abstract]
• forebrain development Source: RGDInferred from sequence orthologyⁱ
  • "PAX8, TITF1, and FOXE1 gene expression patterns during human development: new insights into human thyroid development and thyroid dysgenesis-associated malformations."
    Trueba S.S., Auge J., Mattei G., Etchevers H., Martinovic J., Czernichow P., Vekemans M., Polak M., Attie-Bitach T.
    J. Clin. Endocrinol. Metab. 90:455-462(2005) [PubMed] [Europe PMC] [Abstract]
• forebrain dorsal/ventral pattern formation Source: RGDInferred from sequence orthologyⁱ
  • "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."
    Sussel L., Marin O., Kimura S., Rubenstein J.L.
    Development 126:3359-3370(1999) [PubMed] [Europe PMC] [Abstract]
  • "Cell migration from the ganglionic eminences is required for the development of hippocampal GABAergic interneurons."
    Pleasure S.J., Anderson S., Hevner R., Bagri A., Marin O., Lowenstein D.H., Rubenstein J.L.
    Neuron 28:727-740(2000) [PubMed] [Europe PMC] [Abstract]
  • "Patterning of the basal telencephalon and hypothalamus is essential for guidance of cortical projections."
    Marin O., Baker J., Puelles L., Rubenstein J.L.
    Development 129:761-773(2002) [PubMed] [Europe PMC] [Abstract]
• forebrain neuron differentiation Source: RGDInferred from sequence orthologyⁱ
  • "Cell migration from the ganglionic eminences is required for the development of hippocampal GABAergic interneurons."
    Pleasure S.J., Anderson S., Hevner R., Bagri A., Marin O., Lowenstein D.H., Rubenstein J.L.
    Neuron 28:727-740(2000) [PubMed] [Europe PMC] [Abstract]
• forebrain neuron fate commitment Source: RGDInferred from sequence orthologyⁱ
  • "NKX2.1 specifies cortical interneuron fate by activating Lhx6."
    Du T., Xu Q., Ocbina P.J., Anderson S.A.
    Development 135:1559-1567(2008) [PubMed] [Europe PMC] [Abstract]
• globus pallidus development Source: RGDInferred from sequence orthologyⁱ
  • "Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency."
    Krude H., Schuetz B., Biebermann H., von Moers A., Schnabel D., Neitzel H., Toennies H., Weise D., Lafferty A., Schwarz S., DeFelice M., von Deimling A., van Landeghem F., DiLauro R., Grueters A.
    J. Clin. Invest. 109:475-480(2002) [PubMed] [Europe PMC] [Abstract]
  • "The progenitor zone of the ventral medial ganglionic eminence requires Nkx2-1 to generate most of the globus pallidus but few neocortical interneurons."
    Flandin P., Kimura S., Rubenstein J.L.
    J. Neurosci. 30:2812-2823(2010) [PubMed] [Europe PMC] [Abstract]
• hippocampus development Source: RGDInferred from sequence orthologyⁱ
  • "Cell migration from the ganglionic eminences is required for the development of hippocampal GABAergic interneurons."
    Pleasure S.J., Anderson S., Hevner R., Bagri A., Marin O., Lowenstein D.H., Rubenstein J.L.
    Neuron 28:727-740(2000) [PubMed] [Europe PMC] [Abstract]
• hyperosmotic salinity response Source: RGDInferred from direct assayⁱ
  • "Thyroid transcription factor-1 exhibits osmosensitive transcription in brain-derived cell lines."
    Kim J.G., Bae K.D., Yun C.H., Im H.L., Park J.W., Nam-Goong I.S., Kim Y.I., Lee B.J.
    Biochem. Biophys. Res. Commun. 370:468-472(2008) [PubMed] [Europe PMC] [Abstract]
• Leydig cell differentiation Source: RGDInferred from sequence orthologyⁱ
  • "Pituitary hormones are not required for sexual differentiation of male mice: phenotype of the T/ebp/Nkx2.1 null mutant mice."
    Pakarinen P., Kimura S., El-Gehani F., Pelliniemi L.J., Huhtaniemi I.
    Endocrinology 143:4477-4482(2002) [PubMed] [Europe PMC] [Abstract]
• locomotory behavior Source: RGDInferred from sequence orthologyⁱ
  • "Partial deficiency of thyroid transcription factor 1 produces predominantly neurological defects in humans and mice."
    Pohlenz J., Dumitrescu A., Zundel D., Martine U., Schoenberger W., Koo E., Weiss R.E., Cohen R.N., Kimura S., Refetoff S.
    J. Clin. Invest. 109:469-473(2002) [PubMed] [Europe PMC] [Abstract]
• lung development Source: RGDInferred from sequence orthologyⁱ
  • "Inhibition of distal lung morphogenesis in Nkx2.1(-/-) embryos."
    Yuan B., Li C., Kimura S., Engelhardt R.T., Smith B.R., Minoo P.
    Dev. Dyn. 217:180-190(2000) [PubMed] [Europe PMC] [Abstract]
  • "TTF-1 phosphorylation is required for peripheral lung morphogenesis, perinatal survival, and tissue-specific gene expression."
    DeFelice M., Silberschmidt D., DiLauro R., Xu Y., Wert S.E., Weaver T.E., Bachurski C.J., Clark J.C., Whitsett J.A.
    J. Biol. Chem. 278:35574-35583(2003) [PubMed] [Europe PMC] [Abstract]
  • "PAX8, TITF1, and FOXE1 gene expression patterns during human development: new insights into human thyroid development and thyroid dysgenesis-associated malformations."
    Trueba S.S., Auge J., Mattei G., Etchevers H., Martinovic J., Czernichow P., Vekemans M., Polak M., Attie-Bitach T.
    J. Clin. Endocrinol. Metab. 90:455-462(2005) [PubMed] [Europe PMC] [Abstract]
  • "Thyroid transcription factor in differentiating type II cells: regulation, isoforms, and target genes."
    Kolla V., Gonzales L.W., Gonzales J., Wang P., Angampalli S., Feinstein S.I., Ballard P.L.
    Am. J. Respir. Cell Mol. Biol. 36:213-225(2007) [PubMed] [Europe PMC] [Abstract]
  • "Regulation of lung endoderm progenitor cell behavior by miR302/367."
    Tian Y., Zhang Y., Hurd L., Hannenhalli S., Liu F., Lu M.M., Morrisey E.E.
    Development 138:1235-1245(2011) [PubMed] [Europe PMC] [Abstract]
• lung saccule development Source: RGDInferred from sequence orthologyⁱ
  • "GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo."
    Zhang Y., Rath N., Hannenhalli S., Wang Z., Cappola T., Kimura S., Atochina-Vasserman E., Lu M.M., Beers M.F., Morrisey E.E.
    Development 134:189-198(2007) [PubMed] [Europe PMC] [Abstract]
• negative regulation of cell migration Source: RGDInferred from sequence orthologyⁱ
  • "Thyroid transcription factor-1 inhibits transforming growth factor-beta-mediated epithelial-to-mesenchymal transition in lung adenocarcinoma cells."
    Saito R.A., Watabe T., Horiguchi K., Kohyama T., Saitoh M., Nagase T., Miyazono K.
    Cancer Res. 69:2783-2791(2009) [PubMed] [Europe PMC] [Abstract]
• negative regulation of epithelial to mesenchymal transition Source: RGDInferred from sequence orthologyⁱ
  • "Thyroid transcription factor-1 inhibits transforming growth factor-beta-mediated epithelial-to-mesenchymal transition in lung adenocarcinoma cells."
    Saito R.A., Watabe T., Horiguchi K., Kohyama T., Saitoh M., Nagase T., Miyazono K.
    Cancer Res. 69:2783-2791(2009) [PubMed] [Europe PMC] [Abstract]
• negative regulation of transcription, DNA-templated Source: UniProtKB
• negative regulation of transcription by RNA polymerase II Source: RGDInferred from sequence orthologyⁱ
  • "Postmitotic Nkx2-1 controls the migration of telencephalic interneurons by direct repression of guidance receptors."
    Nobrega-Pereira S., Kessaris N., Du T., Kimura S., Anderson S.A., Marin O.
    Neuron 59:733-745(2008) [PubMed] [Europe PMC] [Abstract]
  • "Kras(G12D) and Nkx2-1 haploinsufficiency induce mucinous adenocarcinoma of the lung."
    Maeda Y., Tsuchiya T., Hao H., Tompkins D.H., Xu Y., Mucenski M.L., Du L., Keiser A.R., Fukazawa T., Naomoto Y., Nagayasu T., Whitsett J.A.
    J. Clin. Invest. 122:4388-4400(2012) [PubMed] [Europe PMC] [Abstract]
• negative regulation of transforming growth factor beta receptor signaling pathway Source: RGDInferred from sequence orthologyⁱ
  • "Thyroid transcription factor-1 inhibits transforming growth factor-beta-mediated epithelial-to-mesenchymal transition in lung adenocarcinoma cells."
    Saito R.A., Watabe T., Horiguchi K., Kohyama T., Saitoh M., Nagase T., Miyazono K.
    Cancer Res. 69:2783-2791(2009) [PubMed] [Europe PMC] [Abstract]
• neuron fate commitment Source: RGDInferred from sequence orthologyⁱ
  • "The requirement of Nkx2-1 in the temporal specification of cortical interneuron subtypes."
    Butt S.J., Sousa V.H., Fuccillo M.V., Hjerling-Leffler J., Miyoshi G., Kimura S., Fishell G.
    Neuron 59:722-732(2008) [PubMed] [Europe PMC] [Abstract]
  • "The progenitor zone of the ventral medial ganglionic eminence requires Nkx2-1 to generate most of the globus pallidus but few neocortical interneurons."
    Flandin P., Kimura S., Rubenstein J.L.
    J. Neurosci. 30:2812-2823(2010) [PubMed] [Europe PMC] [Abstract]
• neuron migration Source: RGDInferred from sequence orthologyⁱ
  • "Dlx2 progenitor migration in wild type and Nkx2.1 mutant telencephalon."
    Nery S., Corbin J.G., Fishell G.
    Cereb. Cortex 13:895-903(2003) [PubMed] [Europe PMC] [Abstract]
• oligodendrocyte differentiation Source: RGDInferred from sequence orthologyⁱ
  • "Sonic hedgehog contributes to oligodendrocyte specification in the mammalian forebrain."
    Nery S., Wichterle H., Fishell G.
    Development 128:527-540(2001) [PubMed] [Europe PMC] [Abstract]
  • "Hedgehog-dependent oligodendrocyte lineage specification in the telencephalon."
    Tekki-Kessaris N., Woodruff R., Hall A.C., Gaffield W., Kimura S., Stiles C.D., Rowitch D.H., Richardson W.D.
    Development 128:2545-2554(2001) [PubMed] [Europe PMC] [Abstract]
• pattern specification process Source: RGDInferred from sequence orthologyⁱ
  • "Combinatorial function of the homeodomain proteins Nkx2.1 and Gsh2 in ventral telencephalic patterning."
    Corbin J.G., Rutlin M., Gaiano N., Fishell G.
    Development 130:4895-4906(2003) [PubMed] [Europe PMC] [Abstract]
• phospholipid metabolic process Source: RGDInferred from sequence orthologyⁱ
  • "GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo."
    Zhang Y., Rath N., Hannenhalli S., Wang Z., Cappola T., Kimura S., Atochina-Vasserman E., Lu M.M., Beers M.F., Morrisey E.E.
    Development 134:189-198(2007) [PubMed] [Europe PMC] [Abstract]
• pituitary gland development Source: RGDInferred from sequence orthologyⁱ
  • "Formation of Rathke's pouch requires dual induction from the diencephalon."
    Takuma N., Sheng H.Z., Furuta Y., Ward J.M., Sharma K., Hogan B.L., Pfaff S.L., Westphal H., Kimura S., Mahon K.A.
    Development 125:4835-4840(1998) [PubMed] [Europe PMC] [Abstract]
• positive regulation of circadian rhythm Source: UniProtKB
• positive regulation of gene expression Source: RGDInferred from sequence orthologyⁱ
  • "Thyroid transcription factor in differentiating type II cells: regulation, isoforms, and target genes."
    Kolla V., Gonzales L.W., Gonzales J., Wang P., Angampalli S., Feinstein S.I., Ballard P.L.
    Am. J. Respir. Cell Mol. Biol. 36:213-225(2007) [PubMed] [Europe PMC] [Abstract]
• positive regulation of transcription, DNA-templated Source: UniProtKBInferred from direct assayⁱ
  • "The paired domain-containing factor Pax8 and the homeodomain-containing factor TTF-1 directly interact and synergistically activate transcription."
    Di Palma T., Nitsch R., Mascia A., Nitsch L., Di Lauro R., Zannini M.
    J. Biol. Chem. 278:3395-3402(2003) [PubMed] [Europe PMC] [Abstract]
  • Ref.4

    "Thyroid transcription factor 1, a homeodomain containing transcription factor, contributes to regulating periodic oscillations in GnRH gene expression."
    Matagne V., Kim J.G., Ryu B.J., Hur M.K., Kim M.S., Kim K., Park B.S., Damante G., Smiley G., Lee B.J., Ojeda S.R.
    J. Neuroendocrinol. 24:916-929(2012) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INDUCTION.
• positive regulation of transcription by RNA polymerase II Source: MGIInferred from direct assayⁱ
  • "Expression and function of B7-1 and B7-2 in hapten-induced contact sensitivity."
    Reiser H., Schneeberger E.E.
    Eur. J. Immunol. 26:880-885(1996) [PubMed] [Europe PMC] [Abstract]
  • "TTF-2, a new forkhead protein, shows a temporal expression in the developing thyroid which is consistent with a role in controlling the onset of differentiation."
    Zannini M., Avantaggiato V., Biffali E., Arnone M.I., Sato K., Pischetola M., Taylor B.A., Phillips S.J., Simeone A., Di Lauro R.
    EMBO J. 16:3185-3197(1997) [PubMed] [Europe PMC] [Abstract]
• regulation of blood volume by renin-angiotensin Source: RGDInferred from direct assayⁱ
  • "TTF-1, a homeodomain-containing transcription factor, participates in the control of body fluid homeostasis by regulating angiotensinogen gene transcription in the rat subfornical organ."
    Son Y.J., Hur M.K., Ryu B.J., Park S.K., Damante G., D'Elia A.V., Costa M.E., Ojeda S.R., Lee B.J.
    J. Biol. Chem. 278:27043-27052(2003) [PubMed] [Europe PMC] [Abstract]
• regulation of transcription, DNA-templated Source: RGDInferred from direct assayⁱ
  • "Thyroid transcription factor-1 exhibits osmosensitive transcription in brain-derived cell lines."
    Kim J.G., Bae K.D., Yun C.H., Im H.L., Park J.W., Nam-Goong I.S., Kim Y.I., Lee B.J.
    Biochem. Biophys. Res. Commun. 370:468-472(2008) [PubMed] [Europe PMC] [Abstract]
• regulation of transcription by RNA polymerase II Source: RGDInferred from sequence orthologyⁱ
  • "CAATT/enhancer-binding proteins alpha and delta interact with NKX2-1 to synergistically activate mouse secretoglobin 3A2 gene expression."
    Tomita T., Kido T., Kurotani R., Iemura S., Sterneck E., Natsume T., Vinson C., Kimura S.
    J. Biol. Chem. 283:25617-25627(2008) [PubMed] [Europe PMC] [Abstract]
• response to ethanol Source: RGDInferred from expression patternⁱ
  • "Prepubertal chronic ethanol administration alters TTF-1 and Oct-2 expression in the hypothalamus of female rats."
    Kim H.J., Sohn H.J., Ha M., Han J.Y., Kang S.S., Choi W.S., Cho G.J.
    Brain Res. Mol. Brain Res. 136:262-266(2005) [PubMed] [Europe PMC] [Abstract]
• response to hormone Source: RGDInferred from sequence orthologyⁱ
  • "Thyroid transcription factor in differentiating type II cells: regulation, isoforms, and target genes."
    Kolla V., Gonzales L.W., Gonzales J., Wang P., Angampalli S., Feinstein S.I., Ballard P.L.
    Am. J. Respir. Cell Mol. Biol. 36:213-225(2007) [PubMed] [Europe PMC] [Abstract]
• response to lipopolysaccharide Source: RGDInferred from direct assayⁱ
  • "Bacterial lipopolysaccharide stimulates the thyrotropin-dependent thyroglobulin gene expression at the transcriptional level by involving the transcription factors thyroid transcription factor-1 and paired box domain transcription factor 8."
    Velez M.L., Costamagna E., Kimura E.T., Fozzatti L., Pellizas C.G., Montesinos M.M., Lucero A.M., Coleoni A.H., Santisteban P., Masini-Repiso A.M.
    Endocrinology 147:3260-3275(2006) [PubMed] [Europe PMC] [Abstract]
• telencephalon cell migration Source: RGDInferred from sequence orthologyⁱ
  • "Postmitotic Nkx2-1 controls the migration of telencephalic interneurons by direct repression of guidance receptors."
    Nobrega-Pereira S., Kessaris N., Du T., Kimura S., Anderson S.A., Marin O.
    Neuron 59:733-745(2008) [PubMed] [Europe PMC] [Abstract]
  • "The progenitor zone of the ventral medial ganglionic eminence requires Nkx2-1 to generate most of the globus pallidus but few neocortical interneurons."
    Flandin P., Kimura S., Rubenstein J.L.
    J. Neurosci. 30:2812-2823(2010) [PubMed] [Europe PMC] [Abstract]
• telencephalon development Source: RGDInferred from sequence orthologyⁱ
  • "The requirement of Nkx2-1 in the temporal specification of cortical interneuron subtypes."
    Butt S.J., Sousa V.H., Fuccillo M.V., Hjerling-Leffler J., Miyoshi G., Kimura S., Fishell G.
    Neuron 59:722-732(2008) [PubMed] [Europe PMC] [Abstract]
• thyroid gland development Source: RGDInferred from sequence orthologyⁱ
  • "Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency."
    Krude H., Schuetz B., Biebermann H., von Moers A., Schnabel D., Neitzel H., Toennies H., Weise D., Lafferty A., Schwarz S., DeFelice M., von Deimling A., van Landeghem F., DiLauro R., Grueters A.
    J. Clin. Invest. 109:475-480(2002) [PubMed] [Europe PMC] [Abstract]
  • "PAX8, TITF1, and FOXE1 gene expression patterns during human development: new insights into human thyroid development and thyroid dysgenesis-associated malformations."
    Trueba S.S., Auge J., Mattei G., Etchevers H., Martinovic J., Czernichow P., Vekemans M., Polak M., Attie-Bitach T.
    J. Clin. Endocrinol. Metab. 90:455-462(2005) [PubMed] [Europe PMC] [Abstract]
  • "An integrated regulatory network controlling survival and migration in thyroid organogenesis."
    Parlato R., Rosica A., Rodriguez-Mallon A., Affuso A., Postiglione M.P., Arra C., Mansouri A., Kimura S., Di Lauro R., De Felice M.
    Dev. Biol. 276:464-475(2004) [PubMed] [Europe PMC] [Abstract]
  • "A mouse model demonstrates a multigenic origin of congenital hypothyroidism."
    Amendola E., De Luca P., Macchia P.E., Terracciano D., Rosica A., Chiappetta G., Kimura S., Mansouri A., Affuso A., Arra C., Macchia V., Di Lauro R., De Felice M.
    Endocrinology 146:5038-5047(2005) [PubMed] [Europe PMC] [Abstract]
  • "Thyroid-specific enhancer-binding protein/NKX2.1 is required for the maintenance of ordered architecture and function of the differentiated thyroid."
    Kusakabe T., Kawaguchi A., Hoshi N., Kawaguchi R., Hoshi S., Kimura S.
    Mol. Endocrinol. 20:1796-1809(2006) [PubMed] [Europe PMC] [Abstract]
• type II pneumocyte differentiation Source: RGDInferred from sequence orthologyⁱ
  • "GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo."
    Zhang Y., Rath N., Hannenhalli S., Wang Z., Cappola T., Kimura S., Atochina-Vasserman E., Lu M.M., Beers M.F., Morrisey E.E.
    Development 134:189-198(2007) [PubMed] [Europe PMC] [Abstract]

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

Keywords - Cellular componentⁱ

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Amino acid modifications

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationⁱ

Keywords - PTMⁱ

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityⁱ

<p>This subsection of the ‘Expression’ section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductionⁱ

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

GO - Molecular functionⁱ

• enzyme binding Source: RGDInferred from sequence orthologyⁱ
  • "A high-confidence interaction map identifies SIRT1 as a mediator of acetylation of USP22 and the SAGA coactivator complex."
    Armour S.M., Bennett E.J., Braun C.R., Zhang X.Y., McMahon S.B., Gygi S.P., Harper J.W., Sinclair D.A.
    Mol. Cell. Biol. 33:1487-1502(2013) [PubMed] [Europe PMC] [Abstract]
• protein homodimerization activity Source: CAFAInferred from mutant phenotypeⁱ
  • "Structural and functional properties of the N transcriptional activation domain of thyroid transcription factor-1: similarities with the acidic activation domains."
    Tell G., Perrone L., Fabbro D., Pellizzari L., Pucillo C., De Felice M., Acquaviva R., Formisano S., Damante G.
    Biochem. J. 329:395-403(1998) [PubMed] [Europe PMC] [Abstract]
• TBP-class protein binding Source: CAFAInferred from physical interactionⁱ
  • "Structural and functional properties of the N transcriptional activation domain of thyroid transcription factor-1: similarities with the acidic activation domains."
    Tell G., Perrone L., Fabbro D., Pellizzari L., Pucillo C., De Felice M., Acquaviva R., Formisano S., Damante G.
    Biochem. J. 329:395-403(1998) [PubMed] [Europe PMC] [Abstract]

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

Compositional bias

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)ⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

        10         20         30         40         50
MSMSPKHTTP FSVSDILSPL EESYKKVGME GGGLGAPLAA YRQGQAAPPA 
        60         70         80         90        100
AAMQQHAVGH HGAVTAAYHM TAAGVPQLSH SAVGGYCNGN LGNMSELPPY 
       110        120        130        140        150
QDTMRNSASG PGWYGANPDP RFPAISRFMG PASGMNMSGM GGLGSLGDVS 
       160        170        180        190        200
KNMAPLPSAP RRKRRVLFSQ AQVYELERRF KQQKYLSAPE REHLASMIHL 
       210        220        230        240        250
TPTQVKIWFQ NHRYKMKRQA KDKAAQQQLQ QDSGGGGGGG GGAGCPQQQQ 
       260        270        280        290        300
AQQQSPRRVA VPVLVKDGKP CQAGAPAPGA ASLQGHAQQQ AQQQAQAAQA 
       310        320        330        340        350
AAAAISVGSG GAGLGAHPGH QPGSAGQSPD LAHHAASPAA LQGQVSSLSH 
       360        370 
LNSSGSDYGA MSCSTLLYGR TW                               

Sequence databases

Genome annotation databases

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 100% Identity
• 90% Identity
• 50% Identity

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Miscellaneous databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

Keywords - Technical termⁱ

Documents

1. PDB cross-references
   Index of Protein Data Bank (PDB) cross-references
2. SIMILARITY comments
   Index of protein domains and families