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 sequence-specific DNA 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%2Dgo%2Devidence%2Dcodes#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%2Dgo%2Devidence%2Dcodes#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_SBInferred from mutant phenotypeⁱ
  • "Nuclear factor of activated T cells regulates transcription of the surfactant protein D gene (Sftpd) via direct interaction with thyroid transcription factor-1 in lung epithelial cells."
    Dave V., Childs T., Whitsett J.A.
    J Biol Chem 279:34578-34588(2004) [PubMed] [Europe PMC] [Abstract]
• 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: RGD
• enzyme binding Source: RGD
• identical protein binding 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]
• intronic transcription regulatory region sequence-specific DNA binding Source: UniProtKB
• RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: UniProtKB
• RNA polymerase II transcription 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%2Dgo%2Devidence%2Dcodes#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 sequence-specific DNA binding Source: RGD

GO - Biological processⁱ

• anatomical structure formation involved in morphogenesis Source: RGD
• animal organ morphogenesis Source: RGD
• axon guidance Source: RGD
• brain development Source: RGD
• 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%2Dgo%2Devidence%2Dcodes#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 Bioinform 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%2Dgo%2Devidence%2Dcodes#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: RGD
• cerebral cortex GABAergic interneuron differentiation Source: RGD
• cerebral cortex neuron differentiation Source: RGD
• 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: RGD
• developmental induction Source: RGD
• 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: RGD
• epithelial tube branching involved in lung morphogenesis Source: RGD
• 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: RGD
• forebrain dorsal/ventral pattern formation Source: RGD
• forebrain neuron differentiation Source: RGD
• forebrain neuron fate commitment Source: RGD
• globus pallidus development Source: RGD
• hippocampus development Source: RGD
• 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: RGD
• locomotory behavior Source: RGD
• lung development Source: RGD
• lung saccule development Source: RGD
• negative regulation of cell migration Source: RGD
• negative regulation of epithelial to mesenchymal transition Source: RGD
• negative regulation of transcription, DNA-templated Source: UniProtKB
• negative regulation of transcription by RNA polymerase II Source: RGD
• negative regulation of transforming growth factor beta receptor signaling pathway Source: RGD
• neuron fate commitment Source: RGD
• neuron migration Source: RGD
• oligodendrocyte differentiation Source: RGD
• pattern specification process Source: RGD
• phospholipid metabolic process Source: RGD
• pituitary gland development Source: RGD
• positive regulation of circadian rhythm Source: UniProtKB
• positive regulation of gene expression Source: RGD
• 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: RGD
• 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: RGD
• 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: RGD
• telencephalon development Source: RGD
• thyroid gland development Source: RGD
• type II pneumocyte differentiation Source: RGD

<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%5Fprocessing%5Fsection">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%5Fsection">'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%5Fsection">'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%5Fsection">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="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

GO - Molecular functionⁱ

• enzyme binding Source: RGD
• identical protein binding 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%5Flength">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%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">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