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Homeobox protein Nkx-2.1 (Thyroid nuclear factor 1) (Thyroid transcription factor 1) (TTF-1) (Thyroid-specific enhancer-binding protein) (T/EBP)

 NKX21_MOUSE             Reviewed;         372 AA.
P50220;
01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
01-OCT-1996, sequence version 1.
07-NOV-2018, entry version 153.
RecName: Full=Homeobox protein Nkx-2.1;
AltName: Full=Thyroid nuclear factor 1;
AltName: Full=Thyroid transcription factor 1;
Short=TTF-1;
AltName: Full=Thyroid-specific enhancer-binding protein;
Short=T/EBP;
Name=Nkx2-1 {ECO:0000312|MGI:MGI:108067};
Synonyms=Nkx-2.1, Titf1, Ttf1;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
STRAIN=129/Sv; TISSUE=Liver;
PubMed=7711079; DOI=10.1016/0167-4781(95)00033-D;
Oguchi H., Pan Y.-T., Kimura S.;
"The complete nucleotide sequence of the mouse thyroid-specific
enhancer-binding protein (T/EBP) gene: extensive identity of the
deduced amino acid sequence with the human protein.";
Biochim. Biophys. Acta 1261:304-306(1995).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=C57BL/6J; TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[3]
FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
PubMed=22955271; DOI=10.1074/jbc.M112.408401;
Varma S., Cao Y., Tagne J.B., Lakshminarayanan M., Li J.,
Friedman T.B., Morell R.J., Warburton D., Kotton D.N., Ramirez M.I.;
"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. 287:37282-37295(2012).
[4]
FUNCTION.
PubMed=22356123; DOI=10.1111/j.1365-2826.2012.02302.x;
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.;
"Thyroid transcription factor 1, a homeodomain containing
transcription factor, contributes to regulating periodic oscillations
in GnRH gene expression.";
J. Neuroendocrinol. 24:916-929(2012).
-!- FUNCTION: Transcription factor that binds and activates the
promoter of thyroid specific genes such as thyroglobulin,
thyroperoxidase, and thyrotropin receptor. Crucial in the
maintenance of the thyroid differentiation phenotype. May play a
role in lung development and surfactant homeostasis. Forms a
regulatory loop with GRHL2 that coordinates lung epithelial cell
morphogenesis and differentiation (PubMed:22955271). Activates the
transcription of GNRHR and plays a role in enhancing the circadian
oscillation of its gene expression. Represses the transcription of
the circadian transcriptional repressor NR1D1 (PubMed:22356123).
{ECO:0000250|UniProtKB:P23441, ECO:0000269|PubMed:22356123,
ECO:0000269|PubMed:22955271}.
-!- SUBUNIT: Interacts with WWTR1. {ECO:0000250|UniProtKB:P43699}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22955271}.
-!- TISSUE SPECIFICITY: Thyroid, lung and brain.
-!- DEVELOPMENTAL STAGE: Expressed in lung at least from to E9.5 to
adulthood. {ECO:0000269|PubMed:22955271}.
-!- PTM: Phosphorylated on serine residues by STK3/MST2.
{ECO:0000250}.
-!- SIMILARITY: Belongs to the NK-2 homeobox family. {ECO:0000305}.
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EMBL; U19755; AAA86100.1; -; Genomic_DNA.
EMBL; BC080868; AAH80868.1; -; mRNA.
CCDS; CCDS25922.1; -.
PIR; S53724; S53724.
RefSeq; NP_033411.3; NM_009385.3.
UniGene; Mm.89972; -.
ProteinModelPortal; P50220; -.
SMR; P50220; -.
BioGrid; 204207; 12.
IntAct; P50220; 1.
STRING; 10090.ENSMUSP00000001536; -.
iPTMnet; P50220; -.
PhosphoSitePlus; P50220; -.
MaxQB; P50220; -.
PaxDb; P50220; -.
PRIDE; P50220; -.
Ensembl; ENSMUST00000001536; ENSMUSP00000001536; ENSMUSG00000001496.
Ensembl; ENSMUST00000178477; ENSMUSP00000136103; ENSMUSG00000001496.
GeneID; 21869; -.
KEGG; mmu:21869; -.
UCSC; uc007npf.3; mouse.
CTD; 7080; -.
MGI; MGI:108067; Nkx2-1.
eggNOG; KOG0842; Eukaryota.
eggNOG; ENOG410XR21; LUCA.
GeneTree; ENSGT00910000144003; -.
HOGENOM; HOG000231923; -.
HOVERGEN; HBG006689; -.
InParanoid; P50220; -.
KO; K09342; -.
OMA; MGHNGTV; -.
OrthoDB; EOG091G0LZ2; -.
PhylomeDB; P50220; -.
TreeFam; TF351204; -.
PRO; PR:P50220; -.
Proteomes; UP000000589; Chromosome 12.
Bgee; ENSMUSG00000001496; Expressed in 80 organ(s), highest expression level in thyroid gland.
CleanEx; MM_NKX2-1; -.
CleanEx; MM_TTF1; -.
Genevisible; P50220; MM.
GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
GO; GO:0005634; C:nucleus; IDA:UniProtKB.
GO; GO:0005667; C:transcription factor complex; IDA:MGI.
GO; GO:0001047; F:core promoter binding; ISO:MGI.
GO; GO:0003677; F:DNA binding; ISO:MGI.
GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
GO; GO:0019899; F:enzyme binding; ISO:MGI.
GO; GO:0044213; F:intronic transcription regulatory region DNA binding; ISO:MGI.
GO; GO:0001161; F:intronic transcription regulatory region sequence-specific DNA binding; IDA:UniProtKB.
GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
GO; GO:0000980; F:RNA polymerase II distal enhancer sequence-specific DNA binding; IDA:UniProtKB.
GO; GO:0000978; F:RNA polymerase II proximal promoter sequence-specific DNA binding; IDA:UniProtKB.
GO; GO:0001012; F:RNA polymerase II regulatory region DNA binding; ISO:MGI.
GO; GO:0000977; F:RNA polymerase II regulatory region sequence-specific DNA binding; IDA:MGI.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
GO; GO:0017025; F:TBP-class protein binding; ISO:MGI.
GO; GO:0003705; F:transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding; IDA:MGI.
GO; GO:0008134; F:transcription factor binding; ISO:MGI.
GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:MGI.
GO; GO:0048646; P:anatomical structure formation involved in morphogenesis; IMP:MGI.
GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI.
GO; GO:0007411; P:axon guidance; IMP:MGI.
GO; GO:0007420; P:brain development; IMP:MGI.
GO; GO:0021795; P:cerebral cortex cell migration; IMP:MGI.
GO; GO:0021892; P:cerebral cortex GABAergic interneuron differentiation; IMP:MGI.
GO; GO:0021895; P:cerebral cortex neuron differentiation; IMP:MGI.
GO; GO:0060486; P:Clara cell differentiation; IGI:MGI.
GO; GO:0031128; P:developmental induction; IMP:MGI.
GO; GO:0007492; P:endoderm development; IMP:MGI.
GO; GO:0060441; P:epithelial tube branching involved in lung morphogenesis; IEA:Ensembl.
GO; GO:0007631; P:feeding behavior; ISO:MGI.
GO; GO:0021798; P:forebrain dorsal/ventral pattern formation; IMP:MGI.
GO; GO:0021879; P:forebrain neuron differentiation; IMP:MGI.
GO; GO:0021877; P:forebrain neuron fate commitment; IMP:MGI.
GO; GO:0021759; P:globus pallidus development; IMP:MGI.
GO; GO:0021766; P:hippocampus development; IMP:MGI.
GO; GO:0042538; P:hyperosmotic salinity response; ISO:MGI.
GO; GO:0033327; P:Leydig cell differentiation; IMP:MGI.
GO; GO:0007626; P:locomotory behavior; IMP:MGI.
GO; GO:0030324; P:lung development; IMP:MGI.
GO; GO:0060430; P:lung saccule development; IGI:MGI.
GO; GO:0030336; P:negative regulation of cell migration; ISO:MGI.
GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; ISO:MGI.
GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:MGI.
GO; GO:0048663; P:neuron fate commitment; IMP:MGI.
GO; GO:0001764; P:neuron migration; IMP:MGI.
GO; GO:0048709; P:oligodendrocyte differentiation; IGI:MGI.
GO; GO:0007389; P:pattern specification process; IGI:MGI.
GO; GO:0006644; P:phospholipid metabolic process; IGI:MGI.
GO; GO:0021983; P:pituitary gland development; IMP:MGI.
GO; GO:0042753; P:positive regulation of circadian rhythm; IMP:UniProtKB.
GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:0002016; P:regulation of blood volume by renin-angiotensin; ISO:MGI.
GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
GO; GO:0009725; P:response to hormone; IEA:Ensembl.
GO; GO:0032496; P:response to lipopolysaccharide; ISO:MGI.
GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
GO; GO:0022029; P:telencephalon cell migration; IMP:MGI.
GO; GO:0021537; P:telencephalon development; IMP:MGI.
GO; GO:0030878; P:thyroid gland development; IMP:MGI.
GO; GO:0060510; P:type II pneumocyte differentiation; IGI:MGI.
CDD; cd00086; homeodomain; 1.
InterPro; IPR009057; Homeobox-like_sf.
InterPro; IPR017970; Homeobox_CS.
InterPro; IPR001356; Homeobox_dom.
InterPro; IPR020479; Homeobox_metazoa.
Pfam; PF00046; Homeobox; 1.
PRINTS; PR00024; HOMEOBOX.
SMART; SM00389; HOX; 1.
SUPFAM; SSF46689; SSF46689; 1.
PROSITE; PS00027; HOMEOBOX_1; 1.
PROSITE; PS50071; HOMEOBOX_2; 1.
2: Evidence at transcript level;
Activator; Biological rhythms; Complete proteome; DNA-binding;
Homeobox; Nucleus; Phosphoprotein; Reference proteome; Repressor;
Transcription; Transcription regulation.
CHAIN 1 372 Homeobox protein Nkx-2.1.
/FTId=PRO_0000049344.
DNA_BIND 161 220 Homeobox. {ECO:0000255|PROSITE-
ProRule:PRU00108}.
COMPBIAS 234 244 Poly-Gly.
COMPBIAS 247 254 Poly-Gln.
COMPBIAS 295 304 Poly-Ala.
MOD_RES 255 255 Phosphoserine.
{ECO:0000250|UniProtKB:P23441}.
SEQUENCE 372 AA; 38570 MW; 377B5CE9B709412F CRC64;
MSMSPKHTTP FSVSDILSPL EESYKKVGME GGGLGAPLAA YRQGQAAPPA AAMQQHAVGH
HGAVTAAYHM TAAGVPQLSH SAVGGYCNGN LGNMSELPPY QDTMRNSASG PGWYGANPDP
RFPAISRFMG PASGMNMSGM GGLGSLGDVS KNMAPLPSAP RRKRRVLFSQ AQVYELERRF
KQQKYLSAPE REHLASMIHL TPTQVKIWFQ NHRYKMKRQA KDKAAQQQLQ QDSGGGGGGG
GGAGCPQQQQ AQQQSPRRVA VPVLVKDGKP CQAGAPAPGA ASLQSHAQQQ AQQQAQAAQA
AAAAISVGSG GAGLGAHPGH QPGSAGQSPD LAHHAASPAG LQGQVSSLSH LNSSGSDYGA
MSCSTLLYGR TW


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