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Protein

Homeobox protein Nkx-2.1

Gene

Nkx2-1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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).By similarity2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi161 – 22060HomeoboxPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. core promoter binding Source: UniProtKB
  2. DNA binding Source: MGI
  3. enzyme binding Source: MGI
  4. intronic transcription regulatory region sequence-specific DNA binding Source: UniProtKB
  5. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: MGI
  6. RNA polymerase II regulatory region sequence-specific DNA binding Source: MGI
  7. sequence-specific DNA binding Source: MGI
  8. sequence-specific DNA binding transcription factor activity Source: UniProtKB
  9. transcription factor binding Source: MGI
  10. transcription regulatory region DNA binding Source: MGI

GO - Biological processi

  1. anatomical structure formation involved in morphogenesis Source: MGI
  2. axon guidance Source: MGI
  3. brain development Source: MGI
  4. cerebral cortex cell migration Source: MGI
  5. cerebral cortex GABAergic interneuron differentiation Source: MGI
  6. cerebral cortex neuron differentiation Source: MGI
  7. Clara cell differentiation Source: MGI
  8. developmental induction Source: MGI
  9. endoderm development Source: MGI
  10. epithelial tube branching involved in lung morphogenesis Source: Ensembl
  11. forebrain dorsal/ventral pattern formation Source: MGI
  12. forebrain neuron differentiation Source: MGI
  13. forebrain neuron fate commitment Source: MGI
  14. globus pallidus development Source: MGI
  15. hippocampus development Source: MGI
  16. Leydig cell differentiation Source: MGI
  17. locomotory behavior Source: MGI
  18. lung development Source: MGI
  19. lung saccule development Source: MGI
  20. negative regulation of cell migration Source: MGI
  21. negative regulation of epithelial to mesenchymal transition Source: MGI
  22. negative regulation of transcription, DNA-templated Source: UniProtKB
  23. negative regulation of transcription from RNA polymerase II promoter Source: MGI
  24. negative regulation of transforming growth factor beta receptor signaling pathway Source: MGI
  25. neuron fate commitment Source: MGI
  26. neuron migration Source: MGI
  27. oligodendrocyte differentiation Source: MGI
  28. organ morphogenesis Source: MGI
  29. pattern specification process Source: MGI
  30. phospholipid metabolic process Source: MGI
  31. pituitary gland development Source: MGI
  32. positive regulation of circadian rhythm Source: UniProtKB
  33. positive regulation of gene expression Source: MGI
  34. positive regulation of transcription, DNA-templated Source: UniProtKB
  35. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  36. regulation of transcription, DNA-templated Source: MGI
  37. regulation of transcription from RNA polymerase II promoter Source: MGI
  38. response to hormone Source: Ensembl
  39. rhythmic process Source: UniProtKB-KW
  40. telencephalon cell migration Source: MGI
  41. telencephalon development Source: MGI
  42. thyroid gland development Source: MGI
  43. transcription from RNA polymerase II promoter Source: GOC
  44. Type II pneumocyte differentiation Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Biological rhythms, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Homeobox protein Nkx-2.1
Alternative name(s):
Thyroid nuclear factor 1
Thyroid transcription factor 1
Short name:
TTF-1
Thyroid-specific enhancer-binding protein
Short name:
T/EBP
Gene namesi
Name:Nkx2-1Imported
Synonyms:Nkx-2.1, Titf1, Ttf1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:108067. Nkx2-1.

Subcellular locationi

Nucleus 1 Publication

GO - Cellular componenti

  1. nucleoplasm Source: UniProtKB
  2. nucleus Source: UniProtKB
  3. transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 372372Homeobox protein Nkx-2.1PRO_0000049344Add
BLAST

Post-translational modificationi

Phosphorylated on serine residues by STK3/MST2.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP50220.
PRIDEiP50220.

PTM databases

PhosphoSiteiP50220.

Expressioni

Tissue specificityi

Thyroid, lung and brain.

Developmental stagei

Expressed in lung at least from to E9.5 to adulthood.1 Publication

Gene expression databases

BgeeiP50220.
CleanExiMM_NKX2-1.
MM_TTF1.
GenevestigatoriP50220.

Interactioni

Subunit structurei

Interacts with WWTR1.By similarity

Protein-protein interaction databases

BioGridi204207. 12 interactions.
STRINGi10090.ENSMUSP00000001536.

Structurei

3D structure databases

ProteinModelPortaliP50220.
SMRiP50220. Positions 161-227.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi234 – 24411Poly-GlyAdd
BLAST
Compositional biasi247 – 2548Poly-Gln
Compositional biasi295 – 30410Poly-Ala

Sequence similaritiesi

Belongs to the NK-2 homeobox family.Curated
Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiNOG328614.
GeneTreeiENSGT00760000118779.
HOGENOMiHOG000231923.
HOVERGENiHBG006689.
InParanoidiP50220.
KOiK09342.
OMAiYGTAMSC.
OrthoDBiEOG769ZK0.
PhylomeDBiP50220.
TreeFamiTF351204.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
[Graphical view]
PfamiPF00046. Homeobox. 1 hit.
[Graphical view]
PRINTSiPR00024. HOMEOBOX.
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P50220-1 [UniParc]FASTAAdd to basket

« Hide

        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 ASLQSHAQQQ AQQQAQAAQA
310 320 330 340 350
AAAAISVGSG GAGLGAHPGH QPGSAGQSPD LAHHAASPAG LQGQVSSLSH
360 370
LNSSGSDYGA MSCSTLLYGR TW
Length:372
Mass (Da):38,570
Last modified:October 1, 1996 - v1
Checksum:i377B5CE9B709412F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U19755 Genomic DNA. Translation: AAA86100.1.
BC080868 mRNA. Translation: AAH80868.1.
CCDSiCCDS25922.1.
PIRiS53724.
RefSeqiNP_001139670.1. NM_001146198.1.
NP_033411.3. NM_009385.3.
UniGeneiMm.89972.

Genome annotation databases

EnsembliENSMUST00000001536; ENSMUSP00000001536; ENSMUSG00000001496.
ENSMUST00000178477; ENSMUSP00000136103; ENSMUSG00000001496.
GeneIDi21869.
KEGGimmu:21869.
UCSCiuc007npf.3. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U19755 Genomic DNA. Translation: AAA86100.1.
BC080868 mRNA. Translation: AAH80868.1.
CCDSiCCDS25922.1.
PIRiS53724.
RefSeqiNP_001139670.1. NM_001146198.1.
NP_033411.3. NM_009385.3.
UniGeneiMm.89972.

3D structure databases

ProteinModelPortaliP50220.
SMRiP50220. Positions 161-227.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204207. 12 interactions.
STRINGi10090.ENSMUSP00000001536.

PTM databases

PhosphoSiteiP50220.

Proteomic databases

PaxDbiP50220.
PRIDEiP50220.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000001536; ENSMUSP00000001536; ENSMUSG00000001496.
ENSMUST00000178477; ENSMUSP00000136103; ENSMUSG00000001496.
GeneIDi21869.
KEGGimmu:21869.
UCSCiuc007npf.3. mouse.

Organism-specific databases

CTDi7080.
MGIiMGI:108067. Nkx2-1.

Phylogenomic databases

eggNOGiNOG328614.
GeneTreeiENSGT00760000118779.
HOGENOMiHOG000231923.
HOVERGENiHBG006689.
InParanoidiP50220.
KOiK09342.
OMAiYGTAMSC.
OrthoDBiEOG769ZK0.
PhylomeDBiP50220.
TreeFamiTF351204.

Miscellaneous databases

NextBioi301368.
PROiP50220.
SOURCEiSearch...

Gene expression databases

BgeeiP50220.
CleanExiMM_NKX2-1.
MM_TTF1.
GenevestigatoriP50220.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
[Graphical view]
PfamiPF00046. Homeobox. 1 hit.
[Graphical view]
PRINTSiPR00024. HOMEOBOX.
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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."
    Oguchi H., Pan Y.-T., Kimura S.
    Biochim. Biophys. Acta 1261:304-306(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: 129/Sv.
    Tissue: Liver.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6.
    Tissue: Brain.
  3. "The transcription factors Grainyhead-like 2 and NK2-homeobox 1 form a regulatory loop that coordinates lung epithelial cell morphogenesis and differentiation."
    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.
    J. Biol. Chem. 287:37282-37295(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
  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(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiNKX21_MOUSE
AccessioniPrimary (citable) accession number: P50220
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: March 4, 2015
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.