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Protein

Homeobox protein Nkx-2.1

Gene

NKX2-1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein 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. 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 (By similarity).By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi161 – 220HomeoboxPROSITE-ProRule annotationAdd BLAST60

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding, Repressor
Biological processBiological rhythms, Transcription, Transcription regulation

Enzyme and pathway databases

SIGNORiP43699

Names & Taxonomyi

Protein namesi
Recommended name:
Homeobox protein Nkx-2.1
Alternative name(s):
Homeobox protein NK-2 homolog A
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:NKX2A, TITF1, TTF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000136352.17
HGNCiHGNC:11825 NKX2-1
MIMi600635 gene
neXtProtiNX_P43699

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Chorea, hereditary benign (BHC)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare autosomal dominant movement disorder, defined by early onset in childhood, a stable or non-progressive course of chorea, and no mental deterioration. Chorea is characterized by involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement.
See also OMIM:118700
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_075209172Q → H in BHC; decrease in DNA-binding; no effect on transcription activation from thyroglobulin/TG, nor from pulmonary surfactant-associated protein C/SFTPC gene promoters. 1 Publication1
Natural variantiVAR_077542179R → P in BHC; unknown pathological significance. 1 Publication1
Natural variantiVAR_015188208W → L in BHC. 1 PublicationCorresponds to variant dbSNP:rs28936672Ensembl.1
Natural variantiVAR_075210208W → S in BHC; loss of transcription activation. 1 Publication1
Natural variantiVAR_015189213R → S in BHC. 1 PublicationCorresponds to variant dbSNP:rs28936671Ensembl.1
Choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction (CAHTP)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disorder that manifests in infancy with neurological disturbances, hypothyroidism, and respiratory problems. It is characterized by movement abnormalities beginning with muscular hypotonia followed by the development of chorea, athetosis, dystonia, ataxia, and dysarthria.
See also OMIM:610978
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073040203T → R in CAHTP. 1 Publication1
Natural variantiVAR_034906205V → F in CAHTP. 2 PublicationsCorresponds to variant dbSNP:rs137852692Ensembl.1
Thyroid cancer, non-medullary, 1 (NMTC1)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms.
See also OMIM:188550
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_075769339A → V in NMTC1; loss of transcription regulatory region DNA binding; decreased transcription factor activity, sequence-specific DNA binding; tested for the thyroglobulin gene; associated with dominant impairment of thyroid-specific genes transcription and increased thyroid cells proliferation. 1 PublicationCorresponds to variant dbSNP:rs537209983Ensembl.1

Keywords - Diseasei

Congenital hypothyroidism, Disease mutation

Organism-specific databases

DisGeNETi7080
MalaCardsiNKX2-1
MIMi118700 phenotype
188550 phenotype
610978 phenotype
OpenTargetsiENSG00000136352
Orphaneti95713 Athyreosis
1429 Benign familial chorea
209905 Brain-lung-thyroid syndrome
146 Papillary or follicular thyroid carcinoma
95720 Thyroid hypoplasia
PharmGKBiPA36531

Polymorphism and mutation databases

BioMutaiNKX2-1
DMDMi1174819

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000493431 – 371Homeobox protein Nkx-2.1Add BLAST371

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei254PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated on serine residues by STK3/MST2.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP43699
PaxDbiP43699
PeptideAtlasiP43699
PRIDEiP43699

PTM databases

iPTMnetiP43699
PhosphoSitePlusiP43699

Expressioni

Tissue specificityi

Thyroid and lung.

Gene expression databases

BgeeiENSG00000136352
CleanExiHS_NKX2-1
HS_TTF1
ExpressionAtlasiP43699 baseline and differential
GenevisibleiP43699 HS

Organism-specific databases

HPAiCAB000078
CAB053633
HPA074316

Interactioni

Subunit structurei

Interacts with WWTR1.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • enzyme binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112936, 10 interactors
IntActiP43699, 8 interactors
MINTiP43699
STRINGi9606.ENSP00000346879

Structurei

3D structure databases

ProteinModelPortaliP43699
SMRiP43699
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi234 – 243Poly-Gly10
Compositional biasi246 – 253Poly-Gln8
Compositional biasi294 – 303Poly-Ala10

Sequence similaritiesi

Belongs to the NK-2 homeobox family.Curated

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiKOG0842 Eukaryota
ENOG410XR21 LUCA
GeneTreeiENSGT00910000144003
HOGENOMiHOG000231923
HOVERGENiHBG006689
InParanoidiP43699
KOiK09342
OMAiMGHNGTV
OrthoDBiEOG091G0LZ2
PhylomeDBiP43699
TreeFamiTF351204

Family and domain databases

CDDicd00086 homeodomain, 1 hit
InterProiView protein in InterPro
IPR009057 Homeobox-like_sf
IPR017970 Homeobox_CS
IPR001356 Homeobox_dom
IPR020479 Homeobox_metazoa
PfamiView protein in Pfam
PF00046 Homeobox, 1 hit
PRINTSiPR00024 HOMEOBOX
SMARTiView protein in SMART
SM00389 HOX, 1 hit
SUPFAMiSSF46689 SSF46689, 1 hit
PROSITEiView protein in PROSITE
PS00027 HOMEOBOX_1, 1 hit
PS50071 HOMEOBOX_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P43699-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSMSPKHTTP FSVSDILSPL EESYKKVGME GGGLGAPLAA YRQGQAAPPT
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 GTGCPQQQQA
260 270 280 290 300
QQQSPRRVAV PVLVKDGKPC QAGAPAPGAA SLQGHAQQQA QHQAQAAQAA
310 320 330 340 350
AAAISVGSGG AGLGAHPGHQ PGSAGQSPDL AHHAASPAAL QGQVSSLSHL
360 370
NSSGSDYGTM SCSTLLYGRT W
Length:371
Mass (Da):38,596
Last modified:November 1, 1995 - v1
Checksum:i5F1E3B40A1BBD862
GO
Isoform 3 (identifier: P43699-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MWSGGSGKARGWEAAAGGRSSPGRLSRRRIM

Show »
Length:401
Mass (Da):41,737
Checksum:i40324D55128D4394
GO

Sequence cautioni

The sequence AAH06221 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA23527 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti49P → H in BAA23527 (Ref. 5) Curated1
Sequence conflicti49P → H in BAA23529 (Ref. 5) Curated1
Sequence conflicti61H → P in BAA23527 (Ref. 5) Curated1
Sequence conflicti61H → P in BAA23529 (Ref. 5) Curated1
Sequence conflicti158S → T in BAA23527 (Ref. 5) Curated1
Sequence conflicti158S → T in BAA23529 (Ref. 5) Curated1
Sequence conflicti161R → G in BAA23527 (Ref. 5) Curated1
Sequence conflicti161R → G in BAA23529 (Ref. 5) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_075209172Q → H in BHC; decrease in DNA-binding; no effect on transcription activation from thyroglobulin/TG, nor from pulmonary surfactant-associated protein C/SFTPC gene promoters. 1 Publication1
Natural variantiVAR_077542179R → P in BHC; unknown pathological significance. 1 Publication1
Natural variantiVAR_073040203T → R in CAHTP. 1 Publication1
Natural variantiVAR_034906205V → F in CAHTP. 2 PublicationsCorresponds to variant dbSNP:rs137852692Ensembl.1
Natural variantiVAR_015188208W → L in BHC. 1 PublicationCorresponds to variant dbSNP:rs28936672Ensembl.1
Natural variantiVAR_075210208W → S in BHC; loss of transcription activation. 1 Publication1
Natural variantiVAR_015189213R → S in BHC. 1 PublicationCorresponds to variant dbSNP:rs28936671Ensembl.1
Natural variantiVAR_075769339A → V in NMTC1; loss of transcription regulatory region DNA binding; decreased transcription factor activity, sequence-specific DNA binding; tested for the thyroglobulin gene; associated with dominant impairment of thyroid-specific genes transcription and increased thyroid cells proliferation. 1 PublicationCorresponds to variant dbSNP:rs537209983Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0378901M → MWSGGSGKARGWEAAAGGRS SPGRLSRRRIM in isoform 3. 3 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U19756 mRNA Translation: AAA86099.1
X82850 mRNA Translation: CAA58053.1
U19816 Genomic DNA Translation: AAC50125.1
U33749 mRNA Translation: AAB52381.1
U43203 mRNA Translation: AAA89066.1
D50739 Genomic DNA Translation: BAA23527.1 Sequence problems.
D50740 mRNA Translation: BAA23529.1
BT009773 mRNA Translation: AAP88775.1
AL132857 Genomic DNA No translation available.
CH471078 Genomic DNA Translation: EAW65858.1
CH471078 Genomic DNA Translation: EAW65856.1
CH471078 Genomic DNA Translation: EAW65859.1
BC006221 mRNA Translation: AAH06221.2 Different initiation.
CCDSiCCDS41945.1 [P43699-3]
CCDS9659.1 [P43699-1]
PIRiG02321
RefSeqiNP_001073136.1, NM_001079668.2 [P43699-3]
NP_003308.1, NM_003317.3 [P43699-1]
UniGeneiHs.94367

Genome annotation databases

EnsembliENST00000354822; ENSP00000346879; ENSG00000136352 [P43699-3]
ENST00000498187; ENSP00000429607; ENSG00000136352 [P43699-1]
ENST00000518149; ENSP00000428341; ENSG00000136352 [P43699-1]
ENST00000522719; ENSP00000429519; ENSG00000136352 [P43699-1]
GeneIDi7080
KEGGihsa:7080
UCSCiuc001wtt.4 human [P43699-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiNKX21_HUMAN
AccessioniPrimary (citable) accession number: P43699
Secondary accession number(s): D3DSA3
, O14954, O14955, Q7KZF6, Q9BRJ8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: May 23, 2018
This is version 179 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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