UniProtKB - P43699 (NKX21_HUMAN)
Homeobox protein Nkx-2.1
NKX2-1
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 similarityRegions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 161 – 220 | HomeoboxPROSITE-ProRule annotationAdd BLAST | 60 |
GO - Molecular functioni
- DNA binding Source: UniProtKB
- DNA-binding transcription factor activity Source: UniProtKB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
- enzyme binding Source: UniProtKB
- intronic transcription regulatory region sequence-specific DNA binding Source: MGI
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: UniProtKB
- RNA polymerase II-specific DNA-binding transcription factor binding Source: ARUK-UCL
- RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: MGI
- transcription cis-regulatory region binding Source: UniProtKB
GO - Biological processi
- brain development Source: UniProtKB
- cell differentiation Source: GO_Central
- epithelial tube branching involved in lung morphogenesis Source: UniProtKB
- forebrain development Source: UniProtKB
- globus pallidus development Source: UniProtKB
- lung development Source: UniProtKB
- negative regulation of cell migration Source: UniProtKB
- negative regulation of epithelial to mesenchymal transition Source: UniProtKB
- negative regulation of transcription, DNA-templated Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: MGI
- negative regulation of transforming growth factor beta receptor signaling pathway Source: UniProtKB
- positive regulation of circadian rhythm Source: UniProtKB
- positive regulation of gene expression Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- regulation of transcription, DNA-templated Source: ComplexPortal
- regulation of transcription by RNA polymerase II Source: GO_Central
- response to hormone Source: UniProtKB
- rhythmic process Source: UniProtKB-KW
- thyroid gland development Source: UniProtKB
Keywordsi
Molecular function | Activator, DNA-binding, Repressor |
Biological process | Biological rhythms, Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | P43699 |
SignaLinki | P43699 |
SIGNORi | P43699 |
Names & Taxonomyi
Protein namesi | Recommended name: Homeobox protein Nkx-2.1Alternative 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 | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:11825, NKX2-1 |
MIMi | 600635, gene |
neXtProti | NX_P43699 |
VEuPathDBi | HostDB:ENSG00000136352 |
Subcellular locationi
Nucleus
- Nucleus By similarity
Nucleus
- nucleoplasm Source: UniProtKB
- nucleus Source: UniProtKB
Other locations
- chromatin Source: NTNU_SB
- transcription regulator complex Source: ComplexPortal
Keywords - Cellular componenti
NucleusPathology & Biotechi
Involvement in diseasei
Chorea, hereditary benign (BHC)4 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_075209 | 172 | Q → 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 Publication | 1 | |
Natural variantiVAR_077542 | 179 | R → P in BHC; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_015188 | 208 | W → L in BHC. 1 PublicationCorresponds to variant dbSNP:rs28936672Ensembl. | 1 | |
Natural variantiVAR_075210 | 208 | W → S in BHC; loss of transcription activation. 1 Publication | 1 | |
Natural variantiVAR_015189 | 213 | R → S in BHC. 1 PublicationCorresponds to variant dbSNP:rs28936671Ensembl. | 1 |
Choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction (CAHTP)5 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_073040 | 203 | T → R in CAHTP. 1 Publication | 1 | |
Natural variantiVAR_034906 | 205 | V → F in CAHTP. 2 PublicationsCorresponds to variant dbSNP:rs137852692Ensembl. | 1 |
Thyroid cancer, non-medullary, 1 (NMTC1)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_075769 | 339 | A → 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 variantOrganism-specific databases
DisGeNETi | 7080 |
GeneReviewsi | NKX2-1 |
MalaCardsi | NKX2-1 |
MIMi | 118700, phenotype 188550, phenotype 610978, phenotype |
OpenTargetsi | ENSG00000136352 |
Orphaneti | 95713, Athyreosis 1429, Benign hereditary chorea 209905, Brain-lung-thyroid syndrome 146, Differentiated thyroid carcinoma |
PharmGKBi | PA36531 |
Miscellaneous databases
Pharosi | P43699, Tbio |
Genetic variation databases
BioMutai | NKX2-1 |
DMDMi | 1174819 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000049343 | 1 – 371 | Homeobox protein Nkx-2.1Add BLAST | 371 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 254 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
PhosphoproteinProteomic databases
MassIVEi | P43699 |
MaxQBi | P43699 |
PaxDbi | P43699 |
PeptideAtlasi | P43699 |
PRIDEi | P43699 |
ProteomicsDBi | 55653 [P43699-1] 55654 [P43699-3] |
PTM databases
iPTMneti | P43699 |
PhosphoSitePlusi | P43699 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000136352, Expressed in left lobe of thyroid gland and 108 other tissues |
ExpressionAtlasi | P43699, baseline and differential |
Genevisiblei | P43699, HS |
Organism-specific databases
HPAi | ENSG00000136352, Group enriched (lung, thyroid gland) |
Interactioni
Subunit structurei
Interacts with WWTR1.
1 PublicationBinary interactionsi
GO - Molecular functioni
- enzyme binding Source: UniProtKB
- RNA polymerase II-specific DNA-binding transcription factor binding Source: ARUK-UCL
Protein-protein interaction databases
BioGRIDi | 112936, 164 interactors |
ComplexPortali | CPX-6062, SMAD3-TTF-1 complex |
IntActi | P43699, 10 interactors |
MINTi | P43699 |
STRINGi | 9606.ENSP00000346879 |
Miscellaneous databases
RNActi | P43699, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 219 – 294 | DisorderedSequence analysisAdd BLAST | 76 | |
Regioni | 310 – 339 | DisorderedSequence analysisAdd BLAST | 30 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 242 – 256 | Polar residuesSequence analysisAdd BLAST | 15 |
Sequence similaritiesi
Keywords - Domaini
HomeoboxPhylogenomic databases
eggNOGi | KOG0842, Eukaryota |
GeneTreei | ENSGT00940000161107 |
HOGENOMi | CLU_052416_0_0_1 |
InParanoidi | P43699 |
OMAi | YGTAMSC |
OrthoDBi | 1209625at2759 |
PhylomeDBi | P43699 |
TreeFami | TF351204 |
Family and domain databases
CDDi | cd00086, homeodomain, 1 hit |
InterProi | View protein in InterPro IPR009057, Homeobox-like_sf IPR017970, Homeobox_CS IPR001356, Homeobox_dom IPR020479, Homeobox_metazoa |
Pfami | View protein in Pfam PF00046, Homeodomain, 1 hit |
PRINTSi | PR00024, HOMEOBOX |
SMARTi | View protein in SMART SM00389, HOX, 1 hit |
SUPFAMi | SSF46689, SSF46689, 1 hit |
PROSITEi | View protein in PROSITE PS00027, HOMEOBOX_1, 1 hit PS50071, HOMEOBOX_2, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A7P0P5T6 | A0A7P0P5T6_HUMAN | Homeobox protein Nkx-2.1 | NKX2-1 | 35 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 49 | P → H in BAA23527 (Ref. 5) Curated | 1 | |
Sequence conflicti | 49 | P → H in BAA23529 (Ref. 5) Curated | 1 | |
Sequence conflicti | 61 | H → P in BAA23527 (Ref. 5) Curated | 1 | |
Sequence conflicti | 61 | H → P in BAA23529 (Ref. 5) Curated | 1 | |
Sequence conflicti | 158 | S → T in BAA23527 (Ref. 5) Curated | 1 | |
Sequence conflicti | 158 | S → T in BAA23529 (Ref. 5) Curated | 1 | |
Sequence conflicti | 161 | R → G in BAA23527 (Ref. 5) Curated | 1 | |
Sequence conflicti | 161 | R → G in BAA23529 (Ref. 5) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_075209 | 172 | Q → 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 Publication | 1 | |
Natural variantiVAR_077542 | 179 | R → P in BHC; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_073040 | 203 | T → R in CAHTP. 1 Publication | 1 | |
Natural variantiVAR_034906 | 205 | V → F in CAHTP. 2 PublicationsCorresponds to variant dbSNP:rs137852692Ensembl. | 1 | |
Natural variantiVAR_015188 | 208 | W → L in BHC. 1 PublicationCorresponds to variant dbSNP:rs28936672Ensembl. | 1 | |
Natural variantiVAR_075210 | 208 | W → S in BHC; loss of transcription activation. 1 Publication | 1 | |
Natural variantiVAR_015189 | 213 | R → S in BHC. 1 PublicationCorresponds to variant dbSNP:rs28936671Ensembl. | 1 | |
Natural variantiVAR_075769 | 339 | A → 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_037890 | 1 | M → MWSGGSGKARGWEAAAGGRS SPGRLSRRRIM in isoform 3. 3 Publications | 1 |
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. |
CCDSi | CCDS41945.1 [P43699-3] CCDS9659.1 [P43699-1] |
PIRi | G02321 |
RefSeqi | NP_001073136.1, NM_001079668.2 [P43699-3] NP_003308.1, NM_003317.3 [P43699-1] |
Genome annotation databases
Ensembli | ENST00000354822; ENSP00000346879; ENSG00000136352 [P43699-3] ENST00000498187; ENSP00000429607; ENSG00000136352 ENST00000518149; ENSP00000428341; ENSG00000136352 |
GeneIDi | 7080 |
KEGGi | hsa:7080 |
MANE-Selecti | ENST00000354822.7; ENSP00000346879.6; NM_001079668.3; NP_001073136.1 [P43699-3] |
UCSCi | uc001wtt.4, human [P43699-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
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. |
CCDSi | CCDS41945.1 [P43699-3] CCDS9659.1 [P43699-1] |
PIRi | G02321 |
RefSeqi | NP_001073136.1, NM_001079668.2 [P43699-3] NP_003308.1, NM_003317.3 [P43699-1] |
3D structure databases
BMRBi | P43699 |
SMRi | P43699 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 112936, 164 interactors |
ComplexPortali | CPX-6062, SMAD3-TTF-1 complex |
IntActi | P43699, 10 interactors |
MINTi | P43699 |
STRINGi | 9606.ENSP00000346879 |
PTM databases
iPTMneti | P43699 |
PhosphoSitePlusi | P43699 |
Genetic variation databases
BioMutai | NKX2-1 |
DMDMi | 1174819 |
Proteomic databases
MassIVEi | P43699 |
MaxQBi | P43699 |
PaxDbi | P43699 |
PeptideAtlasi | P43699 |
PRIDEi | P43699 |
ProteomicsDBi | 55653 [P43699-1] 55654 [P43699-3] |
Protocols and materials databases
Antibodypediai | 3519, 1052 antibodies from 45 providers |
DNASUi | 7080 |
Genome annotation databases
Ensembli | ENST00000354822; ENSP00000346879; ENSG00000136352 [P43699-3] ENST00000498187; ENSP00000429607; ENSG00000136352 ENST00000518149; ENSP00000428341; ENSG00000136352 |
GeneIDi | 7080 |
KEGGi | hsa:7080 |
MANE-Selecti | ENST00000354822.7; ENSP00000346879.6; NM_001079668.3; NP_001073136.1 [P43699-3] |
UCSCi | uc001wtt.4, human [P43699-1] |
Organism-specific databases
CTDi | 7080 |
DisGeNETi | 7080 |
GeneCardsi | NKX2-1 |
GeneReviewsi | NKX2-1 |
HGNCi | HGNC:11825, NKX2-1 |
HPAi | ENSG00000136352, Group enriched (lung, thyroid gland) |
MalaCardsi | NKX2-1 |
MIMi | 118700, phenotype 188550, phenotype 600635, gene 610978, phenotype |
neXtProti | NX_P43699 |
OpenTargetsi | ENSG00000136352 |
Orphaneti | 95713, Athyreosis 1429, Benign hereditary chorea 209905, Brain-lung-thyroid syndrome 146, Differentiated thyroid carcinoma |
PharmGKBi | PA36531 |
VEuPathDBi | HostDB:ENSG00000136352 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0842, Eukaryota |
GeneTreei | ENSGT00940000161107 |
HOGENOMi | CLU_052416_0_0_1 |
InParanoidi | P43699 |
OMAi | YGTAMSC |
OrthoDBi | 1209625at2759 |
PhylomeDBi | P43699 |
TreeFami | TF351204 |
Enzyme and pathway databases
PathwayCommonsi | P43699 |
SignaLinki | P43699 |
SIGNORi | P43699 |
Miscellaneous databases
BioGRID-ORCSi | 7080, 19 hits in 1041 CRISPR screens |
GeneWikii | NK2_homeobox_1 |
GenomeRNAii | 7080 |
Pharosi | P43699, Tbio |
PROi | PR:P43699 |
RNActi | P43699, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000136352, Expressed in left lobe of thyroid gland and 108 other tissues |
ExpressionAtlasi | P43699, baseline and differential |
Genevisiblei | P43699, HS |
Family and domain databases
CDDi | cd00086, homeodomain, 1 hit |
InterProi | View protein in InterPro IPR009057, Homeobox-like_sf IPR017970, Homeobox_CS IPR001356, Homeobox_dom IPR020479, Homeobox_metazoa |
Pfami | View protein in Pfam PF00046, Homeodomain, 1 hit |
PRINTSi | PR00024, HOMEOBOX |
SMARTi | View protein in SMART SM00389, HOX, 1 hit |
SUPFAMi | SSF46689, SSF46689, 1 hit |
PROSITEi | View protein in PROSITE PS00027, HOMEOBOX_1, 1 hit PS50071, HOMEOBOX_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | NKX21_HUMAN | |
Accessioni | P43699Primary (citable) accession number: P43699 Secondary accession number(s): D3DSA3 Q9BRJ8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1995 |
Last sequence update: | November 1, 1995 | |
Last modified: | February 23, 2022 | |
This is version 203 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 14
Human chromosome 14: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families