NKX2-1 NK2 homeobox 1 [Homo sapiens] - Gene

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Summary

Official Symbol: NKX2-1provided by HGNC
Official Full Name: NK2 homeobox 1provided by HGNC
Primary source: HGNC:11825
See related: Ensembl:ENSG00000136352; HPRD:02798; MIM:600635; Vega:OTTHUMG00000140225
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: BCH; BHC; NK-2; TEBP; TTF1; NKX2A; TITF1; TTF-1; NKX2.1
Summary: This gene encodes a protein initially identified as a thyroid-specific transcription factor. The encoded protein binds to the thyroglobulin promoter and regulates the expression of thyroid-specific genes but has also been shown to regulate the expression of genes involved in morphogenesis. Mutations and deletions in this gene are associated with benign hereditary chorea, choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress, and may be associated with thyroid cancer. Multiple transcript variants encoding different isoforms have been found for this gene. This gene shares the symbol/alias 'TFF1' with another gene, transcription termination factor 1, which plays a role in ribosomal gene transcription. [provided by RefSeq, Apr 2011]
Annotation information: Note: TTF1 (GeneID 7270) and NKX2-1 (GeneID 7080) loci share the TTF1 symbol/alias in common. TTF1 is a widely used alternative name for thyroid transcription factor 1 (NKX2-1) conflicting with the official symbol for transcription termination factor, RNA polymerase I (TTF1). [06 May 2008]

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Genomic context

Location :: 14q13

Sequence :: Chromosome: 14; NC_000014.8 (36985602..36989430, complement)

See NKX2-1 in Epigenomics, MapViewer

Chromosome 14 - NC_000014.8 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Merkel cell carcinoma admixed with squamous cell carcinoma can be cytokeratin 20-negative and thyroid transcription factor-1-positive [case report]
Title: Merkel cell carcinoma with cytokeratin 20-negative and thyroid transcription factor-1-positive immunostaining admixed with squamous cell carcinoma.
TNF-alpha inhibits TTF-1 gene transcription and promoter activity, indicating that transcriptional mechanisms play important roles in the inhibition of TTF-1 levels.
Title: Thyroid transcription factor-1 (TTF-1) gene: identification of ZBP-89, Sp1, and TTF-1 sites in the promoter and regulation by TNF-α in lung epithelial cells.
Data suggest that the panels of Napsin A, TTF-1, and p63 were effective in identifying histologic type in NSCLC, and that a combination of either Napsin A and p63 or TTF-1 and p63 should be chosen, depending on morphology.
Title: Comparison of the expression levels of napsin A, thyroid transcription factor-1, and p63 in nonsmall cell lung cancer using cytocentrifuged bronchial brushings.
Thyroid transcription factor-1 expression in four cases of mammary ductal carcinoma.
Title: Thyroid transcription factor-1 expression in rare cases of mammary ductal carcinoma.
Data show that human HOXB5 binds to the promoter region 5' upstream of the binding site of NKX2-1 and regulates RET expression.
Title: HOXB5 cooperates with NKX2-1 in the transcription of human RET.
in combination with napsin A-positive immunostaining helps in differentiating primary lung adenocarcinoma
Title: Combination of napsin A and TTF-1 immunohistochemistry helps in differentiating primary lung adenocarcinoma from metastatic carcinoma in the lung.
NKX2-1 was suppressed in airway epithelial cells from patients with asthma.
Title: Airway epithelial transcription factor NK2 homeobox 1 inhibits mucous cell metaplasia and Th2 inflammation.
TTF-1 is useful in separating adenocarcinoma of the lung from non-pulmonary adenocarcinoma and malignant mesothelioma
Title: Expression of thyroid transcription factor-1 in malignant pleural effusions.
Data show distinct significant correlations between TITF-1 protein expression and DNA copy gain with mutations in the lung adenocarcinoma-prevalent EGFR and KRAS oncogenes.
Title: Abnormalities of the TITF-1 lineage-specific oncogene in NSCLC: implications in lung cancer pathogenesis and prognosis.
co-expression with p63 in lung signet-ring cell carcinoma
Title: Frequent ALK rearrangement and TTF-1/p63 co-expression in lung adenocarcinoma with signet-ring cell component.

Submit: New GeneRIF Correction See all (100)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

Choreoathetosis, hypothyroidism, and neonatal respiratory distress

MIM: 610978

Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations.

Goiter, familial, due to TTF-1 defect

MIM: 600635

Identification of ten loci associated with height highlights new biological pathways in human growth.

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Products	Interactant	Other Gene	Source	Pubs	Description
P43699	P27797	CALR	HPRD	PubMed
P43699	Q92793	CREBBP	HPRD	PubMed
P43699	Q92908	GATA6	HPRD	PubMed
P43699	Q9H2X6	HIPK2	HPRD	PubMed
P43699	P28482	MAPK1	HPRD	PubMed
P43699	Q15788	NCOA1	HPRD	PubMed
P43699	Q15596	NCOA2	HPRD	PubMed
P43699	Q06710	PAX8	HPRD	PubMed
P43699	P10276	RARA	HPRD	PubMed
P43699	Q04206	RELA	HPRD	PubMed
P43699	Q13569	TDG	HPRD	PubMed
P43699	Q9GZV5	WWTR1	HPRD	PubMed
BioGRID:112936	BioGRID:107262	CALR	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:112936	BioGRID:107777	CREBBP	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:112936	BioGRID:118815	HIPK2	BioGRID	PubMed	Two-hybrid
BioGRID:112936	BioGRID:114200	NCOA1	BioGRID	PubMed	Reconstituted Complex
BioGRID:112936	BioGRID:115761	NCOA2	BioGRID	PubMed	Two-hybrid
BioGRID:112936	BioGRID:113841	NCOA3	BioGRID	PubMed	Two-hybrid
BioGRID:112936	BioGRID:113604	PAX8	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:112936	BioGRID:129767	PTRF	BioGRID	PubMed	Reconstituted Complex
BioGRID:112936	BioGRID:111849	RARA	BioGRID	PubMed	Two-hybrid
BioGRID:112936	BioGRID:111902	RELA	BioGRID	PubMed	Affinity Capture-Western

Function	Evidence Code	Pubs
DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
sequence-specific DNA binding	IEA Inferred from Electronic Annotation more info
sequence-specific DNA binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
sequence-specific distal enhancer binding RNA polymerase II transcription factor activity	IEA Inferred from Electronic Annotation more info
transcription regulatory region DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
Clara cell differentiation	IEA Inferred from Electronic Annotation more info
Leydig cell differentiation	IEA Inferred from Electronic Annotation more info
Type II pneumocyte differentiation	IEA Inferred from Electronic Annotation more info
anatomical structure formation involved in morphogenesis	IEA Inferred from Electronic Annotation more info
axon guidance	IEA Inferred from Electronic Annotation more info
brain development	IMP Inferred from Mutant Phenotype more info	PubMed
cerebral cortex GABAergic interneuron differentiation	IEA Inferred from Electronic Annotation more info
cerebral cortex cell migration	IEA Inferred from Electronic Annotation more info
development of primary female sexual characteristics	IEA Inferred from Electronic Annotation more info
developmental induction	IEA Inferred from Electronic Annotation more info
endoderm development	IEA Inferred from Electronic Annotation more info
epithelial tube branching involved in lung morphogenesis	IEP Inferred from Expression Pattern more info	PubMed
feeding behavior	IEA Inferred from Electronic Annotation more info
forebrain development	IEP Inferred from Expression Pattern more info	PubMed
forebrain dorsal/ventral pattern formation	IEA Inferred from Electronic Annotation more info
forebrain neuron fate commitment	IEA Inferred from Electronic Annotation more info
globus pallidus development	IMP Inferred from Mutant Phenotype more info	PubMed
hippocampus development	IEA Inferred from Electronic Annotation more info
hyperosmotic salinity response	IEA Inferred from Electronic Annotation more info
locomotory behavior	IEA Inferred from Electronic Annotation more info
lung development	IEP Inferred from Expression Pattern more info	PubMed
lung saccule development	IEA Inferred from Electronic Annotation more info
menarche	IEA Inferred from Electronic Annotation more info
negative regulation of cell migration	IDA Inferred from Direct Assay more info	PubMed
negative regulation of epithelial to mesenchymal transition	IDA Inferred from Direct Assay more info	PubMed
negative regulation of transcription from RNA polymerase II promoter	IEA Inferred from Electronic Annotation more info
negative regulation of transforming growth factor beta receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
neuron migration	IEA Inferred from Electronic Annotation more info
oligodendrocyte differentiation	IEA Inferred from Electronic Annotation more info
organ morphogenesis	IEA Inferred from Electronic Annotation more info
pattern specification process	IEA Inferred from Electronic Annotation more info
phospholipid metabolic process	IEA Inferred from Electronic Annotation more info
pituitary gland development	IEA Inferred from Electronic Annotation more info
positive regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription from RNA polymerase II promoter	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription, DNA-dependent	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription, DNA-dependent	ISS Inferred from Sequence or Structural Similarity more info
regulation of blood volume by renin-angiotensin	IEA Inferred from Electronic Annotation more info
response to ethanol	IEA Inferred from Electronic Annotation more info
response to hormone stimulus	IEP Inferred from Expression Pattern more info	PubMed
response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
thyroid gland development	IEP Inferred from Expression Pattern more info	PubMed
thyroid gland development	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
nucleoplasm	ISS Inferred from Sequence or Structural Similarity more info
nucleus	IDA Inferred from Direct Assay more info	PubMed
soluble fraction	IEA Inferred from Electronic Annotation more info
transcription factor complex	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: homeobox protein Nkx-2.1

Names: homeobox protein Nkx-2.1; NK-2 homolog A; thyroid nuclear factor 1; thyroid transcription factor 1; homeobox protein NK-2 homolog A

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_013365.1 RefSeqGene

Range

5001..8829

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001079668.2 → NP_001073136.1 homeobox protein Nkx-2.1 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer protein (isoform 1).

Source sequence(s)

AL132857, BM970287, U43203

Consensus CDS

CCDS41945.1

UniProtKB/Swiss-Prot

P43699

Related

ENSP00000346879, OTTHUMP00000178847, ENST00000354822, OTTHUMT00000276689

Conserved Domains (1) summary

cd00086
Location:192 – 249
Blast Score: 199

homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.
NM_003317.3 → NP_003308.1 homeobox protein Nkx-2.1 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and coding region compared to variant 1. The resulting protein (isoform 2) is shorter and has a distinct N-terminus compared to isoform 1.

Source sequence(s)

BC006221, BM970838, U33749

Consensus CDS

CCDS9659.1

UniProtKB/Swiss-Prot

P43699

Related

ENSP00000429607, OTTHUMP00000225297, ENST00000498187, OTTHUMT00000276688

Conserved Domains (1) summary

cd00086
Location:162 – 219
Blast Score: 199

homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000014.8 Reference GRCh37.p5 Primary Assembly

Range

36985602..36989430, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000146.1 Alternate HuRef

Range

17100276..17104039, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AL132857.4 (67148..70977)	None
genomic	CH471078.2	EAW65856.1
		EAW65857.1
		EAW65858.1
		EAW65859.1
genomic	D50739.1	BAA23527.1
genomic	U19816.1	AAC50125.1
genomic	U33627.1	AAA83233.1
mRNA	BC006221.2	AAH06221.2
mRNA	BE796718.1	None
mRNA	BM970287.1	None
mRNA	BM970838.1	None
mRNA	BT009773.1	AAP88775.1
mRNA	D50740.1	BAA23529.1
mRNA	D50741.1	BAA23528.1
mRNA	U19756.1	AAA86099.1
mRNA	U33749.1	AAB52381.1
mRNA	U43203.1	AAA89066.1
mRNA	X82850.1	CAA58053.1
other-genetic	DQ892964.2	ABM83890.1
other-genetic	DQ896211.2	ABM87210.1

Protein Accession	Links
Protein Accession	GenePept Link	UniProtKB Link
O14956	GenPept	UniProtKB/TrEMBL:O14956
P43699.1	GenPept	UniProtKB/Swiss-Prot:P43699
Q13306	GenPept	UniProtKB/TrEMBL:Q13306