Nkx2-1 NK2 homeobox 1 [ Rattus norvegicus (Norway rat) ]

Gene ID: 25628, updated on 17-Aug-2024

Summary

Official Symbol: Nkx2-1provided by RGD
Official Full Name: NK2 homeobox 1provided by RGD
Primary source: RGD:3866
See related: EnsemblRapid:ENSRNOG00000008644 AllianceGenome:RGD:3866
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: TTF1; Titf1
Summary: Enables several functions, including DNA-binding transcription activator activity, RNA polymerase II-specific; TBP-class protein binding activity; and transcription cis-regulatory region binding activity. Involved in several processes, including cellular response to leptin stimulus; embryonic lung development; and hyperosmotic salinity response. Acts upstream of or within positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. Human ortholog(s) of this gene implicated in choreatic disease and thyroid gland papillary carcinoma. Orthologous to human NKX2-1 (NK2 homeobox 1). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Restricted expression toward (RPKM 91.1) See more
Orthologs: human mouse all
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Genomic context

Location:: 6q23

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	6	NC_086024.1 (79731677..79735952, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	6	NC_051341.1 (73996601..74001483, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	6	NC_005105.4 (77418096..77423383, complement)

Chromosome 6 - NC_086024.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Downregulation of TTF1 in the rat hypothalamic ARC or AVPV nucleus inhibits Kiss1 and GnRH expression, leading to puberty delay.
Title: Downregulation of TTF1 in the rat hypothalamic ARC or AVPV nucleus inhibits Kiss1 and GnRH expression, leading to puberty delay.
data indicate that TTF-1 interacts with PPFP to inhibit the pro-adipogenic response to pioglitazone, and that the ability of pioglitazone to decrease TTF-1 expression contributes to its pro-adipogenic action.
Title: Adipogenic Differentiation of Thyroid Cancer Cells Through the Pax8-PPARγ Fusion Protein Is Regulated by Thyroid Transcription Factor 1 (TTF-1).
Dual positive effects of leptin were found on protein expression and transcriptional activity of thyroid transcription factor-1
Title: Leptin promotes fetal lung maturity and upregulates SP-A expression in pulmonary alveoli type-II epithelial cells involving TTF-1 activation.
TTF1 contributes to regulating periodic oscillations in expression of the gonadotrophin-releasing hormone (GnRH) gene expression; TTF1 transactivates GnRH transcription by binding to two sites in the GnRH promoter.
Title: Thyroid transcription factor 1, a homeodomain containing transcription factor, contributes to regulating periodic oscillations in GnRH gene expression.
The expression of Nkx2.1 mRNA in offspring of hypothyroid pregnant rat was reduced. Treatment of pregnant rats with thyroxine restored Nkx2.1 expression to nomal levels in offspring.
Title: [Effects of supplement of thyroxine for hypothyroid pregnant rat on the expression of homeobox gene Nkx2.1 mRNA in the offspring's cerebrum tissue].
There was a significant increase in the expression of both TTF-1 and T1alpha mRNA in the IGF-2 group, in comparison to the control group after 48 h of culture.
Title: Effect of insulin-like growth factors on lung development in a nitrofen-induced CDH rat model.
TTF-1 transcriptionally regulates synthesis of AgRP and alpha-MSH in the ARC and affects feeding behavior via the melanocortin pathway.
Title: Thyroid transcription factor-1 regulates feeding behavior via melanocortin pathway in the hypothalamus.
DNA methylation and chromatin modifications cooperate with Nkx2-1 to regulate Sftpb gene cell specific expression.
Title: Epigenetic mechanisms modulate thyroid transcription factor 1-mediated transcription of the surfactant protein B gene.
Data show that direct interaction between Foxp2 and Nkx2.1 inhibits Nkx2.1 DNA-binding and transcriptional activity and suggest a mechanism for down-regulation of SP-C during transition of AT2 cells to an AT1 cell phenotype.
Title: Foxp2 inhibits Nkx2.1-mediated transcription of SP-C via interactions with the Nkx2.1 homeodomain.
Data suggested that a good degree of isotropy of the global molecular motion, and that the C-terminal fragment of helix III was more flexible than the preceding N-terminal portion, with slightly different limits between rigid and mobile moieties.
Title: Helix mobility and recognition function of the rat thyroid transcription factor 1 homeodomain - hints from 15N-NMR relaxation studies.

Submit: New GeneRIF Correction See all GeneRIFs (23)

General gene information

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Markers

Nkx2-1 (e-PCR), detects polymorphism
- UniSTS:536832

PMC102181P2 (e-PCR)
- UniSTS:270084

Nkx2-1 (e-PCR), detects polymorphism
- UniSTS:546582

RH94604 (e-PCR)
- UniSTS:119852

D6Arb16 (e-PCR)
- UniSTS:239415

D6Wox26 (e-PCR)
- UniSTS:240446

D6Wox28 (e-PCR)
- UniSTS:518786

PMC152810P1 (e-PCR)
- UniSTS:271243

D6Wox31 (e-PCR)
- UniSTS:518795

Titf1 (e-PCR), detects polymorphism
- UniSTS:497301

Nkx2-1 (e-PCR), detects polymorphism
- UniSTS:534422

Titf1 (e-PCR), detects polymorphism
- UniSTS:464797

UniSTS:225218 (e-PCR)
- UniSTS:225218

Nkx2-1 (e-PCR), detects polymorphism
- UniSTS:507093

AA858694 (e-PCR)
- UniSTS:243417

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA binding	ISO Inferred from Sequence Orthology more info
enables DNA binding	TAS Traceable Author Statement more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IC Inferred by Curator more info
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IMP Inferred from Mutant Phenotype more info	PubMed
enables DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables DNA-binding transcription factor activity	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IEA Inferred from Electronic Annotation more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISO Inferred from Sequence Orthology more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IEA Inferred from Electronic Annotation more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISO Inferred from Sequence Orthology more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	ISO Inferred from Sequence Orthology more info
enables RNA polymerase II-specific DNA-binding transcription factor binding	IEA Inferred from Electronic Annotation more info
enables RNA polymerase II-specific DNA-binding transcription factor binding	ISO Inferred from Sequence Orthology more info
enables TBP-class protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables core promoter sequence-specific DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables enzyme binding	IEA Inferred from Electronic Annotation more info
enables enzyme binding	ISO Inferred from Sequence Orthology more info
enables identical protein binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables intronic transcription regulatory region sequence-specific DNA binding	IEA Inferred from Electronic Annotation more info
enables intronic transcription regulatory region sequence-specific DNA binding	ISO Inferred from Sequence Orthology more info
enables intronic transcription regulatory region sequence-specific DNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables sequence-specific DNA binding	ISO Inferred from Sequence Orthology more info
enables transcription cis-regulatory region binding	ISO Inferred from Sequence Orthology more info
enables transcription coactivator activity	IDA Inferred from Direct Assay more info	PubMed
enables transcription coregulator binding	IPI Inferred from Physical Interaction more info	PubMed

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

Component	Evidence Code	Pubs
located_in nucleoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
located_in nucleus	ISO Inferred from Sequence Orthology more info
part_of transcription regulator complex	IEA Inferred from Electronic Annotation more info
part_of transcription regulator complex	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: homeobox protein Nkx-2.1

Names: TTF-1; thyroid nuclear factor 1; thyroid transcription factor 1 TTF-1 NK-2; thyroid-specific transcription factor 1

NCBI Reference Sequences (RefSeq)

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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.

mRNA and Protein(s)

NM_013093.1 → NP_037225.1 homeobox protein Nkx-2.1

See identical proteins and their annotated locations for NP_037225.1

Status: VALIDATED

Source sequence(s)

JAXUCZ010000006

UniProtKB/TrEMBL

A0A060PW62, A6HBN7, G3V740

Conserved Domains (1) summary

pfam00046
Location:164 → 217

Homeobox; Homeobox domain

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

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

Reference GRCr8

Genomic

NC_086024.1 Reference GRCr8

Range

79731677..79735952 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006240117.5 → XP_006240179.1 homeobox protein Nkx-2.1 isoform X2

UniProtKB/TrEMBL

A0A060PW62

Related

ENSRNOP00000101942.1, ENSRNOT00000121637.1

Conserved Domains (1) summary

pfam00046
Location:194 → 247

Homeobox; Homeobox domain
XM_006240116.4 → XP_006240178.1 homeobox protein Nkx-2.1 isoform X1

UniProtKB/TrEMBL

A0A060PW62

Related

ENSRNOP00000011453.5, ENSRNOT00000011453.7

Conserved Domains (1) summary

pfam00046
Location:215 → 268

Homeobox; Homeobox domain
XM_039111813.2 → XP_038967741.1 homeobox protein Nkx-2.1 isoform X3

Conserved Domains (1) summary

pfam00046
Location:36 → 90

Homeobox; Homeobox domain