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    Nkx2-2 NK2 homeobox 2 [ Mus musculus (house mouse) ]

    Gene ID: 18088, updated on 21-Apr-2024

    Summary

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    Official Symbol
    Nkx2-2provided by MGI
    Official Full Name
    NK2 homeobox 2provided by MGI
    Primary source
    MGI:MGI:97347
    See related
    Ensembl:ENSMUSG00000027434 AllianceGenome:MGI:97347
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    Nkx2.2; tinman; Nkx-2.2
    Summary
    Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Acts upstream of or within several processes, including enteroendocrine cell differentiation; neurogenesis; and regulation of neuron differentiation. Located in nucleus. Is expressed in several structures, including central nervous system; genitourinary system; gut; neural ectoderm; and sensory organ. Orthologous to human NKX2-2 (NK2 homeobox 2). [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Biased expression in cerebellum adult (RPKM 1.9), CNS E11.5 (RPKM 1.6) and 10 other tissues See more
    Orthologs
    human all
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    Genomic context

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    Location:
    2 G2; 2 72.63 cM
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 2 NC_000068.8 (146967909..147037270, complement)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 2 NC_000068.7 (147176485..147195434, complement)

    Chromosome 2 - NC_000068.8Genomic Context describing neighboring genes Neighboring gene STARR-seq mESC enhancer starr_05957 Neighboring gene 5'-3' exoribonuclease 2 Neighboring gene predicted gene, 34889 Neighboring gene NK2 homeobox 4 Neighboring gene predicted gene, 57697 Neighboring gene predicted gene 14116 Neighboring gene RIKEN cDNA 6430503K07 gene Neighboring gene Nkx2-2 Hedgehog-responsive enhancer Neighboring gene STARR-seq mESC enhancer starr_05959 Neighboring gene NK2 homeobox 2, opposite strand Neighboring gene predicted gene, 39955 Neighboring gene glyceraldehyde-3-phosphate dehydrogenase pseudogene

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. The transcription factor NKX2-2 regulates oligodendrocyte differentiation through domain-specific interactions with transcriptional corepressors. Zhang C, et al. J Biol Chem, 2020 Feb 14. PMID 31932307, Free PMC Article
    2. Pancreatic β cell identity requires continual repression of non-β cell programs. Gutiérrez GD, et al. J Clin Invest, 2017 Jan 3. PMID 27941248, Free PMC Article
    3. Nkx2.2 regulates cell fate choice in the enteroendocrine cell lineages of the intestine. Desai S, et al. Dev Biol, 2008 Jan 1. PMID 18022152, Free PMC Article
    4. Co-expression pattern of Shh with Prox1 and that of Nkx2.2 with Mash1 in mouse taste bud. Miura H, et al. Gene Expr Patterns, 2003 Aug. PMID 12915306
    5. Distinct gene expression programs function in progenitor and mature islet cells. Watada H, et al. J Biol Chem, 2003 May 9. PMID 12604598

    See all (591) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The transcription factor NKX2-2 regulates oligodendrocyte differentiation through domain-specific interactions with transcriptional corepressors.
      Title: The transcription factor NKX2-2 regulates oligodendrocyte differentiation through domain-specific interactions with transcriptional corepressors.
    2. The transient hypoxia at P7 altered the expression of Nkx2.2, resulting in delayed myelination in the external capsule.
      Title: Region specific oligodendrocyte transcription factor expression in a model of neonatal hypoxic injury.
    3. This suggests that Nkx2.2 is not only required in the early pancreatic progenitors, but has additional essential activities within the endocrine progenitor population.
      Title: Genetic evidence that Nkx2.2 acts primarily downstream of Neurog3 in pancreatic endocrine lineage development.
    4. Lmx1a is expressed in enterochromaffin cells and functions downstream of Nkx2.2.
      Title: The novel enterochromaffin marker Lmx1a regulates serotonin biosynthesis in enteroendocrine cell lineages downstream of Nkx2.2.
    5. nuclear import of Nkx2-2 is mediated not only by the classical import pathway but also directly by imp beta1 or imp 13
      Title: Nuclear import of Nkx2-2 is mediated by multiple pathways.
    6. Demonstrate that a rare mature enteroendocrine cell subpopulation that is demarcated by Nkx2.2 expression display stem cell properties during normal intestinal epithelial homeostasis, but is not easily activated upon injury.
      Title: Nkx2.2 is expressed in a subset of enteroendocrine cells with expanded lineage potential.
    7. that Nkx2.2 and Nkx2.9 proteins play no role in the development of branchiovisceral motor neurons in hindbrain rostral to rhombomere 4.
      Title: Nkx2.2 and Nkx2.9 are the key regulators to determine cell fate of branchial and visceral motor neurons in caudal hindbrain.
    8. These data identify Nkx2.2 as key regulator to determine neuronal subtypes in the p3 domain of the central nervous system.
      Title: Generation of a Nkx2.2(Cre) knock-in mouse line: Analysis of cell lineages in the central nervous system.
    9. The study demonstrates a previously unrecognized mechanism that controls insulin expression through c-Abl-regulated NKx2.2 and GLUT2.
      Title: C-Abl inhibitor imatinib enhances insulin production by β cells: c-Abl negatively regulates insulin production via interfering with the expression of NKx2.2 and GLUT-2.
    10. Our studies reveal that a subset of mouse perineurial cells are CNS-derived, express Nkx2.2, and are essential for motor nerve development.
      Title: Mammalian Nkx2.2+ perineurial glia are essential for motor nerve development.
    Submit: New GeneRIF Correction See all GeneRIFs (38)

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables DNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables DNA-binding transcription activator activity, RNA polymerase II-specific IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables DNA-binding transcription factor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables DNA-binding transcription factor activity, RNA polymerase II-specific IBA
    Inferred from Biological aspect of Ancestor
    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 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables cis-regulatory region sequence-specific DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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 transcription factor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    acts_upstream_of_or_within astrocyte differentiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within cell development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cell differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    acts_upstream_of_or_within cell differentiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within digestive tract development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within endocrine pancreas development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within multicellular organism development IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within negative regulation of neuron differentiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within negative regulation of neuron differentiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within nervous system development IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within neuroendocrine cell differentiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of neuron differentiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of neuron differentiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within neuron fate specification IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of_or_within neuron fate specification IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within oligodendrocyte development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of oligodendrocyte differentiation IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of_or_within pancreatic A cell fate commitment IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of_or_within pancreatic A cell fate commitment IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within pancreatic PP cell fate commitment IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of_or_within positive regulation of epithelial cell differentiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within positive regulation of gene expression IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within positive regulation of neuron differentiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within positive regulation of neuron differentiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within positive regulation of oligodendrocyte differentiation IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within regulation of DNA-templated transcription 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 smoothened signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within spinal cord motor neuron differentiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within spinal cord oligodendrocyte cell differentiation IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of_or_within spinal cord oligodendrocyte cell differentiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within spinal cord oligodendrocyte cell fate specification IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within type B pancreatic cell development IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within type B pancreatic cell development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of type B pancreatic cell differentiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within type B pancreatic cell fate commitment IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within ventral spinal cord interneuron fate determination IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in intracellular anatomical structure IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    homeobox protein Nkx-2.2
    Names
    Drosophila NK2 transcription factor related, locus 2
    NK2 transcription factor related, locus 2
    glycoprotein GP330, renal
    homeobox protein NK-2 homolog B
    homeobox protein Nkx2-2

    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)

    1. NM_001077632.2 → NP_001071100.1  homeobox protein Nkx-2.2 isoform 2

      See identical proteins and their annotated locations for NP_001071100.1

      Status: VALIDATED

      Source sequence(s)
      AL928876, AL929317
      Consensus CDS
      CCDS38259.1
      UniProtKB/TrEMBL
      Q8BRS9
      Related
      ENSMUSP00000105596.4, ENSMUST00000109970.5
      Conserved Domains (1) summary
      pfam00046
      Location:131 → 185
      Homeobox; Homeobox domain

    2. NM_001420453.1 → NP_001407382.1  homeobox protein Nkx-2.2 isoform 3

      Status: VALIDATED

      Source sequence(s)
      AL928876, AL929317

    3. NM_010919.3 → NP_035049.1  homeobox protein Nkx-2.2 isoform 1

      See identical proteins and their annotated locations for NP_035049.1

      Status: VALIDATED

      Source sequence(s)
      AL929317
      Consensus CDS
      CCDS16834.1
      UniProtKB/Swiss-Prot
      P42586
      UniProtKB/TrEMBL
      Q3URZ4
      Related
      ENSMUSP00000069666.6, ENSMUST00000067075.7
      Conserved Domains (1) summary
      pfam00046
      Location:131 → 185
      Homeobox; Homeobox domain

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000068.8 Reference GRCm39 C57BL/6J

      Range
      146967909..147037270 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_036159329.1 → XP_036015222.1  homeobox protein Nkx-2.2 isoform X2

      Conserved Domains (1) summary
      pfam00046
      Location:131 → 185
      Homeobox; Homeobox domain

    2. XM_036159345.1 → XP_036015238.1  homeobox protein Nkx-2.2 isoform X5

      Conserved Domains (1) summary
      pfam00046
      Location:131 → 185
      Homeobox; Homeobox domain

    3. XM_036159330.1 → XP_036015223.1  homeobox protein Nkx-2.2 isoform X3

      Conserved Domains (1) summary
      pfam00046
      Location:131 → 185
      Homeobox; Homeobox domain

    4. XM_036159341.1 → XP_036015234.1  homeobox protein Nkx-2.2 isoform X4

      UniProtKB/TrEMBL
      Q8BRS9
      Conserved Domains (1) summary
      pfam00046
      Location:131 → 185
      Homeobox; Homeobox domain

    5. XM_036159331.1 → XP_036015224.1  homeobox protein Nkx-2.2 isoform X4

      UniProtKB/TrEMBL
      Q8BRS9
      Conserved Domains (1) summary
      pfam00046
      Location:131 → 185
      Homeobox; Homeobox domain

    6. XM_036159335.1 → XP_036015228.1  homeobox protein Nkx-2.2 isoform X4

      UniProtKB/TrEMBL
      Q8BRS9
      Conserved Domains (1) summary
      pfam00046
      Location:131 → 185
      Homeobox; Homeobox domain

    7. XM_036159347.1 → XP_036015240.1  homeobox protein Nkx-2.2 isoform X6

      Conserved Domains (1) summary
      pfam00046
      Location:131 → 185
      Homeobox; Homeobox domain

    8. XM_006498900.5 → XP_006498963.1  homeobox protein Nkx-2.2 isoform X1

      See identical proteins and their annotated locations for XP_006498963.1

      UniProtKB/Swiss-Prot
      P42586
      UniProtKB/TrEMBL
      Q3URZ4
      Conserved Domains (1) summary
      pfam00046
      Location:131 → 185
      Homeobox; Homeobox domain

    9. XM_011239349.4 → XP_011237651.1  homeobox protein Nkx-2.2 isoform X1

      See identical proteins and their annotated locations for XP_011237651.1

      UniProtKB/Swiss-Prot
      P42586
      UniProtKB/TrEMBL
      Q3URZ4
      Conserved Domains (1) summary
      pfam00046
      Location:131 → 185
      Homeobox; Homeobox domain

    10. XM_006498899.4 → XP_006498962.1  homeobox protein Nkx-2.2 isoform X1

      See identical proteins and their annotated locations for XP_006498962.1

      UniProtKB/Swiss-Prot
      P42586
      UniProtKB/TrEMBL
      Q3URZ4
      Conserved Domains (1) summary
      pfam00046
      Location:131 → 185
      Homeobox; Homeobox domain

    11. XM_036159325.1 → XP_036015218.1  homeobox protein Nkx-2.2 isoform X1

      UniProtKB/Swiss-Prot
      P42586
      UniProtKB/TrEMBL
      Q3URZ4
      Conserved Domains (1) summary
      pfam00046
      Location:131 → 185
      Homeobox; Homeobox domain

    RNA

    1. XR_004938823.1 RNA Sequence

    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P42586.2 GenPept UniProtKB/Swiss-Prot:P42586

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Other Literature Sources
    Chemical Information
    Molecular Biology Databases
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