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FLASH GENE
Symbol NKX2-1 contributors: mct - updated : 23-10-2015
HGNC name NK2 homeobox 1
HGNC id 11825
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • helix-turn-helix, DNA binding domain, a homeodomain, preferentially binding to thyroglobulin promoter
  • a TN domain
  • a NK2 specific domain
  • two apparently redundant activation domains and is post-translationally modified by phosphorylation
    • HOMOLOGY
    interspecies homolog to murine Titf1
    intraspecies paralog to NKX2-4
    Homologene
    FAMILY
  • NK family of homeodomain containing transcritpion factor
    • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • activating the promoter of thyroid specific gene (thyroglobulin, thyroperoxidase) and controling the early events underlying the central activation of puberty
  • playing a role in lung morphogenesis
  • required for formation of the lung and differentiation of peripheral respiratory epithelial cells, and for morphogenesis of the fetal diencephalon
  • plays a regulatory role in the transcription of growth hormone and prolactin genes and may regulate transdifferentiation of cells expressing these two hormones
  • differential contribution of SHH-expressing and SHH-responding cells to medial amygdala neuronal diversity as well as the function of NKX2-1 in the development of this important limbic system structure
  • functional role of phosphorylation in NKX2-1
  • plays important roles in thyroglobulin (Tg) gene expression in chondrocytes
  • transcriptionally regulates occludin, which represents another avenue of NKX2-1-mediated metastasis suppression
  • GRHL2 and NKX2-1 form a regulatory loop that coordinates lung epithelial cell morphogenesis and differentiation
  • expression of NKX2-1 is required to specify definitive endoderm to respiratory endoderm
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    text lung morphogenesis
    PATHWAY
    metabolism
    signaling hormonal
    thyroid
    a component
    INTERACTION
    DNA binding to thyroglobulin promoter
    RNA
    small molecule
    protein
  • regulating SCGB3A2 expression
  • interacting with RET promoter
  • target of SLC26A4 (action is a prime factor in controlling thyroid differentiation)
  • interacts physically and functionally with FOXA1(interaction is inhibitory and occurs through the NKX2.1 homeodomain in a DNA-independent manner)
  • binds a highly conserved sequence in the LHX6 promoter, and this sequence appears to mediate the direct activation of LHX6 by NKX2.1
  • HOXB5 binds to the promoter region 5prime upstream of the binding site of NKX2-1 and regulates RET expression
  • MYBPH is a transcriptional target of NKX2-1, a master regulator of lung development that also plays a role as a lineage-survival oncogene in lung adenocarcinoma development
  • transactivated the expression of the epithelial tight junction molecules occludin (OCLN) and CLDN1
  • direct binding of Activin-A-responsive SMAD2 to the NKX2-1 promoter plays essential role during respiratory endoderm specification
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) TGDRD , BHC , DEL14QP
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in thyroid adenocarcinoma
    tumoral       gain of function
    coactivation of NKX2-1 and NKX2–8 pathways in non-small-cell lung cancer resistant to standard cisplatin therapy and with poor prognosis
    tumoral   amplification    
    and overexpression contribute to lung cancer cell proliferation rates and survival and implicate TITF1 as a lineage-specific oncogene in lung cancer
    constitutional germinal mutation      
    in neuroendocrine cell hyperplasia of infancy (NEHI)
    tumoral     --other  
    ectopic expression of NKX2-1 in diffuse large B-cell lymphoma cells, representing the central player in an oncogenic regulative network compromising B-cell differentiation
    Susceptibility to Hirschsprung disease (HSCR)
    Variant & Polymorphism SNP SNP repressing activation of transcription from HSCR-associated RET promoter haplotypes
    Candidate gene lung disease
    Marker
    Therapy target
    ANIMAL & CELL MODELS