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FLASH GENE
Symbol NKX2-1 contributors: mct - updated : 23-10-2015
HGNC name NK2 homeobox 1
HGNC id 11825
Corresponding disease
BHC benign hereditary chorea
DEL14QP chromosome 14q proximal deletion
TGDRD congenital thyroglobulin defect with respiratory distress
Location 14q13.3      Physical location : 36.985.605 - 36.989.430
Synonym name
  • NK-2 (Drosophila) homolog A (thyroid nuclear factor)
  • thyroid transcription factor 1
  • benign chorea
    • Synonym symbol(s) NKX2A, TTF-1, BCH, NK-2, TEBP, TTF1, TITF1, BHC, NKX2.1, NKX2A, T/EBP
    DNA
    TYPE like-sequence
    SPECIAL FEATURE
    text duplicated form (with NKX2-8) of NKX2-2 on chromosome 20p
    STRUCTURE 3.81 kb     2 Exon(s)
    MAPPING cloned Y linked N status confirmed
    Map cen - D14S1017 - NKX2-1 - D14S69 - D14S75 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 2352 38.6 371 - 2009 19336474
    includes exons II and III
    3 - 2183 41 401 expressed differentially during mouse embryonic lung development 2009 19336474
    includes three exons, reduced trancription activity
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Respiratorylung     Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousependymal cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal
    Text embryonic striatum and brain, fetal gut
    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