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FLASH GENE
Symbol NKX3-2 contributors: mct/npt/pgu - updated : 15-07-2013
HGNC name NK3 homeobox 2
HGNC id 951
Corresponding disease
SMMD spondylomegaepiphyseal-metaphyseal dysplasia
Location 4p15.33      Physical location : 13.542.453 - 13.546.114
Synonym name
  • bagpipe homeobox homolog 1 (Drosophila)
  • homeobox protein Nkx-3.2
  • bagpipe homeobox 1
    • Synonym symbol(s) NKX3.2, NKX3B, BAPX1, MGC138171
    DNA
    TYPE functioning gene
    STRUCTURE 3.66 kb     2 Exon(s)
    regulatory sequence Promoter
    text structure
  • palindromic sequence TAATTA, present in promoter, binds the MEOX1 protein and is necessary for MEOX1-induced transactivation of NKX3-2 promoter
  • a critical SOX9 responsive region in the promoter
    • MAPPING cloned Y linked Y status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 2241 34 333 - 2004 15024065
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text paraxial mesoderm, right lateral plate mesoderm giving rise to visceral muscle, mesenchymal condensation of fetal limb and axial skeleton, first branchial arch
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • helix-turn-helix DNA binding domain
  • a homeobox DNA-binding domain
    • HOMOLOGY
    interspecies homolog to Drosophila bagpipe
    Homologene
    FAMILY
  • NK-3 homeobox family
    • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • involved in mesodermal and skeletal development
  • playing an essential role in craniofacial development
  • required for sclerotomal differentiation
  • recruits the RELA-IkappaBalpha heteromeric complex into the nucleus by direct protein-protein interactions and activates RELA through proteasome-dependent IkappaBalpha degradation in the nucleus
  • plays an important role in endochondral ossification of both the axial and appendicular skeleton
  • plays an important role in early somitic chondrogenesis and control of chondrocyte maturation during limb development
  • suppresses a key osteogenic transcriptional factor, Runt-related transcription factor 2 (RUNX2), to maintain the chondrogenic phenotype in mesenchymal lineages
  • may play an important role in hypoxia-dependent maintenance of chondrocyte phenotype by suppressing RUNX2
  • crucial for hypoxia-dependent maintenance of chondrocyte identity
  • promotes chondrogenesis directly by SOX9-independent mechanisms and indirectly by previously characterized SOX9-dependent mechanisms
  • required for SOX9 to promote chondrogenic differentiation in satellite cells
    • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • IHH/WNT5A signalling may play a role in negative regulation of NKX3-2 for appropriate progression of chondrocyte hypertrophy during chondrogenesis
    • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with BARD1 and UBE2D1 (contributing to its ubiquitin ligase activity)
  • ubiquitin chain-dependent, but persistent, interactions between NKX3-2 and IKBKG can give rise to constitutive IKBKB activation in the nucleus
  • interaction with RUNX2 (NKX3.2-dependent suppression of RUNX2 was a crucial factor in hypoxia-dependent maintenance of chondrocyte identity
  • IHH/WNT5A signalling may play a role in negative regulation of NKX3-2 for appropriate progression of chondrocyte hypertrophy during chondrogenesis
  • bound to the COL2A1 enhancer element
  • NKX3-2 and SOX9 repress the activity of the PAX3 promoter and NKX3-2 acts as a transcriptional repressor in this process
    • cell & other
    REGULATION
    activated by MEOX11 (activates its promoter in a dose-dependent manner and this activity is enhanced in the presence of PAX1 and/or PAX9)
    induced by SHH chondrogenic transcription factor induced by Sonic hedgehog (SHH)
    Other initially induced in chondrocyte precursor cells, maintained in early-stage chondrocytes and down-regulated in terminal-stage chondrocytes
    ASSOCIATED DISORDERS
    corresponding disease(s) SMMD
    Susceptibility to oculo-auriculo-vertebral spectrum (OAVS)
    Variant & Polymorphism other cis-acting regulatory variation predisposing to oculo-auriculo-vertebral spectrum (OAVS)
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS