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FLASH GENE
Symbol NKX3-1 contributors: mct - updated : 04-05-2016
HGNC name NK3 transcription factor related, locus 1 (Drosophila)
HGNC id 7838
Location 8p21.2      Physical location : 23.536.206 - 23.540.450
Synonym name
  • NK homeobox (Drosophila), family 3, A
  • NK3 transcription factor homolog A
  • NK3 homeobox 1
  • Synonym symbol(s) HK31, NKX3A, NKX3.1, NKX3, BAPX2
    DNA
    TYPE functioning gene
    STRUCTURE 4.25 kb     2 Exon(s)
    regulatory sequence Promoter
    text structure functional cis-element in the 197 bp region (from -1032 to -836 bp) of the NKX3.1 promoter which was previously identified to present positive regulatory activity on NKX3.1 expression
    MAPPING cloned Y linked N status confirmed
    Physical map
    PPP3CC 8p21.2 protein phosphatase 3 (formerly 2B), catalytic subunit, gamma isoform (calcineurin A gamma) LOC389639 8 LOC389639 SCAM-1 8p21.2 vinexin beta (SH3-containing adaptor molecule-1) PDLIM2 8p21.2 PDZ and LIM domain 2 (mystique) DBC-1 8p22 p30 DBC protein BIN3 8p21.2 bridging integrator 3 FLJ14107 8p21.2 hypothetical protein FLJ14107 EGR3 8p23-p21 early growth response 3 MGC22776 8p21.2 hypothetical protein MGC22776 RHOBTB2 8p21.2 Rho-related BTB domain containing 2 TNFRSF10B 8p21 tumor necrosis factor receptor superfamily, member 10b LOC389640 8 LOC389640 TNFRSF10C 8p21 tumor necrosis factor receptor superfamily, member 10c, decoy without an intracellular domain TNFRSF10D 8p21 tumor necrosis factor receptor superfamily, member 10d, decoy with truncated death domain TNFRSF10A 8p21 tumor necrosis factor receptor superfamily, member 10a LOC389641 8 hypothetical gene supported by AK124295 MGC29816 8p21.2 hypothetical protein MGC29816 LOC203069 8p21.2 hypothetical protein LOC203069 LOXL2 8p21.3-p21.2 lysyl oxidase-like 2 LYSAL1 8p22-p21.3 lysosomal apyrase-like 1 MSCP 8p21.2 mitochondrial solute carrier protein PRO1496 8p21.2 hypothetical protein PRO1496 LOC389642 8 LOC389642 NKX3-1 8p21 NK3 transcription factor related, locus 1 (Drosophila) LOC137814 8p21.2 similar to homeobox protein NKX2-6 STC1 8p21-p11.2 stanniocalcin 1 ADAM28 8p21.3-p12 a disintegrin and metalloproteinase domain 28 ADAMDEC1 8p21.1 ADAM-like, decysin 1 ADAM7 8p21.2 a disintegrin and metalloproteinase domain 7
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 3266 26.2 234 - He, Korkmaz
    - splicing 725 205 185 - He, Korkmaz
    - splicing 724 17.6 159 - He, Korkmaz
    - splicing 724 18.3 165 - He, Korkmaz
    - splicing 603 21 190 - He, Korkmaz
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivemale systemprostate    Homo sapiens
     male systemtestis    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandular  
    cells
    SystemCellPubmedSpeciesStageRna symbol
     mucous cell
    Urinaryepithelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion in the prostatic fluids and urine
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an helix-turn-helix homeobox DNA binding domain, involved in mediating the interaction with multiple protein partners, including prostate-derived Ets factor, serum response factor, Sp proteins and topoisomerase
  • an evolutionarily conserved protein transduction domain essential for its para-transcription factor (PTF) function, implicating potentially common PTF function among homeoproteins
  • HOMOLOGY
    interspecies homolog to Drosophila NK homeobox family member
    Homologene
    FAMILY
  • NK family of homeodomain containing transcription factor
  • NK-3 homeobox family
  • CATEGORY regulatory , transcription factor , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • prostate-specific homeobox gene related to prostate development and prostate cancer
  • putatively involved in the differentiation of prostatic tissue (regulation of proliferation of glandular epithelium and formation of ducts)
  • transcription factor critical for normal prostate development and function
  • can behave as a transcriptional repressor
  • required for prostatic epithelial differentiation and suppression of prostate cancer
  • regulating negatively Sp-mediated transcription via the tethering of histone deacetylases and/or by inhibiting the association of Sp proteins with co-activators
  • haploinsufficient cell growth/differentiation regulator
  • androgen-regulated homeobox gene that encodes a tissue-restricted transcription factor, which plays an important role in the differentiation of the prostate epithelium
  • maintains an active DNA damage response at the intra S progression and contributes to the chemotherapeutic resistance of prostate cancer cells to DNA damaging compounds
  • prostate- and testis-specific nucleoprotein with two conserved domains
  • has potentilly a regulatory role for genome maintenance in prostate cells through activation of the DNA damage response
  • NKX3.1-mediated activation of DNA damage response restores the intra S phase arrest upon DNA damage and, consequently, leads to reprogramming of the cells at the G1/S phase transition
  • functions as a “para-transcription factor (PTF),” with the ability to regulate genes and inhibit cell proliferation in a non-cell autonomous manner
  • can penetrate into prostate epithelial cells and translocate into the nucleus
  • PTF function of NKX3.1 is required for its tumor suppressor role in adjacent cells
  • functions to maintain canonical Wnt signaling activity in developing prostate bud tips
  • role as a tumor suppressor gene through direct regulation of the cell cycle and growth/survival pathways
  • encodes a homeobox protein, which transcriptionally regulates oxidative damage responses and enhances topoisomerase I re-ligation by a direct interaction with the ATM protein in prostate cells
  • androgens and NKX3-1 expression regulate the progression of the cell cycle and concurrently activate the DNA damage response (DDR)
  • plays roles in early prostate development and functions as a prostate-specific tumor suppressor
  • plays essential roles in prostate differentiation and prostate cancer
  • NKX3.1-G9a-UTY transcriptional regulatory network is essential for prostate differentiation, and likely disruption of such a network predisposes to prostate cancer
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    nucleotide, transcription, regulation
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS development , excretion
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding preferentially the consensus sequence 5'-TAAGT[AG]-3'
    RNA
    small molecule
    protein
  • serum response factor
  • PDEF in prostate epithelial cells, and KLK3 (regulation of the activity of promoter)
  • CSNK2A2 is a regulator of NKX3-1 in prostate tumor cells
  • TOPORS, a strong E3 ubiquitin ligase, promotes proteasomal degradation of NKX3.1 through direct interaction, predisposing cells to oncogenic transformation by providing an irreversible growth advantage as the first steps in prostate carcinogenesis
  • interaction between the prostate tumor suppressor NKX3.1 and the ubiquitin E3 ligase TOPORS (negative regulatory role for TOPORS on NKX3.1 in prostate cancer cells through the ubiquitin-proteasome pathway)
  • NKX3-1, AR, and FOXA1 promote prostate cancer cell survival by directly upregulating RAB3B
  • PIM1-mediated NKX3.1 stabilization may be important in maintaining normal cellular homeostasis in normal prostate epithelial cells, and may maintain basal NKX3.1 protein levels in prostate cancer cells
  • binds to the N-terminal region of ATM, accelerates ATM activation
  • NKX3-1 and DYRK1B were shown to interact via the DYRK1B kinase domain
  • cell & other
    REGULATION
    activated by 17 beta estrodiol
    androgens via an AR dependent mechanism in normal prostate epithelium
    induced by androgens and by estrogens in LNCAP cell line
    Other 3'UTR functions as an androgen-responsive enhancer (Thomas 2010)
    modified post-translationally at multiple sites by different protein kinases
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    in prostate carcinoma, promoting increased oxidative damage in prostate carcinogenesis
    tumoral   LOH    
    in prostate carcinoma
    tumoral     --low  
    is an early and consistent event in prostate cancer and is associated with increased proliferation of prostate epithelial cells and poor prognosis
    Susceptibility to prostate carcinoma
    Variant & Polymorphism other
  • functional variant rs11781886 in the 5prime-UTR can affect its transcription by altering the binding affinity of a transcriptional factor Sp1, and might result in prostate carcinoma susceptibility by lowering expression of NKX3-1 in the prostate (
  • Candidate gene
    Marker
  • NKX3-1 reduction may serve as a potential diagnostic marker for Prostate carcinoma
  • Therapy target
    ANIMAL & CELL MODELS