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FLASH GENE
Symbol BTG2 contributors: mct/npt/pgu - updated : 08-11-2016
HGNC name BTG family, member 2
HGNC id 1131
Location 1q32.1      Physical location : 203.274.663 - 203.278.727
Synonym name
  • phreochromocytoma cell 3
  • B cell translocation gene 2
  • NGF-inducible anti-proliferative protein PC3
  • nerve growth factor-inducible anti-proliferative
    • Synonym symbol(s) TIS21, PC3, EVI38, MGC126063, MGC126064, APRO1
    DNA
    TYPE functioning gene
    STRUCTURE 4.07 kb     2 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    text structure TP53 response element located to the codon start
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 2718 - 158 - 1996 8944033
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinethyroid   highly
    Lymphoid/Immunespleen   highly
    Visualeye   highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuroectodermal cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period
    cell cycle     cell cycle, checkpoint, G1S
    Text onset on neurogenesis
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • conserved N-terminal domain spanning 104-106 AAs, a protein-protein interaction module, which is capable of binding to DNA-binding transcription factors as well as the paralogues CNOT7 (human Caf1/Caf1a) and CNOT8 (human Pop2/Calif/Caf1b), two deadenylase subunits of the Ccr4-Not complex
  • two leucine-rich motifs (20LxxLL24 and 92LxxLL96), which are usually found in nuclear receptor co-factors
  • C-terminal regions are less conserved and appear to mediate protein-protein interactions that are unique to each family member, necessary and sufficient to control its stability
    • HOMOLOGY
    interspecies homolog to murine Pc3/Tis21
    intraspecies homolog to BTG1 (see symbol)
    Homologene
    FAMILY
  • BTG/Tob family of antiproliferative proteins
  • BTG/TOB (B-cell translocation gene/transducers of ErbB2) gene family
    • CATEGORY tumor suppressor
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • antiproliferative p53 dependent component of the DNA damage cellular response pathway
  • at the onset of neurogenesis in single neuroepithelial cells that switch from proliferative to neuron-generating divisions
  • transcriptional regulator
  • switch of neuroectodermal cells from proliferating to neuron generating division
  • implicated in the regulation of cell-cycle progression, differentiation of cell lines as well as the control of cellular apoptosis
  • having a suppressive role in the regulation of CNOT7 deadenylase activity
  • identified as an important downstream effector of TP53-dependent arrest of proliferation in human fibroblasts transduced by oncogenic Ras
  • may be a modulator of cell survival and differentiation and could help to protect against cell death by inhibition of necrosis and/or apoptotic signalling pathways
  • implicated in transcription in the nucleus and cytoplasmic mRNA deadenylation and turnover
  • complexing with AR via an LxxLL-dependent mechanism and may play a role in prostate cancer via modulating the AR signaling pathway
  • functions as a novel AR-interacting protein in the repression of AR transcriptional activity, and the 92LxxLL96 motif is not only necessary for the BTG2 and AR interaction, it is also essential for BTG2 repression of AR transcriptional activity
  • implicated in cell cycle regulation, normal development, and possibly tumor suppression
  • role for BTG2 as a co-activator for NFE2L2 in up-regulating cellular antioxidant defenses
  • plays likely an important role in hepatic glucose metabolism.
  • GCG positively regulates insulin gene expression via BTG2, suggesting that BTG2 has a key function in insulin secretion in pancreatic beta-cells
  • participates in the regulation of hepatic glucose homeostasis
  • is required for development of spiral ganglion cells (SGCs)
  • both BTG1 and BTG2 are required for normal vertebral patterning of the axial skeleton, but each gene contributes differently in specifying the identity along the anterior-posterior axis of the skeleton
  • BTG2 expression is likely an endogenous cell death inducer at the downstream of TP53 gene, which might be useful for intractable cancer chemotherapy
  • negatively regulates reactive hypertrophy of cardiomyocyte by negatively regulating RNA accumulation
  • may function as a tumor suppressor by interfering with the WNT/CTNNB1 signaling pathway in skin cancer cells 8)
    • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    nucleotide, repair
    nucleotide, transcription, regulation
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS
    text histogenesis
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with PRKCABP
  • binding the CCR4- NOT complex
  • interact with the Pop2/Caf1 deadenylase (CNOT8)
  • bound to protein arginine methyltransferase (PRMT) 1 via the box C region, an interaction required for anti-IgM-induced growth inhibition
  • directly bound to the androgen receptor (AR) in the absence of 5alpha dihydrotestosterone(DHT)
  • anti-proliferative activity of BTG1, BTG2, BTG3, BTG4, TOB1, TOB2 proteins is mediated through interactions with the CNOT7, CNOT8 deadenylase enzymes
  • is a binding partner for NFE2L2 and increases its transcriptional activity
  • BTG2 is a crucial regulator in GCG-induced insulin gene expression and insulin secretion via upregulation of pancreatic duodenal homeobox-1 (PDX1) in pancreatic beta-cells
  • negatively regulated cancer cell growth by inhibiting IL6 expression through downregulation of STAT3 activation
  • CRP induces G2/M phase cell cycle arrest and apoptosis in monocytes through the upregulation of BTG2 expression
  • is a key player in hepatic hepcidin (HAMP) regulation via induction of Yin Yang 1 (YY1)
  • BTG2 is regulated by STAT3 signaling and inhibits adipocyte differentiation
  • interaction of BTG2 with the first RRM domain of PABPC1 is required for BTG2 to control cell proliferation
    • cell & other
    REGULATION
    Other degraded by the ubiquitin-proteasome system
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in carcinogenesis of thymus, prostate, kidney, and liver
    tumoral     --low  
    in prostate cancer
    Susceptibility to Graves disease
    Variant & Polymorphism SNP
  • SNPs rs12136280, rs6663606, and rs17534202 in BTG2 were associated with Graves disease
    • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivestomach
    in gastric cancer, BTG2 could be thought as a tumor-inhibiting gene in some distance, so the gene could be a potential target of gene therapy
    cancerskin 
    novel therapeutic strategies and agents targeting BTG2 may be potential treatments for skin cancer
    ANIMAL & CELL MODELS