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FLASH GENE
Symbol TARBP2 contributors: shn/mct - updated : 28-12-2015
HGNC name TAR (HIV-1) RNA binding protein 2
HGNC id 11569
Location 12q13.13      Physical location : 53.894.704 - 53.900.213
Synonym name
  • TAR (HIV) RNA binding protein 2
  • trans-activation responsive RNA-binding protein
  • loquacious, Drosophila, homolog of
  • Synonym symbol(s) LOQS, TRBP, TRBP1, TRBP2
    DNA
    TYPE functioning gene
    STRUCTURE 6.23 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (CAAT box)
    cytosine-phosphate-guanine/HTF
    Binding site   transcription factor
    text structure several potential binding sites for transcriptional factors
    MAPPING cloned Y linked N status confirmed
    Map cen - D12S359 - D12S1618 - TARBP2 - D12S1586 - D12S1651 - qter
    Authors Kozak (1995)
    Text TARBP2 gene was mapped to 12p12.1-q13.1 by analysis of somatic cell hybrids
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 splicing 1888 39.1 366 - 2014 24563462
    two adjacent promoters initiate transcription of alternative first exons
    9 splicing 1488 - 345 - 2014 24563462
    two adjacent promoters initiate transcription of alternative first exons
    9 - 1448 - 345 - 2014 24563462
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus    
    Cardiovascularheart    
    Nervousbrain    
    Reproductivemale systemprostate   
    Visualeyeuvea   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connective    
    Lymphoid    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • three dsRNA-binding domains (dsRBDs), the first and second dsRBDs (dsRBD1 and dsRBD2, respectively) have affinities for dsRNA, whereas the third dsRBD (dsRBD3) binds to DICER1
  • mono polymer heteromer , trimer
    HOMOLOGY
    interspecies ortholog to Tarbp2, murine
    ortholog to Tarbp2, Rattus norvegicus
    ortholog to tarbp2, Danio rerio
    homolog to LOC736926, Pan troglodytes
    Homologene
    FAMILY
    CATEGORY RNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • activating HIV-1 gene expression in synergy with the viral Tat protein
  • TARBP2 enhanced expression of the HIV-1 LTR in human
  • and murine cells
  • facilitating the production of small interfering RNA (siRNA) by Dicer
  • TRBP, inhibits the activity of the interferon-induced protein kinase R (PKR)
  • during development, TRBP has a function in spermatogenesis and growth control
  • TRBP regulates the activation of PKR by controlling its accessibility to the PKR activator (PRKRA)
  • double-stranded RNA (dsRNA)-binding protein, which binds to DiCER1 and is required for the RNA interference pathway
  • TRBP has an oncogenic potential due to its interaction with PKR and the tumor suppressor Merlin induces its degradation by ubiquitination
  • its activities at the molecular level impact the cellular function from normal development to cancer and the response to infections
  • double-stranded RNA-specific diffusion activity of TARBP2 contributes to enhancing siRNA and miRNA processing by DICER1
  • cytoplasmic RISC proteins PRKRA, TARBP2, and DICER1 are steroid receptor RNA activator (SRA) binding nuclear receptor coregulators that target steroid-responsive promoters and regulate nuclear receptor activity and downstream gene expression
  • non-canonical and direct role for TARBP2 in gene expression regulation and regulated RNA destabilization through protein-mediated binding of mRNA structural elements can govern cancer progression
  • RNA-binding protein (RBP) involved in miRNA processing and maturation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • PRKRA is associated with a ~500 kDa complex that contains DICER1, AGO2, and TARBP2 and it associates with DICER1 to facilitate the production of small interfering RNA
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interaction with NF2 (merlin-binding protein)
  • TRBP2 binds to HIV-1 TAR RNA and synergizes with HIV-1 Tat to activate the HIV-1 LTR promoter
  • TRAF4
  • protein kinase R (PKR)
  • dicer-TRBP complex associates with Argonaute-2
  • the tumor suppressor Merlin
  • interacts directly with the DICER1 protein and is required for the stabilization of the DICER1 protein (Melo 2009)
  • AGO2, PRKRA and TARBP2 were required for the efficient functioning of DICER1 in cells, and likely one of the roles of these proteins is to assure better synchronization of cleavages triggered by two RNase III domains of DICER1
  • PRKRA and TARBP2 have distinct effects on DICER1-mediated dsRNA processing
  • interface residues conserved between TARBP2 and PRKRA show that the proteins bind to DICER1 in a similar manner and by mutual exclusion
  • FTSJ3 is a 2'O-MTase that is recruited to HIV RNA through TARBP2
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in mesothelioma
    tumoral     --over  
    in endometrial cancer metastasis
    tumoral somatic mutation     loss of function
    truncating mutations in tumors with microsatellite instability causing diminished TRBP protein expression and defective processing of miRNAs (Melo 2009)
    tumoral     --over  
    in many cancers such as prostate cancer, cutaneous malignant melanoma, and adrenocortical carcinoma
    tumoral     --low  
    in some cancers including colorectal cancer, gastric cancer, Ewing sarcoma, and upper urinary tract urothelial carcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • breast cancer patients with TARBP2 cytoplasm expression have unfavorable prognosis, and patients of triple-negative breast cancer (TNBC) and late-stage breast cancer with higher cytoplasm TARBP2 expression have an unfavorable prognosis
  • Therapy target
    ANIMAL & CELL MODELS
  • mice homozygous for the mutant Prkra allele had defects not only in ear development but also growth, craniofacial development and ovarian structure