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FLASH GENE
Symbol TIA1 contributors: mct - updated : 30-09-2011
HGNC name TIA1 cytotoxic granule-associated RNA binding protein
HGNC id 11802
Location 2p13.3      Physical location : 70.436.576 - 70.475.779
Synonym name
  • T-cell-restricted intracellular antigen-1
  • cytotoxic granule-associated RNA-binding protein
  • p40-TIA-1 (containing p15-TIA-1)
  • Synonym symbol(s) TIA-1
    DNA
    TYPE functioning gene
    STRUCTURE 36.00 kb     12 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    motif repetitive sequence   other
    text structure Au rich element (ARE) in 3'utr
    MAPPING cloned Y linked   status confirmed
    regionally located in the PARK3 region
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 splicing 2357 40 375 - 1994 8176212
  • short isoform 1 lacking exon 5
  • 13 splicing 4653 42.9 386 - 1994 8176212
    long isoform 2
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtongue  highly
    Hearing/Equilibriumear   highly
     earinnercochlea highly
    Lymphoid/Immunelymph node   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymphocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • three N-terminal RNA recognition motifs (RRMs), and any one RRM in combination with a Q domain is necessary and sufficient for TIA1-associated regulation of SMN2 exon 7 splicing
  • a prion-related domain
  • a C-terminal glutamine-rich (Q-rich) domain
  • isoforms Precursor p40-TIA1, precursor of a 15 kDa (p15-TIA-1) protein
    HOMOLOGY
    interspecies homolog to murine Tia1
    homolog to rattus LOC312510
    Homologene
    FAMILY
  • Q-rich domain containing RNA-binding proteins
  • CATEGORY RNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic,granule
    intracellular,nucleus
    text also colocalizing with POLR in stress granules, initiated by the phosphorylayion of EIF2A
    basic FUNCTION
  • cytotoxic granule associated RNA binding protein
  • regulator of alternative pre-mRNA splicing
  • may be involved in induction of apoptosis
  • may have dual role in shuttling between DNA and RNA ligands to co-regulate COL2A1 expression at the level of transcription and pre-mRNA alternative splicing
  • major granule associated species
  • translational silencer of COX2, selectively regulating the expression of TNF
  • nucleolytic activity against cytotoxic lymphocyte target cells
  • acting as a post-transcriptional silencer, and suppressing the production of the TNF-alpha protein
  • TIA1, and TIAL1 are mRNA-binding proteins that can aggregate within granules under specific stress conditions
  • its expression counteracts the inhibitory effect of polypyrimidine tract binding protein, a ubiquitously expressed factor recently implicated in regulation of SMN exon 7 splicing
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
  • binding
  • poly(A) binding
  • small molecule
    protein
  • ARE element of TNF
  • binding to FASTK
  • interacts with a conserved AU-rich cis element in COL2A1 intron 2 and modulates alternative splicing of exon 2
  • interacting with RPS6KA3 (the RPS6KA3 N-terminal kinase domain controls the direct interaction with the prion-related domain of TIA1)
  • KHDRBS1 complexed with T-cell intracellular antigen-1 (TIA1), a core SG component, and that the complex formation was correlated with stress granules (SG) recruitment
  • regulate SMN exon 7 splicing by binding to intron 7 sequences away from the 5prime ss
  • TIA1 and TIAL1 proteins are intron-associated positive regulators of SMN2 exon 7 splicing
  • cell & other
    REGULATION
    Other regulated by TARDBP (TARDBP contributes to both the assembly and maintenance of stress granules (SGs)in response to oxidative stress and differentially regulates key SGs components, including TIA1 and G3BP1)
    rapid and severe hypoxia caused co-aggregation of TIAL1/TIA1 and these proteins suppressed HIF1A expression
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    expressed in synovium of patients with rheumatoid arthritis
    constitutional     --over  
    in the thyroid tissues in patients with Graves disease
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS