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FLASH GENE
Symbol TRIO contributors: npt/mct - updated : 19-09-2017
HGNC name triple functional domain (PTPRF interacting)
HGNC id 12303
DNA
TYPE functioning gene
STRUCTURE 365.62 kb     57 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
57 - 10244 - 3097 - 2006 16033331
- splicing - - - specifically expressed in the nervous system 2006 16033331
  • exhibit one or two Rho-GEF domains (GEFDs)
  • could be essential for Trio function in neuronal morphology
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly
    Endocrineneuroendocrinepituitary  highly
    Lymphoid/Immunelymph node   highly
    Nervousbrain     Homo sapiensFetal
     nervecranial nerve  highly
    Respiratorylung    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal DH-PH domain is known to activate RAC1 and RHOG
  • a cral-trio domain
  • two functional GEF domains; the first GEF domain (GEFD1) regulates RAC1 and RHOG activity, and the second GEF domain (GEFD2) regulates RHOA activity
  • four spectrin-like domains
  • a Ig-like domain
  • a serine/threonine kinase domain
  • two SH3 domains
  • a C-terminal Rho-specific DH-PH cassette, activated by GNAQ, and engaging Rho GTPases for their efficient activation , and that can activate RHOA
  • HOMOLOGY
    Homologene
    FAMILY
  • Dbl family of guanine nucleotide exchange factors (GEFs)
  • CAMK Ser/Thr protein kinase family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • likely involved in active cell migration
  • promoting the exchange of GDP by GTP
  • with PTPRF, it could play a role in coordinating cell-matrix and cytoskeletal rearrangements necessary for cell migration and cell growth
  • TRIO acts as a major regulator of cytokinesis, cell migration, axon outgrowth, axon guidance, and dendritic arborization and plays a role in synaptogenesis by modulating excitatory synaptic transmission
  • activated the IKK activity by binding with the IkappaB kinase (IKK) complex
  • Rho-specific guanine nucleotide exchange factor, activates NF-kappaB via physical association with IkappaB kinase complexes
  • GEF TRIO is responsible for lamellipodia formation through its N-terminal DH-PH domain in a RAC1-dependent manner during fibronectin-mediated spreading and migration
  • ANKRD26, TRIO, GPS2 and HMMR are novel and important regulators of adipogenesis
  • upon clustering of ICAM1, the Rho-guanine nucleotide exchange factor TRIO activates RAC1, prior to activating RHOG, in a filamin-dependent manner
  • promotes leukocyte transendothelial migration by inducing endothelial docking structure formation in a filamin-dependent manner through the activation of RAC1 and RHOG
  • crucial role for the Rho-GEF TRIO in stabilizing junctions based around vascular endothelial (VE)-cadherin (also known as CDH5)
  • importance of spatio-temporal regulation of the actin cytoskeleton through TRIO and RAC1 at CDH5-based cell-cell junctions in the maintenance of the endothelial barrier
  • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS
    text putatively involved in cell-matrix and cytoskeletal rearrangements necessary for cell migration
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • forming complex with the LAR transmembrane tyrosine phosphatase (PTPRF)
  • PTPRS interacting with PPFIA4, BCAR1, TRIO
  • both full-length TRIO and the first DH-PH (TRIOD1) domain of TRIO, which can activate RAC1 and RHOG, interact with ICAM1 and are recruited to leukocyte adhesion sites
  • NAV1 interacts and colocalizes with TRIO, a Rho guanine nucleotide exchange factor that enables neurite outgrowth by activating the Rho GTPases RAC1 and RHOG
  • TRIO is a mitotic GEF of RAC1, and TRIO controls RAC1 activation and subsequent F-actin remodeling in dividing cells
  • interact with the C-terminal PBH 9/10 domains of PCLO and BSN via its own N-terminal Spectrin repeats, a domain that is also critical for its localization to the cytoskeletal matrix assembled at the presynaptic active zone (AZ) (CAZ)
  • CDH2-signaling via TRIO assembles adherens junctions to restrict endothelial permeability
  • TRIO acts as a key regulator of neuronal migration, axonal outgrowth, axon guidance, and synaptogenesis by activating the GTPase RAC1 and modulating actin cytoskeleton remodeling
  • cell & other
    REGULATION
    Other phosphorylated on serine residue(s)
    ASSOCIATED DISORDERS
    corresponding disease(s) MRD44
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification --over  
    in soft tissue sarcomas
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • heterozygous or homozygous deletion of Trio in the hippocampus and in the cortex during early embryogenesis results in progressive defects in learning ability, sociability, and motor coordination of these mice