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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
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