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FLASH GENE
Symbol TIAM1 contributors: mct - updated : 31-05-2022
HGNC name TIAM Rac1 associated GEF 1
HGNC id 11805
Corresponding disease
DDIDSDS developmental delay, intellectual disability, speech delay and seizures
Location 21q22.11      Physical location : 32.490.735 - 32.931.290
Synonym name
  • T-cell lymphoma invasion and metastasis 1
  • human T-lymphoma invasion and metastasis inducing TIAM1 protein
  • Synonym symbol(s) FLJ36302, TIAM-1
    DNA
    TYPE functioning gene
    STRUCTURE 440.67 kb     29 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    29 - 7308 - 1591 - 2010 20802514
    28 - 7255 - 1591 - 2010 20802514
    30 - 7593 - 1591 - 2010 20802514
    30 - 7404 - 1591 - 2010 20802514
    28 - 7198 - 1591 - 2010 20802514
    29 - 7375 - 1591 - 2010 20802514
    27 - 7143 - 1566 - 2010 20802514
    28 - 7143 - 1566 - 2010 20802514
    28 - 7218 - 1591 - 2010 20802514
    13 - 4152 - 599 - 2010 20802514
    13 - 4227 - 624 - 2010 20802514
    29 - 7647 - 1591 - 2010 20802514
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain   highly Homo sapiens
     brainlimbic systemhippocampusdentate gyrushighly Homo sapiens
    Reproductivemale systemtestis  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal pleckstrin homology coiled-coiled extension (PHn-CC-Ex) and catalytic DBL homology domain (DH) modulating the activity of Rac1, RHO-like protein
  • a DHR/PDZ (PSD95/disc large/ZO-1) domain
  • C-terminal pleckstrin homology (DH-PHc) domain
  • HOMOLOGY
    interspecies homolog to murine T lymphoma invasion and metastasis inducing gene 1 (Tiam1)
    ortholog to drosophila Sif
    Homologene
    FAMILY DBL-family guanine nucleotide exchange factor (GEF)
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    text
  • TIAM1 localises to centrosomes during S-phase, where it is required for the maintenance of normal centriole number
  • basic FUNCTION
  • putative GDP-GTP exchange factor, involved in neural cell development
  • may function in cellular signaling by activation of a Rho-like GTPase that regulates the cytoskeletal organization
  • playing an important role in invasion and metastasis of colorectal carcinoma and is a metastasis-related gene
  • mediates neurite outgrowth induced by ephrin-B1 and EPHA2
  • required for the activation of Rac1, actin polymerization, relocation of junctional associated proteins, and disruption of interendothelial junctions
  • modulating the balance of Rho GTPase activities in the growth cone and, consequently, to control growth cone behavior
  • required for chemokine- and S1P-induced Rac activation and subsequent cell migration
  • implicated in tumor invasion and metastasis
  • integrates signals from CADM1 to regulate the actin cytoskeleton through RAC activation, which may lead to tissue infiltration of leukemic cells in adult T-cell leukemia patients
  • guanine exchange factor (GEF) for the Rho-family GTPase Rac1 that is crucial for the integrity of adherens junctions, tight junctions, and cell-matrix interactions
  • mediator of NGF/NTRK1-dependent neurite elongation (mediates NTRK1 signaling and neurite outgrowth induced by NGF)
  • implicated in multiple signaling pathways in epithelial tumor cells
  • may have a role in modulating the effects of the tumor microenvironment on malignant cell invasion and metastasis
  • is a metastasis-related gene, that may contribute to hepatocellular carcinoma invasion and metastasis
  • TIAM1 plays a critical role in the development of glutamatergic perforant path-dentate gyrus synapses
  • TIAM1 is a key regulator of dentate gyrus (DG) granule cell stabilization and function within hippocampal circuits
  • promotes the formation and growth of spines and synapses by activating RAC1 signaling pathways that control the actin cytoskeleton
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • activator of Rho-like GTPases RAC
  • SDC1 and CASPR4, are potential TIAM1 PDZ domain binding proteins
  • interactions with different scaffold proteins activating different RAC1-dependent pathways by recruiting specific RAC1 effector proteins
  • two TIAM1-interacting proteins in fibroblasts, insulin receptor substrate protein 53 kDa (BAIAP2) and PPP1R9B
  • plays a role in clathrin-dependent endocytosis of EPHA8-ephrinA5 complexes
  • interacting with ITGB2 (TCR-induced activation of ITGB2 involves signaling through TIAM1)
  • GRIN2C and TIAM1 maturation genes are synergistically controlled by the activity-dependent induction of ETV1 and its phosphorylation by the BDNF signaling cascade
  • RAC1 exchange factor TIAM1 participates in polarized cell migration with the PAR complex of PARD3, PARD6A, and PRKCI
  • MAP1B-TIAM1 interaction, and pleckstrin homology (PH) domains in TIAM1 are responsible for MAP1B binding
  • BAI1 interacts with PARD3/TIAM1 and recruits these proteins to synaptic sites
  • RAB23 promotes squamous cell carcinoma cells migration and invasion by regulating ITGB1/TIAM1/RAC1 pathway
  • TIAM1, and its cognate Rho-family G protein, RAC1, regulate interleukin (IL)17A transcription and autoimmunity
  • SETDB1-TIAM1 compounds were involved in a novel pathway, which regulated epigenetic modification of gene expression in hepatocellular carcinoma (HCC)
  • SH3GL3 stimulates cell migration by binding the Rac GEF TIAM1 leading to activation of small GTPase
  • mediates RAC1 activation and contraction-induced glucose uptake in skeletal muscle cells
  • regulates PLK4 levels through promoting BTRC-mediated degradation independently of RAC1 activation
  • cell & other
    REGULATION
    activated by SIRT1, SIRT2, that positively regulate the levels of TIAM1, a Rac guanine nucleotide exchange factor (GEF)
    Other phosphorylated on Y384 by SRC (which is required for SRC-induced adherens junctions disassembly and cell migration, and creates a docking site on TIAM1 for GRB2)
    is auto-inhibited by its pleckstrin homology coiled-coil extension domain (
    ASSOCIATED DISORDERS
    corresponding disease(s) DDIDSDS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in colorectal cancer, especially in metastatic cases, associated with hypomethylation of promoter region in colorectal cancer tissues
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • prognostic marker for esophageal squamous cell carcinoma (ESCC)
  • may be a prognostic factor for the treatment of thyroid cancers
  • may be a useful biomarker for therapeutic strategy and control in hepatocellular carcinoma (HCC) treatment
  • Therapy target
    SystemTypeDisorderPubmed
    cancer  
    pharmacologic reversal of promoter hypomethylation may inhibit cell proliferation and migration
    immunologyinflammatory 
    activation of a TIAM1-Rac1 signaling module, is a potential novel therapeutic target against increased vascular permeability associated with inflammatory diseases
    cancerendocrinethyroid
    potential therapeutic target for the treatment of thyroid cancers
    immunologyautoimmunemultiple sclerosis
    TIAM1/RAC1 may be a therapeutic target in multiple sclerosis
    ANIMAL & CELL MODELS
  • mice lacking Tiam1 have simplified dendritic arbors, reduced dendritic spine density, and diminished excitatory synaptic transmission in the dentate gyrus