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FLASH GENE
Symbol TIAM1 contributors: mct - updated : 17-08-2014
HGNC name T-cell lymphoma invasion and metastasis 1
HGNC id 11805
Location 21q22.11      Physical location : 32.490.735 - 32.931.290
Synonym symbol(s) FLJ36302, TIAM-1
DNA
TYPE functioning gene
STRUCTURE 440.55 kb     29 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked   status confirmed
Physical map
KRTAP19-7 21q22.1 keratin associated protein 19-7 KRTAP6-3 21q22.1 keratin associated protein 6-3 KRTAP6-2 21q22.1 keratin associated protein 6-2 KRTAP22-1 21q22.1 keratin associated protein 22-1 KRTAP6-1 21q22.1 keratin associated protein 6-1 KRTAP20-1 21q22.1 keratin associated protein 20-1 KRTAP20-2 21q22.1 keratin associated protein 20-2 KRTAP19P4 21q22.1 keratin associated protein 19 pseudogene 4 KRTAP21-2 21q22.1 keratin associated protein 21-2 KRTAP21-1 21q22.1 keratin associated protein 21-1 KRTAP8P1 21q22.1 keratin associated protein 8 pseudogene 1 KRTAP8P2 21q22.1 keratin associated protein 8 pseudogene 2 UBE3AP2 21q21.3 ubiquitin protein ligase E3A pseudogene 2 TIAM1 21q22.1 T-cell lymphoma invasion and metastasis 1 LOC150051 21q22.11 hypothetical LOC150051 FBXW1BP1 21q22.11 F-box and WD-40 domain protein 1B pseudogene 1
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
29 - 7218 - 1591 - 2010 20802514
EXPRESSION
Type
constitutive of
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Nervousbrain   highly
Reproductivemale systemtestis  highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • from the N terminus, a pleckstrin homology domain
  • a coiled coil region, an EX domain
  • a DHR/PDZ (PSD95/disc large/ZO-1) domain
  • a DBL homology domain (DH) modulating the activity of Rac1, RHO-like protein
  • a PH domain
  • HOMOLOGY
    interspecies homolog to murine T lymphoma invasion and metastasis inducing gene 1 (Tiam1)
    Homologene
    FAMILY
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION
    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
  • 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
  • cell & other
    REGULATION
    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)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    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)
  • 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
    ANIMAL & CELL MODELS