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FLASH GENE
Symbol LAT contributors: mct/npt/pgu - updated : 30-08-2017
HGNC name linker for activation of T cells
HGNC id 18874
Corresponding disease
IMD52 immunodeficiency 52
Location 16p11.2      Physical location : 28.996.146 - 29.002.096
Synonym name 36 kDa phospho-tyrosine adaptor protein
Synonym symbol(s) IMD521, LAT1, pp36, p36-38
DNA
TYPE functioning gene
STRUCTURE 5.96 kb     13 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site
text structure
  • promoter contains both positive and negative regulatory regions, and two binding sites for the Ets family of transcription factors have a strong, positive effect on gene expression, ELF1, and overexpression of ELF1 augments LAT promoter activity
  • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 splicing 1680 - 233 - 2009 19380807
    13 splicing 1472 - 262 - 2009 19380807
    12 - 1677 - 232 - 2009 19380807
    11 - 1767 - 262 - 2009 19380807
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately
    Lymphoid/Immunethymus   highly
     tonsils   highly
    Nervousnerve   highly
    Respiratorylung   moderately
    Urinarykidney   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoietic    
    Connective    
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunenatural killer
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text eye, lens anterior segment, retina RPE, choroid
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • multiple potential tyrosine phosphorylation sites
  • HOMOLOGY
    interspecies homolog to murine Lat
    Homologene
    FAMILY
    CATEGORY adaptor
    SUBCELLULAR LOCALIZATION     plasma membrane
    text type III membrane protein
    basic FUNCTION
  • playing a critical role for the differentiation and homeostasis of T-helpers type 2 cells
  • localizes to lipid rafts and acts as a docking site for SH2 domain-containing proteins
  • transmembrane adaptor protein with a role in the development, activation, and maintenance of T cells
  • linker protein essential for activation of T lymphocytes
  • LAT and the linker for activation of B cells (LAB/NTAL/LAT2) are integral proteins in receptor coupling to downstream events
  • adaptor protein that couples TCR engagement to downstream signaling cascades
  • also plays an essential role in thymocyte development during transition from the double-positive to single-positive stage
  • plays a central role in T-cell activation by nucleating signaling complexes that are critical for the propagation of T-cell signals from the plasma membrane to the cellular interior
  • transmembrane adaptor protein that is essential to bridge T cell receptor (TCR) engagement to downstream signaling events
  • LAT-mediated signaling intricately regulates cytotoxic-T-lymphocyte (CTL) cytotoxicity at multiple steps
  • is proteolytically cleaved following FAS engagement in a tyrosine phosphorylation-dependent fashion
  • is a transmembrane adaptor protein that is vital for integrating TCR-mediated signals to modulate T cell development, activation, and proliferation
  • key adaptor in the T cell receptor (TCR) signaling pathway
  • transmembrane adaptor protein that is highly tyrosine phosphorylated upon engagement of the TCR
  • LAT, like CD247 and ZAP70, plays likely a role in neurogenesis and that perturbation of this pathway may lead to neurodevelopmental phenotypes
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • PLCG1 (for T cell development and homeostasis)
  • immediate substrate for LCK in one of the earliest events of T cell activation
  • LAT promotes TCR signal initiation, suggesting that this adaptor may contribute to maintain active LCK in proximity of their substrates
  • STK11 predominately interacted with LAT and PLCG1 following TCR stimulation
  • LAT plays an adapter role in TCR/CD28-induced activation of TRAF6
  • in addition to its GEF activity, SOS1 acted as a scaffold to nucleate oligomerization of the T cell adaptor protein LAT (linker for activation of T cells)
  • upon T cell activation, LAT is phosphorylated and associates with GRB2, GRAP2, and PLCG1 through its four distal tyrosine residues
  • IFT20 is required for the delivery of the intracellular pool of LAT to the immune synapse in naive primary T lymphocytes and for effective T-cell responses
  • novel interactions between the SH2D2A SH2 domain and CD6 phosphotyrosine (pTyr)629 and linker of activated T cells (LAT) pTyr171 , pTyr191 and pTyr226
  • cell & other
    REGULATION
    Other LAT ubiquitylation is a molecular checkpoint for attenuation of T-cell signaling
    ASSOCIATED DISORDERS
    corresponding disease(s) IMD52
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    lower in asthmatic patients than that in healthy people
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • T cells from mice harboring a mutation at the Plcg1 binding site of Lat (Y136F) have impaired calcium flux and Erk activation, and these T cells are highly activated, resulting in the development of a lymphoproliferative syndrome