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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
    Physical map
    LOC388228 16 similar to SH3-binding kinase LOC388229 16 similar to Group X secretory phospholipase A2 precursor (Phosphatidylcholine 2-acylhydrolase GX) (GX sPLA2) (sPLA2-X) EIF3S8 16p11.2 eukaryotic translation initiation factor 3, subunit 8, 110kDa LOC283890 16p12.1 similar to nuclear pore complex interacting protein LOC388230 16 similar to MGC9515 protein LOC388231 16 LOC388231 SULT1A1 16p12.1 sulfotransferase family, cytosolic, 1A, phenol-preferring, member 1 SULT1A2 16p12-p11.2 sulfotransferase family, cytosolic, 1A, phenol-preferring, member 2 LOC112869 16p12.1 hypothetical protein BC011981 P8 16p11.2 p8 protein (candidate of metastasis 1) IL27  interleukin 27 LOC388232 16 similar to apolipoprotein B48 receptor CLN3 16p12.1-p11.2 ceroid-lipofuscinosis, neuronal 3, juvenile (Batten, Spielmeyer-Vogt disease) LOC388233 16 similar to MGC9515 protein APOB48R 16p11 apolipoprotein B48 receptor LOC388234 16 similar to nuclear pore complex interacting protein LOC390688 16 similar to CDC37-like gene LOC388235 16 LOC388235 LOC388236 16 similar to MGC9515 protein A2LP 16p11 ataxin 2 related protein TUFM 16p11.2 Tu translation elongation factor, mitochondrial SH2B 16p12.1 Tu translation elongation factor, mitochondrial ATP2A1 16p12.1 ATPase, Ca++ transporting, cardiac muscle, fast twitch 1 FRA 16p12.1 Fos-related antigen CD19 16p11.2 CD19 antigen FLJ14639 16p12.1 hypothetical protein FLJ14639 SPINL 16p12.1 spinster-like LAT 16p11.2 linker for activation of T cells LOC388237 16 similar to nuclear pore complex interacting protein LOC388238 16 similar to RRN3 LOC283892 16p12.1 hypothetical gene supported by NM_017869; AK023827 LOC283895 16p12.1 hypothetical LOC283895 LOC388239 16 similar to nuclear pore complex interacting protein LOC388240 16 similar to MGC9515 protein LOC388241 16 similar to PI-3-kinase-related kinase SMG-1 isoform 2; lambda/iota protein kinase C-interacting protein; phosphatidylinositol 3-kinase-related protein kinase MGC5178 16p12.1 hypothetical protein MGC5178 LOC388242 16 similar to hypothetical protein BC011981 KIAA0220 16p12.1 KIAA0220 protein LAT1-3TM 16p12 LAT1-3TM protein LOC388243 16 similar to carbonic anhydrase VA, mitochondrial precursor; carbonic anhydrase V, mitochondrial; carbonic dehydratase SPN 16p11.2 sialophorin (gpL115, leukosialin, CD43) QPRT 16q13 quinolinate phosphoribosyltransferase (nicotinate-nucleotide pyrophosphorylase (carboxylating))
    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