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FLASH GENE
Symbol CD226 contributors: mct/npt/pgu - updated : 26-03-2012
HGNC name CD226 molecule
HGNC id 16961
Location 18q22.2      Physical location : 67.530.194 - 67.624.232
Synonym name
  • CD226 antigen
  • DNAX accessory molecule-1
  • T lineage-specific activation antigen 1 antigen
  • adhesion glycoprotein
  • platelet and T cell activation antigen 1
  • platelet and T cell activation antigen 1
  • Synonym symbol(s) DNAM-1, DNAM1, PTA1, TLiSA1, PTA-1
    DNA
    TYPE functioning gene
    STRUCTURE 94.04 kb     7 Exon(s)
    regulatory sequence Promoter
    Binding site   transcription factor
    motif
    text structure
  • two promoters named P1 and P2, which are located at -810 to -287 bp and +33 to +213 bp, respectively, and a negative regulation element between P1 and P2
  • putative binding sites for transcription factors AP-1, Sp1, PEA3, and Ets-1
  • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 2664 - 336 - 2004 15039383
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineparathyroid   highly
    Hearing/Equilibriumearinnercochlea highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmegakaryocyte
    Blood/Hematopoieticplatelet
    Lymphoid/ImmuneB cell
    Lymphoid/Immunenatural killer Homo sapiens
    Lymphoid/ImmuneT cell Homo sapiens
    cell lineage in mononuclear cells and was down-regulated during osteoclastogenesis
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text progenitor cells
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • eight potential N-glycosylation sites
  • a transmembrane domain
  • three potential tyrosine phosphorylation sites
  • a potential GRB2-binding site and two Ig-like domains of the V-set
  • C-terminal peptide of CD226 also can bind discs large and the presence or absence of this peptide greatly influences binding between CD226 and different isoforms of EPB41L2
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to murine Pta1
    Homologene
    FAMILY
  • Ig superfamily
  • CATEGORY signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
    text localized to membrane rafts
    basic FUNCTION
  • involved in adhesion of platelets and megakaryocytic cells to vascular endothelial cells
  • may play a predominant role in inducing cytotoxicity via an interaction with PVR and PVRL2
  • contributes to NK-mediated lysis of tumor cells
  • transduces activating signals resulting in tyrosine phosphorylation of CD226 itself
  • playing an important role in maturation of the megakaryocytes in combination with ITGAL
  • binding of PVR with CD226 negatively regulates osteoclast formation
  • serves to extend the range of target cells that can activate CD8 T cell and NK cells and, hence, may be essential for immunosurveillance against tumors and/or viruses
  • contributes to tumor immune surveillance and plays a crucial role in NK cell-mediated recognition of several types of tumors, including ovarian carcinoma
  • having importance in facilitating activation signals received by NK cells in natural and cytokine-driven responses to tumor metastases
  • involved in T cell differentiation, activation, and cytotoxicity
  • involvement of CD226+ NK cells in immunopathogenesis of systemic lupus erythematosus
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component TIGIT/CD226 axis regulates T cell function, and T cell responses associated with autoimmune disease
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ITGAL-associated molecule, CD226, is localized to membrane rafts and binds the C-terminal domain of isoforms of the actin-binding protein EPB41L2
  • PVR ligand (binding of PVR with CD226 negatively regulates osteoclast formation and cellular fusion process may be inhibited by the PVR-mediated signaling
  • PVRL2
  • PVR appeared to be a key ligand recognized by CD226 in NK cell-mediated suppression of metastases, and CD226-mediated suppression coincided with perforin activity
  • CD226 ligands are CD112 and PVR
  • interacting with TIGIT (exerts immunosuppressive effects by competing with CD226 for the same CD155 ligand)
  • PVR engages the activating receptor CD226, the inhibitory receptor TIGIT, and the CD96 receptor with both activating and inhibitory functions
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in colorectal cancer with a significantly lower risk of death compared to untreated patients, in patients that received adjuvant chemotherapy
    Susceptibility
  • to autoimmune polyendocrinopathy type 2 (APS2)
  • to multiple sclerosis
  • to type 1 diabetes
  • Variant & Polymorphism SNP , other
  • 307Ser variant of the CD226 receptor is associated with APS2 because of its underlying association with type 1 diabetes and autoimmune thyroid disease
  • rs763361 in CD226 confer susceptibility for multiple sclerosis
  • rs763361 within the CD226 gene has recently been reported as a novel susceptible locus for type 1 diabetes
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS