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FLASH GENE
Symbol ICOS contributors: mct/npt/pgu - updated : 29-10-2014
HGNC name inducible T-cell co-stimulator
HGNC id 5351
Corresponding disease
CVID1 common variable immunodeficiency 1
Location 2q33.2      Physical location : 204.801.470 - 204.826.296
Synonym name
  • activation-inducible lymphocyte immunomediatory molecule
  • CD278 antigen
  • Synonym symbol(s) AILIM, CD278, MGC39850
    DNA
    TYPE functioning gene
    STRUCTURE 24.80 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    cytosine-phosphate-guanine/HTF
    text structure
  • DNA methylation status of the intronic CpG island affects transcriptional activity of the ICOS gene and, consequently, modulates the concentration of the expressed ICOS protein
  • MAPPING cloned Y linked N status confirmed
    regionally located in the PPH1 critical region,close to CD28 and CTLA4
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 2620 20.22 199 - 2001 11735222
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestivepharynx    
    Endocrinethyroid    
    Lymphoid/Immunethymus    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymphocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a Ig-like V-type (immunoglobulin-like) domain
  • cytoplasmic tail with an YMFM motif that binds the PIK3R1 subunit of class IA PI3K, similar to the YMNM motif of CD28, suggesting a redundant function of the two receptors in PI3K signaling
  • conjugated GlycoP
    mono polymer homomer , dimer
    HOMOLOGY
    interspecies homolog to murine Icos
    intraspecies homolog to related to CD28
    Homologene
    FAMILY
  • inducible costimulator family (CD28 gene family)
  • CATEGORY immunity/defense , signaling , receptor
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    basic FUNCTION
  • major regulator of the adaptive immune system, required for effective T cell dependent immune responses
  • also critical for CD40-mediated antibody class switching
  • enhancing all basic T-cell responses to a foreign antigen, namely proliferation, secretion
  • of lymphokines, up-regulation of molecules mediating cell-cell interaction
  • critically involved in perpetuating inflammation in chronically immune-mediated disorders of the peripheral nervous system
  • critical involvement in T cell help for late B cell differentiation, class-switching and memory B cell generation
  • could enhance the cytotoxic activity of cytokine-induced killer cells, in part, by augmenting cytokine secretion and prolonging cell survival
  • important for the effector function of T cells, especially for Th2 and T cell dependent B cell responses
  • CD28 and ICOS play complementary non-overlapping roles in the development of Th2 immunity
  • activational signal of Th17 cells during chronic intestinal inflammation, suggesting that under some conditions, control of ICOS expression may help to suppress chronic intestinal inflammation
  • vital role for ICOS signaling in the generation and maintenance of human T(H)17 cells
  • by altering effector T-cell populations differentially, ICOS signaling modulates tuberculosis control in the late stage of infection
  • ICOS-ICOSLG signal plays a direct role in proliferation and differentiation of thyroid follicular cells (TFC) and may exert important effects in the initiation, maintenance and exaggeration of autoimmune responses in local tissue
  • crucial in mediating T cell differentiation and function after allergen contact and thereby strongly affect the immunologic decision between tolerance or allergy development
  • crucial role of ICOS for the generation and suppressive function of Tregs conveying respiratory tolerance
  • ICOS/ICOSLG interaction is a central event in immunosuppression of tumor-associated memory CD4(+) T cells
  • ICOS costimulation-dependent translational control may ensure targeted delivery of IL4 to cognate B cells during T-B collaborations in the germinal center
  • TNFRSF4 and ICOS act in a cooperative, nonredundant manner to maximize and prolong the T follicular helper (Tfh) response that is generated after acute virus infection
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • homodimer, disulfide-linked
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding specifically to BZRP1
  • PIK3R1 is likely a determining factor in ICOS-mediated PI3K activity in T cells
  • regulated by RC3H1 (normally limits ICOS expression by promoting the degradation of ICOS messenger RNA)
  • RC3H1 controls ICOS expression through binding to the 3prime UTR of ICOS mRNA and by interacting with proteins that confer post-transcriptional repression
  • cell & other
    REGULATION
    induced by phorbol myristate acetate (PMA) and ionomycin
    NPM-ALK, acting through STAT3 as the gene transcriptional activator, induces the expression of ICOS
    Other regulated by RC3H1 (normally limits ICOS expression by promoting the degradation of ICOS messenger RNA)
    ASSOCIATED DISORDERS
    corresponding disease(s) CVID1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in samples from patients with Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and vasculitic neuropathy (VN) )compared to hereditary neuropathies
    constitutional     --over  
    of ICOS and ICOSLG in Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and vasculitic neuropathy (VN) vs patients with hereditary neuropathies (HNs)
    Susceptibility
  • to systemic lupus erythematosus (SLE)
  • to breast cancer
  • to preeclampsia (PE)
  • Variant & Polymorphism other
  • variant increasing the risk of systemic lupus erythematosus (SLE)
  • significantly lower frequency of the ICOS (-1564) T allele in women with mild PE compared with the controls
  • polymorphisms are associated with sporadic breast cancer
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    allergyasthm 
    importance of ICOS as a target for primary prevention strategies
    ANIMAL & CELL MODELS
  • Type 1 progression in BDC2.5 mice is associated with a decline in ICOS expression and expansion and suppression by intra-islet Foxp3(+) Tregs
  • Mycobacterium tuberculosis-infected ICOS(-/-) mice showed lower bacterial burden during the late chronic stage of infection as compared to WT controls
  • blockade of Il17 strongly inhibited disease even in ICOS(-/-) mice, showing that Il17 is playing a major role in the pathogenesis of experimental autoimmune encephalomyelitis both in WT and ICOS(-/-) mice