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FLASH GENE
Symbol CTLA4 contributors: mct/shn - updated : 15-12-2015
HGNC name cytotoxic T-lymphocyte-associated protein 4
HGNC id 2505
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Lymphoid/Immunethymuscortex    Homo sapiens
Reproductivemale systemprostate   
Urinarykidney    
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Lymphoid    
cells
SystemCellPubmedSpeciesStageRna symbol
Lymphoid/Immuneactivated B lymphocyte
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES Hydrophobic
STRUCTURE
motifs/domains
  • hydrophobic transmembrane region of 37AA
  • two Ig extracellular domains
  • a long cytoplasmic tail, with two tyrosine based inhibitory motifs (ITIM)
  • conjugated PhosphoP
    isoforms Precursor
    HOMOLOGY
    interspecies ortholog to Ctla4, Mus musculus
    ortholog to Ctla4, Rattus norvegicus
    ortholog to CTLA4, Pan troglodytes
    intraspecies homolog to CD28
    Homologene
    FAMILY
  • inducible costimulator family (CD28 gene family)
  • CATEGORY immunity/defense , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • B7 costimulatory protein receptor for CD80, CD86, negative regulatory T cell presenting costimulatory molecule
  • expressed on activated T lymphocytes and involved in down-regulation of the immune response
  • has a critical role in T cell differentiation (
  • plays an inhibitory role in the immune response and has been suggested to be involved in the pathophysiology of myasthenia gravis
  • acts as an effector molecule to inhibit CD28 costimulation by the cell-extrinsic depletion of ligands
  • functions potentially in a T cell-extrinsic manner
  • is of pivotal importance for self-tolerance, with deficiency or unfavorable polymorphisms leading to autoimmune disease
  • regulates the early development of self-reactive T cells in the thymus and plays a key role in central tolerance
  • in the thymus, works together with other signals to set the required level of TCR avidity and determine the development of both Tconv and Treg cells
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • disulfide-linked homodimer of CTLA4 and CD86 (B7.2)
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • CD28, B7-1 and early T cell costimulatory molecule, ETC-1 (
  • phosphatidylinositol 3-kinase, PI 3-kinase (
  • the tyrosine phosphatase SYP (
  • Lyn, Lck and SHP-2 (
  • Janus Kinase 2, Jak2 (
  • medium chain mu 2 subunit, AP50 (
  • CD80 (
  • CD80 and CD86 (
  • signal transducer and activator of transcription 5, STAT5 (
  • PPP2R4
  • ICOSLG-CD28 interaction was essential for the costimulation of human T cells primary responses to allogeneic antigens and memory recall responses
  • RGMB binds an extracellular domain of CTLA4, and specifically strengthens the binding of the monomeric, soluble form of CTLA4 (sCTLA-4) to CD80
  • cell & other
    REGULATION
    repressed by
  • subunit of the serine/threonine phosphatase 2A, PP2A (
  • ASSOCIATED DISORDERS
    corresponding disease(s) GD5S
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    aberrant expressions of endometrial ID3 and CTLA4 are associated with unexplained repeated implantation failure and recurrent miscarriage
    Susceptibility
  • to celiac disease (
  • to multiple sclerosis
  • to Graves disease (
  • to Hashimoto thyroiditis and Addison's disease (PubMed:9398726)
  • to diabetes mellitus (
  • to thyroid associated orbitopathy
  • to rheumatoid arthritis(RA)
  • to multiple sclerosis
  • to systemic lupus erythematosus(
  • to Addison disease
  • to non-Hodgkin's lymphoma (NHL)
  • to Vogt-Koyanagi-Harada
  • to dilated cardiomyopathy (DCM)
  • to myasthenia gravis (
  • to hepatitis B virus clearance and persistence (
  • Variant & Polymorphism SNP , other
  • exon 3 microsatellite, 106 bp allele conferring susceptibility to Graves disease and to thyroid associated orbitopathy (see also IDDM12)
  • 49A>G increasing the risk of celiac disease and of multiple sclerosis with secondary progressive form
  • allele +49 and CT60 increasing the risk of RA
  • strong association of the CTLA4 49A and the 3'-untranslated region (AT)(82) alleles with NHL
  • polymorphisms associated with the susceptibility to VKH syndrome(Vogt-Koyanagi-Harada)
  • common variant, Thr17Ala, confers susceptibility for DCM, but does not seem to influence the course of the disease 1 year after diagnosis
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyautoimmune 
    a potential therapeutic target in the prevention of autoimmune endocrine disorders
    ANIMAL & CELL MODELS
  • lymph nodes and spleens of CTLA4-deficient mice accumulate T cell blasts which infiltrate liver, heart, lung, and pancreas tissue, and amounts of serum immunoglobulin are elevated leading to early lethality (
  • CTLA-4(-/-) T cells from CTLA-4(-/-) mice have a diverse and unbiased TCR repertoire (
  • specific deficiency of cytotoxic T lymphocyte antigen 4 (CTLA-4) in Tregs results in spontaneous development of systemic lymphoproliferation, fatal T cell-mediated autoimmune disease, and hyperproduction of immunoglobulin E in mice, and it also produces potent tumor immunity (