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FLASH GENE
Symbol CTLA4 contributors: mct/shn - updated : 15-12-2011
HGNC name cytotoxic T-lymphocyte-associated protein 4
HGNC id 2505
Corresponding disease
GD5S Graves disease, susceptibility locus 5
Location 2q33.2      Physical location : 204.732.508 - 204.738.683
Synonym name
  • celiac disease 3
  • cell differentiation antigen CD152
  • cytotoxic T-lymphocyte-associated granule serine protease 4
  • ligand and transmembrane spliced cytotoxic T lymphocyte associated antigen 4
  • cytotoxic T-lymphocyte-associated antigen 4
  • cytotoxic T-lymphocyte-associated serine esterase-4
  • ligand and transmembrane spliced cytotoxic T lymphocyte associated antigen 4
  • cytotoxic T-lymphocyte antigen 4
  • CD152 antigen
  • Synonym symbol(s) CD152, CTLA-4, GSE, CD, CD28, ICOS, GRD4, CELIAC3
    EC.number 3.4.21.-
    DNA
    TYPE functioning gene
    STRUCTURE 6.17 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status confirmed
    Map cen - D2S1391 - D2S307 - CTLA4 - D2S72 - D2S105 - qter
    Physical map
    ALS2CR2 2q33-q34 amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 2 FLJ25351 2q33.2 hypothetical protein FLJ25351 ALS2CR4 2q33 amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 4 MPP4 2q33.2 membrane protein, palmitoylated 4 (MAGUK p55 subfamily member 4) ALS2 2q33.2 amyotrophic lateral sclerosis 2 (juvenile) LOC151256 2q33.2 hypothetical LOC151256 ALS2CR7 2q33.2 amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 7 FZD7 2q33 frizzled homolog 7 (Drosophila) FLJ39061 2q33.2 hypothetical protein FLJ39061 LOC339809 2q33.2 KIAA2012 protein UBL1 2q32.3-q33 ubiquitin-like 1 (sentrin) NOP5/NOP58 2q33.2 ubiquitin-like 1 (sentrin) BMPR2 2q33-q34 bone morphogenetic protein receptor, type II (serine/threonine kinase) FLJ38771 LOC130026 ALS2CR14 2q33 amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 14 WDR12 2q33.2 WD repeat domain 12 ALS2CR8 2q33.2 amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 8 LOC130029 2q33.3 similar to CG1308-PA ALS2CR17 2q33.3 amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 17 CYP20A1 2q33 cytochrome P450, family 20, subfamily A, polypeptide 1 ABI-2 2q33 abl-interactor 2 MRPL50P2 2q34 abl-interactor 2 RAPH1 2q33 Ras association (RalGDS/AF-6)and plekstrin homology 1 LOC344461 2q33.3 similar to ZNF207 protein CD28 2q33 CD28 antigen (Tp44) LOC344462 2q33.3 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) CTLA4 2q33 cytotoxic T-lymphocyte-associated protein 4 ICOS 2q33 inducible T-cell co-stimulator ALS2CR19 2q33 amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 19 NRP2 2q34 neuropilin 2 LOC391473 2 similar to cyclophilin A FLJ20309 2q33.3 hypothetical protein FLJ20309 NDUFS1 2q33-q34 NADH dehydrogenase (ubiquinone) Fe-S protein 1, 75kDa (NADH-coenzyme Q reductase) EEF1B2 2q33 eukaryotic translation elongation factor 1 beta 2 GPR1 2q33.3 G protein-coupled receptor 1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 splicing 1988 - 223 - 2007 17197413
  • also called CTLA4-TM
  • 3 splicing 1878 - 174 - 2007 17197413
  • also called CTLA-4delTM
  • - splicing 214 - 58 - 2008 18595775
  • lower expression of S-CTLA4 mRNA relative to the membrane form in myasthenia gravis patients
  • - splicing 277 - 79 - 2008 18595775
  • more prevalent in myasthenia gravis patients compared to healthy controls
  • 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
  • cell & other
    REGULATION
    repressed by
  • subunit of the serine/threonine phosphatase 2A, PP2A (
  • ASSOCIATED DISORDERS
    corresponding disease(s) GD5S
    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 (