ID:CTLA4_HUMAN DESCRIPTION: RecName: Full=Cytotoxic T-lymphocyte protein 4; AltName: Full=Cytotoxic T-lymphocyte-associated antigen 4; Short=CTLA-4; AltName: CD_antigen=CD152; Flags: Precursor; FUNCTION: Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of their cognate stimulatory coreceptor CD28. SUBUNIT: Homodimer; disulfide-linked. Binds to CD80/B7-1 and CD86/B7.2. INTERACTION: P33681:CD80; NbExp=3; IntAct=EBI-1030991, EBI-1031024; P42081:CD86; NbExp=2; IntAct=EBI-1030991, EBI-1030956; SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Note=Exists primarily an intracellular antigen whose surface expression is tightly regulated by restricted trafficking to the cell surface and rapid internalisation;. TISSUE SPECIFICITY: Widely expressed with highest levels in lymphoid tissues. Detected in activated T-cells where expression levels are 30- to 50-fold less than CD28, the stimulatory coreceptor, on the cell surface following activation. PTM: N-glycosylation is important for dimerization. PTM: Phosphorylation at Tyr-201 prevents binding to the AP-2 adapter complex, blocks endocytosis, and leads to retention of CTLA4 on the cell surface. POLYMORPHISM: Genetic variations in CTLA4 are associated with susceptibility to several autoimmune disorders. They influence responsiveness to hepatitis B virus (HBV) infection [MIM:610424]. DISEASE: Genetic variation in CTLA4 influences susceptibility to systemic lupus erythematosus (SLE) [MIM:152700]. SLE is a chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. SLE is thought to represent a failure of the regulatory mechanisms of the autoimmune system. DISEASE: Note=Genetic variations in CTLA4 may influence susceptibility to Graves disease, an autoimmune disorder associated with overactivity of the thyroid gland and hyperthyroidism. DISEASE: Genetic variation in CTLA4 is the cause of susceptibility to diabetes mellitus insulin-dependent type 12 (IDDM12) [MIM:601388]. A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. DISEASE: Genetic variation in CTLA4 is the cause of susceptibility to celiac disease type 3 (CELIAC3) [MIM:609755]. It is a multifactorial disorder of the small intestine that is influenced by both environmental and genetic factors. It is characterized by malabsorption resulting from inflammatory injury to the mucosa of the small intestine after the ingestion of wheat gluten or related rye and barley proteins. In its classic form, celiac disease is characterized in children by malabsorption and failure to thrive. PHARMACEUTICAL: Engineered fusion proteins consisting of the extracellular domain of CTLA4 and the IgG Fc region (Ctla4-Ig), inhibit T-cell-dependent antibody responses, and are used as immunosuppressive agents. They are soluble, have an enhanced affinity for B7 ligands and act as a competitive inhibitor of CD28. SIMILARITY: Contains 1 Ig-like V-type (immunoglobulin-like) domain. WEB RESOURCE: Name=Wikipedia; Note=CLTA-4 entry; URL="http://en.wikipedia.org/wiki/CTLA-4";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P16410
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0002250 adaptive immune response GO:0002376 immune system process GO:0006955 immune response GO:0006974 cellular response to DNA damage stimulus GO:0030889 negative regulation of B cell proliferation GO:0031295 T cell costimulation GO:0042130 negative regulation of T cell proliferation GO:0043065 positive regulation of apoptotic process GO:0045589 regulation of regulatory T cell differentiation GO:0045590 negative regulation of regulatory T cell differentiation GO:0050777 negative regulation of immune response GO:0050853 B cell receptor signaling pathway
Cellular Component: GO:0005794 Golgi apparatus GO:0005886 plasma membrane GO:0005887 integral component of plasma membrane GO:0009897 external side of plasma membrane GO:0016020 membrane GO:0016021 integral component of membrane GO:0045334 clathrin-coated endocytic vesicle GO:0048471 perinuclear region of cytoplasm GO:0098636 protein complex involved in cell adhesion
Descriptions from all associated GenBank mRNAs
BC070162 - Homo sapiens cytotoxic T-lymphocyte-associated protein 4, mRNA (cDNA clone MGC:88142 IMAGE:30417685), complete cds. AF414120 - Homo sapiens CTLA4 (CTLA4) mRNA, complete cds. LQ882888 - Sequence 37 from Patent WO2018160841. AK313732 - Homo sapiens cDNA, FLJ94332, highly similar to Homo sapiens cytotoxic T-lymphocyte-associated protein 4 (CTLA4), mRNA. BC069566 - Homo sapiens cytotoxic T-lymphocyte-associated protein 4, mRNA (cDNA clone MGC:97034 IMAGE:7262243), complete cds. BC074893 - Homo sapiens cytotoxic T-lymphocyte-associated protein 4, mRNA (cDNA clone MGC:103865 IMAGE:30915247), complete cds. BC074842 - Homo sapiens cytotoxic T-lymphocyte-associated protein 4, mRNA (cDNA clone MGC:104099 IMAGE:30915552), complete cds. AB590653 - Synthetic construct DNA, clone: pFN21AB6904, Homo sapiens CTLA4 gene for cytotoxic T-lymphocyte-associated protein 4, without stop codon, in Flexi system. KJ890998 - Synthetic construct Homo sapiens clone ccsbBroadEn_00392 CTLA4 gene, encodes complete protein. KR712092 - Synthetic construct Homo sapiens clone CCSBHm_00035703 CTLA4 (CTLA4) mRNA, encodes complete protein. AF486806 - Homo sapiens CTLA4 mRNA, partial cds. AY209009 - Homo sapiens cytotoxic T-lymphocyte-associated protein 4 (CTLA4) mRNA, complete cds. AY792514 - Homo sapiens ligand and transmembrane spliced cytotoxic T lymphocyte associated antigen 4 (CTLA4) mRNA, complete cds. AY999702 - Homo sapiens cytotoxic T lymphocyte associated antigen 4 short spliced form mRNA, complete cds, alternatively spliced. DQ785106 - Homo sapiens CD152 isoform (CTLA4) mRNA, partial cds, alternatively spliced. L15006 - Homo sapiens Ig superfamily CTLA-4 mRNA, complete cds. LQ927248 - Sequence 25 from Patent WO2018191660. MP216602 - Sequence 26 from Patent WO2019161400. MP584538 - Sequence 37 from Patent WO2020081767. JD165112 - Sequence 146136 from Patent EP1572962. JD254540 - Sequence 235564 from Patent EP1572962. U90273 - Homo sapiens CTLA-4 mRNA, partial cds. JD171964 - Sequence 152988 from Patent EP1572962. JD313936 - Sequence 294960 from Patent EP1572962. JD410559 - Sequence 391583 from Patent EP1572962. JD533758 - Sequence 514782 from Patent EP1572962. JD314154 - Sequence 295178 from Patent EP1572962. JD181456 - Sequence 162480 from Patent EP1572962. JD119576 - Sequence 100600 from Patent EP1572962. JD102564 - Sequence 83588 from Patent EP1572962. JD074755 - Sequence 55779 from Patent EP1572962. JD302934 - Sequence 283958 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_ctla4Pathway - The Co-Stimulatory Signal During T-cell Activation
Reactome (by CSHL, EBI, and GO)
Protein P16410 (Reactome details) participates in the following event(s):
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
