InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CTLA4

Summary

InnateDB Protein

IDBP-476155.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

CTLA4

Protein Name

cytotoxic T-lymphocyte-associated protein 4

Synonyms

CD; CD152; CELIAC3; CTLA-4; GRD4; GSE; IDDM12;

Species

Homo sapiens

Ensembl Protein

ENSP00000417779

InnateDB Gene

IDBG-79215 (CTLA4)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:16551244, ECO:0000269PubMed:1714933}.

Subcellular Localization

Cell membrane {ECO:0000269PubMed:18468488}; Single-pass type I membrane protein {ECO:0000269PubMed:18468488}. Note=Exists primarily an intracellular antigen whose surface expression is tightly regulated by restricted trafficking to the cell surface and rapid internalisation;.

Disease Associations

Systemic lupus erythematosus (SLE) [MIM:152700]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. {ECO:0000269PubMed:15138458, ECO:0000269PubMed:15688186}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Note=Genetic variations in CTLA4 may influence susceptibility to Graves disease, an autoimmune disorder associated with overactivity of the thyroid gland and hyperthyroidism.Diabetes mellitus, insulin-dependent, 12 (IDDM12) [MIM:601388]: A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features 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. {ECO:0000269PubMed:9259273}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Celiac disease 3 (CELIAC3) [MIM:609755]: A multifactorial, chronic disorder of the small intestine caused by intolerance to gluten. It is characterized by immune-mediated enteropathy associated with failed intestinal absorption, and malnutrition. In predisposed individuals, the ingestion of gluten- containing food such as wheat and rye induces a flat jejunal mucosa with infiltration of lymphocytes. {ECO:0000269PubMed:10189842, ECO:0000269PubMed:15657618}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

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. {ECO:0000269PubMed:10493833, ECO:0000269PubMed:16551244, ECO:0000269PubMed:1713603}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 26 experimentally validated interaction(s) in this database.
They are also associated with 4 interaction(s) predicted by orthology.

Experimentally validated
Total	26 [view]
Protein-Protein	25 [view]
Protein-DNA	0
Protein-RNA	1 [view]
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	4 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding

Biological 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:0043065	positive regulation of apoptotic process
GO:0045087	innate immune response (InnateDB)
GO:0045590	negative regulation of regulatory T cell differentiation
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:0045334	clathrin-coated endocytic vesicle
GO:0048471	perinuclear region of cytoplasm