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CD152 (cytotoxic T-cell protein 4-1, cytotoxic T lymphocyte-associated serine esterase-4, CTLA-4, CD152 antigen, CTLA4, CD152)
Function:
- role in T-cell activation
- interacts with CD80 & CD86 to down regulate T cell activation
- a checkpoint inhibitor
- part of an immunological network that leads to tolerance
- ligands: CD80, CD86, phosphatidylinositol-3-kinase protein tyrosine phsophatase 1D
Structure:
- significant homology to CD28 in the extracellular region
Compartment: membrane
Expression:
- widely expressed with highest levels in lymphoid tissues
- activated T cells & activated B cells
- transcription regulated by:
- AP1, CD28re, IL-2 kappa b, OCT-1
Pathology:
- activated T cells have two transcripts with alternative poly- adenylation sites, the longer transcript contains a repeated -AU- motif, the length of which varies between different individuals, leading to a restriction fragment length polymorphism (RFLP) which has been linked to various human autoimmune diseases
- genetic variation in CTLA4 influences susceptibility to systemic lupus erythematosus
- genetic variation in CTLA4 may be a cause of susceptibility to Graves disease
- genetic variation in CTLA4 is the cause of susceptibility to insulin-dependent diabetes mellitus type 12
- genetic variation in CTLA4 is the cause of susceptibility to celiac disease type 3
- genetic variations in CTLA4 are associated with susceptibility to hepatitis B virus infection
Pharmacology:
- monoclonal antibody to CTLA4, ipilimumab (Yervoy), FDA-approved to treat metastatic melanoma
- monoclonal antibody to CTLA4, tremelimumab, in phase 3 clinical trials for treatment of metastatic melanoma
Comparative biology:
- anti-CTLA4 therapy can result in development of antibodies to gut flora
- anti-CTLA4 therapy decreases numbers of Bacteroidales & Burkholderiales species & increases Clostridiales species in feces of mice
General
cluster-of-differentiation antigen; cluster designation antigen; CD antigen
glycoprotein
immunoglobulin superfamily protein
serine protease
Properties
SIZE: entity length = 223 aa
MW = 25 kD
COMPARTMENT: cellular membrane
CELL: cytotoxic T cell
MOTIF: signal sequence {1-35}
immunoglobulin superfamily domain {39-140}
MOTIF: cysteine residue {C58}
MODIFICATION: cysteine residue {C129}
cysteine residue {C85}
MODIFICATION: cysteine residue {C103}
cysteine residue {C103}
MODIFICATION: cysteine residue {C85}
N-glycosylation site {N113}
cysteine residue {C129}
MODIFICATION: cysteine residue {C58}
transmembrane domain {162-182}
Database Correlations
OMIM correlations
MORBIDMAP 123890
UniProt P16410
Pfam PF07686
Kegg hsa:1493
References
- OMIM :accession 123890
- UniProt :accession P16410
- Protein Reviews on the Web
http://mpr.nci.nih.gov/prow/guide/1686349937_g.htm
- http://www.pathologyoutlines.com/cdmarkers.html
20 May 2003
- Wikipedia; Note: CLTA-4 entry
http://en.wikipedia.org/wiki/CTLA-4
- Vetizou M, Pitt JM, Daillere R et al
Anticancer immunotherapy by CTLA-4 blockade relies on the gut
microbiota.
Science. 2015 Nov 27;350(6264):1079-84
PMID: 26541610