Cytotoxic T-lymphocyte protein 4

Details

Name
Cytotoxic T-lymphocyte protein 4
Synonyms
  • CD152
  • CTLA-4
  • Cytotoxic T-lymphocyte-associated antigen 4
Gene Name
CTLA4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001768|Cytotoxic T-lymphocyte protein 4
MACLGFQRHKAQLNLATRTWPCTLLFFLLFIPVFCKAMHVAQPAVVLASSRGIASFVCEY
ASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLR
AMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDFLLWILAAVSSGLFFYSFL
LTAVSLSKMLKKRSPLTTGVYVKMPPTEPECEKQFQPYFIPIN
Number of residues
223
Molecular Weight
24655.63
Theoretical pI
7.12
GO Classification
Processes
adaptive immune response / B cell receptor signaling pathway / cellular response to DNA damage stimulus / immune response / negative regulation of B cell proliferation / negative regulation of regulatory T cell differentiation / positive regulation of apoptotic process / T cell costimulation
Components
clathrin-coated endocytic vesicle / external side of plasma membrane / Golgi apparatus / integral component of plasma membrane / perinuclear region of cytoplasm / plasma membrane
General Function
Not Available
Specific 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.
Pfam Domain Function
Transmembrane Regions
162-182
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0019026|Cytotoxic T-lymphocyte protein 4 (CTLA4)
ATGGCTTGCCTTGGATTTCAGCGGCACAAGGCTCAGCTGAACCTGGCTACCAGGACCTGG
CCCTGCACTCTCCTGTTTTTTCTTCTCTTCATCCCTGTCTTCTGCAAAGCAATGCACGTG
GCCCAGCCTGCTGTGGTACTGGCCAGCAGCCGAGGCATCGCCAGCTTTGTGTGTGAGTAT
GCATCTCCAGGCAAAGCCACTGAGGTCCGGGTGACAGTGCTTCGGCAGGCTGACAGCCAG
GTGACTGAAGTCTGTGCGGCAACCTACATGATGGGGAATGAGTTGACCTTCCTAGATGAT
TCCATCTGCACGGGCACCTCCAGTGGAAATCAAGTGAACCTCACTATCCAAGGACTGAGG
GCCATGGACACGGGACTCTACATCTGCAAGGTGGAGCTCATGTACCCACCGCCATACTAC
CTGGGCATAGGCAACGGAACCCAGATTTATGTAATTGCTAAAGAAAAGAAGCCCTCTTAC
AACAGGGGTCTATGTGAAAATGCCCCCAACAGAGCCAGAATGTGA
Chromosome Location
2
Locus
2q33
External Identifiers
ResourceLink
UniProtKB IDP16410
UniProtKB Entry NameCTLA4_HUMAN
GenBank Protein ID17646228
GenBank Gene IDAF411058
GenAtlas IDCTLA4
HGNC IDHGNC:2505
General References
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  2. Ling V, Wu PW, Finnerty HF, Agostino MJ, Graham JR, Chen S, Jussiff JM, Fisk GJ, Miller CP, Collins M: Assembly and annotation of human chromosome 2q33 sequence containing the CD28, CTLA4, and ICOS gene cluster: analysis by computational, comparative, and microarray approaches. Genomics. 2001 Dec;78(3):155-68. [Article]
  3. Gu M, Kakoulidou M, Giscombe R, Pirskanen R, Lefvert AK, Klareskog L, Wang X: Identification of CTLA-4 isoforms produced by alternative splicing and their association with myasthenia gravis. Clin Immunol. 2008 Sep;128(3):374-81. doi: 10.1016/j.clim.2008.05.006. Epub 2008 Jul 2. [Article]
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  6. Dariavach P, Mattei MG, Golstein P, Lefranc MP: Human Ig superfamily CTLA-4 gene: chromosomal localization and identity of protein sequence between murine and human CTLA-4 cytoplasmic domains. Eur J Immunol. 1988 Dec;18(12):1901-5. [Article]
  7. Ling V, Wu PW, Finnerty HF, Sharpe AH, Gray GS, Collins M: Complete sequence determination of the mouse and human CTLA4 gene loci: cross-species DNA sequence similarity beyond exon borders. Genomics. 1999 Sep 15;60(3):341-55. [Article]
  8. Linsley PS, Brady W, Urnes M, Grosmaire LS, Damle NK, Ledbetter JA: CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med. 1991 Sep 1;174(3):561-9. [Article]
  9. Shiratori T, Miyatake S, Ohno H, Nakaseko C, Isono K, Bonifacino JS, Saito T: Tyrosine phosphorylation controls internalization of CTLA-4 by regulating its interaction with clathrin-associated adaptor complex AP-2. Immunity. 1997 May;6(5):583-9. [Article]
  10. Schneider H, Schwartzberg PL, Rudd CE: Resting lymphocyte kinase (Rlk/Txk) phosphorylates the YVKM motif and regulates PI 3-kinase binding to T-cell antigen CTLA-4. Biochem Biophys Res Commun. 1998 Nov 9;252(1):14-9. [Article]
  11. Chikuma S, Murakami M, Tanaka K, Uede T: Janus kinase 2 is associated with a box 1-like motif and phosphorylates a critical tyrosine residue in the cytoplasmic region of cytotoxic T lymphocyte associated molecule-4. J Cell Biochem. 2000 May;78(2):241-50. [Article]
  12. Ueda H, Howson JM, Esposito L, Heward J, Snook H, Chamberlain G, Rainbow DB, Hunter KM, Smith AN, Di Genova G, Herr MH, Dahlman I, Payne F, Smyth D, Lowe C, Twells RC, Howlett S, Healy B, Nutland S, Rance HE, Everett V, Smink LJ, Lam AC, Cordell HJ, Walker NM, Bordin C, Hulme J, Motzo C, Cucca F, Hess JF, Metzker ML, Rogers J, Gregory S, Allahabadia A, Nithiyananthan R, Tuomilehto-Wolf E, Tuomilehto J, Bingley P, Gillespie KM, Undlien DE, Ronningen KS, Guja C, Ionescu-Tirgoviste C, Savage DA, Maxwell AP, Carson DJ, Patterson CC, Franklyn JA, Clayton DG, Peterson LB, Wicker LS, Todd JA, Gough SC: Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature. 2003 May 29;423(6939):506-11. Epub 2003 Apr 30. [Article]
  13. Darlington PJ, Kirchhof MG, Criado G, Sondhi J, Madrenas J: Hierarchical regulation of CTLA-4 dimer-based lattice formation and its biological relevance for T cell inactivation. J Immunol. 2005 Jul 15;175(2):996-1004. [Article]
  14. Teft WA, Kirchhof MG, Madrenas J: A molecular perspective of CTLA-4 function. Annu Rev Immunol. 2006;24:65-97. [Article]
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  17. Metzler WJ, Bajorath J, Fenderson W, Shaw SY, Constantine KL, Naemura J, Leytze G, Peach RJ, Lavoie TB, Mueller L, Linsley PS: Solution structure of human CTLA-4 and delineation of a CD80/CD86 binding site conserved in CD28. Nat Struct Biol. 1997 Jul;4(7):527-31. [Article]
  18. Schwartz JC, Zhang X, Fedorov AA, Nathenson SG, Almo SC: Structural basis for co-stimulation by the human CTLA-4/B7-2 complex. Nature. 2001 Mar 29;410(6828):604-8. [Article]
  19. Stamper CC, Zhang Y, Tobin JF, Erbe DV, Ikemizu S, Davis SJ, Stahl ML, Seehra J, Somers WS, Mosyak L: Crystal structure of the B7-1/CTLA-4 complex that inhibits human immune responses. Nature. 2001 Mar 29;410(6828):608-11. [Article]
  20. Yu C, Sonnen AF, George R, Dessailly BH, Stagg LJ, Evans EJ, Orengo CA, Stuart DI, Ladbury JE, Ikemizu S, Gilbert RJ, Davis SJ: Rigid-body ligand recognition drives cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptor triggering. J Biol Chem. 2011 Feb 25;286(8):6685-96. doi: 10.1074/jbc.M110.182394. Epub 2010 Dec 14. [Article]
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  22. Djilali-Saiah I, Schmitz J, Harfouch-Hammoud E, Mougenot JF, Bach JF, Caillat-Zucman S: CTLA-4 gene polymorphism is associated with predisposition to coeliac disease. Gut. 1998 Aug;43(2):187-9. [Article]
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  26. Barreto M, Santos E, Ferreira R, Fesel C, Fontes MF, Pereira C, Martins B, Andreia R, Viana JF, Crespo F, Vasconcelos C, Ferreira C, Vicente AM: Evidence for CTLA4 as a susceptibility gene for systemic lupus erythematosus. Eur J Hum Genet. 2004 Aug;12(8):620-6. [Article]
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  29. Lee YH, Harley JB, Nath SK: CTLA-4 polymorphisms and systemic lupus erythematosus (SLE): a meta-analysis. Hum Genet. 2005 Apr;116(5):361-7. Epub 2005 Feb 2. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB06186IpilimumabapprovedyesinhibitorantibodyDetails
DB11771TremelimumabinvestigationalunknowninhibitorantibodyDetails