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P16410 (CTLA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 166. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cytotoxic T-lymphocyte protein 4
Alternative name(s):
Cytotoxic T-lymphocyte-associated antigen 4
Short name=CTLA-4
CD_antigen=CD152
Gene names
Name:CTLA4
Synonyms:CD152
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length223 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.11 Ref.17

Subunit structure

Homodimer; disulfide-linked. Binds to CD80/B7-1 and CD86/B7.2. Ref.21 Ref.22 Ref.23

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;. Ref.18

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. Ref.1 Ref.10 Ref.17

Post-translational modification

N-glycosylation is important for dimerization.

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].

Involvement in disease

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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.27

Genetic variations in CTLA4 may influence susceptibility to Graves disease, an autoimmune disorder associated with overactivity of the thyroid gland and hyperthyroidism. Ref.27

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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.24 Ref.27

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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.25 Ref.27 Ref.31

Pharmaceutical use

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.

Sequence similarities

Contains 1 Ig-like V-type (immunoglobulin-like) domain.

Ontologies

Keywords
   Biological processAdaptive immunity
Immunity
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDiabetes mellitus
Systemic lupus erythematosus
   DomainImmunoglobulin domain
Signal
Transmembrane
Transmembrane helix
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Pharmaceutical
Reference proteome
Gene Ontology (GO)
   Biological_processB cell receptor signaling pathway

Inferred from mutant phenotype PubMed 17875758. Source: UniProtKB

T cell costimulation

Traceable author statement. Source: Reactome

cellular response to DNA damage stimulus

Inferred from mutant phenotype PubMed 17875758. Source: UniProtKB

immune response

Traceable author statement Ref.8. Source: ProtInc

negative regulation of B cell proliferation

Inferred from mutant phenotype PubMed 17875758. Source: UniProtKB

negative regulation of T cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of immune response

Inferred from electronic annotation. Source: Ensembl

negative regulation of regulatory T cell differentiation

Inferred from direct assay PubMed 18641304. Source: BHF-UCL

positive regulation of apoptotic process

Inferred from mutant phenotype PubMed 17875758. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from direct assay PubMed 15814706. Source: BHF-UCL

clathrin-coated endocytic vesicle

Inferred from direct assay PubMed 15814706. Source: BHF-UCL

external side of plasma membrane

Inferred from direct assay PubMed 18641304. Source: BHF-UCL

integral component of plasma membrane

Traceable author statement Ref.8. Source: ProtInc

perinuclear region of cytoplasm

Inferred from direct assay PubMed 15814706. Source: BHF-UCL

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionprotein binding

Inferred from physical interaction Ref.21Ref.22PubMed 21982860PubMed 7807015PubMed 9398332Ref.13. Source: IntAct

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P16410-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P16410-2)

Also known as: ss-CTLA-4;

The sequence of this isoform differs from the canonical sequence as follows:
     38-204: Missing.
Isoform 3 (identifier: P16410-3)

The sequence of this isoform differs from the canonical sequence as follows:
     38-204: Missing.
     205-223: PPTEPECEKQFQPYFIPIN → KEKKPSYNRGLCENAPNRARM
Isoform 4 (identifier: P16410-4)

The sequence of this isoform differs from the canonical sequence as follows:
     58-58: C → S
     59-204: Missing.
     205-223: PPTEPECEKQFQPYFIPIN → KEKKPSYNRGLCENAPNRARM
Isoform 5 (identifier: P16410-5)

The sequence of this isoform differs from the canonical sequence as follows:
     153-174: DPEPCPDSDFLLWILAAVSSGL → AKEKKPSYNRGLCENAPNRARM
     175-223: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3535 Potential
Chain36 – 223188Cytotoxic T-lymphocyte protein 4
PRO_0000014734

Regions

Topological domain36 – 161126Extracellular Potential
Transmembrane162 – 18221Helical; Potential
Topological domain183 – 22341Cytoplasmic Potential
Domain39 – 140102Ig-like V-type
Region46 – 505Homodimerization
Region150 – 1556Homodimerization

Amino acid modifications

Modified residue2011Phosphotyrosine; by TXK and JAK2 Ref.12 Ref.13 Ref.14
Glycosylation1131N-linked (GlcNAc...) Ref.16 Ref.22 Ref.23
Glycosylation1451N-linked (GlcNAc...) Ref.16 Ref.22
Disulfide bond58 ↔ 129 Ref.21 Ref.22 Ref.23
Disulfide bond85 ↔ 103 Ref.21 Ref.22 Ref.23
Disulfide bond157Interchain Ref.21 Ref.22 Ref.23

Natural variations

Alternative sequence38 – 204167Missing in isoform 2 and isoform 3.
VSP_041284
Alternative sequence581C → S in isoform 4.
VSP_041285
Alternative sequence59 – 204146Missing in isoform 4.
VSP_041286
Alternative sequence153 – 17422DPEPC…VSSGL → AKEKKPSYNRGLCENAPNRA RM in isoform 5.
VSP_047238
Alternative sequence175 – 22349Missing in isoform 5.
VSP_047239
Alternative sequence205 – 22319PPTEP…FIPIN → KEKKPSYNRGLCENAPNRAR M in isoform 3 and isoform 4.
VSP_041287
Natural variant171T → A Increased risk for Graves disease, insulin-dependent diabetes mellitus, thyroid-associated orbitopathy, systemic lupus erythematosus and susceptibility to HBV infection. Ref.1 Ref.3 Ref.24 Ref.26 Ref.27 Ref.28 Ref.30
Corresponds to variant rs231775 [ dbSNP | Ensembl ].
VAR_013577

Experimental info

Sequence conflict371A → V in ABG85285. Ref.3
Sequence conflict1471T → A in AAA52773. Ref.8

Secondary structure

........................... 223
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 10, 2003. Version 3.
Checksum: 6F9466FB2E139A5A

FASTA22324,656
        10         20         30         40         50         60 
MACLGFQRHK AQLNLATRTW PCTLLFFLLF IPVFCKAMHV AQPAVVLASS RGIASFVCEY 

        70         80         90        100        110        120 
ASPGKATEVR VTVLRQADSQ VTEVCAATYM MGNELTFLDD SICTGTSSGN QVNLTIQGLR 

       130        140        150        160        170        180 
AMDTGLYICK VELMYPPPYY LGIGNGTQIY VIDPEPCPDS DFLLWILAAV SSGLFFYSFL 

       190        200        210        220 
LTAVSLSKML KKRSPLTTGV YVKMPPTEPE CEKQFQPYFI PIN 

« Hide

Isoform 2 (ss-CTLA-4) [UniParc].

Checksum: 096CBF7AD57AE9B9
Show »

FASTA566,560
Isoform 3 [UniParc].

Checksum: 5F70948EEDC80A94
Show »

FASTA586,745
Isoform 4 [UniParc].

Checksum: 60CBF1BC1DA59D8A
Show »

FASTA798,855
Isoform 5 [UniParc].

Checksum: 0881BFA757AC3FDB
Show »

FASTA17419,145

References

« Hide 'large scale' references
[1]"CTLA-4 and CD28 activated lymphocyte molecules are closely related in both mouse and human as to sequence, message expression, gene structure, and chromosomal location."
Harper K., Balzano C., Rouvier E., Mattei M.-G., Luciani M.-F., Golstein P.
J. Immunol. 147:1037-1044(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), TISSUE SPECIFICITY, ALTERNATIVE SPLICING, VARIANT ALA-17.
[2]"Assembly and annotation of human chromosome 2q33 sequence containing the CD28, CTLA4, and ICOS gene cluster: analysis by computational, comparative, and microarray approaches."
Ling V., Wu P.W., Finnerty H.F., Agostino M.J., Graham J.R., Chen S., Jussiff J.M., Fisk G.J., Miller C.P., Collins M.
Genomics 78:155-168(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Identification of CTLA-4 isoforms produced by alternative splicing and their association with myasthenia gravis."
Gu M., Kakoulidou M., Giscombe R., Pirskanen R., Lefvert A.K., Klareskog L., Wang X.
Clin. Immunol. 128:374-381(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), VARIANT ALA-17, ALTERNATIVE SPLICING.
[4]"Full length sequence of hCTLA4 cDNA."
Wu P.W., Ling V.
Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]NIEHS SNPs program
Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Lung.
[8]"Human Ig superfamily CTLA-4 gene: chromosomal localization and identity of protein sequence between murine and human CTLA-4 cytoplasmic domains."
Dariavach P., Mattei M.-G., Golstein P., Lefranc M.-P.
Eur. J. Immunol. 18:1901-1905(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 38-223.
Tissue: Lymphocyte.
[9]Oaks M.K.
Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 38-223 (ISOFORM 5).
Tissue: Lymph node.
[10]"Complete sequence determination of the mouse and human CTLA4 gene loci: cross-species DNA sequence similarity beyond exon borders."
Ling V., Wu P.W., Finnerty H.F., Sharpe A.H., Gray G.S., Collins M.
Genomics 60:341-355(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 140-223, TISSUE SPECIFICITY.
[11]"CTLA-4 is a second receptor for the B cell activation antigen B7."
Linsley P.S., Brady W., Urnes M., Griosmaire L.S., Damle N.K., Ledbetter J.A.
J. Exp. Med. 174:561-569(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"Tyrosine phosphorylation controls internalization of CTLA-4 by regulating its interaction with clathrin-associated adaptor complex AP-2."
Shiratori T., Miyatake S., Ohno H., Nakaseko C., Isono K., Bonifacino J.S., Saito T.
Immunity 6:583-589(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-201.
[13]"Resting lymphocyte kinase (Rlk/Txk) phosphorylates the YVKM motif and regulates PI 3-kinase binding to T-cell antigen CTLA-4."
Schneider H., Schwartzberg P.L., Rudd C.E.
Biochem. Biophys. Res. Commun. 252:14-19(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-201.
[14]"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."
Chikuma S., Murakami M., Tanaka K., Uede T.
J. Cell. Biochem. 78:241-250(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-201 BY JAK2.
[15]"Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease."
Ueda H., Howson J.M., Esposito L., Heward J., Snook H., Chamberlain G., Rainbow D.B., Hunter K.M., Smith A.N., Di Genova G., Herr M.H., Dahlman I., Payne F., Smyth D., Lowe C., Twells R.C., Howlett S., Healy B. expand/collapse author list , Nutland S., Rance H.E., Everett V., Smink L.J., Lam A.C., Cordell H.J., Walker N.M., Bordin C., Hulme J., Motzo C., Cucca F., Hess J.F., Metzker M.L., Rogers J., Gregory S., Allahabadia A., Nithiyananthan R., Tuomilehto-Wolf E., Tuomilehto J., Bingley P., Gillespie K.M., Undlien D.E., Ronningen K.S., Guja C., Ionescu-Tirgoviste C., Savage D.A., Maxwell A.P., Carson D.J., Patterson C.C., Franklyn J.A., Clayton D.G., Peterson L.B., Wicker L.S., Todd J.A., Gough S.C.
Nature 423:506-511(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: POLYMORPHISM.
[16]"Hierarchical regulation of CTLA-4 dimer-based lattice formation and its biological relevance for T cell inactivation."
Darlington P.J., Kirchhof M.G., Criado G., Sondhi J., Madrenas J.
J. Immunol. 175:996-1004(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-113 AND ASN-145.
[17]"A molecular perspective of CTLA-4 function."
Teft W.A., Kirchhof M.G., Madrenas J.
Annu. Rev. Immunol. 24:65-97(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[18]"CTLA-4 trafficking and surface expression."
Valk E., Rudd C.E., Schneider H.
Trends Immunol. 29:272-279(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[19]"The clinical utility of inhibiting CD28-mediated costimulation."
Linsley P.S., Nadler S.G.
Immunol. Rev. 229:307-321(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHARMACEUTICAL.
[20]"Solution structure of human CTLA-4 and delineation of a CD80/CD86 binding site conserved in CD28."
Metzler W.J., Bajorath J., Fenderson W., Shaw S.Y., Constantine K.L., Naemura J., Leytze G., Peach R.J., Lavoie T.B., Mueller L., Linsley P.S.
Nat. Struct. Biol. 4:527-531(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 37-165.
[21]"Structural basis for co-stimulation by the human CTLA-4/B7-2 complex."
Schwartz J.C., Zhang X., Fedorov A.A., Nathenson S.G., Almo S.C.
Nature 410:604-608(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 36-161 IN COMPLEX WITH CD86, SUBUNIT, DISULFIDE BONDS.
[22]"Crystal structure of the B7-1/CTLA-4 complex that inhibits human immune responses."
Stamper C.C., Zhang Y., Tobin J.F., Erbe D.V., Ikemizu S., Davis S.J., Stahl M.L., Seehra J., Somers W.S., Mosyak L.
Nature 410:608-611(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 36-161 IN COMPLEX WITH CD80, SUBUNIT, DISULFIDE BONDS, GLYCOSYLATION AT ASN-113 AND ASN-145.
[23]"Rigid-body ligand recognition drives cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptor triggering."
Yu C., Sonnen A.F., George R., Dessailly B.H., Stagg L.J., Evans E.J., Orengo C.A., Stuart D.I., Ladbury J.E., Ikemizu S., Gilbert R.J., Davis S.J.
J. Biol. Chem. 286:6685-6696(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 36-161, GLYCOSYLATION AT ASN-113, SUBUNIT, DISULFIDE BONDS.
[24]"Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups."
Marron M.P., Raffel L.J., Garchon H.-J., Jacob C.O., Serrano-Rios M., Martinez Larrad M.T., Teng W.-P., Park Y., Zhang Z.-X., Goldstein D.R., Tao Y.-W., Beaurain G., Bach J.-F., Huang H.-S., Luo D.-F., Zeidler A., Rotter J.I., Yang M.C.K. expand/collapse author list , Modilevsky T., Maclaren N.K., She J.-X.
Hum. Mol. Genet. 6:1275-1282(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ALA-17, INVOLVEMENT IN IDDM12.
[25]"CTLA-4 gene polymorphism is associated with predisposition to coeliac disease."
Djilali-Saiah I., Schmitz J., Harfouch-Hammoud E., Mougenot J.-F., Bach J.-F., Caillat-Zucman S.
Gut 43:187-189(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: POLYMORPHISM, INVOLVEMENT IN CELIAC3.
[26]"Cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphism confers susceptibility to thyroid associated orbitopathy."
Vaidya B., Imrie H., Perros P., Dickinson J., McCarthy M.I., Kendall-Taylor P., Pearce S.H.S.
Lancet 354:743-744(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ALA-17, INVOLVEMENT IN THYROID ASSOCIATED ORBITOPATHY.
[27]"Complex association analysis of Graves disease using a set of polymorphic markers."
Chistyakov D.A., Savost'anov K.V., Turakulov R.I., Petunina N.A., Trukhina L.V., Kudinova A.V., Balabolkin M.I., Nosikov V.V.
Mol. Genet. Metab. 70:214-218(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ALA-17, INVOLVEMENT IN GRAVES DISEASE.
[28]"Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene."
Deng Z., Morse J.H., Slager S.L., Cuervo N., Moore K.J., Venetos G., Kalachikov S., Cayanis E., Fischer S.G., Barst R.J., Hodge S.E., Knowles J.A.
Am. J. Hum. Genet. 67:737-744(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ALA-17.
[29]"Evidence for CTLA4 as a susceptibility gene for systemic lupus erythematosus."
Barreto M., Santos E., Ferreira R., Fesel C., Fontes M.F., Pereira C., Martins B., Andreia R., Viana J.F., Crespo F., Vasconcelos C., Ferreira C., Vicente A.M.
Eur. J. Hum. Genet. 12:620-626(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SYSTEMIC LUPUS ERYTHEMATOSUS.
[30]"Cytotoxic T-lymphocyte antigen 4 gene and recovery from hepatitis B virus infection."
Thio C.L., Mosbruger T.L., Kaslow R.A., Karp C.L., Strathdee S.A., Vlahov D., O'Brien S.J., Astemborski J., Thomas D.L.
J. Virol. 78:11258-11262(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO HBV INFECTION, VARIANT ALA-17.
[31]"A common CTLA4 haplotype associated with coeliac disease."
Hunt K.A., McGovern D.P.B., Kumar P.J., Ghosh S., Travis S.P.L., Walters J.R.F., Jewell D.P., Playford R.J., van Heel D.A.
Eur. J. Hum. Genet. 13:440-444(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CELIAC3.
[32]"CTLA-4 polymorphisms and systemic lupus erythematosus (SLE): a meta-analysis."
Lee Y.H., Harley J.B., Nath S.K.
Hum. Genet. 116:361-367(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SYSTEMIC LUPUS ERYTHEMATOSUS.
+Additional computationally mapped references.

Web resources

Wikipedia

CLTA-4 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L15006 mRNA. Translation: AAB59385.1.
M74363 Genomic DNA. Translation: AAA52127.1.
AF411058 Genomic DNA. Translation: AAL40932.1.
AY792514 mRNA. Translation: AAV66331.1.
AY999702 mRNA. Translation: AAY00166.1.
DQ785106 mRNA. Translation: ABG85285.1.
AF414120 mRNA. Translation: AAL07473.1.
DQ357942 Genomic DNA. Translation: ABC67470.1.
AC010138 Genomic DNA. Translation: AAX93176.1.
BC074842 mRNA. Translation: AAH74842.1.
BC074893 mRNA. Translation: AAH74893.1.
AH002733 Genomic DNA. Translation: AAA52773.1.
U90273 mRNA. Translation: AAD00698.1.
AF142144 Genomic DNA. Translation: AAF02499.1.
CCDSCCDS2362.1. [P16410-1]
CCDS42803.1. [P16410-5]
PIRS08614.
RefSeqNP_001032720.1. NM_001037631.2. [P16410-5]
NP_005205.2. NM_005214.4. [P16410-1]
UniGeneHs.247824.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1AH1NMR-A37-161[»]
1H6EX-ray3.60P197-207[»]
1I85X-ray3.20C/D36-161[»]
1I8LX-ray3.00C/D36-161[»]
2X44X-ray2.60D36-161[»]
3BX7X-ray2.10C38-161[»]
3OSKX-ray1.80A/B36-161[»]
ProteinModelPortalP16410.
SMRP16410. Positions 38-160.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107875. 11 interactions.
IntActP16410. 3 interactions.
MINTMINT-6631153.
STRING9606.ENSP00000303939.

Chemistry

ChEMBLCHEMBL2364164.
DrugBankDB01281. Abatacept.
GuidetoPHARMACOLOGY2743.

PTM databases

PhosphoSiteP16410.

Polymorphism databases

DMDM27735177.

Proteomic databases

PaxDbP16410.
PRIDEP16410.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000295854; ENSP00000295854; ENSG00000163599. [P16410-5]
ENST00000302823; ENSP00000303939; ENSG00000163599. [P16410-1]
ENST00000427473; ENSP00000409707; ENSG00000163599.
ENST00000472206; ENSP00000417779; ENSG00000163599. [P16410-4]
GeneID1493.
KEGGhsa:1493.
UCSCuc002vak.2. human. [P16410-1]
uc010fty.2. human. [P16410-4]

Organism-specific databases

CTD1493.
GeneCardsGC02P204696.
HGNCHGNC:2505. CTLA4.
MIM109100. phenotype.
123890. gene.
152700. phenotype.
601388. phenotype.
609755. phenotype.
610424. phenotype.
neXtProtNX_P16410.
Orphanet555. Celiac disease.
900. Granulomatosis with polyangiitis.
855. Hashimoto struma.
536. Systemic lupus erythematosus.
PharmGKBPA27006.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG42442.
HOVERGENHBG057978.
InParanoidP16410.
KOK06538.
OMAFSKGMHV.
OrthoDBEOG70GMGW.
PhylomeDBP16410.
TreeFamTF335679.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressP16410.
BgeeP16410.
CleanExHS_CTLA4.
GenevestigatorP16410.

Family and domain databases

Gene3D2.60.40.10. 1 hit.
InterProIPR008096. CTLA4.
IPR013783. Ig-like_fold.
IPR013106. Ig_V-set.
IPR003596. Ig_V-set_subgr.
[Graphical view]
PfamPF07686. V-set. 1 hit.
[Graphical view]
PRINTSPR01720. CTLANTIGEN4.
SMARTSM00406. IGv. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP16410.
GeneWikiCTLA-4.
GenomeRNAi1493.
NextBio13603519.
PROP16410.
SOURCESearch...

Entry information

Entry nameCTLA4_HUMAN
AccessionPrimary (citable) accession number: P16410
Secondary accession number(s): A0N1S0 expand/collapse secondary AC list , E9PDH0, O95653, Q0PP65, Q52MC1, Q53TD5, Q5S005, Q8WXJ1, Q96P43, Q9UKN9
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: January 10, 2003
Last modified: July 9, 2014
This is version 166 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries