P16410 (CTLA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	223 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.10 Ref.15
Subunit structure	Homodimer; disulfide-linked. Binds to CD80/B7-1 and CD86/B7.2. Ref.19 Ref.20
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.16
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.9 Ref.15
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	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. Ref.24 Note=Genetic variations in CTLA4 may influence susceptibility to Graves disease, an autoimmune disorder associated with overactivity of the thyroid gland and hyperthyroidism. Ref.24 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. Ref.21 Ref.24 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 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 process	Adaptive immunity Immunity
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Diabetes mellitus Systemic lupus erythematosus
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Pharmaceutical Reference proteome
Gene Ontology (GO)
Biological process	B cell receptor signaling pathway Inferred from mutant phenotype. Source: UniProtKB T cell costimulation Traceable author statement. Source: Reactome immune response Traceable author statement. Source: ProtInc negative regulation of B cell proliferation Inferred from mutant phenotype. Source: UniProtKB negative regulation of regulatory T cell differentiation Inferred from direct assay. Source: BHF-UCL positive regulation of apoptotic process Inferred from mutant phenotype. Source: UniProtKB response to DNA damage stimulus Inferred from mutant phenotype. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from direct assay. Source: BHF-UCL clathrin-coated endocytic vesicle Inferred from direct assay. Source: BHF-UCL external side of plasma membrane Inferred from direct assay. Source: BHF-UCL integral to plasma membrane Traceable author statement. Source: ProtInc perinuclear region of cytoplasm Inferred from direct assay. Source: BHF-UCL
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CD80	P33681	3	EBI-1030991,EBI-1031024
CD86	P42081	2	EBI-1030991,EBI-1030956

Alternative products

This entry describes 4 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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 35

35

Potential

Chain

36 – 223

188

Cytotoxic T-lymphocyte protein 4

PRO_0000014734

Regions

Topological domain

36 – 161

126

Extracellular Potential

Transmembrane

162 – 182

21

Helical; Potential

Topological domain

183 – 223

41

Cytoplasmic Potential

Domain

39 – 140

102

Ig-like V-type

Region

46 – 50

5

Homodimerization

Region

150 – 155

6

Homodimerization

Amino acid modifications

Modified residue

201

1

Phosphotyrosine; by TXK Ref.11 Ref.12

Glycosylation

113

1

N-linked (GlcNAc...) Ref.14 Ref.20

Glycosylation

145

1

N-linked (GlcNAc...) Ref.14

Disulfide bond

58 ↔ 129

Ref.19 Ref.20

Disulfide bond

85 ↔ 103

Ref.19 Ref.20

Disulfide bond

157

Interchain Ref.19 Ref.20

Natural variations

Alternative sequence

38 – 204

167

Missing in isoform 2 and isoform 3.

VSP_041284

Alternative sequence

58

1

C → S in isoform 4.

VSP_041285

Alternative sequence

59 – 204

146

Missing in isoform 4.

VSP_041286

Alternative sequence

205 – 223

19

PPTEP…FIPIN → KEKKPSYNRGLCENAPNRAR M in isoform 3 and isoform 4.

VSP_041287

Natural variant

17

1

T → 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.21 Ref.23 Ref.24 Ref.25 Ref.27
Corresponds to variant rs231775 [ dbSNP | Ensembl ].

VAR_013577

Experimental info

Sequence conflict

37

1

A → V in ABG85285. Ref.3

Sequence conflict

147

1

T → A in AAA52773. Ref.8

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

223

Helix Strand Turn

Details...

Beta strand

44 – 47

4

Beta strand

57 – 60

4

Beta strand

64 – 66

3

Beta strand

69 – 73

5

Beta strand

76 – 79

4

Beta strand

85 – 89

5

Beta strand

101 – 103

3

Beta strand

109 – 113

5

Turn

121 – 123

3

Beta strand

125 – 127

3

Beta strand

129 – 133

5

Beta strand

135 – 138

4

Beta strand

147 – 150

4

Beta strand

156 – 158

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 10, 2003. Version 3. Checksum: 6F9466FB2E139A5A	FASTA	223	24,656
	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
	Isoform 2 (ss-CTLA-4) [UniParc]. Checksum: 096CBF7AD57AE9B9	FASTA	56	6,560
	10 20 30 40 50 MACLGFQRHK AQLNLATRTW PCTLLFFLLF IPVFCKAPPT EPECEKQFQP YFIPIN
	Isoform 3 [UniParc]. Checksum: 5F70948EEDC80A94	FASTA	58	6,745
	10 20 30 40 50 MACLGFQRHK AQLNLATRTW PCTLLFFLLF IPVFCKAKEK KPSYNRGLCE NAPNRARM
	Isoform 4 [UniParc]. Checksum: 60CBF1BC1DA59D8A	FASTA	79	8,855
	10 20 30 40 50 60 MACLGFQRHK AQLNLATRTW PCTLLFFLLF IPVFCKAMHV AQPAVVLASS RGIASFVSKE 70 KKPSYNRGLC ENAPNRARM

References

	« Hide 'large scale' referencesShow '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: 1713603] [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: 11735222] [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: 18595775] [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. , 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: 15815621] [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: 15489334] [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: 3220103] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 38-223. Tissue: Lymphocyte.
[9]	"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: 10493833] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 140-223, TISSUE SPECIFICITY.
[10]	"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: 1714933] [Abstract] Cited for: FUNCTION.
[11]	"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: 9175836] [Abstract] Cited for: PHOSPHORYLATION AT TYR-201.
[12]	"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: 9813138] [Abstract] Cited for: PHOSPHORYLATION AT TYR-201.
[13]	"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. , 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: 12724780] [Abstract] Cited for: POLYMORPHISM.
[14]	"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: 16002699] [Abstract] Cited for: GLYCOSYLATION AT ASN-113 AND ASN-145.
[15]	"A molecular perspective of CTLA-4 function." Teft W.A., Kirchhof M.G., Madrenas J. Annu. Rev. Immunol. 24:65-97(2006) [PubMed: 16551244] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[16]	"CTLA-4 trafficking and surface expression." Valk E., Rudd C.E., Schneider H. Trends Immunol. 29:272-279(2008) [PubMed: 18468488] [Abstract] Cited for: SUBCELLULAR LOCATION.
[17]	"The clinical utility of inhibiting CD28-mediated costimulation." Linsley P.S., Nadler S.G. Immunol. Rev. 229:307-321(2009) [PubMed: 19426230] [Abstract] Cited for: PHARMACEUTICAL.
[18]	"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: 9228944] [Abstract] Cited for: STRUCTURE BY NMR OF 37-165.
[19]	"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: 11279501] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 36-161 IN COMPLEX WITH CD86, SUBUNIT, DISULFIDE BONDS.
[20]	"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: 21156796] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 36-161, GLYCOSYLATION AT ASN-113, SUBUNIT, DISULFIDE BONDS.
[21]	"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. , Modilevsky T., Maclaren N.K., She J.-X. Hum. Mol. Genet. 6:1275-1282(1997) [PubMed: 9259273] [Abstract] Cited for: VARIANT ALA-17, INVOLVEMENT IN IDDM12.
[22]	"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: 10189842] [Abstract] Cited for: POLYMORPHISM, INVOLVEMENT IN CELIAC3.
[23]	"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: 10475192] [Abstract] Cited for: VARIANT ALA-17, INVOLVEMENT IN THYROID ASSOCIATED ORBITOPATHY.
[24]	"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: 10924276] [Abstract] Cited for: VARIANT ALA-17, INVOLVEMENT IN GRAVES DISEASE.
[25]	"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: 10903931] [Abstract] Cited for: VARIANT ALA-17.
[26]	"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: 15138458] [Abstract] Cited for: INVOLVEMENT IN SYSTEMIC LUPUS ERYTHEMATOSUS.
[27]	"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: 15452244] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO HBV INFECTION, VARIANT ALA-17.
[28]	"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: 15657618] [Abstract] Cited for: INVOLVEMENT IN CELIAC3.
[29]	"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: 15688186] [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.
M37245, M37243, M37244 Genomic DNA. Translation: AAA52773.1.
AF142144 Genomic DNA. Translation: AAF02499.1.

IPI

IPI00028559.
IPI00604432.
IPI00945919.
IPI01018238.

PIR

S08614.

RefSeq

NP_001032720.1. NM_001037631.2.
NP_005205.2. NM_005214.4.

UniGene

Hs.247824.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AH1	NMR	-	A	37-161	[»]
1H6E	X-ray	3.60	P	197-207	[»]
1I85	X-ray	3.20	C/D	36-161	[»]
1I8L	X-ray	3.00	C/D	36-161	[»]
2X44	X-ray	2.60	D	36-161	[»]
3BX7	X-ray	2.10	C	38-161	[»]
3OSK	X-ray	1.80	A/B	36-161	[»]

ProteinModelPortal

P16410.

SMR

P16410. Positions 38-160.

ModBase

Search...

Protein-protein interaction databases

IntAct

P16410. 2 interactions.

STRING

P16410.

PTM databases

PhosphoSite

P16410.

Polymorphism databases

DMDM

27735177.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000302823; ENSP00000303939; ENSG00000163599.

GeneID

1493.

KEGG

hsa:1493.

UCSC

uc002vak.1. human.

Organism-specific databases

CTD

1493.

GeneCards

GC02P204696.

H-InvDB

HIX0029846.

HGNC

HGNC:2505. CTLA4.

MIM

109100. phenotype.
123890. gene.
152700. phenotype.
601388. phenotype.
609755. phenotype.
610424. phenotype.

neXtProt

NX_P16410.

Orphanet

555. Celiac disease.
855. Hashimoto struma.
536. Systemic lupus erythematosus.

GenAtlas

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Phylogenomic databases

HOGENOM

HBG280302.

HOVERGEN

HBG057978.

InParanoid

P16410.

OMA

SGNKVNL.

OrthoDB

EOG4Q58QK.

PhylomeDB

P16410.

Enzyme and pathway databases

Pathway_Interaction_DB

nfat_tfpathway. Calcineurin-regulated NFAT-dependent transcription in lymphocytes.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P16410.

Bgee

P16410.

CleanEx

HS_CTLA4.

Genevestigator

P16410.

GermOnline

ENSG00000163599. Homo sapiens.

Family and domain databases

InterPro

IPR008096. CTLA4.
IPR013783. Ig-like_fold.
IPR013106. Ig_V-set.
IPR003596. Ig_V-set_subgr.
[Graphical view]

Gene3D

G3DSA:2.60.40.10. Ig-like_fold. 1 hit.

KO

K06538.

Pfam

PF07686. V-set. 1 hit.
[Graphical view]

PRINTS

PR01720. CTLANTIGEN4.

SMART

SM00406. IGv. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. False negative.
[Graphical view]

ProtoNet

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Other

DrugBank

DB01281. Abatacept.

NextBio

6133.

SOURCE

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Entry information

Entry name

CTLA4_HUMAN

Accession

Primary (citable) accession number: P16410
Secondary accession number(s): A0N1S0 , E9PDH0, 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:	January 25, 2012
This is version 137 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.