Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P16410

- CTLA4_HUMAN

UniProt

P16410 - CTLA4_HUMAN

Protein

Cytotoxic T-lymphocyte protein 4

Gene

CTLA4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 168 (01 Oct 2014)
      Sequence version 3 (10 Jan 2003)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    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 CD28.2 Publications

    GO - Molecular functioni

    1. protein binding Source: IntAct

    GO - Biological processi

    1. B cell receptor signaling pathway Source: UniProtKB
    2. cellular response to DNA damage stimulus Source: UniProtKB
    3. immune response Source: ProtInc
    4. negative regulation of B cell proliferation Source: UniProtKB
    5. negative regulation of immune response Source: Ensembl
    6. negative regulation of regulatory T cell differentiation Source: BHF-UCL
    7. negative regulation of T cell proliferation Source: Ensembl
    8. positive regulation of apoptotic process Source: UniProtKB
    9. T cell costimulation Source: Reactome

    Keywords - Biological processi

    Adaptive immunity, Immunity

    Enzyme and pathway databases

    ReactomeiREACT_19405. CTLA4 inhibitory signaling.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytotoxic T-lymphocyte protein 4
    Alternative name(s):
    Cytotoxic T-lymphocyte-associated antigen 4
    Short name:
    CTLA-4
    CD_antigen: CD152
    Gene namesi
    Name:CTLA4
    Synonyms:CD152
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:2505. CTLA4.

    Subcellular locationi

    Cell membrane 1 Publication; Single-pass type I membrane protein 1 Publication
    Note: Exists primarily an intracellular antigen whose surface expression is tightly regulated by restricted trafficking to the cell surface and rapid internalisation;.

    GO - Cellular componenti

    1. clathrin-coated endocytic vesicle Source: BHF-UCL
    2. external side of plasma membrane Source: BHF-UCL
    3. Golgi apparatus Source: BHF-UCL
    4. integral component of plasma membrane Source: ProtInc
    5. perinuclear region of cytoplasm Source: BHF-UCL
    6. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    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.2 Publications
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    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.1 Publication
    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.2 Publications
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

    Pharmaceutical usei

    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.

    Keywords - Diseasei

    Diabetes mellitus, Systemic lupus erythematosus

    Organism-specific databases

    MIMi109100. phenotype.
    152700. phenotype.
    601388. phenotype.
    609755. phenotype.
    610424. phenotype.
    Orphaneti555. Celiac disease.
    900. Granulomatosis with polyangiitis.
    855. Hashimoto struma.
    536. Systemic lupus erythematosus.
    PharmGKBiPA27006.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 3535Sequence AnalysisAdd
    BLAST
    Chaini36 – 223188Cytotoxic T-lymphocyte protein 4PRO_0000014734Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi58 ↔ 129
    Disulfide bondi85 ↔ 103
    Glycosylationi113 – 1131N-linked (GlcNAc...)3 Publications
    Glycosylationi145 – 1451N-linked (GlcNAc...)2 Publications
    Disulfide bondi157 – 157Interchain
    Modified residuei201 – 2011Phosphotyrosine; by TXK and JAK23 Publications

    Post-translational modificationi

    N-glycosylation is important for dimerization.3 Publications
    Phosphorylation at Tyr-201 prevents binding to the AP-2 adapter complex, blocks endocytosis, and leads to retention of CTLA4 on the cell surface.3 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiP16410.
    PRIDEiP16410.

    PTM databases

    PhosphoSiteiP16410.

    Expressioni

    Tissue specificityi

    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.3 Publications

    Gene expression databases

    ArrayExpressiP16410.
    BgeeiP16410.
    CleanExiHS_CTLA4.
    GenevestigatoriP16410.

    Interactioni

    Subunit structurei

    Homodimer; disulfide-linked. Binds to CD80/B7-1 and CD86/B7.2.3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CD80P336813EBI-1030991,EBI-1031024
    CD86P420813EBI-1030991,EBI-1030956
    PIK3R1P279863EBI-1030991,EBI-79464

    Protein-protein interaction databases

    BioGridi107875. 11 interactions.
    IntActiP16410. 6 interactions.
    MINTiMINT-6631153.
    STRINGi9606.ENSP00000303939.

    Structurei

    Secondary structure

    1
    223
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi44 – 474
    Beta strandi50 – 523
    Beta strandi54 – 607
    Beta strandi64 – 663
    Beta strandi68 – 7710
    Beta strandi80 – 9011
    Beta strandi102 – 1087
    Beta strandi111 – 1166
    Helixi121 – 1233
    Beta strandi125 – 13814
    Beta strandi140 – 1434
    Beta strandi147 – 1504
    Beta strandi156 – 1583

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    ProteinModelPortaliP16410.
    SMRiP16410. Positions 38-160.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP16410.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini36 – 161126ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini183 – 22341CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei162 – 18221HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini39 – 140102Ig-like V-typeAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni46 – 505Homodimerization
    Regioni150 – 1556Homodimerization

    Sequence similaritiesi

    Keywords - Domaini

    Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG42442.
    HOVERGENiHBG057978.
    InParanoidiP16410.
    KOiK06538.
    OMAiFSKGMHV.
    OrthoDBiEOG70GMGW.
    PhylomeDBiP16410.
    TreeFamiTF335679.

    Family and domain databases

    Gene3Di2.60.40.10. 1 hit.
    InterProiIPR008096. CTLA4.
    IPR013783. Ig-like_fold.
    IPR013106. Ig_V-set.
    IPR003596. Ig_V-set_subgr.
    [Graphical view]
    PfamiPF07686. V-set. 1 hit.
    [Graphical view]
    PRINTSiPR01720. CTLANTIGEN4.
    SMARTiSM00406. IGv. 1 hit.
    [Graphical view]

    Sequences (5)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 5 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P16410-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MACLGFQRHK AQLNLATRTW PCTLLFFLLF IPVFCKAMHV AQPAVVLASS    50
    RGIASFVCEY ASPGKATEVR VTVLRQADSQ VTEVCAATYM MGNELTFLDD 100
    SICTGTSSGN QVNLTIQGLR AMDTGLYICK VELMYPPPYY LGIGNGTQIY 150
    VIDPEPCPDS DFLLWILAAV SSGLFFYSFL LTAVSLSKML KKRSPLTTGV 200
    YVKMPPTEPE CEKQFQPYFI PIN 223
    Length:223
    Mass (Da):24,656
    Last modified:January 10, 2003 - v3
    Checksum:i6F9466FB2E139A5A
    GO
    Isoform 2 (identifier: P16410-2) [UniParc]FASTAAdd to Basket

    Also known as: ss-CTLA-4

    The sequence of this isoform differs from the canonical sequence as follows:
         38-204: Missing.

    Show »
    Length:56
    Mass (Da):6,560
    Checksum:i096CBF7AD57AE9B9
    GO
    Isoform 3 (identifier: P16410-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         38-204: Missing.
         205-223: PPTEPECEKQFQPYFIPIN → KEKKPSYNRGLCENAPNRARM

    Show »
    Length:58
    Mass (Da):6,745
    Checksum:i5F70948EEDC80A94
    GO
    Isoform 4 (identifier: P16410-4) [UniParc]FASTAAdd to Basket

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

    Show »
    Length:79
    Mass (Da):8,855
    Checksum:i60CBF1BC1DA59D8A
    GO
    Isoform 5 (identifier: P16410-5) [UniParc]FASTAAdd to Basket

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

    Show »
    Length:174
    Mass (Da):19,145
    Checksum:i0881BFA757AC3FDB
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti37 – 371A → V in ABG85285. (PubMed:18595775)Curated
    Sequence conflicti147 – 1471T → A in AAA52773. (PubMed:3220103)Curated

    Polymorphismi

    Genetic variations in CTLA4 are associated with susceptibility to several autoimmune disorders. They influence responsiveness to hepatitis B virus (HBV) infection [MIMi:610424].

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti17 – 171T → A Increased risk for Graves disease, insulin-dependent diabetes mellitus, thyroid-associated orbitopathy, systemic lupus erythematosus and susceptibility to HBV infection. 7 Publications
    Corresponds to variant rs231775 [ dbSNP | Ensembl ].
    VAR_013577

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei38 – 204167Missing in isoform 2 and isoform 3. 1 PublicationVSP_041284Add
    BLAST
    Alternative sequencei58 – 581C → S in isoform 4. 1 PublicationVSP_041285
    Alternative sequencei59 – 204146Missing in isoform 4. 1 PublicationVSP_041286Add
    BLAST
    Alternative sequencei153 – 17422DPEPC…VSSGL → AKEKKPSYNRGLCENAPNRA RM in isoform 5. 1 PublicationVSP_047238Add
    BLAST
    Alternative sequencei175 – 22349Missing in isoform 5. 1 PublicationVSP_047239Add
    BLAST
    Alternative sequencei205 – 22319PPTEP…FIPIN → KEKKPSYNRGLCENAPNRAR M in isoform 3 and isoform 4. 1 PublicationVSP_041287Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS2362.1. [P16410-1]
    CCDS42803.1. [P16410-5]
    PIRiS08614.
    RefSeqiNP_001032720.1. NM_001037631.2. [P16410-5]
    NP_005205.2. NM_005214.4. [P16410-1]
    UniGeneiHs.247824.

    Genome annotation databases

    EnsembliENST00000295854; ENSP00000295854; ENSG00000163599. [P16410-5]
    ENST00000302823; ENSP00000303939; ENSG00000163599. [P16410-1]
    ENST00000427473; ENSP00000409707; ENSG00000163599.
    ENST00000472206; ENSP00000417779; ENSG00000163599. [P16410-4]
    GeneIDi1493.
    KEGGihsa:1493.
    UCSCiuc002vak.2. human. [P16410-1]
    uc010fty.2. human. [P16410-4]

    Polymorphism databases

    DMDMi27735177.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Wikipedia

    CLTA-4 entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS2362.1. [P16410-1 ]
    CCDS42803.1. [P16410-5 ]
    PIRi S08614.
    RefSeqi NP_001032720.1. NM_001037631.2. [P16410-5 ]
    NP_005205.2. NM_005214.4. [P16410-1 ]
    UniGenei Hs.247824.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 [» ]
    ProteinModelPortali P16410.
    SMRi P16410. Positions 38-160.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107875. 11 interactions.
    IntActi P16410. 6 interactions.
    MINTi MINT-6631153.
    STRINGi 9606.ENSP00000303939.

    Chemistry

    ChEMBLi CHEMBL2364164.
    DrugBanki DB01281. Abatacept.
    GuidetoPHARMACOLOGYi 2743.

    PTM databases

    PhosphoSitei P16410.

    Polymorphism databases

    DMDMi 27735177.

    Proteomic databases

    PaxDbi P16410.
    PRIDEi P16410.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000295854 ; ENSP00000295854 ; ENSG00000163599 . [P16410-5 ]
    ENST00000302823 ; ENSP00000303939 ; ENSG00000163599 . [P16410-1 ]
    ENST00000427473 ; ENSP00000409707 ; ENSG00000163599 .
    ENST00000472206 ; ENSP00000417779 ; ENSG00000163599 . [P16410-4 ]
    GeneIDi 1493.
    KEGGi hsa:1493.
    UCSCi uc002vak.2. human. [P16410-1 ]
    uc010fty.2. human. [P16410-4 ]

    Organism-specific databases

    CTDi 1493.
    GeneCardsi GC02P204696.
    HGNCi HGNC:2505. CTLA4.
    MIMi 109100. phenotype.
    123890. gene.
    152700. phenotype.
    601388. phenotype.
    609755. phenotype.
    610424. phenotype.
    neXtProti NX_P16410.
    Orphaneti 555. Celiac disease.
    900. Granulomatosis with polyangiitis.
    855. Hashimoto struma.
    536. Systemic lupus erythematosus.
    PharmGKBi PA27006.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG42442.
    HOVERGENi HBG057978.
    InParanoidi P16410.
    KOi K06538.
    OMAi FSKGMHV.
    OrthoDBi EOG70GMGW.
    PhylomeDBi P16410.
    TreeFami TF335679.

    Enzyme and pathway databases

    Reactomei REACT_19405. CTLA4 inhibitory signaling.

    Miscellaneous databases

    EvolutionaryTracei P16410.
    GeneWikii CTLA-4.
    GenomeRNAii 1493.
    NextBioi 13603519.
    PROi P16410.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P16410.
    Bgeei P16410.
    CleanExi HS_CTLA4.
    Genevestigatori P16410.

    Family and domain databases

    Gene3Di 2.60.40.10. 1 hit.
    InterProi IPR008096. CTLA4.
    IPR013783. Ig-like_fold.
    IPR013106. Ig_V-set.
    IPR003596. Ig_V-set_subgr.
    [Graphical view ]
    Pfami PF07686. V-set. 1 hit.
    [Graphical view ]
    PRINTSi PR01720. CTLANTIGEN4.
    SMARTi SM00406. IGv. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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.
      , 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. 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. 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. 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. 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. 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.

    Entry informationi

    Entry nameiCTLA4_HUMAN
    AccessioniPrimary (citable) accession number: P16410
    Secondary accession number(s): A0N1S0
    , E9PDH0, O95653, Q0PP65, Q52MC1, Q53TD5, Q5S005, Q8WXJ1, Q96P43, Q9UKN9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1990
    Last sequence update: January 10, 2003
    Last modified: October 1, 2014
    This is version 168 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Pharmaceutical, Reference proteome

    Documents

    1. Human cell differentiation molecules
      CD nomenclature of surface proteins of human leucocytes and list of entries
    2. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3