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    CTLA4 cytotoxic T-lymphocyte-associated protein 4 [ Homo sapiens ]

    Gene ID: 1493, updated on 19-May-2012

    Summary

    Official Symbol
    CTLA4provided by HGNC
    Official Full Name
    cytotoxic T-lymphocyte-associated protein 4provided by HGNC
    Primary source
    HGNC:2505
    See related
    Ensembl:ENSG00000163599; HPRD:00474; MIM:123890; Vega:OTTHUMG00000132877
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CD; GSE; GRD4; ICOS; CD152; CTLA-4; IDDM12; CELIAC3
    Summary
    This gene is a member of the immunoglobulin superfamily and encodes a protein which transmits an inhibitory signal to T cells. The protein contains a V domain, a transmembrane domain, and a cytoplasmic tail. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. The membrane-bound isoform functions as a homodimer interconnected by a disulfide bond, while the soluble isoform functions as a monomer. Mutations in this gene have been associated with insulin-dependent diabetes mellitus, Graves disease, Hashimoto thyroiditis, celiac disease, systemic lupus erythematosus, thyroid-associated orbitopathy, and other autoimmune diseases. [provided by RefSeq, Jul 2008]

    Genomic context

    Location :
    2q33
    Sequence :
    Chromosome: 2; NC_000002.11 (204732511..204738683)
    See CTLA4 in Epigenomics, MapViewer

    Chromosome 2 - NC_000002.11Genomic Context describing neighboring genes Neighboring gene nucleophosmin (nucleolar phosphoprotein B23, numatrin) pseudogene Neighboring gene keratin 18 pseudogene 39 Neighboring gene inducible T-cell co-stimulator Neighboring gene zinc finger protein 555 pseudogene

    Genomic regions, transcripts, and products

    Bibliography

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    HIV-1 protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp160, precursor env The envelope glycoprotein (gp160)) of HIV-1 is directed to intracellular CTLA-4-containing granules rather than trafficking constitutively from the Golgi to the cell surface PubMed
    Nef nef HIV-1 Nef expression in Jurkat cells upregulates the level of CTLA4 production in the absence of CD3 and CD28 stimulation PubMed
    Vpr vpr HIV-1 Vpr increases the levels of CTLA4 expression in infected T cells PubMed

    Go to the HIV-1, Human Protein Interaction Database

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    NP_005205.2 NP_005182.1 CD80    BIND  PubMed CD80 interacts with CTLA-4. 
    NP_005205.2 NP_004963.1 JAK2    BIND  PubMed CTLA-4 interacts with Jak2. 
    P16410 Q9BXS5 AP1M1    HPRD  PubMed  
    P16410 Q96CW1 AP2M1    HPRD  PubMed  
    P16410 P33681 CD80    HPRD  PubMed  
    P16410 P42081 CD86    HPRD  PubMed  
    P16410 P16410 CTLA4    HPRD  PubMed  
    P16410 P06241 FYN    HPRD  PubMed  
    P16410 O60674 JAK2    HPRD  PubMed  
    P16410 P06239 LCK    HPRD  PubMed  
    P16410 P07948 LYN    HPRD  PubMed  
    P16410 P27986 PIK3R1    HPRD  PubMed  
    P16410 Q15172 PPP2R5A    HPRD  PubMed  
    P16410 Q06124 PTPN11    HPRD  PubMed  
    P16410 P42229 STAT5A    HPRD  PubMed  
    P16410 P51692 STAT5B    HPRD  PubMed  
    P16410 P42681 TXK    HPRD  PubMed  
    BioGRID:107875 BioGRID:114421 AP1M1    BioGRID  PubMed Co-crystal Structure 
    BioGRID:107875 BioGRID:107587 AP2M1    BioGRID  PubMed Affinity Capture-Western; Co-crystal Structure; Reconstituted Complex; Two-hybrid 
    BioGRID:107875 BioGRID:107379 CD80    BioGRID  PubMed Co-crystal Structure; Reconstituted Complex 
    BioGRID:107875 BioGRID:107380 CD86    BioGRID  PubMed Co-crystal Structure 
    BioGRID:107875 BioGRID:107875 CTLA4    BioGRID  PubMed Co-crystal Structure 
    BioGRID:107875 BioGRID:108810 FYN    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107875 BioGRID:109920 JAK2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107875 BioGRID:110124 LCK    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107875 BioGRID:110245 LYN    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107875 BioGRID:111517 PPP2R5A    BioGRID  PubMed Affinity Capture-Western; Two-hybrid 

    General gene information

    Markers

    Homology

    Pathways from BioSystems

    • Adaptive Immune System, organism-specific biosystem (from REACTOME)
      Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
    • Autoimmune thyroid disease, organism-specific biosystem (from KEGG)
      Autoimmune thyroid disease, organism-specific biosystemThe classification of autoimmune throid disease (AITD) includes Hashimoto's thyroiditis (HT) or chronic autoimmune thyroiditis and its variants, Graves' disease (GD) and autoimmune atrophic thyroidi...
    • Autoimmune thyroid disease, conserved biosystem (from KEGG)
      Autoimmune thyroid disease, conserved biosystemThe classification of autoimmune throid disease (AITD) includes Hashimoto's thyroiditis (HT) or chronic autoimmune thyroiditis and its variants, Graves' disease (GD) and autoimmune atrophic thyroidi...
    • CTLA4 inhibitory signaling, organism-specific biosystem (from REACTOME)
      CTLA4 inhibitory signaling, organism-specific biosystemCTLA4 is one of the best studied inhibitory receptors of the CD28 superfamily. CTLA4 inhibits Tcell activation by reducing IL2 production and IL2 expression, and by arresting T cells at the G1 phase ...
    • Calcineurin-regulated NFAT-dependent transcription in lymphocytes, organism-specific biosystem (from Pathway Interaction Database)
      Calcineurin-regulated NFAT-dependent transcription in lymphocytes, organism-specific biosystem
      Calcineurin-regulated NFAT-dependent transcription in lymphocytes
    • Cell adhesion molecules (CAMs), organism-specific biosystem (from KEGG)
      Cell adhesion molecules (CAMs), organism-specific biosystemCell adhesion molecules are (glyco)proteins expressed on the cell surface and play a critical role in a wide array of biologic processes that include hemostasis, the immune response, inflammation, em...
    • Cell adhesion molecules (CAMs), conserved biosystem (from KEGG)
      Cell adhesion molecules (CAMs), conserved biosystemCell adhesion molecules are (glyco)proteins expressed on the cell surface and play a critical role in a wide array of biologic processes that include hemostasis, the immune response, inflammation, em...
    • Costimulation by the CD28 family, organism-specific biosystem (from REACTOME)
      Costimulation by the CD28 family, organism-specific biosystemOptimal activation of T-lymphocytes requires at least two signals. A primary one is delivered by the T-cell receptor (TCR) complex after antigen recognition and additional costimulatory signals are d...
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • Rheumatoid arthritis, organism-specific biosystem (from KEGG)
      Rheumatoid arthritis, organism-specific biosystemRheumatoid arthritis (RA) is a chronic autoimmune joint disease where persistent inflammation affects bone remodeling leading to progressive bone destruction. In RA, abnormal activation of the immune...
    • Rheumatoid arthritis, conserved biosystem (from KEGG)
      Rheumatoid arthritis, conserved biosystemRheumatoid arthritis (RA) is a chronic autoimmune joint disease where persistent inflammation affects bone remodeling leading to progressive bone destruction. In RA, abnormal activation of the immune...
    • T cell receptor signaling pathway, organism-specific biosystem (from KEGG)
      T cell receptor signaling pathway, organism-specific biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
    • T cell receptor signaling pathway, conserved biosystem (from KEGG)
      T cell receptor signaling pathway, conserved biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    B cell receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    T cell costimulation TAS
    Traceable Author Statement
    more info
     
    immune response IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of B cell proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of regulatory T cell differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    response to DNA damage stimulus IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Component Evidence Code Pubs
    Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    clathrin-coated endocytic vesicle IDA
    Inferred from Direct Assay
    more info
    PubMed 
    external side of plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    integral to plasma membrane TAS
    Traceable Author Statement
    more info
    PubMed 
    membrane IEA
    Inferred from Electronic Annotation
    more info
     
    perinuclear region of cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    plasma membrane TAS
    Traceable Author Statement
    more info
     

    General protein information

    Preferred Names
    cytotoxic T-lymphocyte protein 4
    Names
    cytotoxic T-lymphocyte protein 4
    CD152 isoform
    celiac disease 3
    cytotoxic T-lymphocyte antigen 4
    cytotoxic T-lymphocyte-associated antigen 4
    cytotoxic T-lymphocyte-associated serine esterase-4
    cytotoxic T lymphocyte associated antigen 4 short spliced form
    ligand and transmembrane spliced cytotoxic T lymphocyte associated antigen 4

    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_011502.1 RefSeqGene

      Range
      5003..11175
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001037631.2NP_001032720.1  cytotoxic T-lymphocyte protein 4 isoform CTLA-4delTM precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an exon in the coding region, which results in a frameshift and an early stop codon, compared to variant 1. The encoded isoform CTLA-4delTM (also known as sCTLA4) is soluble and lacks the transmembrane domain, compared to isoform a. The exon skip represented in this variant is is based on human U90273.1, and is consistent with mouse U90270.1 and the data published in PMID:10831323 and PMID:10556814.
      Source sequence(s)
      AC010138, AF414120
      Consensus CDS
      CCDS42803.1
      UniProtKB/Swiss-Prot
      P16410
      Related
      ENSP00000295854, OTTHUMP00000216624, ENST00000295854, OTTHUMT00000357541
      Conserved Domains (2) summary
      cd05721
      Location:39152
      Blast Score: 465
      IgV_CTLA-4; Immunoglobulin (Ig) domain of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)
      smart00406
      Location:58131
      Blast Score: 119
      IGv; Immunoglobulin V-Type
    2. NM_005214.4NP_005205.2  cytotoxic T-lymphocyte protein 4 isoform CTLA4-TM precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer membrane-bound isoform CTLA4-TM.
      Source sequence(s)
      AC010138, AF414120
      Consensus CDS
      CCDS2362.1
      UniProtKB/Swiss-Prot
      P16410
      Related
      ENSP00000303939, OTTHUMP00000163781, ENST00000302823, OTTHUMT00000256365
      Conserved Domains (2) summary
      cd05721
      Location:39152
      Blast Score: 468
      IgV_CTLA-4; Immunoglobulin (Ig) domain of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)
      smart00406
      Location:58131
      Blast Score: 118
      IGv; Immunoglobulin V-Type

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000002.11 Reference GRCh37.p5 Primary Assembly

      Range
      204732511..204738683
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000134.1 Alternate HuRef

      Range
      196579809..196585939
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

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