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

    Gene ID: 1493, updated on 13-Jan-2020

    Summary

    Official Symbol
    CTLA4provided by HGNC
    Official Full Name
    cytotoxic T-lymphocyte associated protein 4provided by HGNC
    Primary source
    HGNC:HGNC:2505
    See related
    Ensembl:ENSG00000163599 MIM:123890
    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; ALPS5; 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]
    Expression
    Biased expression in lymph node (RPKM 10.3), appendix (RPKM 9.7) and 8 other tissues See more
    Orthologs

    Genomic context

    See CTLA4 in Genome Data Viewer
    Location:
    2q33.2
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    109.20191205 current GRCh38.p13 (GCF_000001405.39) 2 NC_000002.12 (203867771..203873965)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (204732511..204738683)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene nucleophosmin 1 pseudogene 33 Neighboring gene RNA, U6 small nuclear 474, pseudogene Neighboring gene uncharacterized LOC101927840 Neighboring gene inducible T cell costimulator Neighboring gene zinc finger protein 555 pseudogene

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Autoimmune lymphoproliferatiVe syndrome, type V
    MedGen: C4015214 OMIM: 616100 GeneReviews: Not available
    Compare labs
    Celiac disease 3
    MedGen: C1857845 OMIM: 609755 GeneReviews: Not available
    Compare labs
    Diabetes mellitus, insulin-dependent, 12
    MedGen: C1832392 OMIM: 601388 GeneReviews: Not available
    Compare labs
    Hashimoto thyroiditis
    MedGen: C0677607 OMIM: 140300 GeneReviews: Not available
    Compare labs
    Systemic lupus erythematosus
    MedGen: C0024141 OMIM: 152700 GeneReviews: Not available
    Compare labs

    NHGRI GWAS Catalog

    Description
    A genome-wide association study identifies two new risk loci for Graves' disease.
    NHGRI GWA Catalog
    Genetics of rheumatoid arthritis contributes to biology and drug discovery.
    NHGRI GWA Catalog
    Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases.
    NHGRI GWA Catalog
    Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.
    NHGRI GWA Catalog
    Genome-wide association study in alopecia areata implicates both innate and adaptive immunity.
    NHGRI GWA Catalog
    Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.
    NHGRI GWA Catalog
    Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci.
    NHGRI GWA Catalog
    Multiple common variants for celiac disease influencing immune gene expression.
    NHGRI GWA Catalog
    Novel associations for hypothyroidism include known autoimmune risk loci.
    NHGRI GWA Catalog
    REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.
    NHGRI GWA Catalog

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp160, precursor env HIV-1 Env co-localizes with CTLA4 in HIV-1 infected CD4+ T cells PubMed
    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-mediated CTLA-4 downregulation is associated with upregulation of IL-2 production in infected primary CD4+ T-cells PubMed
    nef HIV-1 Nef downregulates CTLA-4 in 293T cells and infected primary CD4+ T-cells. The Nef-induced downregulation of CTLA-4 requires the EE155, LL165, and DD175 motifs in Nef PubMed
    nef HIV-1 Nef co-localizes with CTLA-4 in early and recycling endosomes with transferrin marker protein in HeLa cells PubMed
    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 Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    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 IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    B cell receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    T cell costimulation TAS
    Traceable Author Statement
    more info
     
    T cell receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    adaptive immune response IEA
    Inferred from Electronic Annotation
    more info
     
    cellular response to DNA damage stimulus IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    immune response TAS
    Traceable Author Statement
    more info
    PubMed 
    immune system process IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    negative regulation of B cell proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of T cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of immune response IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of regulatory T cell differentiation IBA
    Inferred from Biological aspect of Ancestor
    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 
    regulation of regulatory T cell differentiation TAS
    Traceable Author Statement
    more info
     
    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 IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    external side of plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    integral component of plasma membrane IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    perinuclear region of cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    plasma membrane TAS
    Traceable Author Statement
    more info
     
    protein complex involved in cell adhesion IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    cytotoxic T-lymphocyte protein 4
    Names
    CD152 isoform
    celiac disease 3
    cytotoxic T lymphocyte associated antigen 4 short spliced form
    cytotoxic T-lymphocyte-associated serine esterase-4
    insulin-dependent diabetes mellitus 12
    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
      4986..11180
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1220

    mRNA and Protein(s)

    1. NM_001037631.3NP_001032720.1  cytotoxic T-lymphocyte protein 4 isoform CTLA-4delTM

      See identical proteins and their annotated locations for NP_001032720.1

      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, AI733018
      Consensus CDS
      CCDS42803.1
      UniProtKB/Swiss-Prot
      P16410
      Related
      ENSP00000295854.6, ENST00000295854.10
      Conserved Domains (1) summary
      cd05721
      Location:39152
      IgV_CTLA-4; Immunoglobulin (Ig) domain of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)
    2. NM_005214.5NP_005205.2  cytotoxic T-lymphocyte protein 4 isoform CTLA4-TM precursor

      See identical proteins and their annotated locations for NP_005205.2

      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, AI733018
      Consensus CDS
      CCDS2362.1
      UniProtKB/Swiss-Prot
      P16410
      Related
      ENSP00000497102.1, ENST00000648405.2
      Conserved Domains (1) summary
      cd05721
      Location:39152
      IgV_CTLA-4; Immunoglobulin (Ig) domain of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)

    RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20191205

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

    Reference GRCh38.p13 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p13 Primary Assembly

      Range
      203867771..203873965
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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