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

Gene ID: 1493, updated on 6-Jan-2019

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 current GRCh38.p12 (GCF_000001405.38) 2 NC_000002.12 (203867788..203873960)
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 FunctionsWhat'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 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...
  • Allograft Rejection, organism-specific biosystem (from WikiPathways)
    Allograft Rejection, organism-specific biosystemThis pathway illustrates molecular interactions involved in the fundamental adaptive immune response for allograft destruction. This pathway was adapted in large part from the KEGG pathway http://www...
  • 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...
  • T-Cell Receptor and Co-stimulatory Signaling, organism-specific biosystem (from WikiPathways)
    T-Cell Receptor and Co-stimulatory Signaling, organism-specific biosystemThe activation and translocation of transcription factors NFAT, AP-1 and NF-kappa-B via the co-stimulatory signaling cascade triggered by MHC peptide, B7 proteins and PD-L1. The activation of NFAT in...
  • T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection, organism-specific biosystem (from WikiPathways)
    T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection, organism-specific biosystemThis pathway is based on Figure 4 of "A Model of an Integrated Immune System Pathway in Homo sapiens and Its Interaction with Superantigen Producing Expression Regulatory Pathway in Staphylococcus au...

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 IMP
Inferred from Mutant Phenotype
more info
PubMed 
T cell costimulation TAS
Traceable Author Statement
more info
 
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 
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 
regulation of T cell proliferation IEA
Inferred from Electronic Annotation
more info
 
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 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
    ENSP00000303939.3, ENST00000302823.8
    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 Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p12 Primary Assembly

    Range
    203867788..203873960
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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