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

Gene ID: 1493, updated on 7-Jul-2014
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; 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]
See CTLA4 in Epigenomics, MapViewer
Location:
2q33
Exon count :
4
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 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 keratin 18 pseudogene 39 Neighboring gene nucleophosmin 1 (nucleolar phosphoprotein B23, numatrin) pseudogene 33 Neighboring gene uncharacterized LOC101927840 Neighboring gene inducible T-cell co-stimulator Neighboring gene zinc finger protein 555 pseudogene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Associated conditions

Description Tests
Celiac disease 3
MedGen: C1857845 OMIM: 609755 GeneReviews: Not available
not available
Diabetes mellitus, insulin-dependent, 12
MedGen: C1832392 OMIM: 601388 GeneReviews: Not available
not available
Hashimoto thyroiditis
MedGen: C0677607 OMIM: 140300 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
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

Protein interactions

Protein Gene Interaction Pubs
Env, gp160, envelope glycoprotein 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, p27 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 downregulates CTLA-4 in 293T cells. The Nef-induced downregulation of CTLA-4 requires the EE155, LL165, and DD175 motifs in Nef 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, p15 vpr HIV-1 Vpr increases the levels of CTLA4 expression in infected T cells PubMed

Go to the HIV-1, Human Protein Interaction Database

  • 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...
Products Interactant Other Gene Complex Source Pubs Description

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
 
cellular response to DNA damage stimulus IMP
Inferred from Mutant Phenotype
more info
PubMed 
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 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 IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of apoptotic process 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 component of plasma membrane TAS
Traceable Author Statement
more info
PubMed 
perinuclear region of cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
Preferred Names
cytotoxic T-lymphocyte protein 4
Names
cytotoxic T-lymphocyte protein 4
CD152 isoform
celiac disease 3
cytotoxic T-lymphocyte antigen 4
insulin-dependent diabetes mellitus 12
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

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 

    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

    See proteins identical to 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
    Consensus CDS
    CCDS42803.1
    UniProtKB/Swiss-Prot
    P16410
    Conserved Domains (2) summary
    cd05721
    Location:39152
    Blast Score: 456
    IgV_CTLA-4; Immunoglobulin (Ig) domain of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)
    smart00410
    Location:43132
    Blast Score: 93
    IG_like; Immunoglobulin like
  2. NM_005214.4NP_005205.2  cytotoxic T-lymphocyte protein 4 isoform CTLA4-TM precursor

    See proteins identical to 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
    Consensus CDS
    CCDS2362.1
    UniProtKB/Swiss-Prot
    P16410
    Related
    ENSP00000303939, OTTHUMP00000163781, ENST00000302823, OTTHUMT00000256365
    Conserved Domains (2) summary
    cd05721
    Location:39152
    Blast Score: 459
    IgV_CTLA-4; Immunoglobulin (Ig) domain of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)
    smart00410
    Location:43132
    Blast Score: 92
    IG_like; Immunoglobulin like

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000002.12 

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

RNA

  1. XR_427072.1 RNA Sequence

  2. XR_241294.1 RNA Sequence

Alternate HuRef

Genomic

  1. AC_000134.1 

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

Alternate CHM1_1.1

Genomic

  1. NC_018913.2 

    Range
    204739066..204745196
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

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