CTLA4

Protein identityUniProt · HPA

UniProt accession

P16410

Gene

CTLA4

Ensembl

ENSG00000163599

Chromosome

2

Canonical length

223 aa

Protein class

CD markers, Disease related genes, FDA approved drug targets, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins

Quaternary structure

Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

223 residues, UniProt reviewed canonical sequence.

>P16410|CTLA4
     1  MACLGFQRHK AQLNLATRTW PCTLLFFLLF IPVFCKAMHV AQPAVVLASS RGIASFVCEY
    61  ASPGKATEVR VTVLRQADSQ VTEVCAATYM MGNELTFLDD SICTGTSSGN QVNLTIQGLR
   121  AMDTGLYICK VELMYPPPYY LGIGNGTQIY VIDPEPCPDS DFLLWILAAV SSGLFFYSFL
   181  LTAVSLSKML KKRSPLTTGV YVKMPPTEPE CEKQFQPYFI PIN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CTLA4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.46

Highest tissue expression

35 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CTLA4.

Disease | AllUniProt

Conditions CTLA4 is implicated in, by any mechanism.

• Systemic lupus erythematosus (SLE) MIM:152700
• Type 1 diabetes mellitus 12 (T1D12) MIM:601388
• Celiac disease 3 (CELIAC3) MIM:609755
• Immune dysregulation with autoimmunity, immunodeficiency, and lymphoproliferation (IDAIL) MIM:616100

Disease | GeneticClinVar

63 pathogenic / likely-pathogenic of 301 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
• Type 1 diabetes mellitus 12
• Celiac disease, susceptibility to, 3
• Systemic lupus erythematosus
• Hashimoto thyroiditis

Disease | ImmuneIEDB

Conditions an epitope on CTLA4 was assayed in.

• rheumatoid arthritis B cell

ReferencesPubMed · IEDB

Publications for CTLA4 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.33

gnomAD pLI

0.94

gnomAD missense Z

1.69

DepMap mean gene effect

-0.05

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adaptive immune response
• B cell receptor signaling pathway
• DNA damage response
• immune response
• negative regulation of B cell proliferation
• negative regulation of regulatory T cell differentiation
• negative regulation of T cell activation
• negative regulation of T cell proliferation
• negative regulation of T cell receptor signaling pathway
• positive regulation of apoptotic process
• T cell receptor signaling pathway

Molecular functions

• receptor decoy activity

Cellular components

• clathrin-coated endocytic vesicle
• external side of plasma membrane
• Golgi apparatus
• perinuclear region of cytoplasm
• plasma membrane
• protein complex involved in cell adhesion

Protein domainsUniProt · Pfam · InterPro

• Immunoglobulin domain subtype
• Immunoglobulin V-set domain
• Immunoglobulin-like fold
• Immunoglobulin-like domain superfamily
• Cytotoxic T-lymphocyte protein 4/CD28
• Immunoglobulin V-set domain
• Cytotoxic T-lymphocyte antigen 4

KeywordsUniProt

• Adaptive immunity
• Cell membrane
• Diabetes mellitus
• Disulfide bond
• Glycoprotein
• Immunity
• Immunoglobulin domain
• Membrane
• Pharmaceutical
• Phosphoprotein
• Signal
• Systemic lupus erythematosus
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of CTLA4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ICOSLG
• CD80
• CD86