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Entry version 213 (16 Oct 2019)
Sequence version 3 (10 Jan 2003)
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Protein

Cytotoxic T-lymphocyte protein 4

Gene

CTLA4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of their cognate stimulatory coreceptor CD28.2 Publications

Miscellaneous

The therapeutic antibody Ipilimumab competes for the binding site of the endogenous ligands CD80/B7-1, CD86/B7-2 and ICOSLG.

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Biological processAdaptive immunity, Immunity

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-389513 CTLA4 inhibitory signaling
R-HSA-8877330 RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)

SIGNOR Signaling Network Open Resource

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SIGNORi
P16410

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Cytotoxic T-lymphocyte protein 4
Alternative name(s):
Cytotoxic T-lymphocyte-associated antigen 4
Short name:
CTLA-4
CD_antigen: CD152
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:CTLA4
Synonyms:CD152
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 2

Organism-specific databases

Human Gene Nomenclature Database

More...
HGNCi
HGNC:2505 CTLA4

Online Mendelian Inheritance in Man (OMIM)

More...
MIMi
123890 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_P16410

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini36 – 161Extracellular1 PublicationAdd BLAST126
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei162 – 182HelicalSequence analysisAdd BLAST21
Topological domaini183 – 223CytoplasmicSequence analysisAdd BLAST41

Keywords - Cellular componenti

Cell membrane, Membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Systemic lupus erythematosus (SLE)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
Related information in OMIM
Genetic variations in CTLA4 may influence susceptibility to Graves disease, an autoimmune disorder associated with overactivity of the thyroid gland and hyperthyroidism.1 Publication
Diabetes mellitus, insulin-dependent, 12 (IDDM12)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Related information in OMIM
Celiac disease 3 (CELIAC3)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA multifactorial, chronic disorder of the small intestine caused by intolerance to gluten. It is characterized by immune-mediated enteropathy associated with failed intestinal absorption, and malnutrition. In predisposed individuals, the ingestion of gluten-containing food such as wheat and rye induces a flat jejunal mucosa with infiltration of lymphocytes.
Related information in OMIM
Autoimmune lymphoproliferative syndrome 5 (ALPS5)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant primary immunodeficiency characterized by severe autoimmunity, infiltration of non-lymphoid organs, such as the intestine, lungs and brain, by hyperactive T cells and B cells, autoimmune cytopenias, and hypogammaglobulinemia in early childhood.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_07268170R → W in ALPS5. 1 PublicationCorresponds to variant dbSNP:rs606231422EnsemblClinVar.1

<p>This subsection of the ‘Pathology and Biotech’ section describes the use of a protein as a pharmaceutical drug. It indicates the name of the drug, the name of the firm that commercializes it and explains in a few words in which context the drug is used. In some cases, drugs that are under development are also described.<p><a href='/help/pharmaceutical_use' target='_top'>More...</a></p>Pharmaceutical usei

Engineered fusion proteins consisting of the extracellular domain of CTLA4 and the IgG Fc region (Ctla4-Ig), inhibit T-cell-dependent antibody responses, and are used as immunosuppressive agents. They are soluble, have an enhanced affinity for B7 ligands and act as a competitive inhibitor of CD28.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi45V → D: Strongly reduced interaction with CD80, CD86 and ICOSLG. 1 Publication1
Mutagenesisi47L → D: Strongly reduced interaction with CD80, CD86 and ICOSLG. 1 Publication1
Mutagenesisi49S → A: Strongly reduced interaction with CD80, CD86 and ICOSLG. 1 Publication1
Mutagenesisi70R → A or D: Strongly reduced interaction with CD80, CD86 and ICOSLG. 1 Publication1
Mutagenesisi130K → A or D: Strongly reduced interaction with CD80, CD86 and ICOSLG. 1 Publication1
Mutagenesisi132E → A or R: Strongly reduced interaction with CD80, CD86 and ICOSLG. 1 Publication1
Mutagenesisi139Y → A or D: Strongly reduced interaction with CD80, CD86 and ICOSLG. 1 Publication1
Mutagenesisi143I → A or D: Strongly reduced interaction with CD80, CD86 and ICOSLG. 1 Publication1

Keywords - Diseasei

Diabetes mellitus, Disease mutation, Systemic lupus erythematosus

Organism-specific databases

DisGeNET

More...
DisGeNETi
1493

MalaCards human disease database

More...
MalaCardsi
CTLA4
MIMi109100 phenotype
152700 phenotype
601388 phenotype
609755 phenotype
610424 phenotype
616100 phenotype

Open Targets

More...
OpenTargetsi
ENSG00000163599

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...
Orphaneti
391490 Adult-onset myasthenia gravis
436159 Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency
2584 Classic mycosis fungoides
900 Granulomatosis with polyangiitis
3162 Sezary syndrome
536 Systemic lupus erythematosus

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...
PharmGKBi
PA27006

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...
Pharosi
P16410

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL2364164

Drug and drug target database

More...
DrugBanki
DB06186 Ipilimumab

DrugCentral

More...
DrugCentrali
P16410

IUPHAR/BPS Guide to PHARMACOLOGY

More...
GuidetoPHARMACOLOGYi
2743

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
CTLA4

Domain mapping of disease mutations (DMDM)

More...
DMDMi
27735177

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 35Sequence analysisAdd BLAST35
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000001473436 – 223Cytotoxic T-lymphocyte protein 4Add BLAST188

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi58 ↔ 129Combined sources6 Publications
Disulfide bondi85 ↔ 103Combined sources6 Publications
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi113N-linked (GlcNAc...) asparagine3 Publications1
Glycosylationi145N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi157InterchainCombined sources2 Publications
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei201Phosphotyrosine; by TXK and JAK23 Publications1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

N-glycosylation is important for dimerization.3 Publications
Phosphorylation at Tyr-201 prevents binding to the AP-2 adapter complex, blocks endocytosis, and leads to retention of CTLA4 on the cell surface.3 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDb, a database of protein abundance averages across all three domains of life

More...
PaxDbi
P16410

PeptideAtlas

More...
PeptideAtlasi
P16410

PRoteomics IDEntifications database

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PRIDEi
P16410

ProteomicsDB: a multi-organism proteome resource

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ProteomicsDBi
50980
53354 [P16410-1]
53355 [P16410-2]
53356 [P16410-3]
53357 [P16410-4]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
P16410

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
P16410

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Widely expressed with highest levels in lymphoid tissues. Detected in activated T-cells where expression levels are 30- to 50-fold less than CD28, the stimulatory coreceptor, on the cell surface following activation.3 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSG00000163599 Expressed in 110 organ(s), highest expression level in lymph node

Genevisible search portal to normalized and curated expression data from Genevestigator

More...
Genevisiblei
P16410 HS

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer; disulfide-linked (PubMed:11279501, PubMed:11279502, Ref. 23, PubMed:21156796, PubMed:28484017). Binds to CD80/B7-1 and CD86/B7.2 (PubMed:11279501, PubMed:11279502, PubMed:28484017).

Interacts with ICOSLG (PubMed:28484017).

5 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...
BioGridi
107875, 109 interactors

Database of interacting proteins

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DIPi
DIP-35607N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

More...
ELMi
P16410

Protein interaction database and analysis system

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IntActi
P16410, 15 interactors

Molecular INTeraction database

More...
MINTi
P16410

STRING: functional protein association networks

More...
STRINGi
9606.ENSP00000303939

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1223
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P16410

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

More...
PDBe-KBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...
EvolutionaryTracei
P16410

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini39 – 140Ig-like V-typeAdd BLAST102

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni46 – 50Homodimerization1 Publication5
Regioni134 – 139Important for interaction with CD80 and CD861 Publication6
Regioni150 – 155Homodimerization2 Publications6

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
ENOG410IJ05 Eukaryota
ENOG410YUQR LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00530000063873

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000112047

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
P16410

KEGG Orthology (KO)

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KOi
K06538

Identification of Orthologs from Complete Genome Data

More...
OMAi
ERMYPPP

Database of Orthologous Groups

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OrthoDBi
614790at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
P16410

TreeFam database of animal gene trees

More...
TreeFami
TF335679

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
2.60.40.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR008096 CTLA4
IPR040216 CTLA4/CD28
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003599 Ig_sub
IPR013106 Ig_V-set

The PANTHER Classification System

More...
PANTHERi
PTHR11494 PTHR11494, 1 hit
PTHR11494:SF8 PTHR11494:SF8, 1 hit

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF07686 V-set, 1 hit

Protein Motif fingerprint database; a protein domain database

More...
PRINTSi
PR01720 CTLANTIGEN4

Simple Modular Architecture Research Tool; a protein domain database

More...
SMARTi
View protein in SMART
SM00409 IG, 1 hit
SM00406 IGv, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF48726 SSF48726, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (5)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: P16410-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MACLGFQRHK AQLNLATRTW PCTLLFFLLF IPVFCKAMHV AQPAVVLASS
60 70 80 90 100
RGIASFVCEY ASPGKATEVR VTVLRQADSQ VTEVCAATYM MGNELTFLDD
110 120 130 140 150
SICTGTSSGN QVNLTIQGLR AMDTGLYICK VELMYPPPYY LGIGNGTQIY
160 170 180 190 200
VIDPEPCPDS DFLLWILAAV SSGLFFYSFL LTAVSLSKML KKRSPLTTGV
210 220
YVKMPPTEPE CEKQFQPYFI PIN
Length:223
Mass (Da):24,656
Last modified:January 10, 2003 - v3
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i6F9466FB2E139A5A
GO
Isoform 2 (identifier: P16410-2) [UniParc]FASTAAdd to basket
Also known as: ss-CTLA-4

The sequence of this isoform differs from the canonical sequence as follows:
     38-204: Missing.

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Length:56
Mass (Da):6,560
Checksum:i096CBF7AD57AE9B9
GO
Isoform 3 (identifier: P16410-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     38-204: Missing.
     205-223: PPTEPECEKQFQPYFIPIN → KEKKPSYNRGLCENAPNRARM

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Length:58
Mass (Da):6,745
Checksum:i5F70948EEDC80A94
GO
Isoform 4 (identifier: P16410-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     58-58: C → S
     59-204: Missing.
     205-223: PPTEPECEKQFQPYFIPIN → KEKKPSYNRGLCENAPNRARM

Show »
Length:79
Mass (Da):8,855
Checksum:i60CBF1BC1DA59D8A
GO
Isoform 5 (identifier: P16410-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     153-174: DPEPCPDSDFLLWILAAVSSGL → AKEKKPSYNRGLCENAPNRARM
     175-223: Missing.

Show »
Length:174
Mass (Da):19,145
Checksum:i0881BFA757AC3FDB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti37A → V in ABG85285 (PubMed:18595775).Curated1
Sequence conflicti147T → A in AAA52773 (PubMed:3220103).Curated1

<p>This subsection of the ‘Sequence’ section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement_in_disease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>Polymorphismi

Genetic variations in CTLA4 are associated with susceptibility to several autoimmune disorders (PubMed:18595775, PubMed:12724780, PubMed:10189842, PubMed:10924276, PubMed:15138458, PubMed:15657618, PubMed:15688186, PubMed:25329329, PubMed:25213377). They influence responsiveness to hepatitis B virus (HBV) infection [MIMi:610424] (PubMed:15452244).10 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01357717T → A Increased risk for Graves disease, insulin-dependent diabetes mellitus, thyroid-associated orbitopathy, systemic lupus erythematosus and susceptibility to HBV infection. 7 PublicationsCorresponds to variant dbSNP:rs231775EnsemblClinVar.1
Natural variantiVAR_07268170R → W in ALPS5. 1 PublicationCorresponds to variant dbSNP:rs606231422EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_04128438 – 204Missing in isoform 2 and isoform 3. 1 PublicationAdd BLAST167
Alternative sequenceiVSP_04128558C → S in isoform 4. 1 Publication1
Alternative sequenceiVSP_04128659 – 204Missing in isoform 4. 1 PublicationAdd BLAST146
Alternative sequenceiVSP_047238153 – 174DPEPC…VSSGL → AKEKKPSYNRGLCENAPNRA RM in isoform 5. 1 PublicationAdd BLAST22
Alternative sequenceiVSP_047239175 – 223Missing in isoform 5. 1 PublicationAdd BLAST49
Alternative sequenceiVSP_041287205 – 223PPTEP…FIPIN → KEKKPSYNRGLCENAPNRAR M in isoform 3 and isoform 4. 1 PublicationAdd BLAST19

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

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DDBJi
Links Updated
L15006 mRNA Translation: AAB59385.1
M74363 Genomic DNA Translation: AAA52127.1
AF411058 Genomic DNA Translation: AAL40932.1
AY792514 mRNA Translation: AAV66331.1
AY999702 mRNA Translation: AAY00166.1
DQ785106 mRNA Translation: ABG85285.1
AF414120 mRNA Translation: AAL07473.1
DQ357942 Genomic DNA Translation: ABC67470.1
AC010138 Genomic DNA Translation: AAX93176.1
BC074842 mRNA Translation: AAH74842.1
BC074893 mRNA Translation: AAH74893.1
AH002733 Genomic DNA Translation: AAA52773.1
U90273 mRNA Translation: AAD00698.1
AF142144 Genomic DNA Translation: AAF02499.1

The Consensus CDS (CCDS) project

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CCDSi
CCDS2362.1 [P16410-1]
CCDS42803.1 [P16410-5]

Protein sequence database of the Protein Information Resource

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PIRi
S08614

NCBI Reference Sequences

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RefSeqi
NP_001032720.1, NM_001037631.2 [P16410-5]
NP_005205.2, NM_005214.4 [P16410-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

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Ensembli
ENST00000295854; ENSP00000295854; ENSG00000163599 [P16410-5]
ENST00000472206; ENSP00000417779; ENSG00000163599 [P16410-4]
ENST00000487393; ENSP00000497319; ENSG00000163599 [P16410-3]
ENST00000648405; ENSP00000497102; ENSG00000163599 [P16410-1]

Database of genes from NCBI RefSeq genomes

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GeneIDi
1493

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:1493

UCSC genome browser

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UCSCi
uc002vak.3 human [P16410-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Wikipedia

CLTA-4 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L15006 mRNA Translation: AAB59385.1
M74363 Genomic DNA Translation: AAA52127.1
AF411058 Genomic DNA Translation: AAL40932.1
AY792514 mRNA Translation: AAV66331.1
AY999702 mRNA Translation: AAY00166.1
DQ785106 mRNA Translation: ABG85285.1
AF414120 mRNA Translation: AAL07473.1
DQ357942 Genomic DNA Translation: ABC67470.1
AC010138 Genomic DNA Translation: AAX93176.1
BC074842 mRNA Translation: AAH74842.1
BC074893 mRNA Translation: AAH74893.1
AH002733 Genomic DNA Translation: AAA52773.1
U90273 mRNA Translation: AAD00698.1
AF142144 Genomic DNA Translation: AAF02499.1
CCDSiCCDS2362.1 [P16410-1]
CCDS42803.1 [P16410-5]
PIRiS08614
RefSeqiNP_001032720.1, NM_001037631.2 [P16410-5]
NP_005205.2, NM_005214.4 [P16410-1]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AH1NMR-A37-161[»]
1H6EX-ray3.60P197-207[»]
1I85X-ray3.20C/D36-161[»]
1I8LX-ray3.00C/D36-161[»]
2X44X-ray2.60D36-161[»]
3BX7X-ray2.10C38-161[»]
3OSKX-ray1.80A/B36-161[»]
5GGVX-ray2.00Y36-161[»]
5TRUX-ray3.00C/c37-154[»]
5XJ3X-ray3.20C/F/I/L36-161[»]
SMRiP16410
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGridi107875, 109 interactors
DIPiDIP-35607N
ELMiP16410
IntActiP16410, 15 interactors
MINTiP16410
STRINGi9606.ENSP00000303939

Chemistry databases

ChEMBLiCHEMBL2364164
DrugBankiDB06186 Ipilimumab
DrugCentraliP16410
GuidetoPHARMACOLOGYi2743

PTM databases

iPTMnetiP16410
PhosphoSitePlusiP16410

Polymorphism and mutation databases

BioMutaiCTLA4
DMDMi27735177

Proteomic databases

PaxDbiP16410
PeptideAtlasiP16410
PRIDEiP16410
ProteomicsDBi50980
53354 [P16410-1]
53355 [P16410-2]
53356 [P16410-3]
53357 [P16410-4]

Protocols and materials databases

ABCD curated depository of sequenced antibodies

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ABCDi
P16410

Genome annotation databases

EnsembliENST00000295854; ENSP00000295854; ENSG00000163599 [P16410-5]
ENST00000472206; ENSP00000417779; ENSG00000163599 [P16410-4]
ENST00000487393; ENSP00000497319; ENSG00000163599 [P16410-3]
ENST00000648405; ENSP00000497102; ENSG00000163599 [P16410-1]
GeneIDi1493
KEGGihsa:1493
UCSCiuc002vak.3 human [P16410-1]

Organism-specific databases

Comparative Toxicogenomics Database

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CTDi
1493
DisGeNETi1493

GeneCards: human genes, protein and diseases

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GeneCardsi
CTLA4
HGNCiHGNC:2505 CTLA4
MalaCardsiCTLA4
MIMi109100 phenotype
123890 gene
152700 phenotype
601388 phenotype
609755 phenotype
610424 phenotype
616100 phenotype
neXtProtiNX_P16410
OpenTargetsiENSG00000163599
Orphaneti391490 Adult-onset myasthenia gravis
436159 Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency
2584 Classic mycosis fungoides
900 Granulomatosis with polyangiitis
3162 Sezary syndrome
536 Systemic lupus erythematosus
PharmGKBiPA27006

GenAtlas: human gene database

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GenAtlasi
Search...

Phylogenomic databases

eggNOGiENOG410IJ05 Eukaryota
ENOG410YUQR LUCA
GeneTreeiENSGT00530000063873
HOGENOMiHOG000112047
InParanoidiP16410
KOiK06538
OMAiERMYPPP
OrthoDBi614790at2759
PhylomeDBiP16410
TreeFamiTF335679

Enzyme and pathway databases

ReactomeiR-HSA-389513 CTLA4 inhibitory signaling
R-HSA-8877330 RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)
SIGNORiP16410

Miscellaneous databases

EvolutionaryTraceiP16410

The Gene Wiki collection of pages on human genes and proteins

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GeneWikii
CTLA-4

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

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GenomeRNAii
1493
PharosiP16410

Protein Ontology

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PROi
PR:P16410

The Stanford Online Universal Resource for Clones and ESTs

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SOURCEi
Search...

Gene expression databases

BgeeiENSG00000163599 Expressed in 110 organ(s), highest expression level in lymph node
GenevisibleiP16410 HS

Family and domain databases

Gene3Di2.60.40.10, 1 hit
InterProiView protein in InterPro
IPR008096 CTLA4
IPR040216 CTLA4/CD28
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003599 Ig_sub
IPR013106 Ig_V-set
PANTHERiPTHR11494 PTHR11494, 1 hit
PTHR11494:SF8 PTHR11494:SF8, 1 hit
PfamiView protein in Pfam
PF07686 V-set, 1 hit
PRINTSiPR01720 CTLANTIGEN4
SMARTiView protein in SMART
SM00409 IG, 1 hit
SM00406 IGv, 1 hit
SUPFAMiSSF48726 SSF48726, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

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ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiCTLA4_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P16410
Secondary accession number(s): A0N1S0
, E9PDH0, O95653, Q0PP65, Q52MC1, Q53TD5, Q5S005, Q8WXJ1, Q96P43, Q9UKN9
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: January 10, 2003
Last modified: October 16, 2019
This is version 213 of the entry and version 3 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Pharmaceutical, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  3. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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