CTLA4

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.

GO - Biological processⁱ

adaptive immune response Source: UniProtKB-KW
B cell receptor signaling pathway
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- "ATM, CTLA4, MNDA, and HEM1 in high versus low CD38 expressing B-cell chronic lymphocytic leukemia."
  Joshi A.D., Hegde G.V., Dickinson J.D., Mittal A.K., Lynch J.C., Eudy J.D., Armitage J.O., Bierman P.J., Bociek R.G., Devetten M.P., Vose J.M., Joshi S.S.
  Clin Cancer Res 13:5295-5304(2007) [PubMed] [Europe PMC] [Abstract]
cellular response to DNA damage stimulus
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- "ATM, CTLA4, MNDA, and HEM1 in high versus low CD38 expressing B-cell chronic lymphocytic leukemia."
  Joshi A.D., Hegde G.V., Dickinson J.D., Mittal A.K., Lynch J.C., Eudy J.D., Armitage J.O., Bierman P.J., Bociek R.G., Devetten M.P., Vose J.M., Joshi S.S.
  Clin Cancer Res 13:5295-5304(2007) [PubMed] [Europe PMC] [Abstract]
immune response
Source: ProtInc
Traceable author statementⁱ
- Ref.8
  "Human Ig superfamily CTLA-4 gene: chromosomal localization and identity of protein sequence between murine and human CTLA-4 cytoplasmic domains."
  Dariavach P., Mattei M.-G., Golstein P., Lefranc M.-P.
  Eur. J. Immunol. 18:1901-1905(1988) [PubMed] [Europe PMC] [Abstract]
  Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 38-223.
negative regulation of B cell proliferation
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- "ATM, CTLA4, MNDA, and HEM1 in high versus low CD38 expressing B-cell chronic lymphocytic leukemia."
  Joshi A.D., Hegde G.V., Dickinson J.D., Mittal A.K., Lynch J.C., Eudy J.D., Armitage J.O., Bierman P.J., Bociek R.G., Devetten M.P., Vose J.M., Joshi S.S.
  Clin Cancer Res 13:5295-5304(2007) [PubMed] [Europe PMC] [Abstract]
negative regulation of immune response Source: Ensembl
negative regulation of regulatory T cell differentiation
Source: BHF-UCL
Inferred from direct assayⁱ
- "Acquisition of suppressive function by activated human CD4+ CD25- T cells is associated with the expression of CTLA-4 not FoxP3."
  Zheng Y., Manzotti C.N., Burke F., Dussably L., Qureshi O., Walker L.S., Sansom D.M.
  J Immunol 181:1683-1691(2008) [PubMed] [Europe PMC] [Abstract]
negative regulation of T cell proliferation Source: Ensembl
positive regulation of apoptotic process
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- "ATM, CTLA4, MNDA, and HEM1 in high versus low CD38 expressing B-cell chronic lymphocytic leukemia."
  Joshi A.D., Hegde G.V., Dickinson J.D., Mittal A.K., Lynch J.C., Eudy J.D., Armitage J.O., Bierman P.J., Bociek R.G., Devetten M.P., Vose J.M., Joshi S.S.
  Clin Cancer Res 13:5295-5304(2007) [PubMed] [Europe PMC] [Abstract]
regulation of regulatory T cell differentiation Source: Reactome
T cell costimulation Source: Reactome
T cell receptor signaling pathway
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
  Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
  Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]

Complete GO annotation on QuickGO ...

Keywordsⁱ

Biological process	Adaptive immunity, Immunity

Biological process

Adaptive immunity, Immunity

Enzyme and pathway databases

PathwayCommonsⁱ	P16410
Reactomeⁱ	R-HSA-389513, CTLA4 inhibitory signaling R-HSA-8877330, RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)
SIGNORⁱ	P16410

Names & Taxonomyⁱ

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
Gene namesⁱ	Name:CTLA4 Synonyms:CD152
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 2

Organism-specific databases

Human Gene Nomenclature Database More...HGNCⁱ	HGNC:2505, CTLA4
MIMⁱ	123890, gene
neXtProtⁱ	NX_P16410
VEuPathDBⁱ	HostDB:ENSG00000163599.14

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	36 – 161	Extracellular1 PublicationAdd BLAST	126
Transmembraneⁱ	162 – 182	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	183 – 223	CytoplasmicSequence analysisAdd BLAST	41

Keywords - Cellular componentⁱ

Cell membrane, Membrane

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Systemic lupus erythematosus (SLE)2 Publications

Disease susceptibility is associated with variants 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 variants 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 variants 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 variants 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 key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_072681	70	R → W in ALPS5. 1 PublicationCorresponds to variant dbSNP:rs606231422EnsemblClinVar.		1

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 key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	45	V → D: Strongly reduced interaction with CD80, CD86 and ICOSLG. 1 Publication	1
Mutagenesisⁱ	47	L → D: Strongly reduced interaction with CD80, CD86 and ICOSLG. 1 Publication	1
Mutagenesisⁱ	49	S → A: Strongly reduced interaction with CD80, CD86 and ICOSLG. 1 Publication	1
Mutagenesisⁱ	70	R → A or D: Strongly reduced interaction with CD80, CD86 and ICOSLG. 1 Publication	1
Mutagenesisⁱ	130	K → A or D: Strongly reduced interaction with CD80, CD86 and ICOSLG. 1 Publication	1
Mutagenesisⁱ	132	E → A or R: Strongly reduced interaction with CD80, CD86 and ICOSLG. 1 Publication	1
Mutagenesisⁱ	139	Y → A or D: Strongly reduced interaction with CD80, CD86 and ICOSLG. 1 Publication	1
Mutagenesisⁱ	143	I → A or D: Strongly reduced interaction with CD80, CD86 and ICOSLG. 1 Publication	1

Keywords - Diseaseⁱ

Diabetes mellitus, Disease variant, Systemic lupus erythematosus

Organism-specific databases

DisGeNET More...DisGeNETⁱ	1493
MalaCards human disease database More...MalaCardsⁱ	CTLA4
MIMⁱ	109100, phenotype 152700, phenotype 601388, phenotype 609755, phenotype 610424, phenotype 616100, phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000163599
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
PharmGKBⁱ	PA27006

Miscellaneous databases

Pharosⁱ	P16410, Tclin

Pharosⁱ

P16410, Tclin

Chemistry databases

ChEMBLⁱ	CHEMBL2364164
Drug and drug target database More...DrugBankⁱ	DB06186, Ipilimumab DB11771, Tremelimumab
DrugCentral More...DrugCentralⁱ	P16410
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	2743

Genetic variation databases

BioMutaⁱ	CTLA4
DMDMⁱ	27735177

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Signal peptideⁱ	1 – 35	Sequence analysisAdd BLAST		35
ChainⁱPRO_0000014734	36 – 223	Cytotoxic T-lymphocyte protein 4Add BLAST		188

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Disulfide bondⁱ	58 ↔ 129	Combined sources6 Publications
Disulfide bondⁱ	85 ↔ 103	Combined sources6 Publications
Glycosylationⁱ	113	N-linked (GlcNAc...) asparagine3 Publications	1
Glycosylationⁱ	145	N-linked (GlcNAc...) asparagine2 Publications	1
Disulfide bondⁱ	157	InterchainCombined sources2 Publications
Modified residueⁱ	201	Phosphotyrosine; by TXK and JAK23 Publications	1

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

PaxDbⁱ	P16410
PeptideAtlas More...PeptideAtlasⁱ	P16410
PRIDEⁱ	P16410
ProteomicsDBⁱ	50980 53354 [P16410-1] 53355 [P16410-2] 53356 [P16410-3] 53357 [P16410-4]

PTM databases

GlyGenⁱ	P16410, 2 sites
iPTMnetⁱ	P16410
PhosphoSitePlusⁱ	P16410

Expressionⁱ

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

Bgeeⁱ	ENSG00000163599, Expressed in lymph node and 129 other tissues
Genevisibleⁱ	P16410, HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	ENSG00000163599, Tissue enhanced (blood, lymphoid tissue)

HPAⁱ

ENSG00000163599, Tissue enhanced (blood, lymphoid tissue)

Interactionⁱ

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

Binary interactionsⁱ

Hide details

P16410

With	#Exp.	IntAct
CD80 [P33681]	7	EBI-1030991,EBI-1031024
CD86 [P42081]	3	EBI-1030991,EBI-1030956
CTXN3 [Q4LDR2]	3	EBI-1030991,EBI-12019274
MALL [Q13021]	3	EBI-1030991,EBI-750078
PIK3R1 [P27986]	3	EBI-1030991,EBI-79464
TMEM218 [A2RU14]	3	EBI-1030991,EBI-10173151

Protein-protein interaction databases

BioGRIDⁱ	107875, 112 interactors
Database of interacting proteins More...DIPⁱ	DIP-35607N
ELMⁱ	P16410
IntActⁱ	P16410, 15 interactors
Molecular INTeraction database More...MINTⁱ	P16410
STRINGⁱ	9606.ENSP00000303939

Miscellaneous databases

RNActⁱ	P16410, protein

RNActⁱ

P16410, protein

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	39 – 41	Combined sources	3
Beta strandⁱ	44 – 47	Combined sources	4
Beta strandⁱ	50 – 52	Combined sources	3
Beta strandⁱ	54 – 60	Combined sources	7
Beta strandⁱ	64 – 66	Combined sources	3
Beta strandⁱ	68 – 77	Combined sources	10
Beta strandⁱ	80 – 90	Combined sources	11
Turnⁱ	91 – 93	Combined sources	3
Beta strandⁱ	95 – 99	Combined sources	5
Beta strandⁱ	102 – 108	Combined sources	7
Beta strandⁱ	111 – 116	Combined sources	6
Helixⁱ	121 – 123	Combined sources	3
Beta strandⁱ	125 – 138	Combined sources	14
Beta strandⁱ	140 – 143	Combined sources	4
Beta strandⁱ	147 – 150	Combined sources	4
Beta strandⁱ	156 – 158	Combined sources	3

Show more details

3D structure databases

SMRⁱ	P16410
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	P16410

EvolutionaryTraceⁱ

P16410

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	39 – 140	Ig-like V-typeAdd BLAST		102

Region

Feature key	Position(s)	DescriptionActions	Length
Regionⁱ	46 – 50	Homodimerization1 Publication	5
Regionⁱ	134 – 139	Important for interaction with CD80 and CD861 Publication	6
Regionⁱ	150 – 155	Homodimerization2 Publications	6

Keywords - Domainⁱ

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGⁱ	ENOG502RZVK, Eukaryota
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00530000063873
HOGENOMⁱ	CLU_085095_0_0_1
InParanoidⁱ	P16410
OMAⁱ	YVKMPSE
Database of Orthologous Groups More...OrthoDBⁱ	1222373at2759
PhylomeDBⁱ	P16410
TreeFamⁱ	TF335679

Family and domain databases

Gene3Dⁱ	2.60.40.10, 1 hit
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
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
PRINTSⁱ	PR01720, CTLANTIGEN4
SMARTⁱ	View protein in SMART SM00409, IG, 1 hit SM00406, IGv, 1 hit
SUPFAMⁱ	SSF48726, SSF48726, 1 hit

Sequences (5)ⁱ

Sequence statusⁱ: Complete.

Sequence processingⁱ: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsⁱ produced by alternative splicing. Align Add to basket

Isoform 1 (identifier: P16410-1) [UniParc]FASTA Add to basket

This isoform has been chosen as the 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

Checksum:ⁱ6F9466FB2E139A5A

GO

Isoform 2 (identifier: P16410-2) [UniParc]FASTA Add to basket

Also known as: ss-CTLA-4

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

« Hide

        10         20         30         40         50
MACLGFQRHK AQLNLATRTW PCTLLFFLLF IPVFCKAPPT EPECEKQFQP 

YFIPIN

Show »

Length:56

Mass (Da):6,560

Checksum:ⁱ096CBF7AD57AE9B9

GO

Isoform 3 (identifier: P16410-3) [UniParc]FASTA Add to basket

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

« Hide

        10         20         30         40         50
MACLGFQRHK AQLNLATRTW PCTLLFFLLF IPVFCKAKEK KPSYNRGLCE 

NAPNRARM

Show »

Length:58

Mass (Da):6,745

Checksum:ⁱ5F70948EEDC80A94

GO

Isoform 4 (identifier: P16410-4) [UniParc]FASTA Add 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

« Hide

        10         20         30         40         50
MACLGFQRHK AQLNLATRTW PCTLLFFLLF IPVFCKAMHV AQPAVVLASS 
        60         70 
RGIASFVSKE KKPSYNRGLC ENAPNRARM

Show »

Length:79

Mass (Da):8,855

Checksum:ⁱ60CBF1BC1DA59D8A

GO

Isoform 5 (identifier: P16410-5) [UniParc]FASTA Add to basket

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

« 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 
VIAKEKKPSY NRGLCENAPN RARM

Show »

Length:174

Mass (Da):19,145

Checksum:ⁱ0881BFA757AC3FDB

GO

Experimental Info

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	37	A → V in ABG85285 (PubMed:18595775).Curated		1
Sequence conflictⁱ	147	T → A in AAA52773 (PubMed:3220103).Curated		1

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 key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_013577	17	T → 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_072681	70	R → W in ALPS5. 1 PublicationCorresponds to variant dbSNP:rs606231422EnsemblClinVar.		1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Length
Alternative sequenceⁱVSP_041284	38 – 204	Missing in isoform 2 and isoform 3. 1 PublicationAdd BLAST	167
Alternative sequenceⁱVSP_041285	58	C → S in isoform 4. 1 Publication	1
Alternative sequenceⁱVSP_041286	59 – 204	Missing in isoform 4. 1 PublicationAdd BLAST	146
Alternative sequenceⁱVSP_047238	153 – 174	DPEPC…VSSGL → AKEKKPSYNRGLCENAPNRA RM in isoform 5. 1 PublicationAdd BLAST	22
Alternative sequenceⁱVSP_047239	175 – 223	Missing in isoform 5. 1 PublicationAdd BLAST	49
Alternative sequenceⁱVSP_041287	205 – 223	PPTEP…FIPIN → KEKKPSYNRGLCENAPNRAR M in isoform 3 and isoform 4. 1 PublicationAdd BLAST	19

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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS2362.1 [P16410-1] CCDS42803.1 [P16410-5]
PIRⁱ	S08614
NCBI Reference Sequences More...RefSeqⁱ	NP_001032720.1, NM_001037631.2 [P16410-5] NP_005205.2, NM_005214.4 [P16410-1]

Genome annotation databases

Ensemblⁱ	ENST00000295854; ENSP00000295854; ENSG00000163599 [P16410-5] ENST00000472206; ENSP00000417779; ENSG00000163599 [P16410-4] ENST00000487393; ENSP00000497319; ENSG00000163599 [P16410-3] ENST00000648405; ENSP00000497102; ENSG00000163599 [P16410-1]
GeneIDⁱ	1493
KEGGⁱ	hsa:1493
UCSC genome browser More...UCSCⁱ	uc002vak.3, human [P16410-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
P16410	Cytotoxic T-lymphocyte protein 4		PANTR		223	UniRef100_P16410
Cytotoxic T-lymphocyte protein 4		PANPA		223
Cytotoxic T-lymphocyte protein 4		GORGO		223
Cytotoxic T-lymphocyte protein 4 (Fragment)		HUMAN		160
Cytotoxic T-lymphocyte protein 4		PANTR		223
+10
P16410-4	CTLA4 isoform 3		PONAB		79	UniRef100_A0A2J8WUM4
CTLA4 isoform 3		PANTR		79
P16410-5	Cytotoxic T-lymphocyte protein 4		PANTR		174	UniRef100_A0A6D2WB89
Cytotoxic T-lymphocyte protein 4		PANPA		174
Cytotoxic T-lymphocyte protein 4		GORGO		174
Cytotoxic T-lymphocyte protein 4		PANTR		174
Cytotoxic T-lymphocyte protein 4		PANTR		137

Protein	Similar proteins		Species	Score	Length	Source
P16410	Cytotoxic T-lymphocyte protein 4		PANTR		223	UniRef90_P16410
Cytotoxic T-lymphocyte protein 4		PANPA		223
Cytotoxic T-lymphocyte protein 4		GORGO		223
Cytotoxic T-lymphocyte protein 4 (Fragment)		HUMAN		160
Cytotoxic T-lymphocyte protein 4		CALJA		223
+43
P16410-4	CTLA4 isoform 3		PONAB		79	UniRef90_A0A2J8WUM4
CTLA4 isoform 3		PANTR		79
P16410-5	Cytotoxic T-lymphocyte protein 4		NOMLE		174	UniRef90_A0A2I3FRI8
Cytotoxic T-lymphocyte protein 4		RHIRO		174
Cytotoxic T-lymphocyte protein 4		RHIBE		174
Cytotoxic T-lymphocyte protein 4		CERAT		174
Cytotoxic T-lymphocyte protein 4		MANLE		174
+16

Protein	Similar proteins		Species	Score	Length	Source
P16410	Cytotoxic T-lymphocyte protein 4		PIG		223	UniRef50_P16410
Cytotoxic T-lymphocyte protein 4		RABIT		223
Cytotoxic T-lymphocyte protein 4	)	MOUSE		223
Cytotoxic T-lymphocyte protein 4		CANLF		223
Cytotoxic T-lymphocyte protein 4		PANTR		223
+189
P16410-3	Uncharacterized protein		PIG		58	UniRef50_P16410-3
Cytotoxic T-lymphocyte associated protein 4		LYNCA		58
P16410-4	CTLA4 isoform 3		PONAB		79	UniRef50_A0A2J8WUM4
CTLA4 isoform 3		PANTR		79
P16410-5	Cytotoxic T-lymphocyte protein 4		RAT		174	UniRef50_G3V7D2
Cytotoxic T-lymphocyte protein 4		PTEVA		174
Cytotoxic T-lymphocyte protein 4		CARSF		174
Cytotoxic T-lymphocyte protein 4		CALUR		174
Cytotoxic T-lymphocyte protein 4		ZALCA		174
+123

Cross-referencesⁱ

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
CCDSⁱ	CCDS2362.1 [P16410-1] CCDS42803.1 [P16410-5]
PIRⁱ	S08614
RefSeqⁱ	NP_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 More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	1AH1	NMR	-	A	37-161	[»]
	1H6E	X-ray	3.60	P	197-207	[»]
	1I85	X-ray	3.20	C/D	36-161	[»]
	1I8L	X-ray	3.00	C/D	36-161	[»]
	2X44	X-ray	2.60	D	36-161	[»]
	3BX7	X-ray	2.10	C	38-161	[»]
	3OSK	X-ray	1.80	A/B	36-161	[»]
	5GGV	X-ray	2.00	Y	36-161	[»]
	5TRU	X-ray	3.00	C/c	37-154	[»]
	5XJ3	X-ray	3.20	C/F/I/L	36-161	[»]
	6RP8	X-ray	2.60	C/c	37-154	[»]
	6RPJ	X-ray	3.25	A/C/E/G	37-156	[»]
	6RQM	X-ray	3.00	A	37-161	[»]
	6XY2	X-ray	3.05	A	38-160	[»]
	7CIO	X-ray	1.10	B	199-206	[»]
SMRⁱ	P16410
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Protein-protein interaction databases

BioGRIDⁱ	107875, 112 interactors
DIPⁱ	DIP-35607N
ELMⁱ	P16410
IntActⁱ	P16410, 15 interactors
MINTⁱ	P16410
STRINGⁱ	9606.ENSP00000303939

Chemistry databases

ChEMBLⁱ	CHEMBL2364164
DrugBankⁱ	DB06186, Ipilimumab DB11771, Tremelimumab
DrugCentralⁱ	P16410
GuidetoPHARMACOLOGYⁱ	2743

PTM databases

GlyGenⁱ	P16410, 2 sites
iPTMnetⁱ	P16410
PhosphoSitePlusⁱ	P16410

Genetic variation databases

BioMutaⁱ	CTLA4
DMDMⁱ	27735177

Proteomic databases

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

Protocols and materials databases

ABCDⁱ	P16410, 160 sequenced antibodies
Antibodypediaⁱ	19961, 1727 antibodies
The CPTC Antibody Portal More...CPTCⁱ	P16410, 1 antibody
The DNASU plasmid repository More...DNASUⁱ	1493

Genome annotation databases

Ensemblⁱ	ENST00000295854; ENSP00000295854; ENSG00000163599 [P16410-5] ENST00000472206; ENSP00000417779; ENSG00000163599 [P16410-4] ENST00000487393; ENSP00000497319; ENSG00000163599 [P16410-3] ENST00000648405; ENSP00000497102; ENSG00000163599 [P16410-1]
GeneIDⁱ	1493
KEGGⁱ	hsa:1493
UCSCⁱ	uc002vak.3, human [P16410-1]

Organism-specific databases

CTDⁱ	1493
DisGeNETⁱ	1493
GeneCardsⁱ	CTLA4
HGNCⁱ	HGNC:2505, CTLA4
HPAⁱ	ENSG00000163599, Tissue enhanced (blood, lymphoid tissue)
MalaCardsⁱ	CTLA4
MIMⁱ	109100, phenotype 123890, gene 152700, phenotype 601388, phenotype 609755, phenotype 610424, phenotype 616100, phenotype
neXtProtⁱ	NX_P16410
OpenTargetsⁱ	ENSG00000163599
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
PharmGKBⁱ	PA27006
VEuPathDBⁱ	HostDB:ENSG00000163599.14
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	ENOG502RZVK, Eukaryota
GeneTreeⁱ	ENSGT00530000063873
HOGENOMⁱ	CLU_085095_0_0_1
InParanoidⁱ	P16410
OMAⁱ	YVKMPSE
OrthoDBⁱ	1222373at2759
PhylomeDBⁱ	P16410
TreeFamⁱ	TF335679

Enzyme and pathway databases

PathwayCommonsⁱ	P16410
Reactomeⁱ	R-HSA-389513, CTLA4 inhibitory signaling R-HSA-8877330, RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)
SIGNORⁱ	P16410

Miscellaneous databases

BioGRID-ORCSⁱ	1493, 3 hits in 985 CRISPR screens
EvolutionaryTraceⁱ	P16410
GeneWikiⁱ	CTLA-4
GenomeRNAiⁱ	1493
Pharosⁱ	P16410, Tclin
Protein Ontology More...PROⁱ	PR:P16410
RNActⁱ	P16410, protein
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000163599, Expressed in lymph node and 129 other tissues
Genevisibleⁱ	P16410, HS

Family and domain databases

Gene3Dⁱ	2.60.40.10, 1 hit
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
PANTHERⁱ	PTHR11494, PTHR11494, 1 hit PTHR11494:SF8, PTHR11494:SF8, 1 hit
Pfamⁱ	View protein in Pfam PF07686, V-set, 1 hit
PRINTSⁱ	PR01720, CTLANTIGEN4
SMARTⁱ	View protein in SMART SM00409, IG, 1 hit SM00406, IGv, 1 hit
SUPFAMⁱ	SSF48726, SSF48726, 1 hit
MobiDBⁱ	Search...

Entry informationⁱ

Entry nameⁱ	CTLA4_HUMAN
Accessionⁱ	P16410Primary (citable) accession number: P16410 Secondary accession number(s): A0N1S0 Q9UKN9
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
	Last sequence update:	January 10, 2003
	Last modified:	June 2, 2021
	This is version 223 of the entry and version 3 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any 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.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Pharmaceutical, Reference proteome

Documents

Human cell differentiation molecules
CD nomenclature of surface proteins of human leucocytes and list of entries
Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM
Human entries with genetic variants
List of human entries with genetic variants
Human variants curated from literature reports
Index of human variants curated from literature reports
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PDB cross-references
Index of Protein Data Bank (PDB) cross-references

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UniProtKB - P16410 (CTLA4_HUMAN)

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Cytotoxic T-lymphocyte protein 4

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<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

Miscellaneous

<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

Enzyme and pathway databases

<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

Organism-specific databases

<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

Plasma membrane

Golgi apparatus

Plasma Membrane

Other locations

Topology

Keywords - Cellular componenti

<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

Mutagenesis

Keywords - Diseasei

Organism-specific databases

Miscellaneous databases

Chemistry databases

Genetic variation databases

<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

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<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

Gene expression databases

Organism-specific databases

<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

P16410

Protein-protein interaction databases

Miscellaneous databases

<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

3D structure databases

Miscellaneous databases

<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

Region

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Experimental Info

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<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%5Freferences%5Fsection">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

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Genetic variation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<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 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

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Functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Keywords - Domainⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ