Reactome | UniProt:P16410 CTLA4

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UniProt:P16410 CTLA4 Show undefined attributes

chain	signal peptide:1-35 chain:36-223
checksum	6F9466FB2E139A5A
comment	FUNCTION Inhibitory receptor acting as a major negative regulator of T-cell responses (PubMed:11279501, PubMed:11279502, PubMed:16551244, PubMed:1714933, PubMed:18641304, PubMed:28484017). Acts as a decoy receptor: 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 (PubMed:11279501, PubMed:11279502, PubMed:16551244, PubMed:1714933, PubMed:28484017).SUBUNIT Homodimer; disulfide-linked (PubMed:11279501, PubMed:11279502, PubMed:21156796, PubMed:28484017, Ref.24). Interacts with ICOSLG (PubMed:28484017).INTERACTION Exists primarily an intracellular antigen whose surface expression is tightly regulated by restricted trafficking to the cell surface and rapid internalization.ALTERNATIVE PRODUCTS 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.PTM N-glycosylation is important for dimerization.PTM Phosphorylation at Tyr-201 prevents binding to the AP-2 adapter complex, blocks endocytosis, and leads to retention of CTLA4 on the cell surface.POLYMORPHISM Genetic variations in CTLA4 are associated with susceptibility to several autoimmune disorders (PubMed:10189842, PubMed:10924276, PubMed:12724780, PubMed:15138458, PubMed:15657618, PubMed:15688186, PubMed:18595775, PubMed:25213377, PubMed:25329329). They influence responsiveness to hepatitis B virus (HBV) infection [MIM:610424] (PubMed:15452244).DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.DISEASE Genetic variations in CTLA4 may influence susceptibility to Graves disease, an autoimmune disorder associated with overactivity of the thyroid gland and hyperthyroidism.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.PHARMACEUTICAL 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.MISCELLANEOUS The therapeutic antibody Ipilimumab competes for the binding site of the endogenous ligands CD80/B7-1, CD86/B7-2 and ICOSLG.ONLINE INFORMATION CLTA-4 entry
crossReference	[DatabaseIdentifier:12154744] PDB:8GAB [DatabaseIdentifier:12401740] RefSeq:NP_001032720.1 [DatabaseIdentifier:12401739] RefSeq:NP_005205.2 [DatabaseIdentifier:12281865] Pharos - Targets:P16410 [DatabaseIdentifier:12239413] PRO:P16410 [DatabaseIdentifier:12154740] PDB:1I85 [DatabaseIdentifier:12154758] PDB:2X44 [DatabaseIdentifier:12154754] PDB:5GGV [DatabaseIdentifier:12154746] PDB:7SU0 [DatabaseIdentifier:12154748] PDB:6RPJ [DatabaseIdentifier:12154757] PDB:6RP8 [DatabaseIdentifier:12154751] PDB:5XJ3 [DatabaseIdentifier:12154743] PDB:7CIO [DatabaseIdentifier:12154750] PDB:7DV4 [DatabaseIdentifier:12154738] PDB:6RQM [DatabaseIdentifier:12154752] PDB:3BX7 [DatabaseIdentifier:12154739] PDB:8HIT [DatabaseIdentifier:12154755] PDB:1I8L [DatabaseIdentifier:12154741] PDB:6XY2 [DatabaseIdentifier:11487120] ENSEMBL:ENSG00000163599 [DatabaseIdentifier:11591694] ENSEMBL:ENSP00000497319 [DatabaseIdentifier:11591692] ENSEMBL:ENSP00000295854 [DatabaseIdentifier:11591693] ENSEMBL:ENSP00000497102 [DatabaseIdentifier:11714391] ENSEMBL:ENST00000295854 [DatabaseIdentifier:11714393] ENSEMBL:ENST00000648405 [DatabaseIdentifier:11714392] ENSEMBL:ENST00000487393 [DatabaseIdentifier:11780915] Guide to Pharmacology - Targets:2743 [DatabaseIdentifier:11783949] GeneCards:CTLA4 [DatabaseIdentifier:11799480] GlyGen:P16410 [DatabaseIdentifier:11837052] HPA:ENSG00000163599-CTLA4 [DatabaseIdentifier:12121540] OpenTargets:ENSG00000163599 [DatabaseIdentifier:12136258] Orphanet:CTLA4 [DatabaseIdentifier:12154745] PDB:3OSK [DatabaseIdentifier:12154742] PDB:7SU1 [DatabaseIdentifier:12154756] PDB:5TRU [DatabaseIdentifier:12154737] PDB:7ELX [DatabaseIdentifier:12154747] PDB:1AH1 [DatabaseIdentifier:12154753] PDB:9DQ3 [DatabaseIdentifier:12154749] PDB:1H6E
databaseName	UniProt
dbId	53042
description	recommendedName: Cytotoxic T-lymphocyte protein 4 alternativeName: Cytotoxic T-lymphocyte-associated antigen 4 shortName: CTLA-4 cdAntigenNameCD152/cdAntigenName
displayName	UniProt:P16410 CTLA4
geneName	CTLA4 CD152
identifier	P16410
isSequenceChanged	false
keyword	3D-structure Adaptive immunity Alternative splicing Cell membrane Diabetes mellitus Disease variant Disulfide bond Glycoprotein Immunity Immunoglobulin domain Membrane Pharmaceutical Phosphoprotein Proteomics identification Reference proteome Signal Systemic lupus erythematosus Transmembrane Transmembrane helix
modified	[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType	Protein
name	CTLA4
otherIdentifier	11730636_a_at 11730637_a_at 11753826_x_at 11753866_x_at 1493 16889819 221331_PM_x_at 221331_x_at 231794_PM_at 231794_at 234362_PM_s_at 234362_s_at 236341_PM_at 236341_at 2523856 2523857 2523858 2523859 2523860 2523861 2523862 8047692 81915_at A_14_P101727 A_23_P102481 A_33_P3396139 A_33_P3401556 GE62661 GO:0002250 GO:0002376 GO:0005515 GO:0005794 GO:0005886 GO:0006955 GO:0006974 GO:0009897 GO:0016020 GO:0030889 GO:0031410 GO:0042129 GO:0042130 GO:0043065 GO:0045334 GO:0045590 GO:0048471 GO:0050852 GO:0050853 GO:0098636 HMNXSV003041410 Hs.247824.2.S1_3p_a_at Hs.313929.0.A1_3p_at ILMN_1763487 ILMN_2261627 ILMN_2348905 M37245_at PH_hs_0013114 TC02001201.hg TC02003774.hg
physicalEntity	[EntityWithAccessionedSequence:R-HSA-179764] CTLA4 [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-388754] p-Y201,Y218-CTLA4 [plasma membrane] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000163599] ENSEMBL:ENSG00000163599 CTLA4 [ReferenceDNASequence:12746158] UCSC:P16410 CTLA4 [ReferenceDNASequence:11352393] BioGPS Gene:1493 CTLA4 [ReferenceDNASequence:11400942] COSMIC - genes:CTLA4 CTLA4 [ReferenceDNASequence:11407723] CTD Gene:1493 CTLA4 [ReferenceDNASequence:11438191] dbSNP Gene:1493 CTLA4 [ReferenceDNASequence:11815573] HGNC:2505 CTLA4 [ReferenceDNASequence:11892088] KEGG:hsa:1493 CTLA4 [ReferenceDNASequence:11982182] Monarch:1493 CTLA4 [ReferenceDNASequence:12066275] NCBI Gene:1493 CTLA4 [ReferenceDNASequence:12107226] OMIM:123890 CTLA4
referenceTranscript	[ReferenceRNASequence:12583460] RefSeq:NM_005214.4 CTLA4 [ReferenceRNASequence:12583461] RefSeq:NM_001037631.3 CTLA4
schemaClass	ReferenceGeneProduct
secondaryIdentifier	CTLA4_HUMAN A0N1S0 E9PDH0 O95653 Q0PP65 Q52MC1 Q53TD5 Q5S005 Q8WXJ1 Q96P43 Q9UKN9
sequenceLength	223
species	[Species:48887] Homo sapiens
stId	uniprot:P16410
url	http://purl.uniprot.org/uniprot/P16410

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-179764] CTLA4 [plasma membrane] [EntityWithAccessionedSequence:R-HSA-388754] p-Y201,Y218-CTLA4 [plasma membrane]
(referenceSequence)	[ModifiedResidue:388753] O4'-phospho-L-tyrosine at 201 [ModifiedResidue:388752] O4'-phospho-L-tyrosine at 218
(interactor)	[UndirectedInteraction:11175583] UniProt:Q08050 <-> UniProt:P16410 (IntAct) [UndirectedInteraction:11182359] UniProt:P27986 <-> UniProt:P16410 (IntAct) [UndirectedInteraction:11195019] UniProt:P16410 <-> UniProt:P33681 (IntAct) [UndirectedInteraction:11195021] UniProt:P16410 <-> UniProt:P42081 (IntAct) [UndirectedInteraction:11195023] UniProt:P16410 <-> UniProt:P50851 (IntAct) [UndirectedInteraction:11195025] UniProt:P16410 <-> UniProt:A2RU14 (IntAct) [UndirectedInteraction:11195027] UniProt:P16410 <-> UniProt:Q4LDR2 (IntAct) [UndirectedInteraction:11195029] UniProt:P16410 <-> UniProt:Q13021 (IntAct) [UndirectedInteraction:11195031] UniProt:P16410 <-> UniProt:O43286 (IntAct) [UndirectedInteraction:11195035] UniProt:P16410 <-> UniProt:Q9BXJ8 (IntAct) [UndirectedInteraction:11195037] UniProt:P16410 <-> UniProt:Q9Y2U8 (IntAct) [UndirectedInteraction:11195039] UniProt:P16410 <-> UniProt:Q13332 (IntAct) [UndirectedInteraction:11195041] UniProt:P16410 <-> UniProt:Q9H2G9 (IntAct)