Reactome | UniProt:P07766 CD3E

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UniProt:P07766 CD3E Show undefined attributes

chain	signal peptide:1-22 chain:23-207
checksum	A1603D01CE9957D7
comment	FUNCTION Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response (PubMed:15294938, PubMed:15546002, PubMed:2470098, PubMed:40592325, PubMed:8490660). When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD247/CD3Z (PubMed:2470098, PubMed:40592325). All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain (PubMed:2470098, PubMed:40592325). Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways (PubMed:2470098, PubMed:40592325). CD3E ITAM phosphorylation creates docking sites for the protein kinase ZAP70 leading to ZAP70 phosphorylation and its conversion into a catalytically active enzyme (By similarity). In addition of this role of signal transduction in T-cell activation, CD3E plays an essential role in correct T-cell development (By similarity). Also participates in internalization and cell surface down-regulation of TCR-CD3 complexes via endocytosis sequences present in CD3E cytosolic region (PubMed:10384095, PubMed:26507128). In addition to its role as a TCR coreceptor, it serves as a receptor for ITPRIPL1 (PubMed:38614099). Ligand recognition inhibits T-cell activation by promoting interaction with NCK1, which prevents CD3E-ZAP70 interaction and blocks the ERK-NFkB signaling cascade and calcium influx (PubMed:12110186, PubMed:38614099).SUBUNIT The TCR-CD3 complex is composed of a CD3D-CD3E and a CD3G-CD3E heterodimers that preferentially associate with TCRalpha and TCRbeta, respectively, to form TCRalpha-CD3E-CD3G and TCRbeta/CD3G-CD3E trimers (PubMed:15136729, PubMed:15534202, PubMed:40592325). In turn, the hexamer interacts with CD247/CD3Z homodimer to form the TCR-CD3 complex (PubMed:15136729, PubMed:15534202). Alternatively, TCRalpha and TCRbeta can be replaced by TCRgamma and TCRdelta. Interacts with CD6 (PubMed:15294938). Interacts (via Proline-rich sequence) with NCK1; the interaction is ligand dependent but independent of tyrosine kinase activation (PubMed:12110186, PubMed:15972658, PubMed:38614099). Interacts with NUMB; this interaction is important for TCR-CD3 internalization and subsequent degradation (PubMed:26507128). Interacts (when tyrosine phosphorylated) with LAG3; disrupting the association between CD3E and LCK and preventing TCR activation (PubMed:15534202).INTERACTION Phosphorylated on Tyr residues after T-cell receptor triggering by LCK in association with CD4/CD8.DISEASE The disease is caused by variants affecting the gene represented in this entry.ONLINE INFORMATION CD3E mutation db
crossReference	[DatabaseIdentifier:12181528] PDB:7FJF [DatabaseIdentifier:12429136] RefSeq:NP_000724.1 [DatabaseIdentifier:12290777] Pharos - Targets:P07766 [DatabaseIdentifier:12252801] PRO:P07766 [DatabaseIdentifier:12215690] PDB:8F0L [DatabaseIdentifier:12154196] PDB:7PHR [DatabaseIdentifier:12181527] PDB:7FJE [DatabaseIdentifier:12212456] PDB:9CI8 [DatabaseIdentifier:12148413] PDB:5QU2 [DatabaseIdentifier:12194130] PDB:8ES9 [DatabaseIdentifier:12179368] PDB:9IPE [DatabaseIdentifier:12215688] PDB:1XIW [DatabaseIdentifier:12215687] PDB:8VY4 [DatabaseIdentifier:12181539] PDB:8TW4 [DatabaseIdentifier:12212459] PDB:8ZA6 [DatabaseIdentifier:12194129] PDB:8ES8 [DatabaseIdentifier:12212449] PDB:8TW6 [DatabaseIdentifier:12212462] PDB:9CQ4 [DatabaseIdentifier:11500426] ENSEMBL:ENSG00000198851 [DatabaseIdentifier:11610519] ENSEMBL:ENSP00000354566 [DatabaseIdentifier:11733218] ENSEMBL:ENST00000361763 [DatabaseIdentifier:11779329] Guide to Pharmacology - Targets:2742 [DatabaseIdentifier:11792936] GeneCards:CD3E [DatabaseIdentifier:11809010] GlyGen:P07766 [DatabaseIdentifier:11845924] HPA:ENSG00000198851-CD3E [DatabaseIdentifier:12130576] OpenTargets:ENSG00000198851 [DatabaseIdentifier:12135256] Orphanet:CD3E [DatabaseIdentifier:12179369] PDB:9IPD [DatabaseIdentifier:12179310] PDB:9IP8 [DatabaseIdentifier:12212461] PDB:8WYI [DatabaseIdentifier:12212450] PDB:8JC0 [DatabaseIdentifier:12215689] PDB:2ROL [DatabaseIdentifier:12179362] PDB:9IPC [DatabaseIdentifier:12212458] PDB:8JCB [DatabaseIdentifier:12181397] PDB:9BBC [DatabaseIdentifier:12212460] PDB:8YC0 [DatabaseIdentifier:12181529] PDB:7FJD [DatabaseIdentifier:12212453] PDB:8WXE [DatabaseIdentifier:12212457] PDB:1SY6 [DatabaseIdentifier:12212451] PDB:8ES7 [DatabaseIdentifier:12179364] PDB:9IPA [DatabaseIdentifier:12212452] PDB:8WY0 [DatabaseIdentifier:12215691] PDB:1A81 [DatabaseIdentifier:12181519] PDB:9C3E [DatabaseIdentifier:12212454] PDB:9CIA [DatabaseIdentifier:12179305] PDB:9IP9 [DatabaseIdentifier:12181540] PDB:6JXR
databaseName	UniProt
dbId	51654
description	recommendedName: T-cell surface glycoprotein CD3 epsilon chain alternativeName: T-cell surface antigen T3/Leu-4 epsilon chain cdAntigenNameCD3e/cdAntigenName
displayName	UniProt:P07766 CD3E
geneName	CD3E T3E
identifier	P07766
isSequenceChanged	false
keyword	3D-structure Adaptive immunity Cell membrane Disulfide bond Immunity Immunoglobulin domain Membrane Phosphoprotein Proteomics identification Receptor Reference proteome Signal Transmembrane Transmembrane helix
modified	[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType	Protein
name	CD3E
otherIdentifier	11729855_at 11761574_a_at 16731795 205456_PM_at 205456_at 3351284 3351285 3351286 3351287 3351288 3351289 3351290 3351291 3351292 3351293 3351294 3351295 3351296 3351297 36277_at 7944179 916 A_14_P117535 A_23_P416747 A_24_P86968 GE60506 GO:0001772 GO:0001954 GO:0002250 GO:0002376 GO:0002669 GO:0002870 GO:0004888 GO:0005515 GO:0005783 GO:0005794 GO:0005886 GO:0005911 GO:0007166 GO:0007169 GO:0007172 GO:0007186 GO:0007224 GO:0009897 GO:0009966 GO:0010628 GO:0010629 GO:0016020 GO:0016358 GO:0017124 GO:0019722 GO:0019901 GO:0021549 GO:0030159 GO:0031295 GO:0032729 GO:0032743 GO:0032753 GO:0033634 GO:0035739 GO:0042098 GO:0042101 GO:0042102 GO:0042105 GO:0042106 GO:0042110 GO:0042608 GO:0042802 GO:0042981 GO:0043197 GO:0043410 GO:0044297 GO:0045059 GO:0045060 GO:0045879 GO:0046629 GO:0046631 GO:0046649 GO:0048856 GO:0050850 GO:0050852 GO:0050870 GO:0060090 GO:0065003 GO:0097190 GO:2000563 HMNXSV003040023 ILMN_1739794 M23323_s_at PH_hs_0000378 TC11001060.hg g4502670_3p_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-202228] p-Y188,Y199-CD3E [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-197906] CD3E [plasma membrane] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000198851] ENSEMBL:ENSG00000198851 CD3E [ReferenceDNASequence:12702941] UCSC:P07766 CD3E [ReferenceDNASequence:11365721] BioGPS Gene:916 CD3E [ReferenceDNASequence:11394641] COSMIC - genes:CD3E CD3E [ReferenceDNASequence:11421261] CTD Gene:916 CD3E [ReferenceDNASequence:11430728] dbSNP Gene:916 CD3E [ReferenceDNASequence:11824621] HGNC:1674 CD3E [ReferenceDNASequence:11904209] KEGG:hsa:916 CD3E [ReferenceDNASequence:11995510] Monarch:916 CD3E [ReferenceDNASequence:12079603] NCBI Gene:916 CD3E [ReferenceDNASequence:12115121] OMIM:186830 CD3E
referenceTranscript	[ReferenceRNASequence:12610654] RefSeq:NM_000733.4 CD3E
schemaClass	ReferenceGeneProduct
secondaryIdentifier	CD3E_HUMAN A8K997
sequenceLength	207
species	[Species:48887] Homo sapiens
stId	uniprot:P07766
url	http://purl.uniprot.org/uniprot/P07766

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-202228] p-Y188,Y199-CD3E [plasma membrane] [EntityWithAccessionedSequence:R-HSA-197906] CD3E [plasma membrane]
(referenceSequence)	[ModifiedResidue:202261] O4'-phospho-L-tyrosine at 188 [ModifiedResidue:202264] O4'-phospho-L-tyrosine at 199
(interactor)	[UndirectedInteraction:11140229] UniProt:P43403 <-> UniProt:P07766 (IntAct) [UndirectedInteraction:11215095] UniProt:O43639 <-> UniProt:P07766 (IntAct) [UndirectedInteraction:11251175] UniProt:P43405 <-> UniProt:P07766 (IntAct) [UndirectedInteraction:11275281] UniProt:P16333 <-> UniProt:P07766 (IntAct)