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Details on Person UniProt:P07766 CD3E

Class:IdReferenceGeneProduct:51654
_chainChangeLogsignal peptide:1-22 added on Fri February 6 2015;chain:23-207 added on Fri February 6 2015
_displayNameUniProt:P07766 CD3E
_timestamp2026-02-20 22:41:42
chainsignal peptide:1-22
chain:23-207
checksumA1603D01CE9957D7
commentFUNCTION 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
descriptionrecommendedName: T-cell surface glycoprotein CD3 epsilon chain alternativeName: T-cell surface antigen T3/Leu-4 epsilon chain cdAntigenNameCD3e/cdAntigenName
geneNameCD3E
T3E
identifierP07766
isSequenceChangedFALSE
keyword3D-structure
Adaptive immunity
Cell membrane
Disulfide bond
Immunity
Immunoglobulin domain
Membrane
Phosphoprotein
Proteomics identification
Receptor
Reference proteome
Signal
Transmembrane
Transmembrane helix
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
[InstanceEdit:9948485] Weiser, Joel, 2025-05-21
[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
nameCD3E
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8995326] ENSEMBL:ENSG00000198851 CD3E [Homo sapiens]
secondaryIdentifierCD3E_HUMAN
A8K997
sequenceLength207
species[Species:48887] Homo sapiens
(referenceEntity)[EntityWithAccessionedSequence:197906] CD3E [plasma membrane] [Homo sapiens]
[EntityWithAccessionedSequence:202228] p-Y188,Y199-CD3E [plasma membrane] [Homo sapiens]
(referenceSequence)[ModifiedResidue:202261] O4'-phospho-L-tyrosine at 188
[ModifiedResidue:202264] O4'-phospho-L-tyrosine at 199
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