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Protein

T-cell surface glycoprotein CD3 epsilon chain

Gene

CD3E

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. 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 CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. 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). In addition of this role of signal transduction in T-cell activation, CD3E plays an essential role in correct T-cell developement. Initiates the TCR-CD3 complex assembly by forming the two heterodimers CD3D/CD3E and CD3G/CD3E. Participates also in internalization and cell surface down-regulation of TCR-CD3 complexes via endocytosis sequences present in CD3E cytosolic region (PubMed:10384095, PubMed:26507128).6 Publications

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: CAFA
  • protein kinase binding Source: UniProtKB
  • receptor signaling complex scaffold activity Source: UniProtKB
  • SH3 domain binding Source: UniProtKB
  • signal transducer activity, downstream of receptor Source: ProtInc
  • T cell receptor binding Source: UniProtKB
  • transmembrane signaling receptor activity Source: UniProtKB

GO - Biological processi

  • apoptotic signaling pathway Source: Ensembl
  • cell surface receptor signaling pathway Source: UniProtKB
  • cerebellum development Source: Ensembl
  • dendrite development Source: Ensembl
  • G-protein coupled receptor signaling pathway Source: ProtInc
  • negative regulation of gene expression Source: UniProtKB
  • negative regulation of smoothened signaling pathway Source: Ensembl
  • negative thymic T cell selection Source: Ensembl
  • positive regulation of alpha-beta T cell proliferation Source: Ensembl
  • positive regulation of calcium-mediated signaling Source: Ensembl
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of interferon-gamma production Source: Ensembl
  • positive regulation of interleukin-2 biosynthetic process Source: Ensembl
  • positive regulation of interleukin-4 production Source: Ensembl
  • positive regulation of peptidyl-tyrosine phosphorylation Source: Ensembl
  • positive regulation of T cell anergy Source: Ensembl
  • positive regulation of T cell proliferation Source: UniProtKB
  • protein complex assembly Source: UniProtKB
  • protein homooligomerization Source: CAFA
  • regulation of apoptotic process Source: UniProtKB
  • regulation of immune response Source: Reactome
  • response to nutrient Source: Ensembl
  • signal complex assembly Source: ProtInc
  • T cell activation Source: UniProtKB
  • T cell costimulation Source: Reactome
  • T cell receptor signaling pathway Source: Reactome
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: ProtInc

Keywordsi

Molecular functionReceptor
Biological processAdaptive immunity, Immunity

Enzyme and pathway databases

ReactomeiR-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
R-HSA-202424. Downstream TCR signaling.
R-HSA-202427. Phosphorylation of CD3 and TCR zeta chains.
R-HSA-202430. Translocation of ZAP-70 to Immunological synapse.
R-HSA-202433. Generation of second messenger molecules.
R-HSA-389948. PD-1 signaling.
SignaLinkiP07766.
SIGNORiP07766.

Names & Taxonomyi

Protein namesi
Recommended name:
T-cell surface glycoprotein CD3 epsilon chain
Alternative name(s):
T-cell surface antigen T3/Leu-4 epsilon chain
CD_antigen: CD3e
Gene namesi
Name:CD3E
Synonyms:T3E
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000198851.9.
HGNCiHGNC:1674. CD3E.

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; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini23 – 126ExtracellularSequence analysisAdd BLAST104
Transmembranei127 – 152HelicalSequence analysisAdd BLAST26
Topological domaini153 – 207CytoplasmicSequence analysisAdd BLAST55

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency 18 (IMD18)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive primary immunodeficiency characterized by onset in infancy or early childhood of recurrent infections. The severity is variable, encompassing both a mild immunodeficiency and severe combined immunodeficiency (SCID), resulting in early death without bone marrow transplantation in some patients. Immunologic work-up of the IMD18 SCID patients shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype, whereas T-cell development is not impaired in the mild form of IMD18.
See also OMIM:615615

Organism-specific databases

DisGeNETi916.
MalaCardsiCD3E.
MIMi615615. phenotype.
OpenTargetsiENSG00000198851.
Orphaneti169160. T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta.
PharmGKBiPA26216.

Chemistry databases

ChEMBLiCHEMBL1975.
DrugBankiDB00075. Muromonab.
GuidetoPHARMACOLOGYi2742.

Polymorphism and mutation databases

BioMutaiCD3E.
DMDMi1345708.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Add BLAST22
ChainiPRO_000001460723 – 207T-cell surface glycoprotein CD3 epsilon chainAdd BLAST185

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi49 ↔ 982 Publications
Modified residuei188PhosphotyrosinePROSITE-ProRule annotationCombined sources1 Publication1
Modified residuei199PhosphotyrosinePROSITE-ProRule annotation1 Publication1

Post-translational modificationi

Phosphorylated on Tyr residues after T-cell receptor triggering by LCK in association with CD4/CD8.1 Publication

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

MaxQBiP07766.
PaxDbiP07766.
PeptideAtlasiP07766.
PRIDEiP07766.

PTM databases

iPTMnetiP07766.
PhosphoSitePlusiP07766.

Expressioni

Gene expression databases

BgeeiENSG00000198851.
CleanExiHS_CD3E.
ExpressionAtlasiP07766. baseline and differential.
GenevisibleiP07766. HS.

Organism-specific databases

HPAiCAB000010.
CAB072863.
CAB072864.
HPA040957.
HPA043955.

Interactioni

Subunit structurei

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. In turn, the hexamer interacts with CD3Z homodimer to form the TCR-CD3 complex. Alternatively, TCRalpha and TCRbeta can be replaced by TCRgamma and TCRdelta. Interacts with CD6 (PubMed:15294938). Interacts with NCK1 (PubMed:15972658). Interacts with NUMB; this interaction is important for TCR-CD3 internalization and subsequent degradation (PubMed:26507128).6 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: CAFA
  • protein kinase binding Source: UniProtKB
  • receptor signaling complex scaffold activity Source: UniProtKB
  • SH3 domain binding Source: UniProtKB
  • T cell receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107354. 25 interactors.
ELMiP07766.
IntActiP07766. 16 interactors.
MINTiMINT-7213890.
STRINGi9606.ENSP00000354566.

Structurei

Secondary structure

1207
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi37 – 41Combined sources5
Beta strandi44 – 48Combined sources5
Beta strandi57 – 61Combined sources5
Beta strandi64 – 69Combined sources6
Beta strandi75 – 78Combined sources4
Beta strandi81 – 84Combined sources4
Helixi89 – 92Combined sources4
Beta strandi94 – 100Combined sources7
Helixi105 – 107Combined sources3
Beta strandi110 – 116Combined sources7
Helixi193 – 195Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A81X-ray3.00B/D/F/H/J/L186-203[»]
1SY6X-ray2.10A21-118[»]
1XIWX-ray1.90A/E23-126[»]
2ROLNMR-B181-192[»]
DisProtiDP00506.
ProteinModelPortaliP07766.
SMRiP07766.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP07766.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini32 – 112Ig-likeAdd BLAST81
Domaini178 – 205ITAMPROSITE-ProRule annotationAdd BLAST28

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni175 – 192NUMB-binding region1 PublicationAdd BLAST18

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IYD1. Eukaryota.
ENOG41123JN. LUCA.
GeneTreeiENSGT00510000048592.
HOGENOMiHOG000290664.
HOVERGENiHBG102121.
InParanoidiP07766.
KOiK06451.
OMAiQRGQNKE.
OrthoDBiEOG091G0PKE.
PhylomeDBiP07766.
TreeFamiTF335892.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiView protein in InterPro
IPR015484. CD3_esu/gsu/dsu.
IPR036179. Ig-like_dom_sf.
IPR013783. Ig-like_fold.
IPR003598. Ig_sub2.
IPR003110. Phos_immunorcpt_sig_ITAM.
PANTHERiPTHR10570. PTHR10570. 1 hit.
PfamiView protein in Pfam
PF02189. ITAM. 1 hit.
SMARTiView protein in SMART
SM00408. IGc2. 1 hit.
SM00077. ITAM. 1 hit.
SUPFAMiSSF48726. SSF48726. 1 hit.
PROSITEiView protein in PROSITE
PS51055. ITAM_1. 1 hit.

Sequencei

Sequence statusi: Complete.

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

P07766-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQSGTHWRVL GLCLLSVGVW GQDGNEEMGG ITQTPYKVSI SGTTVILTCP
60 70 80 90 100
QYPGSEILWQ HNDKNIGGDE DDKNIGSDED HLSLKEFSEL EQSGYYVCYP
110 120 130 140 150
RGSKPEDANF YLYLRARVCE NCMEMDVMSV ATIVIVDICI TGGLLLLVYY
160 170 180 190 200
WSKNRKAKAK PVTRGAGAGG RQRGQNKERP PPVPNPDYEP IRKGQRDLYS

GLNQRRI
Length:207
Mass (Da):23,147
Last modified:February 1, 1996 - v2
Checksum:iA1603D01CE9957D7
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X03884 mRNA. Translation: CAA27516.1.
M23323
, M23317, M23318, M23319, M23320, M23321, L34846, M23322 Genomic DNA. Translation: AAA52295.1.
AK292612 mRNA. Translation: BAF85301.1.
CH471065 Genomic DNA. Translation: EAW67364.1.
BC049847 mRNA. Translation: AAH49847.1.
CCDSiCCDS31685.1.
PIRiA32069.
RefSeqiNP_000724.1. NM_000733.3.
UniGeneiHs.3003.

Genome annotation databases

EnsembliENST00000361763; ENSP00000354566; ENSG00000198851.
GeneIDi916.
KEGGihsa:916.
UCSCiuc001psq.5. human.

Similar proteinsi

Entry informationi

Entry nameiCD3E_HUMAN
AccessioniPrimary (citable) accession number: P07766
Secondary accession number(s): A8K997
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: February 1, 1996
Last modified: October 25, 2017
This is version 189 of the entry and version 2 of the sequence. See complete history.
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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references