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Protein

T-cell surface glycoprotein CD3 epsilon chain

Gene

CD3E

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 development. 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
  • T cell receptor binding Source: UniProtKB
  • transmembrane signaling receptor activity Source: GO_Central

GO - Biological processi

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
MIMi186830 gene
neXtProtiNX_P07766

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
ProteomicsDBi52027

PTM databases

iPTMnetiP07766
PhosphoSitePlusiP07766

Expressioni

Gene expression databases

BgeeiENSG00000198851 Expressed in 107 organ(s), highest expression level in leukocyte
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107354, 25 interactors
ELMiP07766
IntActiP07766, 21 interactors
MINTiP07766
STRINGi9606.ENSP00000354566

Structurei

Secondary structure

1207
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiVGAWGQE
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

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PSH8E9PSH8_HUMAN
T-cell surface glycoprotein CD3 eps...
CD3E
201Annotation score:

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

Cross-referencesi

Web resourcesi

CD3Ebase

CD3E mutation db

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

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...

Protein-protein interaction databases

BioGridi107354, 25 interactors
ELMiP07766
IntActiP07766, 21 interactors
MINTiP07766
STRINGi9606.ENSP00000354566

Chemistry databases

ChEMBLiCHEMBL1975
DrugBankiDB00075 Muromonab
GuidetoPHARMACOLOGYi2742

PTM databases

iPTMnetiP07766
PhosphoSitePlusiP07766

Polymorphism and mutation databases

BioMutaiCD3E
DMDMi1345708

Proteomic databases

MaxQBiP07766
PaxDbiP07766
PeptideAtlasiP07766
PRIDEiP07766
ProteomicsDBi52027

Protocols and materials databases

DNASUi916
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi916
DisGeNETi916
EuPathDBiHostDB:ENSG00000198851.9
GeneCardsiCD3E
HGNCiHGNC:1674 CD3E
HPAiCAB000010
CAB072863
CAB072864
HPA040957
HPA043955
MalaCardsiCD3E
MIMi186830 gene
615615 phenotype
neXtProtiNX_P07766
OpenTargetsiENSG00000198851
Orphaneti169160 T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta
PharmGKBiPA26216
GenAtlasiSearch...

Phylogenomic databases

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

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

Miscellaneous databases

ChiTaRSiCD3E human
EvolutionaryTraceiP07766
GeneWikiiT-cell_surface_glycoprotein_CD3_epsilon_chain
GenomeRNAii916
PROiPR:P07766
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198851 Expressed in 107 organ(s), highest expression level in leukocyte
CleanExiHS_CD3E
ExpressionAtlasiP07766 baseline and differential
GenevisibleiP07766 HS

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
ProtoNetiSearch...

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: November 7, 2018
This is version 198 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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  4. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
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Main funding by: National Institutes of Health

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