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P07766 (CD3E_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 162. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
T-cell surface glycoprotein CD3 epsilon chain
Alternative name(s):
T-cell surface antigen T3/Leu-4 epsilon chain
CD_antigen=CD3e
Gene names
Name:CD3E
Synonyms:T3E
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length207 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

The CD3 complex mediates signal transduction.

Subunit structure

The TCR/CD3 complex of T-lymphocytes consists of either a TCR alpha/beta or TCR gamma/delta heterodimer coexpressed at the cell surface with the invariant subunits of CD3 labeled gamma, delta, epsilon, zeta, and eta. Ref.14 Ref.15

Subcellular location

Membrane; Single-pass type I membrane protein.

Involvement in disease

Immunodeficiency 18 (IMD18) [MIM:615615]: An 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.10

Sequence similarities

Contains 1 Ig-like (immunoglobulin-like) domain.

Contains 1 ITAM domain.

Ontologies

Keywords
   Cellular componentMembrane
   DomainImmunoglobulin domain
Signal
Transmembrane
Transmembrane helix
   Molecular functionReceptor
   PTMDisulfide bond
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Traceable author statement PubMed 8530500. Source: ProtInc

T cell activation

Non-traceable author statement PubMed 12110186. Source: UniProtKB

T cell costimulation

Traceable author statement. Source: Reactome

T cell receptor signaling pathway

Traceable author statement. Source: Reactome

apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

cell surface receptor signaling pathway

Non-traceable author statement PubMed 12110186. Source: UniProtKB

intracellular signal transduction

Traceable author statement PubMed 1370449. Source: GOC

negative regulation of smoothened signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative thymic T cell selection

Inferred from electronic annotation. Source: Ensembl

positive regulation of T cell anergy

Inferred from electronic annotation. Source: Ensembl

positive regulation of T cell proliferation

Inferred from mutant phenotype PubMed 12110186. Source: UniProtKB

positive regulation of alpha-beta T cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of calcium-mediated signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of interferon-gamma production

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-2 biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-4 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from electronic annotation. Source: Ensembl

protein complex assembly

Non-traceable author statement PubMed 9886373. Source: UniProtKB

regulation of apoptotic process

Non-traceable author statement PubMed 12567487. Source: UniProtKB

regulation of immune response

Traceable author statement. Source: Reactome

response to nutrient

Inferred from electronic annotation. Source: Ensembl

signal complex assembly

Traceable author statement Ref.7. Source: ProtInc

transmembrane receptor protein tyrosine kinase signaling pathway

Traceable author statement PubMed 8530500. Source: ProtInc

   Cellular_componentT cell receptor complex

Non-traceable author statement PubMed 9485181. Source: UniProtKB

alpha-beta T cell receptor complex

Inferred from electronic annotation. Source: Ensembl

external side of plasma membrane

Inferred from direct assay PubMed 11390434PubMed 17213291. Source: MGI

immunological synapse

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Non-traceable author statement PubMed 9485181. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 11390434. Source: MGI

   Molecular_functionSH3 domain binding

Inferred from physical interaction PubMed 12110186. Source: UniProtKB

T cell receptor binding

Non-traceable author statement PubMed 11186279. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 11855827PubMed 17617578PubMed 18644376PubMed 18955169PubMed 7761456Ref.13. Source: IntAct

protein heterodimerization activity

Inferred from physical interaction PubMed 9485181. Source: UniProtKB

protein kinase binding

Non-traceable author statement PubMed 12110186. Source: UniProtKB

receptor signaling complex scaffold activity

Non-traceable author statement PubMed 9886373. Source: UniProtKB

receptor signaling protein activity

Traceable author statement PubMed 1370449. Source: ProtInc

transmembrane signaling receptor activity

Non-traceable author statement PubMed 9485181. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222
Chain23 – 207185T-cell surface glycoprotein CD3 epsilon chain
PRO_0000014607

Regions

Topological domain23 – 126104Extracellular Potential
Transmembrane127 – 15226Helical; Potential
Topological domain153 – 20755Cytoplasmic Potential
Domain32 – 11281Ig-like
Domain178 – 20528ITAM

Amino acid modifications

Modified residue1881Phosphotyrosine Ref.11 Ref.12 Ref.13
Modified residue1991Phosphotyrosine Ref.13
Disulfide bond49 ↔ 98 Ref.14 Ref.15

Secondary structure

....................... 207
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P07766 [UniParc].

Last modified February 1, 1996. Version 2.
Checksum: A1603D01CE9957D7

FASTA20723,147
        10         20         30         40         50         60 
MQSGTHWRVL GLCLLSVGVW GQDGNEEMGG ITQTPYKVSI SGTTVILTCP QYPGSEILWQ 

        70         80         90        100        110        120 
HNDKNIGGDE DDKNIGSDED HLSLKEFSEL EQSGYYVCYP RGSKPEDANF YLYLRARVCE 

       130        140        150        160        170        180 
NCMEMDVMSV ATIVIVDICI TGGLLLLVYY WSKNRKAKAK PVTRGAGAGG RQRGQNKERP 

       190        200 
PPVPNPDYEP IRKGQRDLYS GLNQRRI 

« Hide

References

« Hide 'large scale' references
[1]"Isolation of cDNA clones encoding the 20K non-glycosylated polypeptide chain of the human T-cell receptor/T3 complex."
Gold D.P., Puck J.M., Pettey C.L., Cho M., Coligan J., Woody J.N., Terhorst C.
Nature 321:431-434(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]Terhorst C.
Submitted (JAN-1987) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[3]"Human CD3-epsilon gene contains three miniexons and is transcribed from a non-TATA promoter."
Clevers H.C., Dunlap S., Wileman T.E., Terhorst C.
Proc. Natl. Acad. Sci. U.S.A. 85:8156-8160(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Blood.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Thymus.
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Blood.
[7]"Independent mutations of the human CD3-epsilon gene resulting in a T cell receptor/CD3 complex immunodeficiency."
Soudais C., de Villartay J.P., Le Deist F., Fischer A., Lisowska-Grospierre B.
Nat. Genet. 3:77-81(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN IMD18.
[8]"Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry."
Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T., Ericson C., Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C.
Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry."
Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C.
Anal. Chem. 76:2763-2772(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[10]"Severe combined immunodeficiency caused by deficiency in either the delta or the epsilon subunit of CD3."
de Saint Basile G., Geissmann F., Flori E., Uring-Lambert B., Soudais C., Cavazzana-Calvo M., Durandy A., Jabado N., Fischer A., Le Deist F.
J. Clin. Invest. 114:1512-1517(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN IMD18.
[11]"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-188, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-188, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[13]"Structural basis for Syk tyrosine kinase ubiquity in signal transduction pathways revealed by the crystal structure of its regulatory SH2 domains bound to a dually phosphorylated ITAM peptide."
Fuetterer K., Wong J., Grucza R.A., Chan A.C., Waksman G.
J. Mol. Biol. 281:523-537(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 186-203 IN COMPLEX WITH SYK, PHOSPHORYLATION AT TYR-188 AND TYR-199.
[14]"Crystal structure of the human T cell receptor CD3 epsilon gamma heterodimer complexed to the therapeutic mAb OKT3."
Kjer-Nielsen L., Dunstone M.A., Kostenko L., Ely L.K., Beddoe T., Mifsud N.A., Purcell A.W., Brooks A.G., McCluskey J., Rossjohn J.
Proc. Natl. Acad. Sci. U.S.A. 101:7675-7680(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 21-118 IN COMPLEX WITH CD3G AND ANTIBODY, SUBUNIT, DISULFIDE BOND.
[15]"Crystal structure of a human CD3-epsilon/delta dimer in complex with a UCHT1 single-chain antibody fragment."
Arnett K.L., Harrison S.C., Wiley D.C.
Proc. Natl. Acad. Sci. U.S.A. 101:16268-16273(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 23-126 IN COMPLEX WITH CD3D AND ANTIBODY FRAGMENT, SUBUNIT, DISULFIDE BOND.
+Additional computationally mapped references.

Web resources

CD3Ebase

CD3E mutation db

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X03884 mRNA. Translation: CAA27516.1.
M23323 expand/collapse EMBL AC list , 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.
CCDSCCDS31685.1.
PIRA32069.
RefSeqNP_000724.1. NM_000733.3.
UniGeneHs.3003.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1A81X-ray3.00B/D/F/H/J/L186-203[»]
1SY6X-ray2.10A21-118[»]
1XIWX-ray1.90A/E23-126[»]
2ROLNMR-B181-192[»]
DisProtDP00506.
ProteinModelPortalP07766.
SMRP07766. Positions 33-123, 152-207.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107354. 19 interactions.
IntActP07766. 14 interactions.
MINTMINT-7213890.
STRING9606.ENSP00000354566.

Chemistry

ChEMBLCHEMBL2364168.
DrugBankDB00075. Muromonab.
GuidetoPHARMACOLOGY2742.

PTM databases

PhosphoSiteP07766.

Polymorphism databases

DMDM1345708.

Proteomic databases

MaxQBP07766.
PaxDbP07766.
PeptideAtlasP07766.
PRIDEP07766.

Protocols and materials databases

DNASU916.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000361763; ENSP00000354566; ENSG00000198851.
GeneID916.
KEGGhsa:916.
UCSCuc001psq.4. human.

Organism-specific databases

CTD916.
GeneCardsGC11P118209.
HGNCHGNC:1674. CD3E.
HPACAB000010.
MIM186830. gene.
615615. phenotype.
neXtProtNX_P07766.
Orphanet169160. T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta.
PharmGKBPA26216.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG78872.
HOGENOMHOG000290664.
HOVERGENHBG102121.
InParanoidP07766.
KOK06451.
OMAYLRARVC.
OrthoDBEOG7N0C6H.
PhylomeDBP07766.
TreeFamTF335892.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkP07766.

Gene expression databases

ArrayExpressP07766.
BgeeP07766.
CleanExHS_CD3E.
GenevestigatorP07766.

Family and domain databases

Gene3D2.60.40.10. 1 hit.
InterProIPR015484. CD3_esu/gsu/dsu.
IPR013783. Ig-like_fold.
IPR003598. Ig_sub2.
IPR003110. Phos_immunorcpt_sig_ITAM.
[Graphical view]
PANTHERPTHR10570. PTHR10570. 1 hit.
PfamPF02189. ITAM. 1 hit.
[Graphical view]
SMARTSM00408. IGc2. 1 hit.
SM00077. ITAM. 1 hit.
[Graphical view]
PROSITEPS51055. ITAM_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCD3E. human.
EvolutionaryTraceP07766.
GeneWikiT-cell_surface_glycoprotein_CD3_epsilon_chain.
GenomeRNAi916.
NextBio3790.
PROP07766.
SOURCESearch...

Entry information

Entry nameCD3E_HUMAN
AccessionPrimary (citable) accession number: P07766
Secondary accession number(s): A8K997
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: February 1, 1996
Last modified: July 9, 2014
This is version 162 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries