P07766 (CD3E_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	CD3E
Synonyms:	T3E

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	207 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.12 Ref.13
Subcellular location	Membrane; Single-pass type I membrane protein.
Sequence similarities	Contains 1 Ig-like (immunoglobulin-like) domain. Contains 1 ITAM domain.

Ontologies

Keywords
Cellular component	Membrane
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-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 negative regulation of smoothened signaling pathway Inferred from electronic annotation. Source: Compara negative thymic T cell selection Inferred from electronic annotation. Source: Compara positive regulation of T cell anergy Inferred from electronic annotation. Source: Compara 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: Compara positive regulation of calcium-mediated signaling Inferred from electronic annotation. Source: Compara positive regulation of interferon-gamma production Inferred from electronic annotation. Source: Compara positive regulation of interleukin-2 biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of interleukin-4 production Inferred from electronic annotation. Source: Compara positive regulation of peptidyl-tyrosine phosphorylation Inferred from electronic annotation. Source: Compara regulation of apoptotic process Non-traceable author statement PubMed 12567487. Source: UniProtKB response to nutrient Inferred from electronic annotation. Source: Compara signal complex assembly Traceable author statement PubMed 8490660. Source: ProtInc transmembrane receptor protein tyrosine kinase signaling pathway Traceable author statement PubMed 8530500. Source: ProtInc
Cellular_component	T cell receptor complex Non-traceable author statement PubMed 9485181. Source: UniProtKB alpha-beta T cell receptor complex Inferred from electronic annotation. Source: Compara external side of plasma membrane Inferred from direct assay PubMed 11390434PubMed 17213291. Source: MGI immunological synapse Inferred from electronic annotation. Source: Compara integral to plasma membrane Non-traceable author statement PubMed 9485181. Source: UniProtKB
Molecular_function	T cell receptor binding Non-traceable author statement PubMed 11186279. 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Chain

23 – 207

185

T-cell surface glycoprotein CD3 epsilon chain

PRO_0000014607

Regions

Topological domain

23 – 126

104

Extracellular Potential

Transmembrane

127 – 152

26

Helical; Potential

Topological domain

153 – 207

55

Cytoplasmic Potential

Domain

32 – 112

81

Ig-like

Domain

178 – 205

28

ITAM

Amino acid modifications

Modified residue

188

1

Phosphotyrosine Ref.9 Ref.10 Ref.11

Modified residue

199

1

Phosphotyrosine Ref.11

Disulfide bond

49 ↔ 98

Ref.12 Ref.13

Secondary structure

1

.

.

.

.

.

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.

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.

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.

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.

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207

Helix Strand Turn

Details...

Beta strand

37 – 41

5

Beta strand

44 – 48

5

Beta strand

57 – 61

5

Beta strand

64 – 69

6

Beta strand

75 – 78

4

Beta strand

81 – 84

4

Helix

89 – 92

4

Beta strand

94 – 100

7

Helix

105 – 107

3

Beta strand

110 – 116

7

Helix

193 – 195

3

Sequences

	Sequence		Length	Mass (Da)
	P07766 [UniParc]. Last modified February 1, 1996. Version 2. Checksum: A1603D01CE9957D7	FASTA	207	23,147
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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]	"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].
[8]	"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.
[9]	"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, MASS SPECTROMETRY.
[10]	"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, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[11]	"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.
[12]	"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.
[13]	"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

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00012923.

PIR

A32069.

RefSeq

NP_000724.1. NM_000733.3.

UniGene

Hs.3003.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A81	X-ray	3.00	B/D/F/H/J/L	186-203	[»]
1SY6	X-ray	2.10	A	23-118	[»]
1XIW	X-ray	1.90	A/E	23-126	[»]
2ROL	NMR	-	B	181-192	[»]

DisProt

DP00506.

ProteinModelPortal

P07766.

ModBase

Search...

Protein-protein interaction databases

IntAct

P07766. 3 interactions.

MINT

MINT-7213890.

STRING

9606.ENSP00000354566.

PTM databases

PhosphoSite

P07766.

Polymorphism databases

DMDM

1345708.

Proteomic databases

PaxDb

P07766.

PeptideAtlas

P07766.

PRIDE

P07766.

Protocols and materials databases

DNASU

916.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000361763; ENSP00000354566; ENSG00000198851.

GeneID

916.

KEGG

hsa:916.

UCSC

uc001psq.4. human.

Organism-specific databases

CTD

916.

GeneCards

GC11P118209.

HGNC

HGNC:1674. CD3E.

HPA

CAB000010.

MIM

186830. gene+phenotype.

neXtProt

NX_P07766.

Orphanet

169160. Severe combined immunodeficiency T- B+ due to CD3delta/CD3epsilon/CD3zeta.

PharmGKB

PA26216.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG78872.

HOGENOM

HOG000290664.

HOVERGEN

HBG102121.

InParanoid

P07766.

KO

K06451.

OMA

IVDICIT.

OrthoDB

EOG4SF97J.

PhylomeDB

P07766.

Enzyme and pathway databases

Pathway_Interaction_DB

cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
il12_stat4pathway. IL12 signaling mediated by STAT4.
il12_2pathway. IL12-mediated signaling events.
il23pathway. IL23-mediated signaling events.
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.

Reactome

REACT_6900. Immune System.

SignaLink

P07766.

Gene expression databases

ArrayExpress

P07766.

Bgee

P07766.

CleanEx

HS_CD3E.

Genevestigator

P07766.

GermOnline

ENSG00000198851. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 1 hit.

InterPro

IPR015477. CD3_epsilon.
IPR013783. Ig-like_fold.
IPR003598. Ig_sub2.
IPR003110. Phos_immunorcpt_sig_ITAM.
[Graphical view]

PANTHER

PTHR10506. PTHR10506. 1 hit.

Pfam

PF02189. ITAM. 1 hit.
[Graphical view]

SMART

SM00408. IGc2. 1 hit.
SM00077. ITAM. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. False negative.
PS51055. ITAM_1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL1975.

ChiTaRS

CD3E. human.

DrugBank

DB00075. Muromonab.

EvolutionaryTrace

P07766.

GenomeRNAi

916.

NextBio

3790.

SOURCE

Search...

Entry information

Entry name

CD3E_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 150 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.