CD3E_MOUSE
ID CD3E_MOUSE Reviewed; 189 AA.
AC P22646;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=T-cell surface glycoprotein CD3 epsilon chain;
DE AltName: Full=T-cell surface antigen T3/Leu-4 epsilon chain;
DE AltName: CD_antigen=CD3e;
DE Flags: Precursor;
GN Name=Cd3e;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3478717; DOI=10.1073/pnas.84.21.7649;
RA Gold D.P., Clevers H., Alarcon B., Dunlap S., Novotny J., Williams A.F.,
RA Terhorst C.;
RT "Evolutionary relationship between the T3 chains of the T-cell receptor
RT complex and the immunoglobulin supergene family.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:7649-7653(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2973066; DOI=10.1073/pnas.85.22.8623;
RA Clevers H., Dunlap S., Saito H., Georgopoulos K., Wileman T., Terhorst C.;
RT "Characterization and expression of the murine CD3-epsilon gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:8623-8627(1988).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=9843989; DOI=10.1073/pnas.95.25.14909;
RA DeJarnette J.B., Sommers C.L., Huang K., Woodside K.J., Emmons R., Katz K.,
RA Shores E.W., Love P.E.;
RT "Specific requirement for CD3epsilon in T cell development.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:14909-14914(1998).
RN [4]
RP FUNCTION.
RX PubMed=19956738; DOI=10.1371/journal.pbio.1000253;
RA Wang Y., Becker D., Vass T., White J., Marrack P., Kappler J.W.;
RT "A conserved CXXC motif in CD3epsilon is critical for T cell development
RT and TCR signaling.";
RL PLoS Biol. 7:E1000253-E1000253(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP STRUCTURE BY NMR OF 22-100, AND DISULFIDE BONDS.
RX PubMed=11439187; DOI=10.1016/s0092-8674(01)00395-6;
RA Sun Z.J., Kim K.S., Wagner G., Reinherz E.L.;
RT "Mechanisms contributing to T cell receptor signaling and assembly revealed
RT by the solution structure of an ectodomain fragment of the CD3 epsilon
RT gamma heterodimer.";
RL Cell 105:913-923(2001).
RN [7]
RP FUNCTION, INTERACTION WITH NCK1, AND SUBCELLULAR LOCATION.
RX PubMed=24470497; DOI=10.4049/jimmunol.1203414;
RA Borroto A., Arellano I., Blanco R., Fuentes M., Orfao A., Dopfer E.P.,
RA Prouza M., Suchanek M., Schamel W.W., Alarcon B.;
RT "Relevance of Nck-CD3 epsilon interaction for T cell activation in vivo.";
RL J. Immunol. 192:2042-2053(2014).
RN [8]
RP FUNCTION.
RX PubMed=24899501; DOI=10.4049/jimmunol.1400322;
RA Bettini M.L., Guy C., Dash P., Vignali K.M., Hamm D.E., Dobbins J.,
RA Gagnon E., Thomas P.G., Wucherpfennig K.W., Vignali D.A.;
RT "Membrane association of the CD3epsilon signaling domain is required for
RT optimal T cell development and function.";
RL J. Immunol. 193:258-267(2014).
CC -!- FUNCTION: Part of the TCR-CD3 complex present on T-lymphocyte cell
CC surface that plays an essential role in adaptive immune response. When
CC antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-
CC mediated signals are transmitted across the cell membrane by the CD3
CC chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor
CC tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain.
CC Upon TCR engagement, these motifs become phosphorylated by Src family
CC protein tyrosine kinases LCK and FYN, resulting in the activation of
CC downstream signaling pathways. In addition of this role of signal
CC transduction in T-cell activation, CD3E plays an essential role in
CC correct T-cell development (PubMed:19956738, PubMed:24899501).
CC Participates also in internalization and cell surface down-regulation
CC of TCR-CD3 complexes via endocytosis sequences present in CD3E
CC cytosolic region. {ECO:0000250|UniProtKB:P07766,
CC ECO:0000269|PubMed:19956738, ECO:0000269|PubMed:24470497,
CC ECO:0000269|PubMed:24899501, ECO:0000269|PubMed:9843989}.
CC -!- SUBUNIT: The TCR-CD3 complex is composed of a CD3D/CD3E and a CD3G/CD3E
CC heterodimers that preferentially associate with TCRalpha and TCRbeta,
CC respectively, to form TCRalpha/CD3E/CD3G and TCRbeta/CD3G/CD3E trimers.
CC In turn, the hexamer interacts with CD3Z homodimer to form the TCR-CD3
CC complex. Alternatively, TCRalpha and TCRbeta can be replaced by
CC TCRgamma and TCRdelta. Interacts with CD6. Interacts with NCK1
CC (PubMed:24470497). {ECO:0000250|UniProtKB:P07766,
CC ECO:0000269|PubMed:24470497}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24470497};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P07766}.
CC -!- PTM: Phosphorylated on Tyr residues after T-cell receptor triggering by
CC LCK in association with CD4/CD8. {ECO:0000250|UniProtKB:P07766}.
CC -!- DISRUPTION PHENOTYPE: Absence of CD3E leads to the complete absence of
CC mature T-cells. Thymocyte development is arrested at the early double-
CC negative (DN) stage. {ECO:0000269|PubMed:9843989}.
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DR EMBL; J02990; AAA40296.1; -; mRNA.
DR EMBL; M23376; AAA72720.1; -; Genomic_DNA.
DR EMBL; M23370; AAA72720.1; JOINED; Genomic_DNA.
DR EMBL; M23371; AAA72720.1; JOINED; Genomic_DNA.
DR EMBL; M23372; AAA72720.1; JOINED; Genomic_DNA.
DR EMBL; M23373; AAA72720.1; JOINED; Genomic_DNA.
DR EMBL; M23374; AAA72720.1; JOINED; Genomic_DNA.
DR EMBL; M23375; AAA72720.1; JOINED; Genomic_DNA.
DR CCDS; CCDS23125.1; -.
DR PIR; A31348; A31348.
DR RefSeq; NP_031674.1; NM_007648.4.
DR RefSeq; XP_006510029.1; XM_006509966.3.
DR PDB; 1JBJ; NMR; -; A=22-100.
DR PDB; 1XMW; NMR; -; A=22-100.
DR PDB; 2K4F; NMR; -; A=134-189.
DR PDB; 3R08; X-ray; 4.10 A; E=22-100.
DR PDBsum; 1JBJ; -.
DR PDBsum; 1XMW; -.
DR PDBsum; 2K4F; -.
DR PDBsum; 3R08; -.
DR AlphaFoldDB; P22646; -.
DR SMR; P22646; -.
DR BioGRID; 198596; 6.
DR CORUM; P22646; -.
DR IntAct; P22646; 3.
DR MINT; P22646; -.
DR STRING; 10090.ENSMUSP00000099896; -.
DR iPTMnet; P22646; -.
DR PhosphoSitePlus; P22646; -.
DR SwissPalm; P22646; -.
DR EPD; P22646; -.
DR jPOST; P22646; -.
DR MaxQB; P22646; -.
DR PaxDb; P22646; -.
DR PRIDE; P22646; -.
DR ProteomicsDB; 279968; -.
DR ABCD; P22646; 2 sequenced antibodies.
DR Antibodypedia; 3494; 7099 antibodies from 58 providers.
DR DNASU; 12501; -.
DR Ensembl; ENSMUST00000102832; ENSMUSP00000099896; ENSMUSG00000032093.
DR GeneID; 12501; -.
DR KEGG; mmu:12501; -.
DR UCSC; uc009pez.1; mouse.
DR CTD; 916; -.
DR MGI; MGI:88332; Cd3e.
DR VEuPathDB; HostDB:ENSMUSG00000032093; -.
DR eggNOG; ENOG502S8KB; Eukaryota.
DR GeneTree; ENSGT00940000153312; -.
DR HOGENOM; CLU_117945_0_0_1; -.
DR InParanoid; P22646; -.
DR OMA; RVCENCV; -.
DR OrthoDB; 1362562at2759; -.
DR PhylomeDB; P22646; -.
DR TreeFam; TF335892; -.
DR Reactome; R-MMU-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR Reactome; R-MMU-202424; Downstream TCR signaling.
DR Reactome; R-MMU-202427; Phosphorylation of CD3 and TCR zeta chains.
DR Reactome; R-MMU-202430; Translocation of ZAP-70 to Immunological synapse.
DR Reactome; R-MMU-202433; Generation of second messenger molecules.
DR Reactome; R-MMU-389948; PD-1 signaling.
DR BioGRID-ORCS; 12501; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Cd3e; mouse.
DR EvolutionaryTrace; P22646; -.
DR PRO; PR:P22646; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; P22646; protein.
DR Bgee; ENSMUSG00000032093; Expressed in peripheral lymph node and 55 other tissues.
DR ExpressionAtlas; P22646; baseline and differential.
DR Genevisible; P22646; MM.
DR GO; GO:0042105; C:alpha-beta T cell receptor complex; IDA:MGI.
DR GO; GO:0044297; C:cell body; IDA:ARUK-UCL.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0043197; C:dendritic spine; IDA:ARUK-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0001772; C:immunological synapse; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0042101; C:T cell receptor complex; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0017124; F:SH3 domain binding; ISO:MGI.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IBA:GO_Central.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0097190; P:apoptotic signaling pathway; IDA:MGI.
DR GO; GO:0019722; P:calcium-mediated signaling; IDA:MGI.
DR GO; GO:0035739; P:CD4-positive, alpha-beta T cell proliferation; IDA:MGI.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IDA:MGI.
DR GO; GO:0021549; P:cerebellum development; IMP:ARUK-UCL.
DR GO; GO:0016358; P:dendrite development; IMP:ARUK-UCL.
DR GO; GO:0046649; P:lymphocyte activation; IMP:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IDA:MGI.
DR GO; GO:0045060; P:negative thymic T cell selection; IDA:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IDA:MGI.
DR GO; GO:2000563; P:positive regulation of CD4-positive, alpha-beta T cell proliferation; IDA:MGI.
DR GO; GO:0033634; P:positive regulation of cell-cell adhesion mediated by integrin; IGI:BHF-UCL.
DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; IGI:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IDA:MGI.
DR GO; GO:0032743; P:positive regulation of interleukin-2 production; IDA:MGI.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; IDA:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0050870; P:positive regulation of T cell activation; IDA:MGI.
DR GO; GO:0002669; P:positive regulation of T cell anergy; IDA:MGI.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:MGI.
DR GO; GO:0045059; P:positive thymic T cell selection; IBA:GO_Central.
DR GO; GO:0007584; P:response to nutrient; ISO:MGI.
DR GO; GO:0007224; P:smoothened signaling pathway; IDA:MGI.
DR GO; GO:0042110; P:T cell activation; IDA:MGI.
DR GO; GO:0002870; P:T cell anergy; IDA:MGI.
DR GO; GO:0031295; P:T cell costimulation; IGI:MGI.
DR GO; GO:0042098; P:T cell proliferation; IDA:MGI.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IDA:MGI.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR015484; CD3_esu/gsu/dsu.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR003110; Phos_immunorcpt_sig_ITAM.
DR PANTHER; PTHR10570; PTHR10570; 1.
DR Pfam; PF02189; ITAM; 1.
DR SMART; SM00408; IGc2; 1.
DR SMART; SM00077; ITAM; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS51055; ITAM_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Cell membrane; Disulfide bond; Immunity;
KW Immunoglobulin domain; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT CHAIN 22..189
FT /note="T-cell surface glycoprotein CD3 epsilon chain"
FT /id="PRO_0000014609"
FT TOPO_DOM 23..108
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 109..134
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 135..189
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 23..99
FT /note="Ig-like"
FT DOMAIN 160..187
FT /note="ITAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00379"
FT REGION 143..189
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 170
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P07766,
FT ECO:0000255|PROSITE-ProRule:PRU00379"
FT MOD_RES 181
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P07766,
FT ECO:0000255|PROSITE-ProRule:PRU00379"
FT DISULFID 42..83
FT /evidence="ECO:0000269|PubMed:11439187,
FT ECO:0007744|PDB:1JBJ"
FT STRAND 30..34
FT /evidence="ECO:0007829|PDB:1JBJ"
FT STRAND 37..41
FT /evidence="ECO:0007829|PDB:1JBJ"
FT STRAND 51..54
FT /evidence="ECO:0007829|PDB:1JBJ"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:1JBJ"
FT STRAND 65..71
FT /evidence="ECO:0007829|PDB:1JBJ"
FT TURN 74..76
FT /evidence="ECO:0007829|PDB:1JBJ"
FT STRAND 79..84
FT /evidence="ECO:0007829|PDB:1JBJ"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:1JBJ"
FT TURN 135..137
FT /evidence="ECO:0007829|PDB:2K4F"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:2K4F"
FT HELIX 168..170
FT /evidence="ECO:0007829|PDB:2K4F"
FT HELIX 179..182
FT /evidence="ECO:0007829|PDB:2K4F"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:2K4F"
FT TURN 186..188
FT /evidence="ECO:0007829|PDB:2K4F"
SQ SEQUENCE 189 AA; 21393 MW; 5CE92F784FA13B96 CRC64;
MRWNTFWGIL CLSLLAVGTC QDDAENIEYK VSISGTSVEL TCPLDSDENL KWEKNGQELP
QKHDKHLVLQ DFSEVEDSGY YVCYTPASNK NTYLYLKARV CEYCVEVDLT AVAIIIIVDI
CITLGLLMVI YYWSKNRKAK AKPVTRGTGA GSRPRGQNKE RPPPVPNPDY EPIRKGQRDL
YSGLNQRAV
