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 27-MAR-2024, entry version 192. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 10090-ENSMUSP00000099896; -. DR ProteomicsDB; 279968; -. DR ABCD; P22646; 2 sequenced antibodies. DR Antibodypedia; 3494; 7805 antibodies from 59 providers. DR DNASU; 12501; -. DR Ensembl; ENSMUST00000102832.3; ENSMUSP00000099896.2; ENSMUSG00000032093.8. DR GeneID; 12501; -. DR KEGG; mmu:12501; -. DR UCSC; uc009pez.1; mouse. DR AGR; MGI:88332; -. 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; RVVLTCP; -. DR OrthoDB; 5358054at2759; -. 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 77 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 56 other cell types or tissues. DR ExpressionAtlas; P22646; baseline and differential. 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: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: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: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:0032729; P:positive regulation of type II interferon production; 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; Immunoglobulins; 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:SF9; T-CELL SURFACE GLYCOPROTEIN CD3 EPSILON CHAIN; 1. DR PANTHER; PTHR10570; T-CELL SURFACE GLYCOPROTEIN CD3 GAMMA CHAIN / DELTA CHAIN; 1. DR Pfam; PF16681; Ig_5; 1. DR Pfam; PF02189; ITAM; 1. DR SMART; SM00408; IGc2; 1. DR SMART; SM00077; ITAM; 1. DR SUPFAM; SSF48726; Immunoglobulin; 1. DR PROSITE; PS50835; IG_LIKE; 1. DR PROSITE; PS51055; ITAM_1; 1. DR Genevisible; P22646; MM. 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 //