ID CD3Z_HUMAN Reviewed; 164 AA. AC P20963; B1AK49; Q5VX13; Q8TAX4; DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot. DT 10-OCT-2002, sequence version 2. DT 04-NOV-2026, entry version 243. DE RecName: Full=T-cell surface glycoprotein CD3 zeta chain; DE AltName: Full=T-cell receptor T3 zeta chain; DE AltName: CD_antigen=CD247; DE Flags: Precursor; GN Name=CD247; Synonyms=CD3Z, T3Z, TCRZ; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RX PubMed=2974162; DOI=10.1073/pnas.85.24.9709; RA Weissman A.M., Hou D., Orloff D.G., Modi W.S., Seuanez H., O'Brien S.J., RA Klausner R.D.; RT "Molecular cloning and chromosomal localization of the human T-cell RT receptor zeta chain: distinction from the molecular CD3 complex."; RL Proc. Natl. Acad. Sci. U.S.A. 85:9709-9713(1988). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Skeletal muscle; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Pancreas; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP SUBUNIT, AND INTERACTION WITH FCGR3A. RX PubMed=2532305; DOI=10.1038/342803a0; RA Lanier L.L., Yu G., Phillips J.H.; RT "Co-association of CD3 zeta with a receptor (CD16) for IgG Fc on human RT natural killer cells."; RL Nature 342:803-805(1989). RN [8] RP FUNCTION, AND PHOSPHORYLATION BY LCK. RX PubMed=2470098; DOI=10.1073/pnas.86.9.3277; RA Barber E.K., Dasgupta J.D., Schlossman S.F., Trevillyan J.M., Rudd C.E.; RT "The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) RT that phosphorylates the CD3 complex."; RL Proc. Natl. Acad. Sci. U.S.A. 86:3277-3281(1989). RN [9] RP SUBUNIT, INTERACTION WITH FCGR3A AND FCER1G, AND MUTAGENESIS OF ASP-36. RX PubMed=1825220; DOI=10.4049/jimmunol.146.5.1571; RA Lanier L.L., Yu G., Phillips J.H.; RT "Analysis of Fc gamma RIII (CD16) membrane expression and association with RT CD3 zeta and Fc epsilon RI-gamma by site-directed mutation."; RL J. Immunol. 146:1571-1576(1991). RN [10] RP FUNCTION, AND INTERACTION WITH CD5. RX PubMed=1385158; DOI=10.1002/eji.1830221135; RA Osman N., Ley S.C., Crumpton M.J.; RT "Evidence for an association between the T cell receptor/CD3 antigen RT complex and the CD5 antigen in human T lymphocytes."; RL Eur. J. Immunol. 22:2995-3000(1992). RN [11] RP FUNCTION, AND INTERACTION WITH CD5. RX PubMed=1384049; DOI=10.1073/pnas.89.19.9311; RA Burgess K.E., Yamamoto M., Prasad K.V., Rudd C.E.; RT "CD5 acts as a tyrosine kinase substrate within a receptor complex RT comprising T-cell receptor zeta chain/CD3 and protein-tyrosine kinases RT p56lck and p59fyn."; RL Proc. Natl. Acad. Sci. U.S.A. 89:9311-9315(1992). RN [12] RP FUNCTION, AND INTERACTION WITH ZAP70. RX PubMed=7509083; DOI=10.1126/science.7509083; RA Iwashima M., Irving B.A., van Oers N.S., Chan A.C., Weiss A.; RT "Sequential interactions of the TCR with two distinct cytoplasmic tyrosine RT kinases."; RL Science 263:1136-1139(1994). RN [13] RP INTERACTION WITH HIV-2 NEF (MICROBIAL INFECTION). RX PubMed=9811718; DOI=10.1128/jvi.72.12.9827-9834.1998; RA Howe A.Y., Jung J.U., Desrosiers R.C.; RT "Zeta chain of the T-cell receptor interacts with nef of simian RT immunodeficiency virus and human immunodeficiency virus type 2."; RL J. Virol. 72:9827-9834(1998). RN [14] RP INTERACTION WITH SHB. RX PubMed=9484780; DOI=10.1038/sj.onc.1201607; RA Welsh M., Songyang Z., Frantz J.D., Trueb T., Reedquist K.A., Karlsson T., RA Miyazaki M., Cantley L.C., Band H., Shoelson S.E.; RT "Stimulation through the T cell receptor leads to interactions between SHB RT and several signaling proteins."; RL Oncogene 16:891-901(1998). RN [15] RP INTERACTION WITH HIV-1 NEF (MICROBIAL INFECTION). RX PubMed=10224289; DOI=10.1084/jem.189.9.1489; RA Xu X.-N., Laffert B., Screaton G.R., Kraft M., Wolf D., Kolanus W., RA Mongkolsapay J., McMichael A.J., Baur A.S.; RT "Induction of Fas ligand expression by HIV involves the interaction of Nef RT with the T cell receptor zeta chain."; RL J. Exp. Med. 189:1489-1496(1999). RN [16] RP INTERACTION WITH SLA. RX PubMed=10449770; DOI=10.1073/pnas.96.17.9775; RA Tang J., Sawasdikosol S., Chang J.-H., Burakoff S.J.; RT "SLAP, a dimeric adapter protein, plays a functional role in T cell RT receptor signaling."; RL Proc. Natl. Acad. Sci. U.S.A. 96:9775-9780(1999). RN [17] RP TISSUE SPECIFICITY. RX PubMed=11722641; DOI=10.1046/j.1365-2567.2001.01323.x; RA Seitzer U., Kayser K., Hoehn H., Entzian P., Wacker H.H., Ploetz S., RA Flad H.D., Gerdes J., Maeurer M.J.; RT "Reduced T-cell receptor CD3zeta-chain protein and sustained CD3epsilon RT expression at the site of mycobacterial infection."; RL Immunology 104:269-277(2001). RN [18] RP INTERACTION WITH TRAT1. RX PubMed=11390434; DOI=10.1084/jem.193.11.1269; RA Kirchgessner H., Dietrich J., Scherer J., Isomaeki P., Korinek V., RA Hilgert I., Bruyns E., Leo A., Cope A.P., Schraven B.; RT "The transmembrane adaptor protein TRIM regulates T-cell receptor (TCR) RT expression and TCR-mediated signaling via an association with the TCR zeta RT chain."; RL J. Exp. Med. 193:1269-1284(2001). RN [19] RP INTERACTION WITH DOCK2. RX PubMed=12176041; DOI=10.1016/s0006-291x(02)00931-2; RA Nishihara H., Maeda M., Tsuda M., Makino Y., Sawa H., Nagashima K., RA Tanaka S.; RT "DOCK2 mediates T cell receptor-induced activation of Rac2 and IL-2 RT transcription."; RL Biochem. Biophys. Res. Commun. 296:716-720(2002). RN [20] RP SUBUNIT, AND INTERACTION WITH CD160. RX PubMed=11978774; DOI=10.1093/intimm/14.5.445; RA Nikolova M., Marie-Cardine A., Boumsell L., Bensussan A.; RT "BY55/CD160 acts as a co-receptor in TCR signal transduction of a human RT circulating cytotoxic effector T lymphocyte subset lacking CD28 RT expression."; RL Int. Immunol. 14:445-451(2002). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-83; TYR-111 AND TYR-142, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=12522270; DOI=10.1073/pnas.2436191100; RA Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T., Ericson C., RA Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C.; RT "Profiling of tyrosine phosphorylation pathways in human cells using mass RT spectrometry."; RL Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58; TYR-64; TYR-72; TYR-111 RP AND TYR-142, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=15144186; DOI=10.1021/ac035352d; RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., RA Peters E.C.; RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from RT human T cells using immobilized metal affinity chromatography and tandem RT mass spectrometry."; RL Anal. Chem. 76:2763-2772(2004). RN [23] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SLAP1. RX PubMed=16027224; DOI=10.1083/jcb.200501164; RA Myers M.D., Dragone L.L., Weiss A.; RT "Src-like adaptor protein down-regulates T cell receptor (TCR)-CD3 RT expression by targeting TCRzeta for degradation."; RL J. Cell Biol. 170:285-294(2005). RN [24] RP INTERACTION WITH HIV-2 NEF (MICROBIAL INFECTION). RX PubMed=16051847; DOI=10.1128/jvi.79.16.10547-10560.2005; RA Munch J., Schindler M., Wildum S., Rucker E., Bailer N., Knoop V., RA Novembre F.J., Kirchhoff F.; RT "Primary sooty mangabey simian immunodeficiency virus and human RT immunodeficiency virus type 2 nef alleles modulate cell surface expression RT of various human receptors and enhance viral infectivity and replication."; RL J. Virol. 79:10547-10560(2005). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-64; TYR-72; TYR-111 AND RP TYR-142, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-64; TYR-72; TYR-111; TYR-123; RP TYR-142 AND TYR-153, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [27] RP INTERACTION WITH CD81, INTERACTION WITH ICAM1, AND INTERACTION WITH CD9. RX PubMed=23858057; DOI=10.1128/mcb.00302-13; RA Rocha-Perugini V., Zamai M., Gonzalez-Granado J.M., Barreiro O., Tejera E., RA Yanez-Mo M., Caiolfa V.R., Sanchez-Madrid F.; RT "CD81 controls sustained T cell activation signaling and defines the RT maturation stages of cognate immunological synapses."; RL Mol. Cell. Biol. 33:3644-3658(2013). RN [28] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [29] RP INTERACTION WITH ZAP70. RX PubMed=26783323; DOI=10.1084/jem.20150888; RA Chan A.Y., Punwani D., Kadlecek T.A., Cowan M.J., Olson J.L., Mathes E.F., RA Sunderam U., Fu S.M., Srinivasan R., Kuriyan J., Brenner S.E., Weiss A., RA Puck J.M.; RT "A novel human autoimmune syndrome caused by combined hypomorphic and RT activating mutations in ZAP-70."; RL J. Exp. Med. 213:155-165(2016). RN [30] RP FUNCTION, AND INTERACTION WITH CRK. RX PubMed=28465009; DOI=10.1016/j.cellsig.2017.04.022; RA Dong G., Kalifa R., Nath P.R., Babichev Y., Gelkop S., Isakov N.; RT "Crk adaptor proteins regulate CD3zeta chain phosphorylation and TCR/CD3 RT down-modulation in activated T cells."; RL Cell. Signal. 36:117-126(2017). RN [31] RP INTERACTION WITH FCGR3A. RX PubMed=28652325; DOI=10.1073/pnas.1706483114; RA Blazquez-Moreno A., Park S., Im W., Call M.J., Call M.E., Reyburn H.T.; RT "Transmembrane features governing Fc receptor CD16A assembly with CD16A RT signaling adaptor molecules."; RL Proc. Natl. Acad. Sci. U.S.A. 114:E5645-E5654(2017). RN [32] RP STRUCTURE BY NMR OF 136-149. RX PubMed=7680960; DOI=10.1016/0092-8674(93)90405-f; RA Waksman G., Shoelson S.E., Pant N., Cowburn D., Kuriyan J.; RT "Binding of a high affinity phosphotyrosyl peptide to the Src SH2 domain: RT crystal structures of the complexed and peptide-free forms."; RL Cell 72:779-790(1993). RN [33] RP INVOLVEMENT IN IMD25. RX PubMed=16672702; DOI=10.1056/nejmoa053750; RA Rieux-Laucat F., Hivroz C., Lim A., Mateo V., Pellier I., Selz F., RA Fischer A., Le Deist F.; RT "Inherited and somatic CD3zeta mutations in a patient with T-cell RT deficiency."; RL N. Engl. J. Med. 354:1913-1921(2006). RN [34] RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH ZAP70, AND INTERACTION WITH ZAP70. RX PubMed=7659156; DOI=10.1038/377032a0; RA Hatada M.H., Lu X., Laird E.R., Green J., Morgenstern J.P., Lou M., RA Marr C.S., Phillips T.B., Ram M.K., Theriault K., Zoller M.J., Karas L.K.; RT "Molecular basis for interaction of the protein tyrosine kinase ZAP-70 with RT the T-cell receptor."; RL Nature 377:32-38(1995). RN [35] RP STRUCTURE BY NMR OF 137-150 IN COMPLEX WITH SHC1, AND INTERACTION WITH RP SHC1. RX PubMed=7544002; DOI=10.1073/pnas.92.17.7784; RA Zhou M.-M., Meadows R.P., Logan T.M., Yoon H.S., Wade W.S., RA Ravichandran K.S., Burakoff S.J., Fesik S.W.; RT "Solution structure of the Shc SH2 domain complexed with a tyrosine- RT phosphorylated peptide from the T-cell receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 92:7784-7788(1995). RN [36] RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH PTPRC, AND INTERACTION WITH PTPRC. RX PubMed=15684325; DOI=10.1084/jem.20041890; RA Nam H.J., Poy F., Saito H., Frederick C.A.; RT "Structural basis for the function and regulation of the receptor protein RT tyrosine phosphatase CD45."; RL J. Exp. Med. 201:441-452(2005). RN [37] RP STRUCTURE BY NMR OF 30-60, IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION RP WITH THE T-CELL RECEPTOR, AND SUBUNIT. RX PubMed=17055436; DOI=10.1016/j.cell.2006.08.044; RA Call M.E., Schnell J.R., Xu C., Lutz R.A., Chou J.J., Wucherpfennig K.W.; RT "The structure of the zetazeta transmembrane dimer reveals features RT essential for its assembly with the T cell receptor."; RL Cell 127:355-368(2006). 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 CD247/CD3Z. All CD3 chains contain CC immunoreceptor tyrosine-based activation motifs (ITAMs) in their CC cytoplasmic domain. Upon TCR engagement, these motifs become CC phosphorylated by Src family protein tyrosine kinases LCK and FYN, CC resulting in the activation of downstream signaling pathways CC (PubMed:1384049, PubMed:1385158, PubMed:2470098, PubMed:7509083). CC CD247/CD3Z ITAMs phosphorylation creates multiple docking sites for the CC protein kinase ZAP70 leading to ZAP70 phosphorylation and its CC conversion into a catalytically active enzyme (PubMed:7509083). Plays CC an important role in intrathymic T-cell differentiation. Additionally, CC participates in the activity-dependent synapse formation of retinal CC ganglion cells (RGCs) in both the retina and dorsal lateral geniculate CC nucleus (dLGN) (By similarity). {ECO:0000250|UniProtKB:P24161, CC ECO:0000269|PubMed:1384049, ECO:0000269|PubMed:1385158, CC ECO:0000269|PubMed:16027224, ECO:0000269|PubMed:2470098, CC ECO:0000269|PubMed:28465009, ECO:0000269|PubMed:7509083}. 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 CD247/CD3Z homodimer to form the CC TCR-CD3 complex. Alternatively, TCRalpha and TCRbeta can be replaced by CC TCRgamma and TCRdelta (PubMed:17055436). Interacts with SLA CC (PubMed:10449770). Interacts with TRAT1 (PubMed:11390434). Interacts CC with DOCK2 (PubMed:12176041). Interacts with SLA2. Interacts with SHB CC (PubMed:9484780). Interacts with ZAP70 (PubMed:26783323, CC PubMed:7659156). Interacts (tyrosine phosphorylated) with SHC1 (via SH2 CC domain) (PubMed:7544002). Interacts with PTPRC (PubMed:15684325). CC Interacts with CRK; this interaction regulates CD247/CD3Z CC phosphorylation (PubMed:28465009). Interacts (on T cell side) with CC CD81, ICAM1 and CD9 at immunological synapses between antigen- CC presenting cells and T cells (PubMed:23858057). Interacts with CD160 CC (PubMed:11978774). Interacts with LY6E (By similarity). The signaling CC subunit of immunoglobulin gamma (IgG) Fc receptor complex. As a CC homodimer or a heterodimer with FCER1G, associates with the ligand CC binding subunit FCGR3A (via transmembrane domain); this interaction is CC a prerequisite for Fc receptor complex expression on the cell surface. CC Interacts with CD5 (PubMed:1384049, PubMed:1385158). CC {ECO:0000250|UniProtKB:P24161, ECO:0000269|PubMed:10449770, CC ECO:0000269|PubMed:11390434, ECO:0000269|PubMed:11978774, CC ECO:0000269|PubMed:12176041, ECO:0000269|PubMed:1384049, CC ECO:0000269|PubMed:1385158, ECO:0000269|PubMed:15684325, CC ECO:0000269|PubMed:17055436, ECO:0000269|PubMed:1825220, CC ECO:0000269|PubMed:23858057, ECO:0000269|PubMed:2532305, CC ECO:0000269|PubMed:26783323, ECO:0000269|PubMed:28465009, CC ECO:0000269|PubMed:28652325, ECO:0000269|PubMed:7544002, CC ECO:0000269|PubMed:7659156, ECO:0000269|PubMed:9484780}. CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 Nef; this CC interaction up-regulates the expression of the Fas ligand (FASLG) at CC the cell surface. {ECO:0000269|PubMed:10224289}. CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-2 Nef protein; this CC interaction induces down-regulation of cell surface TCR-CD3 complexes. CC {ECO:0000269|PubMed:16051847, ECO:0000269|PubMed:9811718}. CC -!- INTERACTION: CC P20963; P49407: ARRB1; NbExp=9; IntAct=EBI-1165705, EBI-743313; CC P20963; Q99700-5: ATXN2; NbExp=3; IntAct=EBI-1165705, EBI-25891409; CC P20963; P20963: CD247; NbExp=6; IntAct=EBI-1165705, EBI-1165705; CC P20963; P16333: NCK1; NbExp=2; IntAct=EBI-1165705, EBI-389883; CC P20963; Q9Y2R2: PTPN22; NbExp=4; IntAct=EBI-1165705, EBI-1211241; CC P20963; O60880: SH2D1A; NbExp=5; IntAct=EBI-1165705, EBI-6983382; CC P20963; P43403: ZAP70; NbExp=23; IntAct=EBI-1165705, EBI-1211276; CC P20963; P47774: Ccr7; Xeno; NbExp=2; IntAct=EBI-1165705, EBI-8038963; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P24161}; CC Single-pass type I membrane protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=CD-3-zeta; CC IsoId=P20963-1; Sequence=Displayed; CC Name=2; Synonyms=CD-3-eta; CC IsoId=P20963-2; Sequence=Not described; CC Name=3; CC IsoId=P20963-3; Sequence=VSP_036459; CC -!- TISSUE SPECIFICITY: Expressed in normal lymphoid tissue and in CC peripheral blood mononuclear cells (PBMCs) (PubMed:11722641). CC {ECO:0000269|PubMed:11722641}. CC -!- DOMAIN: The ITAM domains mediate interaction with SHB. CC -!- PTM: Phosphorylated on Tyr residues after T-cell receptor triggering by CC LCK in association with CD4/CD8. {ECO:0000269|PubMed:2470098}. CC -!- DISEASE: Immunodeficiency 25 (IMD25) [MIM:610163]: An immunological CC deficiency characterized by T-cells impaired immune response to CC alloantigens, tetanus toxoid and mitogens. CC {ECO:0000269|PubMed:16672702}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the CD3Z/FCER1G family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=CD247base; Note=CD247 mutation db; CC URL="https://databases.lovd.nl/shared/genes/CD247"; 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; J04132; AAA60394.1; -; mRNA. DR EMBL; AK313946; BAG36664.1; -; mRNA. DR EMBL; DQ072717; AAY57330.1; -; Genomic_DNA. DR EMBL; AL031733; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL359962; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471067; EAW90792.1; -; Genomic_DNA. DR EMBL; BC025703; AAH25703.1; -; mRNA. DR CCDS; CCDS1260.1; -. [P20963-3] DR CCDS; CCDS1261.1; -. [P20963-1] DR PIR; A31768; A31768. DR RefSeq; NP_000725.1; NM_000734.4. [P20963-3] DR RefSeq; NP_932170.1; NM_198053.3. [P20963-1] DR PDB; 1TCE; NMR; -; B=137-150. DR PDB; 1YGR; X-ray; 2.90 A; C/D=80-85. DR PDB; 2HAC; NMR; -; A/B=28-60. DR PDB; 2OQ1; X-ray; 1.90 A; B=69-87. DR PDB; 3IK5; X-ray; 2.05 A; B/D=63-80. DR PDB; 3IOZ; X-ray; 3.70 A; B=51-93. DR PDB; 4XZ1; X-ray; 2.80 A; B=69-87. DR PDB; 6JXR; EM; 3.70 A; a/b=1-164. DR PDB; 7FJD; EM; 3.20 A; a/b=1-164. DR PDB; 7FJE; EM; 3.00 A; a/b=1-164. DR PDB; 7FJF; EM; 3.10 A; a/b=1-164. DR PDB; 7PHR; EM; 3.08 A; Z/z=22-57. DR PDB; 8ES7; EM; 3.04 A; Y/Z=1-164. DR PDB; 8ES8; EM; 2.65 A; Y/Z=1-164. DR PDB; 8ES9; EM; 3.25 A; Y/Z=1-164. DR PDB; 8J8I; NMR; -; A=25-164. DR PDB; 8JC0; EM; 3.40 A; a/b=1-164. DR PDB; 8JCB; EM; 9.50 A; A/B/a/b=1-164. DR PDB; 8TW4; EM; 3.30 A; X/Y=1-164. DR PDB; 8TW6; EM; 3.10 A; X/Y=1-164. DR PDB; 8WXE; EM; 4.00 A; a/b=1-164. DR PDB; 8WY0; EM; 3.80 A; a/b=1-164. DR PDB; 8WYI; EM; 3.90 A; a/b=1-164. DR PDB; 8YC0; EM; 4.12 A; a/b=1-164. DR PDB; 8ZA6; EM; 3.43 A; a/b=1-164. DR PDB; 9BBC; EM; 3.30 A; X/Y=1-164. DR PDB; 9C3E; EM; 3.50 A; X/Y=1-164. DR PDB; 9CI8; EM; 3.01 A; a/b=27-57. DR PDB; 9CIA; EM; 3.39 A; a/b=27-55. DR PDB; 9CQ4; EM; 3.27 A; Y/Z=1-164. DR PDB; 9IRS; EM; 3.18 A; a/b=1-164. DR PDB; 9IRU; EM; 3.14 A; a/b=1-164. DR PDB; 9JXZ; EM; 3.31 A; a/b=1-164. DR PDB; 9JY0; EM; 3.69 A; a/b=1-164. DR PDB; 9JY1; EM; 3.08 A; A/B/a/b=1-164. DR PDB; 9JY2; EM; 3.24 A; a/b=26-56. DR PDB; 9JY3; EM; 3.35 A; A/B/a/b=26-56. DR PDB; 9JY4; EM; 3.29 A; A/B/a/b=1-164. DR BMRB; P20963; -. DR SMR; P20963; -. DR BioGRID; 107357; 37. DR ComplexPortal; CPX-6482; Alpha-beta T cell receptor complex, TRBC2 variant. DR ComplexPortal; CPX-6581; Alpha-beta T cell receptor complex, TRBC1 variant. DR ComplexPortal; CPX-6582; Gamma-delta T cell receptor complex, TRGC1 variant. DR ComplexPortal; CPX-6603; Gamma-delta T cell receptor complex, TRGC2 variant. DR CORUM; P20963; -. DR DIP; DIP-35404N; -. DR ELM; P20963; -. DR IntAct; P20963; 164. DR STRING; 9606.ENSP00000354782; -. DR NDEx; IQUERY-CP-CD247; 16 NDEx IQuery Curated Pathways. DR DrugBank; DB15395; Elranatamab. DR DrugBank; DB16371; Glofitamab. DR DrugBank; DB00075; Muromonab. DR DrugBank; DB16684; Odronextamab. DR DrugBank; DB16678; Talquetamab. DR DrugBank; DB17256; Tarlatamab. DR DrugBank; DB16655; Teclistamab. DR TCDB; 8.A.128.7.1; the signaling adaptor protein karap/dap12/tyrobp (sap-kdt) family. DR iPTMnet; P20963; -. DR PhosphoSitePlus; P20963; -. DR BioMuta; CD247; -. DR DMDM; 23830999; -. DR PaxDb; 9606-ENSP00000354782; -. DR PeptideAtlas; P20963; -. DR ProteomicsDB; 53833; -. [P20963-1] DR ProteomicsDB; 53834; -. [P20963-3] DR jPOST; P20963; -. DR MassIVE; P20963; -. DR DNASU; 919; -. DR Ensembl; ENST00000362089.10; ENSP00000354782.5; ENSG00000198821.13. [P20963-1] DR Ensembl; ENST00000392122.4; ENSP00000375969.3; ENSG00000198821.13. [P20963-3] DR GeneID; 919; -. DR KEGG; hsa:919; -. DR MANE-Select; ENST00000362089.10; ENSP00000354782.5; NM_198053.3; NP_932170.1. DR UCSC; uc001gei.5; human. [P20963-1] DR CTD; 919; -. DR DisGeNET; 919; -. DR VEuPathDB; HostDB:ENSG00000198821; -. DR GeneCards; CD247; -. DR HGNC; HGNC:1677; CD247. DR AGR; HGNC:1677; -. DR HPA; ENSG00000198821; Group enriched (bone marrow, lymphoid tissue). DR MalaCards; CD247; -. DR MIM; 186780; gene. DR MIM; 610163; phenotype. DR OpenTargets; ENSG00000198821; -. DR Orphanet; 85410; Oligoarticular juvenile idiopathic arthritis. DR Orphanet; 85408; Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis. DR Orphanet; 169160; T-B+NK+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta deficiency. DR ClinPGx; PA26219; -. DR eggNOG; ENOG502S5AZ; Eukaryota. DR GeneTree; ENSGT00390000018208; -. DR HOGENOM; CLU_119104_0_0_1; -. DR InParanoid; P20963; -. DR OMA; AADEPIY; -. DR OrthoDB; 9941225at2759; -. DR PhylomeDB; P20963; -. DR Reactome; R-HSA-164944; Nef and signal transduction. [P20963-1] DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell. [P20963-1] DR Reactome; R-HSA-202424; Downstream TCR signaling. [P20963-1] DR Reactome; R-HSA-202427; Phosphorylation of CD3 and TCR zeta chains. [P20963-1] DR Reactome; R-HSA-202430; Translocation of ZAP-70 to Immunological synapse. [P20963-1] DR Reactome; R-HSA-202433; Generation of second messenger molecules. [P20963-1] DR Reactome; R-HSA-2029481; FCGR activation. [P20963-1] DR Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation. [P20963-1] DR Reactome; R-HSA-2029485; Role of phospholipids in phagocytosis. [P20963-1] DR Reactome; R-HSA-389948; Co-inhibition by PD-1. [P20963-1] DR Reactome; R-HSA-9664323; FCGR3A-mediated IL10 synthesis. [P20963-1] DR Reactome; R-HSA-9664422; FCGR3A-mediated phagocytosis. [P20963-1] DR SignaLink; P20963; -. DR SIGNOR; P20963; -. DR ChiTaRS; CD247; human. DR EvolutionaryTrace; P20963; -. DR Agora; ENSG00000198821; -. DR GeneWiki; CD247; -. DR GenomeRNAi; 919; -. DR PRO; PR:P20963; -. DR Bgee; ENSG00000198821; Expressed in granulocyte and 109 other cell types or tissues. DR ExpressionAtlas; P20963; baseline and differential. DR IDEAL; IID00544; -. DR InterPro; IPR021663; CD3_zeta/IgE_Fc_rcpt_gamma. DR InterPro; IPR003110; Phos_immunorcpt_sig_ITAM. DR InterPro; IPR024128; T-cell_CD3_zeta. DR PANTHER; PTHR10035; T-CELL SURFACE GLYCOPROTEIN CD3 ZETA CHAIN; 1. DR PANTHER; PTHR10035:SF2; T-CELL SURFACE GLYCOPROTEIN CD3 ZETA CHAIN; 1. DR Pfam; PF02189; ITAM; 2. DR Pfam; PF11628; TCR_zetazeta; 1. DR SMART; SM00077; ITAM; 3. DR PROSITE; PS51055; ITAM_1; 3. DR DisProt; DP00200; -. DR GO; GO:0042105; C:alpha-beta T cell receptor complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0033001; C:Fc-gamma receptor III complex; IDA:UniProtKB. DR GO; GO:0042106; C:gamma-delta T cell receptor complex; NAS:ComplexPortal. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0042101; C:T cell receptor complex; IDA:MGI. DR GO; GO:0042802; F:identical protein binding; IDA:CAFA. DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:1990782; F:protein tyrosine kinase binding; IPI:CAFA. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:UniProtKB. DR GO; GO:0004888; F:transmembrane signaling receptor activity; IC:UniProtKB. DR GO; GO:0002250; P:adaptive immune response; NAS:ComplexPortal. DR GO; GO:0046631; P:alpha-beta T cell activation; NAS:ComplexPortal. DR GO; GO:0007166; P:cell surface receptor signaling pathway; IC:UniProtKB. DR GO; GO:0038094; P:Fc-gamma receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0046629; P:gamma-delta T cell activation; NAS:ComplexPortal. DR GO; GO:0051259; P:protein complex oligomerization; IPI:DisProt. DR GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB. DR GO; GO:0050852; P:T cell receptor signaling pathway; IDA:UniProtKB. DR Proteomes; UP000005640; Chromosome 1. DR PathwayCommons; P20963; -. DR Pharos; P20963; Tbio. DR ABCD; P20963; 81 sequenced antibodies. DR Antibodypedia; 1663; 1923 antibodies from 49 providers. DR RNAct; P20963; protein. DR BioGRID-ORCS; 919; 11 hits in 1161 CRISPR screens. DR AlphaFoldDB; P20963; -. DR EMDB; EMD-13427; -. DR EMDB; EMD-28570; -. DR EMDB; EMD-28571; -. DR EMDB; EMD-28572; -. DR EMDB; EMD-31618; -. DR EMDB; EMD-31619; -. DR EMDB; EMD-31620; -. DR EMDB; EMD-36149; -. DR EMDB; EMD-36156; -. DR EMDB; EMD-37904; -. DR EMDB; EMD-37914; -. DR EMDB; EMD-37929; -. DR EMDB; EMD-39128; -. DR EMDB; EMD-39874; -. DR EMDB; EMD-44417; -. DR EMDB; EMD-45166; -. DR EMDB; EMD-45614; -. DR EMDB; EMD-45615; -. DR EMDB; EMD-45808; -. DR EMDB; EMD-60818; -. DR EMDB; EMD-60821; -. DR EMDB; EMD-61882; -. DR EMDB; EMD-61883; -. DR EMDB; EMD-61884; -. DR EMDB; EMD-61885; -. DR EMDB; EMD-61886; -. DR EMDB; EMD-61887; -. DR EMDB; EMD-9895; -. DR FunCoup; P20963; 457. DR PAN-GO; P20963; 2 GO annotations based on evolutionary models. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; Alternative splicing; Cell membrane; KW Host-virus interaction; Immunity; Membrane; Phosphoprotein; KW Proteomics identification; Receptor; Reference proteome; Repeat; Signal; KW Transmembrane; Transmembrane helix. FT SIGNAL 1..21 FT CHAIN 22..164 FT /note="T-cell surface glycoprotein CD3 zeta chain" FT /id="PRO_0000016493" FT TOPO_DOM 22..30 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 31..51 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 52..164 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 61..89 FT /note="ITAM 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00379" FT DOMAIN 100..128 FT /note="ITAM 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00379" FT DOMAIN 131..159 FT /note="ITAM 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00379" FT REGION 83..111 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 128..154 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 83..96 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 58 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:15144186" FT MOD_RES 64 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:15144186, FT ECO:0007744|PubMed:15592455, ECO:0007744|PubMed:19690332" FT MOD_RES 72 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:15144186, FT ECO:0007744|PubMed:15592455, ECO:0007744|PubMed:19690332" FT MOD_RES 83 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:12522270" FT MOD_RES 111 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:12522270, FT ECO:0007744|PubMed:15144186, ECO:0007744|PubMed:15592455, FT ECO:0007744|PubMed:19690332" FT MOD_RES 123 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 142 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:12522270, FT ECO:0007744|PubMed:15144186, ECO:0007744|PubMed:15592455, FT ECO:0007744|PubMed:19690332" FT MOD_RES 153 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19690332" FT VAR_SEQ 101 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:2974162" FT /id="VSP_036459" FT MUTAGEN 36 FT /note="D->E,L,V: Decreases cell surface expression of IgGFc FT receptor complex." FT /evidence="ECO:0000269|PubMed:1825220" FT CONFLICT 60..61 FT /note="DA -> EP (in Ref. 1; AAA60394)" FT /evidence="ECO:0000305" FT HELIX 25..27 FT /evidence="ECO:0007829|PDB:7PHR" FT HELIX 30..55 FT /evidence="ECO:0007829|PDB:8ES8" FT STRAND 57..60 FT /evidence="ECO:0007829|PDB:8J8I" FT HELIX 72..75 FT /evidence="ECO:0007829|PDB:2OQ1" FT HELIX 77..79 FT /evidence="ECO:0007829|PDB:2OQ1" FT STRAND 83..89 FT /evidence="ECO:0007829|PDB:8J8I" FT STRAND 116..119 FT /evidence="ECO:0007829|PDB:8J8I" FT STRAND 121..124 FT /evidence="ECO:0007829|PDB:8J8I" SQ SEQUENCE 164 AA; 18696 MW; 9408260374856EE9 CRC64; MKWKALFTAA ILQAQLPITE AQSFGLLDPK LCYLLDGILF IYGVILTALF LRVKFSRSAD APAYQQGQNQ LYNELNLGRR EEYDVLDKRR GRDPEMGGKP QRRKNPQEGL YNELQKDKMA EAYSEIGMKG ERRRGKGHDG LYQGLSTATK DTYDALHMQA LPPR //