CD3Z_HUMAN
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 03-AUG-2022, entry version 224.
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;
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 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 [11]
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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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 [30]
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 [31]
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 [32]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 69-87 IN COMPLEX WITH ZAP70, AND
RP 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 [33]
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 [34]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 80-85 IN COMPLEX WITH PTPRC, AND
RP 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 [35]
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 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 (PubMed:2470098, PubMed:7509083). CD3Z
CC ITAMs phosphorylation creates multiple docking sites for the protein
CC kinase ZAP70 leading to ZAP70 phosphorylation and its conversion into a
CC catalytically active enzyme (PubMed:7509083). Plays an important role
CC in intrathymic T-cell differentiation. Additionally, participates in
CC the activity-dependent synapse formation of retinal ganglion cells
CC (RGCs) in both the retina and dorsal lateral geniculate nucleus (dLGN)
CC (By similarity). {ECO:0000250|UniProtKB:P24161,
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 CD3Z homodimer to form the TCR-CD3
CC 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 CD3Z phosphorylation
CC (PubMed:28465009). Interacts (on T cell side) with CD81, ICAM1 and CD9
CC at immunological synapses between antigen-presenting cells and T cells
CC (PubMed:23858057). Interacts with CD160 (PubMed:11978774). Interacts
CC with LY6E (By similarity). The signaling subunit of immunoglobulin
CC gamma (IgG) Fc receptor complex. As a homodimer or a heterodimer with
CC FCER1G, associates with the ligand binding subunit FCGR3A (via
CC transmembrane domain); this interaction is a prerequisite for Fc
CC receptor complex expression on the cell surface.
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: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: CD3Z is 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="http://structure.bmc.lu.se/idbase/CD247base/";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cd3z/";
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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_000734.3. [P20963-3]
DR RefSeq; NP_932170.1; NM_198053.2. [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 PDBsum; 1TCE; -.
DR PDBsum; 1YGR; -.
DR PDBsum; 2HAC; -.
DR PDBsum; 2OQ1; -.
DR PDBsum; 3IK5; -.
DR PDBsum; 3IOZ; -.
DR PDBsum; 4XZ1; -.
DR PDBsum; 6JXR; -.
DR AlphaFoldDB; P20963; -.
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; 160.
DR MINT; P20963; -.
DR STRING; 9606.ENSP00000354782; -.
DR DrugBank; DB00075; Muromonab.
DR TCDB; 8.A.128.7.1; the signaling adaptor protein karap/dap12/tyrobp (sap) family.
DR iPTMnet; P20963; -.
DR PhosphoSitePlus; P20963; -.
DR BioMuta; CD247; -.
DR DMDM; 23830999; -.
DR jPOST; P20963; -.
DR MassIVE; P20963; -.
DR MaxQB; P20963; -.
DR PaxDb; P20963; -.
DR PeptideAtlas; P20963; -.
DR PRIDE; P20963; -.
DR ProteomicsDB; 53833; -. [P20963-1]
DR ProteomicsDB; 53834; -. [P20963-3]
DR ABCD; P20963; 1 sequenced antibody.
DR Antibodypedia; 1663; 1501 antibodies from 45 providers.
DR DNASU; 919; -.
DR Ensembl; ENST00000362089.10; ENSP00000354782.5; ENSG00000198821.11. [P20963-1]
DR Ensembl; ENST00000392122.3; ENSP00000375969.3; ENSG00000198821.11. [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 GeneCards; CD247; -.
DR HGNC; HGNC:1677; CD247.
DR HPA; ENSG00000198821; Group enriched (bone marrow, lymphoid tissue).
DR MalaCards; CD247; -.
DR MIM; 186780; gene.
DR MIM; 610163; phenotype.
DR neXtProt; NX_P20963; -.
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+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta.
DR PharmGKB; PA26219; -.
DR VEuPathDB; HostDB:ENSG00000198821; -.
DR eggNOG; ENOG502S5AZ; Eukaryota.
DR GeneTree; ENSGT00390000018208; -.
DR HOGENOM; CLU_119104_0_0_1; -.
DR InParanoid; P20963; -.
DR OMA; MKWKRIA; -.
DR OrthoDB; 1389458at2759; -.
DR PhylomeDB; P20963; -.
DR TreeFam; TF330937; -.
DR PathwayCommons; 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; PD-1 signaling. [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 BioGRID-ORCS; 919; 6 hits in 1072 CRISPR screens.
DR ChiTaRS; CD247; human.
DR EvolutionaryTrace; P20963; -.
DR GeneWiki; CD247; -.
DR GenomeRNAi; 919; -.
DR Pharos; P20963; Tbio.
DR PRO; PR:P20963; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P20963; protein.
DR Bgee; ENSG00000198821; Expressed in granulocyte and 108 other tissues.
DR Genevisible; P20963; HS.
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; IC:ComplexPortal.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0004888; F:transmembrane signaling receptor activity; IC:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IC:ComplexPortal.
DR GO; GO:0046631; P:alpha-beta T cell activation; IC: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; IC:ComplexPortal.
DR GO; GO:2000010; P:positive regulation of protein localization to cell surface; IEA:Ensembl.
DR GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IBA:GO_Central.
DR DisProt; DP00200; -.
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; PTHR10035; 1.
DR Pfam; PF02189; ITAM; 3.
DR Pfam; PF11628; TCR_zetazeta; 1.
DR SMART; SM00077; ITAM; 3.
DR PROSITE; PS51055; ITAM_1; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Cell membrane;
KW Host-virus interaction; Immunity; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Signal; 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..102
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 IgG
FT Fc 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 31..54
FT /evidence="ECO:0007829|PDB:2HAC"
FT HELIX 64..73
FT /evidence="ECO:0007829|PDB:3IK5"
FT TURN 74..76
FT /evidence="ECO:0007829|PDB:3IK5"
FT HELIX 77..79
FT /evidence="ECO:0007829|PDB:2OQ1"
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
