ZAP70_MOUSE
ID ZAP70_MOUSE Reviewed; 618 AA.
AC P43404; P97455; Q80VV2; Q8CHJ3;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 3.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Tyrosine-protein kinase ZAP-70;
DE EC=2.7.10.2;
DE AltName: Full=70 kDa zeta-chain associated protein;
DE AltName: Full=Syk-related tyrosine kinase;
GN Name=Zap70; Synonyms=Srk, Zap-70;
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] (ISOFORM 1).
RC TISSUE=Thymus;
RX PubMed=8196616; DOI=10.1128/mcb.14.6.3729-3741.1994;
RA Gauen L.K.T., Zhu Y., Letourner F., Hu Q., Bolen J.B., Matis L.A.,
RA Klausner R.D., Shaw A.S.;
RT "Interactions of p59fyn and ZAP-70 with T-cell receptor activation motifs:
RT defining the nature of a signalling motif.";
RL Mol. Cell. Biol. 14:3729-3741(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ST CYS-464.
RC STRAIN=C57BL/6J; TISSUE=Thymocyte;
RX PubMed=9208839; DOI=10.1016/s1074-7613(00)80442-2;
RA Wiest D.L., Ashe J.M., Howcroft T.K., Lee H.-M., Kemper D.M., Negishi I.,
RA Singer D.S., Singer A., Abe R.;
RT "A spontaneously arising mutation in the DLAARN motif of murine ZAP-70
RT abrogates kinase activity and arrests thymocyte development.";
RL Immunity 6:663-671(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J; TISSUE=Thymus;
RX PubMed=14985102; DOI=10.1016/j.bbrc.2004.01.127;
RA Kuroyama H., Ikeda T., Kasai M., Yamasaki S., Tatsumi M., Utsuyama M.,
RA Saito T., Hirokawa K.;
RT "Identification of a novel isoform of ZAP-70, truncated ZAP kinase.";
RL Biochem. Biophys. Res. Commun. 315:935-941(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Ikeda T., Kuroyama H.;
RT "Mouse TZK-2.";
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Salivary gland;
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 [8]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=7630421; DOI=10.1038/376435a0;
RA Negishi I., Motoyama N., Nakayama K., Nakayama K., Senju S., Hatakeyama S.,
RA Zhang Q., Chan A.C., Loh D.Y.;
RT "Essential role for ZAP-70 in both positive and negative selection of
RT thymocytes.";
RL Nature 376:435-438(1995).
RN [9]
RP INTERACTION WITH SLA.
RX PubMed=10662792; DOI=10.1084/jem.191.3.463;
RA Sosinowski T., Pandey A., Dixit V.M., Weiss A.;
RT "Src-like adaptor protein (SLAP) is a negative regulator of T cell receptor
RT signaling.";
RL J. Exp. Med. 191:463-474(2000).
RN [10]
RP INTERACTION WITH CBLB.
RX PubMed=10646608; DOI=10.1038/35003228;
RA Bachmaier K., Krawczyk C., Kozieradzki I., Kong Y.-Y., Sasaki T.,
RA Oliveira-dos-Santos A., Mariathasan S., Bouchard D., Wakeham A., Itie A.,
RA Le J., Ohashi P.S., Sarosi I., Nishina H., Lipkowitz S., Penninger J.M.;
RT "Negative regulation of lymphocyte activation and autoimmunity by the
RT molecular adaptor Cbl-b.";
RL Nature 403:211-216(2000).
RN [11]
RP INTERACTION WITH SLA2.
RX PubMed=11891219; DOI=10.1074/jbc.m110318200;
RA Pandey A., Ibarrola N., Kratchmarova I., Fernandez M.M.,
RA Constantinescu S.N., Ohara O., Sawasdikosol S., Lodish H.F., Mann M.;
RT "A novel Src homology 2 domain-containing molecule, Src-like adapter
RT protein-2 (SLAP-2), which negatively regulates T cell receptor signaling.";
RL J. Biol. Chem. 277:19131-19138(2002).
RN [12]
RP INTERACTION WITH DEF6.
RX PubMed=12648457; DOI=10.1016/s1074-7613(03)00054-2;
RA Tanaka Y., Bi K., Kitamura R., Hong S., Altman Y., Matsumoto A., Tabata H.,
RA Lebedeva S., Bushway P.J., Altman A.;
RT "SWAP-70-like adapter of T cells, an adapter protein that regulates early
RT TCR-initiated signaling in Th2 lineage cells.";
RL Immunity 18:403-414(2003).
RN [13]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=12705855; DOI=10.1016/s1074-7613(03)00082-7;
RA Schweighoffer E., Vanes L., Mathiot A., Nakamura T., Tybulewicz V.L.;
RT "Unexpected requirement for ZAP-70 in pre-B cell development and allelic
RT exclusion.";
RL Immunity 18:523-533(2003).
RN [14]
RP INTERACTION WITH NFAM1.
RX PubMed=15143214; DOI=10.1073/pnas.0401119101;
RA Ohtsuka M., Arase H., Takeuchi A., Yamasaki S., Shiina R., Suenaga T.,
RA Sakurai D., Yokosuka T., Arase N., Iwashima M., Kitamura T., Moriya H.,
RA Saito T.;
RT "NFAM1, an immunoreceptor tyrosine-based activation motif-bearing molecule
RT that regulates B cell development and signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:8126-8131(2004).
RN [15]
RP SUBCELLULAR LOCATION, INTERACTION WITH RHOH, AND DOMAIN.
RX PubMed=17028588; DOI=10.1038/ni1396;
RA Gu Y., Chae H.-D., Siefring J.E., Jasti A.C., Hildeman D.A., Williams D.A.;
RT "RhoH GTPase recruits and activates Zap70 required for T cell receptor
RT signaling and thymocyte development.";
RL Nat. Immunol. 7:1182-1190(2006).
RN [16]
RP FUNCTION IN THYMOCYTE DEVELOPMENT.
RX PubMed=17606633; DOI=10.1084/jem.20070405;
RA Palacios E.H., Weiss A.;
RT "Distinct roles for Syk and ZAP-70 during early thymocyte development.";
RL J. Exp. Med. 204:1703-1715(2007).
RN [17]
RP FUNCTION, INTERACTION WITH OTUD7B AND UBASH3B, UBIQUITINATION, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=26903241; DOI=10.1084/jem.20151426;
RA Hu H., Wang H., Xiao Y., Jin J., Chang J.H., Zou Q., Xie X., Cheng X.,
RA Sun S.C.;
RT "Otud7b facilitates T cell activation and inflammatory responses by
RT regulating Zap70 ubiquitination.";
RL J. Exp. Med. 213:399-414(2016).
CC -!- FUNCTION: Tyrosine kinase that plays an essential role in regulation of
CC the adaptive immune response. Regulates motility, adhesion and cytokine
CC expression of mature T-cells, as well as thymocyte development.
CC Contributes also to the development and activation of primary B-
CC lymphocytes. When antigen presenting cells (APC) activate T-cell
CC receptor (TCR), a serie of phosphorylations lead to the recruitment of
CC ZAP70 to the doubly phosphorylated TCR component CD3Z through ITAM
CC motif at the plasma membrane. This recruitment serves to localization
CC to the stimulated TCR and to relieve its autoinhibited conformation.
CC Release of ZAP70 active conformation is further stabilized by
CC phosphorylation mediated by LCK. Subsequently, ZAP70 phosphorylates at
CC least 2 essential adapter proteins: LAT and LCP2. In turn, a large
CC number of signaling molecules are recruited and ultimately lead to
CC lymphokine production, T-cell proliferation and differentiation.
CC Furthermore, ZAP70 controls cytoskeleton modifications, adhesion and
CC mobility of T-lymphocytes, thus ensuring correct delivery of effectors
CC to the APC. ZAP70 is also required for TCR-CD3Z internalization and
CC degradation through interaction with the E3 ubiquitin-protein ligase
CC CBL and adapter proteins SLA and SLA2. Thus, ZAP70 regulates both T-
CC cell activation switch on and switch off by modulating TCR expression
CC at the T-cell surface. During thymocyte development, ZAP70 promotes
CC survival and cell-cycle progression of developing thymocytes before
CC positive selection (when cells are still CD4/CD8 double negative).
CC Additionally, ZAP70-dependent signaling pathway may also contribute to
CC primary B-cells formation and activation through B-cell receptor (BCR).
CC {ECO:0000269|PubMed:12705855, ECO:0000269|PubMed:14985102,
CC ECO:0000269|PubMed:17606633, ECO:0000269|PubMed:26903241,
CC ECO:0000269|PubMed:7630421}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation at Tyr-492 in the
CC activation loop.
CC -!- SUBUNIT: Interacts with CD247/CD3Z; this interaction docks ZAP70 at the
CC stimulated TCR (By similarity). Interacts with NFAM1 (PubMed:15143214).
CC Interacts with adapter protein SLA; this interaction negatively
CC regulates T-cell receptor signaling (PubMed:10662792). Interacts with
CC VAV1 (By similarity). Interacts with CBL; this interaction promotes
CC ubiquitination, internalization and subsequent degradation of
CC CD247/CD3Z (By similarity). Identified in a complex with CBL and UBE2L3
CC (By similarity). Interacts with SHB (By similarity). Interacts with
CC adapter protein SLA2; this interaction negatively regulates T-cell
CC receptor signaling (PubMed:11891219). Interacts with CBLB
CC (PubMed:10646608). Interacts (via SH2 domains) with RHOH; this
CC interaction regulates ZAP70 subcellular localization (PubMed:17028588).
CC Interacts with DEF6 (PubMed:12648457). Interacts (ubiquitinated form)
CC with OTUD7B and UBASH3B (PubMed:26903241).
CC {ECO:0000250|UniProtKB:P43403, ECO:0000269|PubMed:10646608,
CC ECO:0000269|PubMed:10662792, ECO:0000269|PubMed:11891219,
CC ECO:0000269|PubMed:12648457, ECO:0000269|PubMed:15143214,
CC ECO:0000269|PubMed:17028588, ECO:0000269|PubMed:26903241}.
CC -!- INTERACTION:
CC P43404; P24161: Cd247; NbExp=4; IntAct=EBI-3862932, EBI-7803400;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Peripheral membrane
CC protein. Note=In quiescent T-lymphocytes, ZAP70 is cytoplasmic. Upon
CC TCR activation, it is recruited at the plasma membrane by interacting
CC with CD3Z. Colocalizes together with RHOH in the immunological synapse.
CC RHOH is required for its proper localization to the cell membrane and
CC cytoskeleton fractions in the thymocytes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P43404-1; Sequence=Displayed;
CC Name=2; Synonyms=TZK;
CC IsoId=P43404-2; Sequence=VSP_031159;
CC Name=3; Synonyms=TZK-2;
CC IsoId=P43404-3; Sequence=VSP_031160, VSP_031161;
CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 2 are expressed in thymus,
CC spleen and lymph nodes. {ECO:0000269|PubMed:14985102}.
CC -!- DEVELOPMENTAL STAGE: Isoform 2 is expressed in developing thymocytes
CC from the CD44+CD25- stage up to mature T-cells. Isoform 1 is not
CC expressed in thymocytes at the CD44+CD25- or CD44+CD25+ stages.
CC {ECO:0000269|PubMed:14985102}.
CC -!- DOMAIN: Composed of 2 N-terminal SH2 domains and a C-terminal kinase
CC domain. The tandem SH2 domains bind to the doubly phosphorylated
CC tyrosine-based activation motif (ITAM) of CD247/CD3Z and the non-
CC canonical phosphorylated tyrosine-based activation motif (TAM) of RHOH
CC (By similarity). The interdomain B located between the second SH2 and
CC the kinase domain has been implicated in binding to other signaling
CC molecules including CBL or VAV1. Thus, ZAP70 can also function as a
CC scaffold by recruiting additional factors to the stimulated TCR complex
CC (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated on tyrosine residues upon T-cell antigen receptor
CC (TCR) stimulation. Phosphorylation of Tyr-314 and Tyr-314 are essential
CC for ZAP70 positive function on T-lymphocyte activation whereas Tyr-290
CC has a negative regulatory role. Within the C-terminal kinase domain,
CC Tyr-491 and Tyr-492 are phosphorylated after TCR induction, Tyr-491
CC playing a negative regulatory role and Tyr-492 a positive. Tyr-492 is
CC dephosphorylated by PTN22.
CC -!- PTM: Ubiquitinated in response to T cell activation. Deubiquitinated by
CC OTUD7B. {ECO:0000269|PubMed:26903241}.
CC -!- DISRUPTION PHENOTYPE: Mice lack both CD4 and CD8 positive mature T-
CC lymphocytes. Displays a complete block in B-Cell development at the
CC pro-B cell stage in the absence of both SYK and ZAP70.
CC {ECO:0000269|PubMed:12705855, ECO:0000269|PubMed:7630421}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. SYK/ZAP-70 subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; U04379; AAA19250.1; -; mRNA.
DR EMBL; U77667; AAB36538.1; -; mRNA.
DR EMBL; AB083210; BAC43746.1; -; mRNA.
DR EMBL; AB084383; BAC67015.1; -; mRNA.
DR EMBL; AK039883; BAC30471.1; -; mRNA.
DR EMBL; AC084389; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC029727; AAH29727.1; -; mRNA.
DR CCDS; CCDS14888.1; -. [P43404-1]
DR PIR; I48914; I48914.
DR RefSeq; NP_001276541.1; NM_001289612.1. [P43404-2]
DR RefSeq; NP_001276694.1; NM_001289765.1. [P43404-1]
DR RefSeq; NP_033565.2; NM_009539.3. [P43404-1]
DR RefSeq; XP_006495959.1; XM_006495896.2. [P43404-1]
DR AlphaFoldDB; P43404; -.
DR SMR; P43404; -.
DR BioGRID; 204628; 10.
DR CORUM; P43404; -.
DR IntAct; P43404; 39.
DR MINT; P43404; -.
DR STRING; 10090.ENSMUSP00000027291; -.
DR BindingDB; P43404; -.
DR ChEMBL; CHEMBL2034801; -.
DR iPTMnet; P43404; -.
DR PhosphoSitePlus; P43404; -.
DR EPD; P43404; -.
DR jPOST; P43404; -.
DR MaxQB; P43404; -.
DR PaxDb; P43404; -.
DR PRIDE; P43404; -.
DR ProteomicsDB; 275262; -. [P43404-1]
DR ProteomicsDB; 275263; -. [P43404-2]
DR ProteomicsDB; 275264; -. [P43404-3]
DR Antibodypedia; 685; 2256 antibodies from 50 providers.
DR DNASU; 22637; -.
DR Ensembl; ENSMUST00000027291; ENSMUSP00000027291; ENSMUSG00000026117. [P43404-1]
DR GeneID; 22637; -.
DR KEGG; mmu:22637; -.
DR UCSC; uc007aqz.2; mouse. [P43404-1]
DR UCSC; uc007arb.2; mouse. [P43404-3]
DR CTD; 7535; -.
DR MGI; MGI:99613; Zap70.
DR VEuPathDB; HostDB:ENSMUSG00000026117; -.
DR eggNOG; ENOG502QT06; Eukaryota.
DR GeneTree; ENSGT00940000159185; -.
DR HOGENOM; CLU_000288_7_2_1; -.
DR InParanoid; P43404; -.
DR OMA; ACPNTSA; -.
DR OrthoDB; 796831at2759; -.
DR PhylomeDB; P43404; -.
DR TreeFam; TF351629; -.
DR BRENDA; 2.7.10.2; 3474.
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-9013407; RHOH GTPase cycle.
DR BioGRID-ORCS; 22637; 6 hits in 74 CRISPR screens.
DR ChiTaRS; Zap70; mouse.
DR PRO; PR:P43404; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; P43404; protein.
DR Bgee; ENSMUSG00000026117; Expressed in thymus and 61 other tissues.
DR ExpressionAtlas; P43404; baseline and differential.
DR Genevisible; P43404; MM.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0001772; C:immunological synapse; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0042101; C:T cell receptor complex; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IDA:MGI.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; ISO:MGI.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IPI:MGI.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:MGI.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0046632; P:alpha-beta T cell differentiation; IMP:MGI.
DR GO; GO:0043366; P:beta selection; IGI:MGI.
DR GO; GO:0019722; P:calcium-mediated signaling; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0006955; P:immune response; ISO:MGI.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; IMP:MGI.
DR GO; GO:0045060; P:negative thymic T cell selection; IMP:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0046638; P:positive regulation of alpha-beta T cell differentiation; IMP:MGI.
DR GO; GO:0046641; P:positive regulation of alpha-beta T cell proliferation; IGI:MGI.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IMP:MGI.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; IMP:MGI.
DR GO; GO:0045059; P:positive thymic T cell selection; IMP:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:0030217; P:T cell differentiation; IMP:MGI.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IMP:MGI.
DR GO; GO:0045061; P:thymic T cell selection; IMP:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd09938; SH2_N-SH2_Zap70_Syk_like; 1.
DR Gene3D; 1.10.930.10; -; 1.
DR Gene3D; 3.30.505.10; -; 2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR023420; Kinase_SYK/ZAP-70_inter-SH2_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR035838; SYK/ZAP-70_N_SH2.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR012234; Tyr_kinase_non-rcpt_SYK/ZAP70.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00017; SH2; 2.
DR PIRSF; PIRSF000604; TyrPK_SYK; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00252; SH2; 2.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF55550; SSF55550; 2.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50001; SH2; 2.
PE 1: Evidence at protein level;
KW Adaptive immunity; Alternative splicing; ATP-binding; Cell membrane;
KW Cytoplasm; Immunity; Isopeptide bond; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat; SH2 domain; Transferase;
KW Tyrosine-protein kinase; Ubl conjugation.
FT CHAIN 1..618
FT /note="Tyrosine-protein kinase ZAP-70"
FT /id="PRO_0000088169"
FT DOMAIN 10..102
FT /note="SH2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 163..254
FT /note="SH2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 337..597
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 103..162
FT /note="Interdomain A"
FT REGION 255..336
FT /note="Interdomain B"
FT REGION 270..320
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 270..286
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 460
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 343..351
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 368
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 248
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43403"
FT MOD_RES 287
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43403"
FT MOD_RES 290
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43403"
FT MOD_RES 314
FT /note="Phosphotyrosine; by LCK"
FT /evidence="ECO:0000250|UniProtKB:P43403"
FT MOD_RES 318
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43403"
FT MOD_RES 491
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43403"
FT MOD_RES 492
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43403"
FT CROSSLNK 543
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P43403"
FT VAR_SEQ 1..309
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_031160"
FT VAR_SEQ 1..306
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14985102"
FT /id="VSP_031159"
FT VAR_SEQ 310..360
FT /note="DTSVYESPYSDPEELKDKKLFLKRENLLVADIELGCGNFGSVRQGVYRMRK
FT -> MAYGRVSGVSELSRVLYVPFPPPPFLSNPGVHDTRMYTQHAMLSVASHLGR (in
FT isoform 3)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_031161"
FT VARIANT 464
FT /note="R -> C (in ST; causes an absence of mature T-cells
FT due to thymocyte development being arrested at the CD4+CD8+
FT stage)"
FT /evidence="ECO:0000269|PubMed:9208839"
FT CONFLICT 124
FT /note="R -> C (in Ref. 1; AAA19250)"
FT /evidence="ECO:0000305"
FT CONFLICT 526..529
FT /note="VTMW -> GHHV (in Ref. 4; BAC67015)"
FT /evidence="ECO:0000305"
FT CONFLICT 546
FT /note="E -> Q (in Ref. 1; AAA19250)"
FT /evidence="ECO:0000305"
FT CONFLICT 599
FT /note="L -> P (in Ref. 1; AAA19250 and 2; AAB36538)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 618 AA; 70112 MW; 9E0D18B240B28392 CRC64;
MPDPAAHLPF FYGSISRAEA EEHLKLAGMA DGLFLLRQCL RSLGGYVLSL VHDVRFHHFP
IERQLNGTYA IAGGKAHCGP AELCQFYSQD PDGLPCNLRK PCNRPPGLEP QPGVFDCLRD
AMVRDYVRQT WKLEGDALEQ AIISQAPQVE KLIATTAHER MPWYHSSLTR EEAERKLYSG
QQTDGKFLLR PRKEQGTYAL SLVYGKTVYH YLISQDKAGK YCIPEGTKFD TLWQLVEYLK
LKADGLIYRL KEVCPNSSAS AAVAAPTLPA HPSTFTQPQR RVDTLNSDGY TPEPARLASS
TDKPRPMPMD TSVYESPYSD PEELKDKKLF LKRENLLVAD IELGCGNFGS VRQGVYRMRK
KQIDVAIKVL KQGTEKADKD EMMREAQIMH QLDNPYIVRL IGVCQAEALM LVMEMAGGGP
LHKFLLGKKE EIPVSNVAEL LHQVAMGMKY LEEKNFVHRD LAARNVLLVN RHYAKISDFG
LSKALGADDS YYTARSAGKW PLKWYAPECI NFRKFSSRSD VWSYGVTMWE AFSYGQKPYK
KMKGPEVLDF IKQGKRMECP PECPPEMYAL MSDCWIYKWE DRPDFLTVEQ RMRNYYYSLA
SRAEGPPQCE QVAEAACG
