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 04-NOV-2026, entry version 213. 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 FUNCTION. RX PubMed=10952314; DOI=10.1038/35020093; RA Saint-Ruf C., Panigada M., Azogui O., Debey P., von Boehmer H., Grassi F.; RT "Different initiation of pre-TCR and gammadeltaTCR signalling."; RL Nature 406:524-527(2000). RN [12] 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 [13] 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 [14] 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 [15] 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 [16] 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 [17] 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 [18] 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. Also CC contributes to the development and activation of primary B-lymphocytes. CC When antigen presenting cells (APC) activate T-cell receptor (TCR), a CC serie of phosphorylations lead to the recruitment of ZAP70 to the CC phosphorylated TCR components CD3E and CD247/CD3Z through ITAM motif at CC the plasma membrane (PubMed:10952314). This recruitment serves to CC localization to the stimulated TCR and to relieve its autoinhibited CC conformation. Release of ZAP70 active conformation is further CC stabilized by phosphorylation mediated by LCK. Subsequently, ZAP70 CC phosphorylates at least 2 essential adapter proteins: LAT and LCP2. In CC turn, a large number of signaling molecules are recruited and CC ultimately lead to lymphokine production, T-cell proliferation and CC differentiation. Furthermore, ZAP70 controls cytoskeleton CC modifications, adhesion and mobility of T-lymphocytes, thus ensuring CC correct delivery of effectors to the APC. ZAP70 is also required for CC TCR-CD3Z internalization and degradation through interaction with the CC E3 ubiquitin-protein ligase CBL and adapter proteins SLA and SLA2. CC Thus, ZAP70 regulates both T-cell activation switch on and switch off CC by modulating TCR expression at the T-cell surface. During thymocyte CC development, ZAP70 promotes survival and cell-cycle progression of CC developing thymocytes before positive selection (when cells are still CC CD4/CD8 double negative). Additionally, ZAP70-dependent signaling CC pathway may also contribute to primary B-cells formation and activation CC through B-cell receptor (BCR). {ECO:0000269|PubMed:10952314, 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=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:20101, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:61978, 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}. 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; 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_001289612.2. [P43404-2] DR RefSeq; NP_001276694.1; NM_001289765.2. [P43404-1] DR RefSeq; NP_001407579.1; NM_001420650.1. [P43404-1] DR RefSeq; NP_033565.2; NM_009539.4. [P43404-1] DR AlphaFoldDB; P43404; -. DR SMR; P43404; -. DR BioGRID; 204628; 12. DR CORUM; P43404; -. DR FunCoup; P43404; 599. DR IntAct; P43404; 39. DR STRING; 10090.ENSMUSP00000027291; -. DR BindingDB; P43404; -. DR ChEMBL; CHEMBL2034801; -. DR iPTMnet; P43404; -. DR PhosphoSitePlus; P43404; -. DR jPOST; P43404; -. DR PaxDb; 10090-ENSMUSP00000027291; -. DR ProteomicsDB; 275262; -. [P43404-1] DR ProteomicsDB; 275263; -. [P43404-2] DR ProteomicsDB; 275264; -. [P43404-3] DR Antibodypedia; 685; 2538 antibodies from 54 providers. DR DNASU; 22637; -. DR Ensembl; ENSMPUT00000011408; ENSMPUP00000011220; ENSMPUG00000011312. DR Ensembl; ENSMUST00000027291.7; ENSMUSP00000027291.5; ENSMUSG00000026117.11. [P43404-1] DR GeneID; 22637; -. DR KEGG; mmu:22637; -. DR UCSC; uc007aqz.2; mouse. [P43404-1] DR UCSC; uc007arb.2; mouse. [P43404-3] DR AGR; MGI:99613; -. 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; AACPDRM; -. DR OrthoDB; 535945at2759; -. DR PhylomeDB; P43404; -. 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 79 CRISPR screens. DR PRO; PR:P43404; -. DR Proteomes; UP000000589; Chromosome 1. DR RNAct; P43404; protein. DR Bgee; ENSMUSG00000026117; Expressed in thymus and 64 other cell types or tissues. DR ExpressionAtlas; P43404; baseline and differential. 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:0001772; C:immunological synapse; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:MGI. DR GO; GO:0045121; C:membrane raft; IEA:Ensembl. 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:GO_Central. 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:0043366; P:beta selection; IGI:MGI. DR GO; GO:0006955; P:immune response; ISO: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:0043410; P:positive regulation of MAPK cascade; ISO:GO_Central. 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:0042110; P:T cell activation; ISO:GO_Central. DR GO; GO:0050852; P:T cell receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0045061; P:thymic T cell selection; IMP:MGI. DR CDD; cd05115; PTKc_Zap-70; 1. DR CDD; cd09938; SH2_N-SH2_Zap70_Syk_like; 1. DR FunFam; 1.10.930.10:FF:000001; Tyrosine-protein kinase; 1. DR FunFam; 3.30.200.20:FF:000185; Tyrosine-protein kinase; 1. DR FunFam; 3.30.505.10:FF:000031; Tyrosine-protein kinase; 1. DR FunFam; 3.30.505.10:FF:000063; Tyrosine-protein kinase; 1. DR FunFam; 1.10.510.10:FF:000216; Tyrosine-protein kinase SYK; 1. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1. DR Gene3D; 3.30.505.10; SH2 domain; 2. DR Gene3D; 1.10.930.10; Syk Kinase, Chain A, domain 2; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR023420; Kinase_SYK/ZAP-70_inter-SH2_sf. DR InterPro; IPR050198; Non-receptor_tyrosine_kinases. 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 PANTHER; PTHR24418; TYROSINE-PROTEIN KINASE; 1. 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; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF55550; SH2 domain; 2. 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 273..289 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 //