LYN_HUMAN
ID LYN_HUMAN Reviewed; 512 AA.
AC P07948; A0AVQ5;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 251.
DE RecName: Full=Tyrosine-protein kinase Lyn;
DE EC=2.7.10.2;
DE AltName: Full=Lck/Yes-related novel protein tyrosine kinase;
DE AltName: Full=V-yes-1 Yamaguchi sarcoma viral related oncogene homolog;
DE AltName: Full=p53Lyn;
DE AltName: Full=p56Lyn;
GN Name=LYN; Synonyms=JTK8;
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 1), AND TISSUE SPECIFICITY.
RX PubMed=3561390; DOI=10.1128/mcb.7.1.237-243.1987;
RA Yamanashi Y., Fukushige S., Semba K., Sukegawa J., Miyajima N.,
RA Matsubara K., Yamamoto T., Toyoshima K.;
RT "The yes-related cellular gene lyn encodes a possible tyrosine kinase
RT similar to p56lck.";
RL Mol. Cell. Biol. 7:237-243(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND ALTERNATIVE SPLICING.
RX PubMed=8125304; DOI=10.1016/0378-1119(94)90811-7;
RA Rider L.G., Raben N., Miller L., Jelsema C.;
RT "The cDNAs encoding two forms of the LYN protein tyrosine kinase are
RT expressed in rat mast cells and human myeloid cells.";
RL Gene 138:219-222(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 369-424.
RX PubMed=2247464; DOI=10.1073/pnas.87.22.8913;
RA Partanen J., Maekelae T.P., Alitalo R., Lehvaeslaiho H., Alitalo K.;
RT "Putative tyrosine kinases expressed in K-562 human leukemia cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:8913-8917(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 369-424.
RX PubMed=1510669; DOI=10.1016/s0006-291x(05)81562-1;
RA Bielke W., Ziemiecki A., Kappos L., Miescher G.C.;
RT "Expression of the B cell-associated tyrosine kinase gene Lyn in primary
RT neuroblastoma tumours and its modulation during the differentiation of
RT neuroblastoma cell lines.";
RL Biochem. Biophys. Res. Commun. 186:1403-1409(1992).
RN [6]
RP FUNCTION IN CD19 PHOSPHORYLATION, AND INTERACTION WITH CD19.
RX PubMed=7687428; DOI=10.1006/bbrc.1993.1807;
RA Roifman C.M., Ke S.;
RT "CD19 is a substrate of the antigen receptor-associated protein tyrosine
RT kinase in human B cells.";
RL Biochem. Biophys. Res. Commun. 194:222-225(1993).
RN [7]
RP CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, AND INTERACTION WITH HCLS1.
RX PubMed=7682714; DOI=10.1073/pnas.90.8.3631;
RA Yamanashi Y., Okada M., Semba T., Yamori T., Umemori H., Tsunasawa S.,
RA Toyoshima K., Kitamura D., Watanabe T., Yamamoto T.;
RT "Identification of HS1 protein as a major substrate of protein-tyrosine
RT kinase(s) upon B-cell antigen receptor-mediated signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:3631-3635(1993).
RN [8]
RP INTERACTION WITH FCGR1A, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND
RP PHOSPHORYLATION.
RX PubMed=8064233; DOI=10.1084/jem.180.3.1165;
RA Wang A.V., Scholl P.R., Geha R.S.;
RT "Physical and functional association of the high affinity immunoglobulin G
RT receptor (Fc gamma RI) with the kinases Hck and Lyn.";
RL J. Exp. Med. 180:1165-1170(1994).
RN [9]
RP PHOSPHORYLATION AT TYR-397 AND TYR-508, AND ACTIVITY REGULATION.
RX PubMed=7935444; DOI=10.1128/mcb.14.11.7306-7313.1994;
RA Hata A., Sabe H., Kurosaki T., Takata M., Hanafusa H.;
RT "Functional analysis of Csk in signal transduction through the B-cell
RT antigen receptor.";
RL Mol. Cell. Biol. 14:7306-7313(1994).
RN [10]
RP INTERACTION WITH EPSTEIN-BARR VIRUS LMP2A (MICROBIAL INFECTION).
RX PubMed=7895172; DOI=10.1016/s1074-7613(95)80040-9;
RA Miller C.L., Burkhardt A.L., Lee J.H., Stealey B., Longnecker R.,
RA Bolen J.B., Kieff E.;
RT "Integral membrane protein 2 of Epstein-Barr virus regulates reactivation
RT from latency through dominant negative effects on protein-tyrosine
RT kinases.";
RL Immunity 2:155-166(1995).
RN [11]
RP PHOSPHORYLATION AT TYR-508 BY MATK.
RC TISSUE=Platelet;
RX PubMed=9171348; DOI=10.1093/emboj/16.9.2342;
RA Hirao A., Hamaguchi I., Suda T., Yamaguchi N.;
RT "Translocation of the Csk homologous kinase (Chk/Hyl) controls activity of
RT CD36-anchored Lyn tyrosine kinase in thrombin-stimulated platelets.";
RL EMBO J. 16:2342-2351(1997).
RN [12]
RP INTERACTION WITH FCGR2B.
RX PubMed=9232445; DOI=10.1016/s0165-2478(97)00055-2;
RA Sarmay G., Koncz G., Pecht I., Gergely J.;
RT "Fc gamma receptor type IIb induced recruitment of inositol and protein
RT phosphatases to the signal transductory complex of human B-cell.";
RL Immunol. Lett. 57:159-164(1997).
RN [13]
RP INTERACTION WITH KIT, AND PHOSPHORYLATION.
RX PubMed=9341198; DOI=10.1074/jbc.272.43.27450;
RA Linnekin D., DeBerry C.S., Mou S.;
RT "Lyn associates with the juxtamembrane region of c-Kit and is activated by
RT stem cell factor in hematopoietic cell lines and normal progenitor cells.";
RL J. Biol. Chem. 272:27450-27455(1997).
RN [14]
RP FUNCTION IN DNA DAMAGE RESPONSE; APOPTOSIS AND PHOSPHORYLATION OF
RP PTPN6/SHPTP1, AND INTERACTION WITH PTPN6/SHPTP1.
RX PubMed=10574931; DOI=10.1074/jbc.274.49.34663;
RA Yoshida K., Kharbanda S., Kufe D.;
RT "Functional interaction between SHPTP1 and the Lyn tyrosine kinase in the
RT apoptotic response to DNA damage.";
RL J. Biol. Chem. 274:34663-34668(1999).
RN [15]
RP INTERACTION WITH CBLC.
RX PubMed=10362357; DOI=10.1038/sj.onc.1202753;
RA Keane M.M., Ettenberg S.A., Nau M.M., Banerjee P., Cuello M., Penninger J.,
RA Lipkowitz S.;
RT "cbl-3: a new mammalian cbl family protein.";
RL Oncogene 18:3365-3375(1999).
RN [16]
RP FUNCTION IN CD79A PHOSPHORYLATION, AND INTERACTION WITH CD79A.
RX PubMed=10748115; DOI=10.1074/jbc.m909044199;
RA Gaul B.S., Harrison M.L., Geahlen R.L., Burton R.A., Post C.B.;
RT "Substrate recognition by the Lyn protein-tyrosine kinase. NMR structure of
RT the immunoreceptor tyrosine-based activation motif signaling region of the
RT B cell antigen receptor.";
RL J. Biol. Chem. 275:16174-16182(2000).
RN [17]
RP FUNCTION IN REGULATION OF MAST CELL PROLIFERATION, AND MUTAGENESIS OF
RP LYS-275.
RX PubMed=11435302; DOI=10.1182/blood.v98.2.343;
RA O'Laughlin-Bunner B., Radosevic N., Taylor M.L., Shivakrupa R., DeBerry C.,
RA Metcalfe D.D., Zhou M., Lowell C., Linnekin D.;
RT "Lyn is required for normal stem cell factor-induced proliferation and
RT chemotaxis of primary hematopoietic cells.";
RL Blood 98:343-350(2001).
RN [18]
RP INTERACTION WITH PDE4A.
RC TISSUE=Brain;
RX PubMed=11306681; DOI=10.1124/mol.59.5.996;
RA Rena G., Begg F., Ross A., MacKenzie C., McPhee I., Campbell L., Huston E.,
RA Sullivan M., Houslay M.D.;
RT "Molecular cloning, genomic positioning, promoter identification, and
RT characterization of the novel cyclic AMP-specific phosphodiesterase
RT PDE4A10.";
RL Mol. Pharmacol. 59:996-1011(2001).
RN [19]
RP FUNCTION.
RX PubMed=10891478; DOI=10.1128/mcb.20.15.5370-5380.2000;
RA Yoshida K., Weichselbaum R., Kharbanda S., Kufe D.;
RT "Role for Lyn tyrosine kinase as a regulator of stress-activated protein
RT kinase activity in response to DNA damage.";
RL Mol. Cell. Biol. 20:5370-5380(2000).
RN [20]
RP FUNCTION IN DNA DAMAGE RESPONSE; APOPTOSIS AND PHOSPHORYLATION OF PPP1R15A,
RP INTERACTION WITH PPP1R15A, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-275.
RX PubMed=11517336; DOI=10.1073/pnas.191130798;
RA Grishin A.V., Azhipa O., Semenov I., Corey S.J.;
RT "Interaction between growth arrest-DNA damage protein 34 and Src kinase Lyn
RT negatively regulates genotoxic apoptosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:10172-10177(2001).
RN [21]
RP FUNCTION IN PHOSPHORYLATION OF KIT AND DOK1, CATALYTIC ACTIVITY, AND
RP INTERACTION WITH KIT.
RX PubMed=11825908; DOI=10.1074/jbc.m200277200;
RA Liang X., Wisniewski D., Strife A., Shivakrupa R., Clarkson B., Resh M.D.;
RT "Phosphatidylinositol 3-kinase and Src family kinases are required for
RT phosphorylation and membrane recruitment of Dok-1 in c-Kit signaling.";
RL J. Biol. Chem. 277:13732-13738(2002).
RN [22]
RP INTERACTION WITH MUC1.
RX PubMed=12750561; DOI=10.4161/cbt.2.2.282;
RA Li Y., Chen W., Ren J., Yu W.H., Li Q., Yoshida K., Kufe D.;
RT "DF3/MUC1 signaling in multiple myeloma cells is regulated by interleukin-
RT 7.";
RL Cancer Biol. Ther. 2:187-193(2003).
RN [23]
RP INTERACTION WITH UNC119.
RX PubMed=12496276; DOI=10.1074/jbc.m208261200;
RA Cen O., Gorska M.M., Stafford S.J., Sur S., Alam R.;
RT "Identification of UNC119 as a novel activator of SRC-type tyrosine
RT kinases.";
RL J. Biol. Chem. 278:8837-8845(2003).
RN [24]
RP FUNCTION IN THPO-MEDIATED CELL PROLIFERATION.
RX PubMed=14726379; DOI=10.1182/blood-2003-10-3566;
RA Lannutti B.J., Drachman J.G.;
RT "Lyn tyrosine kinase regulates thrombopoietin-induced proliferation of
RT hematopoietic cell lines and primary megakaryocytic progenitors.";
RL Blood 103:3736-3743(2004).
RN [25]
RP SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF LYS-275; ASP-346; GLU-353;
RP ASP-498 AND ASP-499.
RX PubMed=15173188; DOI=10.1083/jcb.200403011;
RA Kasahara K., Nakayama Y., Ikeda K., Fukushima Y., Matsuda D., Horimoto S.,
RA Yamaguchi N.;
RT "Trafficking of Lyn through the Golgi caveolin involves the charged
RT residues on alphaE and alphaI helices in the kinase domain.";
RL J. Cell Biol. 165:641-652(2004).
RN [26]
RP REVIEW ON ROLE IN KIT SIGNALING.
RX PubMed=16129412; DOI=10.1016/j.bbrc.2005.08.055;
RA Roskoski R. Jr.;
RT "Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor.";
RL Biochem. Biophys. Res. Commun. 337:1-13(2005).
RN [27]
RP FUNCTION IN PHOSPHORYLATION OF HCLS1.
RX PubMed=15795233; DOI=10.1074/jbc.m412634200;
RA Brunati A.M., Deana R., Folda A., Massimino M.L., Marin O., Ledro S.,
RA Pinna L.A., Donella-Deana A.;
RT "Thrombin-induced tyrosine phosphorylation of HS1 in human platelets is
RT sequentially catalyzed by Syk and Lyn tyrosine kinases and associated with
RT the cellular migration of the protein.";
RL J. Biol. Chem. 280:21029-21035(2005).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-508, AND IDENTIFICATION BY
RP 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 [29]
RP FUNCTION.
RX PubMed=16467205; DOI=10.1182/blood-2005-08-3343;
RA Nakata Y., Tomkowicz B., Gewirtz A.M., Ptasznik A.;
RT "Integrin inhibition through Lyn-dependent cross talk from CXCR4 chemokine
RT receptors in normal human CD34+ marrow cells.";
RL Blood 107:4234-4239(2006).
RN [30]
RP INTERACTION WITH ABL1.
RX PubMed=16912036; DOI=10.1074/jbc.m605902200;
RA Meyn M.A. III, Wilson M.B., Abdi F.A., Fahey N., Schiavone A.P., Wu J.,
RA Hochrein J.M., Engen J.R., Smithgall T.E.;
RT "Src family kinases phosphorylate the Bcr-Abl SH3-SH2 region and modulate
RT Bcr-Abl transforming activity.";
RL J. Biol. Chem. 281:30907-30916(2006).
RN [31]
RP INTERACTION WITH PAG1, MUTAGENESIS OF TYR-397 AND TYR-508, ACTIVITY
RP REGULATION, AND UBIQUITINATION.
RX PubMed=16920712; DOI=10.1074/jbc.m602637200;
RA Ingley E., Schneider J.R., Payne C.J., McCarthy D.J., Harder K.W.,
RA Hibbs M.L., Klinken S.P.;
RT "Csk-binding protein mediates sequential enzymatic down-regulation and
RT degradation of Lyn in erythropoietin-stimulated cells.";
RL J. Biol. Chem. 281:31920-31929(2006).
RN [32]
RP INTERACTION WITH TGFB1I1.
RX PubMed=17233630; DOI=10.1042/bj20061618;
RA Rathore V.B., Okada M., Newman P.J., Newman D.K.;
RT "Paxillin family members function as Csk-binding proteins that regulate Lyn
RT activity in human and murine platelets.";
RL Biochem. J. 403:275-281(2007).
RN [33]
RP FUNCTION IN PHOSPHORYLATION OF LPXN, AND INTERACTION WITH LPXN.
RX PubMed=17640867; DOI=10.1074/jbc.m704625200;
RA Chew V., Lam K.P.;
RT "Leupaxin negatively regulates B cell receptor signaling.";
RL J. Biol. Chem. 282:27181-27191(2007).
RN [34]
RP INTERACTION WITH TOM1L1, AND FUNCTION IN TOM1L1 PHOSPHORYLATION.
RX PubMed=17977829; DOI=10.1074/jbc.m705168200;
RA Zhang J., Suzuki K., Hitomi T., Siraganian R.P.;
RT "TOM1L1 is a Lyn substrate involved in FcepsilonRI signaling in mast
RT cells.";
RL J. Biol. Chem. 282:37669-37677(2007).
RN [35]
RP FUNCTION IN CELL PROLIFERATION AND SURVIVAL, PHOSPHORYLATION, SUBCELLULAR
RP LOCATION, AND ROLE IN DISEASE.
RX PubMed=18056483; DOI=10.1182/blood-2007-04-082099;
RA Dos Santos C., Demur C., Bardet V., Prade-Houdellier N., Payrastre B.,
RA Recher C.;
RT "A critical role for Lyn in acute myeloid leukemia.";
RL Blood 111:2269-2279(2008).
RN [36]
RP FUNCTION, PHOSPHORYLATION AT TYR-397 AND TYR-508, INTERACTION WITH PAG1 AND
RP STAT3, AND SUBCELLULAR LOCATION.
RX PubMed=18070987; DOI=10.1182/blood-2007-05-090985;
RA Tauzin S., Ding H., Khatib K., Ahmad I., Burdevet D.,
RA van Echten-Deckert G., Lindquist J.A., Schraven B., Din N.U., Borisch B.,
RA Hoessli D.C.;
RT "Oncogenic association of the Cbp/PAG adaptor protein with the Lyn tyrosine
RT kinase in human B-NHL rafts.";
RL Blood 111:2310-2320(2008).
RN [37]
RP INTERACTION WITH CBL AND BCR-ABL, FUNCTION IN PHOSPHORYLATION OF BCR-ABL,
RP AND ROLE IN DISEASE.
RX PubMed=18235045; DOI=10.1182/blood-2007-08-109330;
RA Wu J., Meng F., Lu H., Kong L., Bornmann W., Peng Z., Talpaz M.,
RA Donato N.J.;
RT "Lyn regulates BCR-ABL and Gab2 tyrosine phosphorylation and c-Cbl protein
RT stability in imatinib-resistant chronic myelogenous leukemia cells.";
RL Blood 111:3821-3829(2008).
RN [38]
RP SUBCELLULAR LOCATION, MYRISTOYLATION AT GLY-2, PALMITOYLATION AT CYS-3, AND
RP MUTAGENESIS OF GLY-2; CYS-3 AND LYS-275.
RX PubMed=18817770; DOI=10.1016/j.yexcr.2008.08.019;
RA Ikeda K., Nakayama Y., Togashi Y., Obata Y., Kuga T., Kasahara K.,
RA Fukumoto Y., Yamaguchi N.;
RT "Nuclear localization of Lyn tyrosine kinase mediated by inhibition of its
RT kinase activity.";
RL Exp. Cell Res. 314:3392-3404(2008).
RN [39]
RP FUNCTION IN ADHESION AND CELL MIGRATION.
RX PubMed=18802065; DOI=10.4049/jimmunol.181.7.4632;
RA Malik M., Chen Y.-Y., Kienzle M.F., Tomkowicz B.E., Collman R.G.,
RA Ptasznik A.;
RT "Monocyte migration and LFA-1-mediated attachment to brain microvascular
RT endothelia is regulated by SDF-1 alpha through Lyn kinase.";
RL J. Immunol. 181:4632-4637(2008).
RN [40]
RP PHOSPHORYLATION AT TYR-193 AND TYR-460, AND ROLE IN DISEASE.
RX PubMed=18577747; DOI=10.1093/jnci/djn188;
RA Wu J., Meng F., Kong L.Y., Peng Z., Ying Y., Bornmann W.G., Darnay B.G.,
RA Lamothe B., Sun H., Talpaz M., Donato N.J.;
RT "Association between imatinib-resistant BCR-ABL mutation-negative leukemia
RT and persistent activation of LYN kinase.";
RL J. Natl. Cancer Inst. 100:926-939(2008).
RN [41]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [42]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11; SER-13; TYR-473 AND
RP TYR-508, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [43]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [44]
RP INTERACTION WITH FASLG.
RX PubMed=19807924; DOI=10.1186/1471-2172-10-53;
RA Voss M., Lettau M., Janssen O.;
RT "Identification of SH3 domain interaction partners of human FasL (CD178) by
RT phage display screening.";
RL BMC Immunol. 10:53-53(2009).
RN [45]
RP INTERACTION WITH ADAM15.
RX PubMed=19718658; DOI=10.1002/jcb.22317;
RA Kleino I., Ortiz R.M., Yritys M., Huovila A.P., Saksela K.;
RT "Alternative splicing of ADAM15 regulates its interactions with cellular
RT SH3 proteins.";
RL J. Cell. Biochem. 108:877-885(2009).
RN [46]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11; SER-13; SER-228; TYR-306;
RP TYR-316; TYR-473 AND TYR-508, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [47]
RP FUNCTION IN LTR4 AND LTR6 HETERODIMERIZATION, AND INTERACTION WITH CD36.
RX PubMed=20037584; DOI=10.1038/ni.1836;
RA Stewart C.R., Stuart L.M., Wilkinson K., van Gils J.M., Deng J., Halle A.,
RA Rayner K.J., Boyer L., Zhong R., Frazier W.A., Lacy-Hulbert A.,
RA El Khoury J., Golenbock D.T., Moore K.J.;
RT "CD36 ligands promote sterile inflammation through assembly of a Toll-like
RT receptor 4 and 6 heterodimer.";
RL Nat. Immunol. 11:155-161(2010).
RN [48]
RP INTERACTION WITH NDFIP1 AND NDFIP2, AND UBIQUITINATION.
RX PubMed=20534535; DOI=10.1073/pnas.0911714107;
RA Mund T., Pelham H.R.;
RT "Regulation of PTEN/Akt and MAP kinase signaling pathways by the ubiquitin
RT ligase activators Ndfip1 and Ndfip2.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:11429-11434(2010).
RN [49]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [50]
RP INTERACTION WITH SCIMP.
RX PubMed=21930792; DOI=10.1128/mcb.05817-11;
RA Draber P., Vonkova I., Stepanek O., Hrdinka M., Kucova M., Skopcova T.,
RA Otahal P., Angelisova P., Horejsi V., Yeung M., Weiss A., Brdicka T.;
RT "SCIMP, a transmembrane adapter protein involved in major
RT histocompatibility complex class II signaling.";
RL Mol. Cell. Biol. 31:4550-4562(2011).
RN [51]
RP REVIEW.
RX PubMed=15220000; DOI=10.1016/j.molimm.2004.04.010;
RA Lowell C.A.;
RT "Src-family kinases: rheostats of immune cell signaling.";
RL Mol. Immunol. 41:631-643(2004).
RN [52]
RP REVIEW ON ROLE IN B CELLS.
RX PubMed=15489917; DOI=10.1038/sj.onc.1208075;
RA Gauld S.B., Cambier J.C.;
RT "Src-family kinases in B-cell development and signaling.";
RL Oncogene 23:8001-8006(2004).
RN [53]
RP REVIEW ON ROLE IN B CELLS.
RX PubMed=15664155; DOI=10.1016/j.immuni.2004.12.004;
RA Xu Y., Harder K.W., Huntington N.D., Hibbs M.L., Tarlinton D.M.;
RT "Lyn tyrosine kinase: accentuating the positive and the negative.";
RL Immunity 22:9-18(2005).
RN [54]
RP REVIEW ON ROLE IN GROWTH FACTOR SIGNALING.
RX PubMed=16801133; DOI=10.1080/08977190600581327;
RA Hibbs M.L., Harder K.W.;
RT "The duplicitous nature of the Lyn tyrosine kinase in growth factor
RT signaling.";
RL Growth Factors 24:137-149(2006).
RN [55]
RP REVIEW ON ROLE IN MAST CELLS.
RX PubMed=18772004; DOI=10.1016/s0065-2776(08)00403-3;
RA Rivera J., Fierro N.A., Olivera A., Suzuki R.;
RT "New insights on mast cell activation via the high affinity receptor for
RT IgE.";
RL Adv. Immunol. 98:85-120(2008).
RN [56]
RP ROLE IN MYELOID CELL FUNCTION, AND SIGNALING.
RX PubMed=19290919; DOI=10.1111/j.1600-065x.2008.00758.x;
RA Scapini P., Pereira S., Zhang H., Lowell C.A.;
RT "Multiple roles of Lyn kinase in myeloid cell signaling and function.";
RL Immunol. Rev. 228:23-40(2009).
RN [57]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11 AND SER-13, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [58]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11 AND SER-13, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [59]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11 AND SER-13, AND
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 [60]
RP MYRISTOYLATION AT GLY-2, CLEAVAGE OF INITIATOR METHIONINE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=25255805; DOI=10.1038/ncomms5919;
RA Thinon E., Serwa R.A., Broncel M., Brannigan J.A., Brassat U., Wright M.H.,
RA Heal W.P., Wilkinson A.J., Mann D.J., Tate E.W.;
RT "Global profiling of co- and post-translationally N-myristoylated proteomes
RT in human cells.";
RL Nat. Commun. 5:4919-4919(2014).
RN [61]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [62]
RP STRUCTURE BY NMR OF 61-123 IN COMPLEX WITH SAIMIRIINE HERPESVIRUS 2
RP TYROSINE KINASE INTERACTING PROTEIN (MICROBIAL INFECTION).
RX PubMed=11955060; DOI=10.1021/bi015986j;
RA Schweimer K., Hoffmann S., Bauer F., Friedrich U., Kardinal C.,
RA Feller S.M., Biesinger B., Sticht H.;
RT "Structural investigation of the binding of a herpesviral protein to the
RT SH3 domain of tyrosine kinase Lck.";
RL Biochemistry 41:5120-5130(2002).
RN [63]
RP STRUCTURE BY NMR OF 61-122, AND INTERACTION WITH HERPESVIRUS TYROSINE
RP KINASE INTERACTING PROTEIN (MICROBIAL INFECTION).
RX PubMed=16155203; DOI=10.1110/ps.051563605;
RA Bauer F., Schweimer K., Meiselbach H., Hoffmann S., Rosch P., Sticht H.;
RT "Structural characterization of Lyn-SH3 domain in complex with a
RT herpesviral protein reveals an extended recognition motif that enhances
RT binding affinity.";
RL Protein Sci. 14:2487-2498(2005).
RN [64]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 233-512 IN COMPLEX WITH
RP STAUROSPORINE.
RX PubMed=19857964; DOI=10.1016/j.bmcl.2009.10.038;
RA Miyano N., Kinoshita T., Nakai R., Kirii Y., Yokota K., Tada T.;
RT "Structural basis for the inhibitor recognition of human Lyn kinase
RT domain.";
RL Bioorg. Med. Chem. Lett. 19:6557-6560(2009).
RN [65]
RP VARIANT [LARGE SCALE ANALYSIS] TYR-385.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Non-receptor tyrosine-protein kinase that transmits signals
CC from cell surface receptors and plays an important role in the
CC regulation of innate and adaptive immune responses, hematopoiesis,
CC responses to growth factors and cytokines, integrin signaling, but also
CC responses to DNA damage and genotoxic agents. Functions primarily as
CC negative regulator, but can also function as activator, depending on
CC the context. Required for the initiation of the B-cell response, but
CC also for its down-regulation and termination. Plays an important role
CC in the regulation of B-cell differentiation, proliferation, survival
CC and apoptosis, and is important for immune self-tolerance. Acts
CC downstream of several immune receptors, including the B-cell receptor,
CC CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2 and TLR4.
CC Plays a role in the inflammatory response to bacterial
CC lipopolysaccharide. Mediates the responses to cytokines and growth
CC factors in hematopoietic progenitors, platelets, erythrocytes, and in
CC mature myeloid cells, such as dendritic cells, neutrophils and
CC eosinophils. Acts downstream of EPOR, KIT, MPL, the chemokine receptor
CC CXCR4, as well as the receptors for IL3, IL5 and CSF2. Plays an
CC important role in integrin signaling. Regulates cell proliferation,
CC survival, differentiation, migration, adhesion, degranulation, and
CC cytokine release. Down-regulates signaling pathways by phosphorylation
CC of immunoreceptor tyrosine-based inhibitory motifs (ITIM), that then
CC serve as binding sites for phosphatases, such as PTPN6/SHP-1,
CC PTPN11/SHP-2 and INPP5D/SHIP-1, that modulate signaling by
CC dephosphorylation of kinases and their substrates. Phosphorylates LIME1
CC in response to CD22 activation. Phosphorylates BTK, CBL, CD5, CD19,
CC CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B,
CC SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1,
CC PTPN11/SHP-2 and INPP5D/SHIP-1. Mediates phosphorylation of the BCR-ABL
CC fusion protein. Required for rapid phosphorylation of FER in response
CC to FCER1 activation. Mediates KIT phosphorylation. Acts as an effector
CC of EPOR (erythropoietin receptor) in controlling KIT expression and may
CC play a role in erythroid differentiation during the switch between
CC proliferation and maturation. Depending on the context, activates or
CC inhibits several signaling cascades. Regulates phosphatidylinositol 3-
CC kinase activity and AKT1 activation. Regulates activation of the MAP
CC kinase signaling cascade, including activation of MAP2K1/MEK1,
CC MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2. Mediates activation
CC of STAT5A and/or STAT5B. Phosphorylates LPXN on 'Tyr-72'. Kinase
CC activity facilitates TLR4-TLR6 heterodimerization and signal
CC initiation. Phosphorylates SCIMP on 'Tyr-107'; this enhances binding of
CC SCIMP to TLR4, promoting the phosphorylation of TLR4, and a selective
CC cytokine response to lipopolysaccharide in macrophages (By similarity).
CC Phosphorylates CLNK (By similarity). {ECO:0000250|UniProtKB:P25911,
CC ECO:0000269|PubMed:10574931, ECO:0000269|PubMed:10748115,
CC ECO:0000269|PubMed:10891478, ECO:0000269|PubMed:11435302,
CC ECO:0000269|PubMed:11517336, ECO:0000269|PubMed:11825908,
CC ECO:0000269|PubMed:14726379, ECO:0000269|PubMed:15795233,
CC ECO:0000269|PubMed:16467205, ECO:0000269|PubMed:17640867,
CC ECO:0000269|PubMed:17977829, ECO:0000269|PubMed:18056483,
CC ECO:0000269|PubMed:18070987, ECO:0000269|PubMed:18235045,
CC ECO:0000269|PubMed:18577747, ECO:0000269|PubMed:18802065,
CC ECO:0000269|PubMed:19290919, ECO:0000269|PubMed:20037584,
CC ECO:0000269|PubMed:7687428}.
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 ECO:0000269|PubMed:11517336, ECO:0000269|PubMed:11825908,
CC ECO:0000269|PubMed:7682714, ECO:0000269|PubMed:8064233};
CC -!- ACTIVITY REGULATION: Subject to autoinhibition, mediated by
CC intramolecular interactions between the SH2 domain and the C-terminal
CC phosphotyrosine. Phosphorylation at Tyr-397 is required for optimal
CC activity. Phosphorylated by CSK at Tyr-508; phosphorylation at Tyr-508
CC inhibits kinase activity. Kinase activity is modulated by
CC dephosphorylation by PTPRC/CD45. Inhibited by Dasatinib, PP2, and
CC SU6656. {ECO:0000269|PubMed:16920712, ECO:0000269|PubMed:7935444}.
CC -!- SUBUNIT: Interacts with TEC. Interacts (via SH2 domain) with FLT3
CC (tyrosine phosphorylated). Interacts with LIME1 and with CD79A upon
CC activation of the B-cell antigen receptor. Interacts with the B-cell
CC receptor complex. Interacts with phosphorylated THEMIS2. Interacts with
CC EPOR. Interacts with MS4A2/FCER1B. Interaction (via the SH2 and SH3
CC domains) with MUC1 is stimulated by IL7 and the subsequent
CC phosphorylation increases the binding between MUC1 and CTNNB1/beta-
CC catenin. Interacts with ADAM15. Interacts with NDFIP2 and more weakly
CC with NDFIP1. Interacts with FASLG. Interacts with KIT. Interacts with
CC HCLS1. Interacts with FCGR2B. Interacts with FCGR1A; the interaction
CC may be indirect. Interacts with CD19, CD22, CD79A and CD79B. Interacts
CC (via SH3 domain) with CBLC, PPP1R15A and PDE4A. Interacts with TGFB1I1.
CC Interacts (via SH3 domain) with PIK3R1, the regulatory subunit of
CC phosphatidylinositol 3-kinase; this interaction enhances
CC phosphatidylinositol 3-kinase activity. Interacts with CSF2RB, the
CC common subunit of the IL3, IL5 and CSF2 receptors. Interacts with PAG1;
CC identified in a complex with PAG1 and STAT3. Interacts with ABL1.
CC Interacts with PTPN6/SHP-1. Interacts (via SH3 domain) with SCIMP (via
CC proline-rich region) (PubMed:21930792). This interaction facilitates
CC the phosphorylation of SCIMP on 'Tyr-107', which enhances binding of
CC SCIMP to TLR4, and consequently the phosphorylation of TLR4 in response
CC to stimulation by lipopolysaccharide in macrophages (By similarity).
CC Interacts with LPXN (via LD motif 3) and the interaction is induced
CC upon B-cell antigen receptor (BCR) activation. Interacts (via SH3-
CC domain) with ANKRD54 (via ankyrin repeat region) in an activation-
CC independent status of LYN. Forms a multiprotein complex with ANKRD54
CC and HCLS1. Interacts (via SH2 and SH3 domains) with UNC119; leading to
CC LYN activation. Interacts with CD36. Interacts with LYN (By
CC similarity). Interacts with SKAP1 and FYB1; this interaction promotes
CC the phosphorylation of CLNK (By similarity).
CC {ECO:0000250|UniProtKB:P25911, ECO:0000269|PubMed:10362357,
CC ECO:0000269|PubMed:10574931, ECO:0000269|PubMed:10748115,
CC ECO:0000269|PubMed:11306681, ECO:0000269|PubMed:11517336,
CC ECO:0000269|PubMed:11825908, ECO:0000269|PubMed:12496276,
CC ECO:0000269|PubMed:12750561, ECO:0000269|PubMed:16912036,
CC ECO:0000269|PubMed:16920712, ECO:0000269|PubMed:17233630,
CC ECO:0000269|PubMed:17640867, ECO:0000269|PubMed:17977829,
CC ECO:0000269|PubMed:18070987, ECO:0000269|PubMed:18235045,
CC ECO:0000269|PubMed:19718658, ECO:0000269|PubMed:19807924,
CC ECO:0000269|PubMed:19857964, ECO:0000269|PubMed:20037584,
CC ECO:0000269|PubMed:20534535, ECO:0000269|PubMed:21930792,
CC ECO:0000269|PubMed:7682714, ECO:0000269|PubMed:7687428,
CC ECO:0000269|PubMed:8064233, ECO:0000269|PubMed:9232445,
CC ECO:0000269|PubMed:9341198}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus LMP2A.
CC {ECO:0000269|PubMed:7895172}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Herpes virus saimiri
CC tyrosine kinase interacting protein (Tip).
CC {ECO:0000269|PubMed:11955060, ECO:0000269|PubMed:16155203}.
CC -!- INTERACTION:
CC P07948; P01023: A2M; NbExp=3; IntAct=EBI-79452, EBI-640741;
CC P07948; O43184: ADAM12; NbExp=2; IntAct=EBI-79452, EBI-2625825;
CC P07948; Q13444: ADAM15; NbExp=2; IntAct=EBI-79452, EBI-77818;
CC P07948; P05067: APP; NbExp=3; IntAct=EBI-79452, EBI-77613;
CC P07948; P10275: AR; NbExp=5; IntAct=EBI-79452, EBI-608057;
CC P07948; Q8NDB2: BANK1; NbExp=3; IntAct=EBI-79452, EBI-2837677;
CC P07948; Q96GW7: BCAN; NbExp=3; IntAct=EBI-79452, EBI-2690445;
CC P07948; P20273: CD22; NbExp=2; IntAct=EBI-79452, EBI-78277;
CC P07948; P25063: CD24; NbExp=6; IntAct=EBI-79452, EBI-6267018;
CC P07948; P16671: CD36; NbExp=3; IntAct=EBI-79452, EBI-2808214;
CC P07948; P11049: CD37; NbExp=5; IntAct=EBI-79452, EBI-6139068;
CC P07948; P46527: CDKN1B; NbExp=2; IntAct=EBI-79452, EBI-519280;
CC P07948; P50570-2: DNM2; NbExp=3; IntAct=EBI-79452, EBI-10968534;
CC P07948; P00533: EGFR; NbExp=7; IntAct=EBI-79452, EBI-297353;
CC P07948; Q9BS26: ERP44; NbExp=3; IntAct=EBI-79452, EBI-541644;
CC P07948; Q13480: GAB1; NbExp=7; IntAct=EBI-79452, EBI-517684;
CC P07948; Q9HCN6: GP6; NbExp=5; IntAct=EBI-79452, EBI-515278;
CC P07948; Q9HCN6-1: GP6; NbExp=2; IntAct=EBI-79452, EBI-15816577;
CC P07948; P08238: HSP90AB1; NbExp=2; IntAct=EBI-79452, EBI-352572;
CC P07948; P05556: ITGB1; NbExp=4; IntAct=EBI-79452, EBI-703066;
CC P07948; P10721: KIT; NbExp=7; IntAct=EBI-79452, EBI-1379503;
CC P07948; Q96L34: MARK4; NbExp=3; IntAct=EBI-79452, EBI-302319;
CC P07948; P33993: MCM7; NbExp=4; IntAct=EBI-79452, EBI-355924;
CC P07948; P51608: MECP2; NbExp=3; IntAct=EBI-79452, EBI-1189067;
CC P07948; P08581: MET; NbExp=2; IntAct=EBI-79452, EBI-1039152;
CC P07948; Q9NWQ8: PAG1; NbExp=16; IntAct=EBI-79452, EBI-2828115;
CC P07948; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-79452, EBI-9090282;
CC P07948; P07602: PSAP; NbExp=3; IntAct=EBI-79452, EBI-716699;
CC P07948; P63244: RACK1; NbExp=2; IntAct=EBI-79452, EBI-296739;
CC P07948; Q6UWF3: SCIMP; NbExp=3; IntAct=EBI-79452, EBI-2872510;
CC P07948; P37840: SNCA; NbExp=3; IntAct=EBI-79452, EBI-985879;
CC P07948; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-79452, EBI-5235340;
CC P07948; P12931: SRC; NbExp=4; IntAct=EBI-79452, EBI-621482;
CC P07948; Q8R5G7: Arap3; Xeno; NbExp=2; IntAct=EBI-79452, EBI-621463;
CC P07948; Q08857: Cd36; Xeno; NbExp=2; IntAct=EBI-79452, EBI-8346984;
CC P07948; O92972; Xeno; NbExp=2; IntAct=EBI-79452, EBI-710506;
CC P07948; P22575; Xeno; NbExp=3; IntAct=EBI-79452, EBI-866709;
CC P07948; P27958; Xeno; NbExp=4; IntAct=EBI-79452, EBI-706378;
CC P07948; Q9WMX2; Xeno; NbExp=3; IntAct=EBI-79452, EBI-710918;
CC P07948-1; P00533: EGFR; NbExp=2; IntAct=EBI-6895930, EBI-297353;
CC P07948-1; P33993: MCM7; NbExp=5; IntAct=EBI-6895930, EBI-355924;
CC -!- SUBCELLULAR LOCATION: Cell membrane. Nucleus. Cytoplasm. Cytoplasm,
CC perinuclear region. Golgi apparatus. Membrane {ECO:0000305}; Lipid-
CC anchor {ECO:0000305}. Note=Accumulates in the nucleus by inhibition of
CC CRM1-mediated nuclear export. Nuclear accumulation is increased by
CC inhibition of its kinase activity. The trafficking from the Golgi
CC apparatus to the plasma membrane occurs in a kinase domain-dependent
CC but kinase activity independent manner and is mediated by exocytic
CC vesicular transport. Detected on plasma membrane lipid rafts.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=LYN A, p56lyn;
CC IsoId=P07948-1; Sequence=Displayed;
CC Name=2; Synonyms=LYN B, p53lyn;
CC IsoId=P07948-2; Sequence=VSP_005002;
CC -!- TISSUE SPECIFICITY: Detected in monocytes (at protein level). Detected
CC in placenta, and in fetal brain, lung, liver and kidney. Widely
CC expressed in a variety of organs, tissues, and cell types such as
CC epidermoid, hematopoietic, and neuronal cells. Expressed in primary
CC neuroblastoma tumors. {ECO:0000269|PubMed:3561390,
CC ECO:0000269|PubMed:8064233}.
CC -!- DOMAIN: The protein kinase domain plays an important role in its
CC localization in the cell membrane. {ECO:0000269|PubMed:15173188}.
CC -!- PTM: Ubiquitinated by CBL, leading to its degradation. Ubiquitination
CC is SH3-dependent. {ECO:0000269|PubMed:16920712,
CC ECO:0000269|PubMed:20534535}.
CC -!- PTM: Autophosphorylated. Phosphorylated on tyrosine residues in
CC response to KIT signaling. Phosphorylation at Tyr-397 is required for
CC optimal activity. Phosphorylation at Tyr-508 inhibits kinase activity.
CC Phosphorylated at Tyr-508 by CSK. Dephosphorylated by PTPRC/CD45.
CC Becomes rapidly phosphorylated upon activation of the B-cell receptor
CC and the immunoglobulin receptor FCGR1A. {ECO:0000269|PubMed:18056483,
CC ECO:0000269|PubMed:18070987, ECO:0000269|PubMed:18577747,
CC ECO:0000269|PubMed:7935444, ECO:0000269|PubMed:8064233,
CC ECO:0000269|PubMed:9171348, ECO:0000269|PubMed:9341198}.
CC -!- DISEASE: Note=Constitutively phosphorylated and activated in cells from
CC a number of chronic myelogenous leukemia (CML) and acute myeloid
CC leukemia (AML) patients. Mediates phosphorylation of the BCR-ABL fusion
CC protein. Abnormally elevated expression levels or activation of LYN
CC signaling may play a role in survival and proliferation of some types
CC of cancer cells.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. SRC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; M16038; AAA59540.1; -; mRNA.
DR EMBL; M79321; AAB50019.1; -; mRNA.
DR EMBL; BC075001; AAH75001.1; -; mRNA.
DR EMBL; BC075002; AAH75002.1; -; mRNA.
DR EMBL; BC126456; AAI26457.1; -; mRNA.
DR EMBL; BC126458; AAI26459.1; -; mRNA.
DR CCDS; CCDS47859.1; -. [P07948-2]
DR CCDS; CCDS6162.1; -. [P07948-1]
DR PIR; A26719; TVHULY.
DR RefSeq; NP_001104567.1; NM_001111097.2. [P07948-2]
DR RefSeq; NP_002341.1; NM_002350.3. [P07948-1]
DR RefSeq; XP_016868905.1; XM_017013416.1. [P07948-2]
DR PDB; 1W1F; NMR; -; A=61-123.
DR PDB; 1WA7; NMR; -; A=61-123.
DR PDB; 3A4O; X-ray; 3.00 A; X=233-512.
DR PDB; 5XY1; X-ray; 2.70 A; A=239-512.
DR PDB; 6NMW; X-ray; 1.20 A; A=63-125.
DR PDBsum; 1W1F; -.
DR PDBsum; 1WA7; -.
DR PDBsum; 3A4O; -.
DR PDBsum; 5XY1; -.
DR PDBsum; 6NMW; -.
DR AlphaFoldDB; P07948; -.
DR BMRB; P07948; -.
DR SMR; P07948; -.
DR BioGRID; 110245; 694.
DR CORUM; P07948; -.
DR DIP; DIP-1056N; -.
DR ELM; P07948; -.
DR IntAct; P07948; 141.
DR MINT; P07948; -.
DR STRING; 9606.ENSP00000428924; -.
DR BindingDB; P07948; -.
DR ChEMBL; CHEMBL3905; -.
DR DrugBank; DB03023; 1-Tert-Butyl-3-(4-Chloro-Phenyl)-1h-Pyrazolo[3,4-D]Pyrimidin-4-Ylamine.
DR DrugBank; DB06616; Bosutinib.
DR DrugBank; DB01254; Dasatinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB09079; Nintedanib.
DR DrugBank; DB08901; Ponatinib.
DR DrugCentral; P07948; -.
DR GuidetoPHARMACOLOGY; 2060; -.
DR iPTMnet; P07948; -.
DR PhosphoSitePlus; P07948; -.
DR SwissPalm; P07948; -.
DR BioMuta; LYN; -.
DR DMDM; 125480; -.
DR REPRODUCTION-2DPAGE; P07948; -.
DR CPTAC; CPTAC-2785; -.
DR EPD; P07948; -.
DR jPOST; P07948; -.
DR MassIVE; P07948; -.
DR MaxQB; P07948; -.
DR PaxDb; P07948; -.
DR PeptideAtlas; P07948; -.
DR PRIDE; P07948; -.
DR ProteomicsDB; 52045; -. [P07948-1]
DR ProteomicsDB; 52046; -. [P07948-2]
DR Antibodypedia; 51187; 924 antibodies from 45 providers.
DR DNASU; 4067; -.
DR Ensembl; ENST00000519728.6; ENSP00000428924.1; ENSG00000254087.8. [P07948-1]
DR Ensembl; ENST00000520220.6; ENSP00000428424.1; ENSG00000254087.8. [P07948-2]
DR GeneID; 4067; -.
DR KEGG; hsa:4067; -.
DR MANE-Select; ENST00000519728.6; ENSP00000428924.1; NM_002350.4; NP_002341.1.
DR UCSC; uc003xsk.5; human. [P07948-1]
DR CTD; 4067; -.
DR DisGeNET; 4067; -.
DR GeneCards; LYN; -.
DR HGNC; HGNC:6735; LYN.
DR HPA; ENSG00000254087; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 165120; gene.
DR neXtProt; NX_P07948; -.
DR OpenTargets; ENSG00000254087; -.
DR PharmGKB; PA30498; -.
DR VEuPathDB; HostDB:ENSG00000254087; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000158011; -.
DR HOGENOM; CLU_000288_7_2_1; -.
DR InParanoid; P07948; -.
DR OMA; PKAQRPW; -.
DR OrthoDB; 597979at2759; -.
DR PhylomeDB; P07948; -.
DR TreeFam; TF351634; -.
DR BRENDA; 2.7.10.2; 2681.
DR PathwayCommons; P07948; -.
DR Reactome; R-HSA-114604; GPVI-mediated activation cascade.
DR Reactome; R-HSA-1433557; Signaling by SCF-KIT.
DR Reactome; R-HSA-1433559; Regulation of KIT signaling.
DR Reactome; R-HSA-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-HSA-2029481; FCGR activation.
DR Reactome; R-HSA-210990; PECAM1 interactions.
DR Reactome; R-HSA-2454202; Fc epsilon receptor (FCERI) signaling.
DR Reactome; R-HSA-2682334; EPH-Ephrin signaling.
DR Reactome; R-HSA-2730905; Role of LAT2/NTAL/LAB on calcium mobilization.
DR Reactome; R-HSA-2871796; FCERI mediated MAPK activation.
DR Reactome; R-HSA-2871809; FCERI mediated Ca+2 mobilization.
DR Reactome; R-HSA-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-HSA-389356; CD28 co-stimulation.
DR Reactome; R-HSA-389513; CTLA4 inhibitory signaling.
DR Reactome; R-HSA-3928662; EPHB-mediated forward signaling.
DR Reactome; R-HSA-3928663; EPHA-mediated growth cone collapse.
DR Reactome; R-HSA-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-HSA-5621480; Dectin-2 family.
DR Reactome; R-HSA-5621575; CD209 (DC-SIGN) signaling.
DR Reactome; R-HSA-5690714; CD22 mediated BCR regulation.
DR Reactome; R-HSA-69231; Cyclin D associated events in G1.
DR Reactome; R-HSA-75892; Platelet Adhesion to exposed collagen.
DR Reactome; R-HSA-9006335; Signaling by Erythropoietin.
DR Reactome; R-HSA-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K).
DR Reactome; R-HSA-9027277; Erythropoietin activates Phospholipase C gamma (PLCG).
DR Reactome; R-HSA-9027283; Erythropoietin activates STAT5.
DR Reactome; R-HSA-9027284; Erythropoietin activates RAS.
DR Reactome; R-HSA-912631; Regulation of signaling by CBL.
DR Reactome; R-HSA-9664323; FCGR3A-mediated IL10 synthesis.
DR Reactome; R-HSA-9664422; FCGR3A-mediated phagocytosis.
DR Reactome; R-HSA-9670439; Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants.
DR Reactome; R-HSA-9674555; Signaling by CSF3 (G-CSF).
DR Reactome; R-HSA-9705462; Inactivation of CSF3 (G-CSF) signaling.
DR Reactome; R-HSA-982772; Growth hormone receptor signaling.
DR Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR SignaLink; P07948; -.
DR SIGNOR; P07948; -.
DR BioGRID-ORCS; 4067; 12 hits in 1120 CRISPR screens.
DR ChiTaRS; LYN; human.
DR EvolutionaryTrace; P07948; -.
DR GeneWiki; LYN; -.
DR GenomeRNAi; 4067; -.
DR Pharos; P07948; Tclin.
DR PRO; PR:P07948; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P07948; protein.
DR Bgee; ENSG00000254087; Expressed in monocyte and 187 other tissues.
DR ExpressionAtlas; P07948; baseline and differential.
DR Genevisible; P07948; HS.
DR GO; GO:0005912; C:adherens junction; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0034666; C:integrin alpha2-beta1 complex; IEA:Ensembl.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0030061; C:mitochondrial crista; IEA:Ensembl.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0099091; C:postsynaptic specialization, intracellular component; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0046875; F:ephrin receptor binding; IPI:ARUK-UCL.
DR GO; GO:0043015; F:gamma-tubulin binding; IEA:Ensembl.
DR GO; GO:0043208; F:glycosphingolipid binding; IEA:Ensembl.
DR GO; GO:0005178; F:integrin binding; IEA:Ensembl.
DR GO; GO:0016301; F:kinase activity; NAS:ARUK-UCL.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IMP:ARUK-UCL.
DR GO; GO:0051219; F:phosphoprotein binding; IEA:Ensembl.
DR GO; GO:0140031; F:phosphorylation-dependent protein binding; IPI:UniProtKB.
DR GO; GO:0005161; F:platelet-derived growth factor receptor binding; IEA:Ensembl.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0097110; F:scaffold protein binding; IPI:ARUK-UCL.
DR GO; GO:0017124; F:SH3 domain binding; IEA:Ensembl.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:BHF-UCL.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0001782; P:B cell homeostasis; ISS:UniProtKB.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0038159; P:C-X-C chemokine receptor CXCR4 signaling pathway; IMP:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; IEA:Ensembl.
DR GO; GO:0034605; P:cellular response to heat; IEA:Ensembl.
DR GO; GO:0071300; P:cellular response to retinoic acid; IMP:BHF-UCL.
DR GO; GO:0097028; P:dendritic cell differentiation; ISS:UniProtKB.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; TAS:Reactome.
DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0002774; P:Fc receptor mediated inhibitory signaling pathway; ISS:UniProtKB.
DR GO; GO:0002431; P:Fc receptor mediated stimulatory signaling pathway; ISS:UniProtKB.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0060397; P:growth hormone receptor signaling pathway via JAK-STAT; TAS:Reactome.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IMP:UniProtKB.
DR GO; GO:0002553; P:histamine secretion by mast cell; IEA:Ensembl.
DR GO; GO:0002768; P:immune response-regulating cell surface receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:Ensembl.
DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; IBA:GO_Central.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0050777; P:negative regulation of immune response; TAS:UniProtKB.
DR GO; GO:0002862; P:negative regulation of inflammatory response to antigenic stimulus; TAS:Reactome.
DR GO; GO:1902532; P:negative regulation of intracellular signal transduction; ISS:UniProtKB.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; ISS:UniProtKB.
DR GO; GO:0070667; P:negative regulation of mast cell proliferation; ISS:UniProtKB.
DR GO; GO:0002762; P:negative regulation of myeloid leukocyte differentiation; IEA:Ensembl.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0034136; P:negative regulation of toll-like receptor 2 signaling pathway; ISS:UniProtKB.
DR GO; GO:0034144; P:negative regulation of toll-like receptor 4 signaling pathway; ISS:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; IBA:GO_Central.
DR GO; GO:0014003; P:oligodendrocyte development; IEA:Ensembl.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0002576; P:platelet degranulation; ISS:UniProtKB.
DR GO; GO:1902961; P:positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process; IMP:ARUK-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:2000670; P:positive regulation of dendritic cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0060369; P:positive regulation of Fc receptor mediated stimulatory signaling pathway; IEA:Ensembl.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IEA:Ensembl.
DR GO; GO:0070668; P:positive regulation of mast cell proliferation; IMP:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:BHF-UCL.
DR GO; GO:0070447; P:positive regulation of oligodendrocyte progenitor proliferation; IEA:Ensembl.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IEA:Ensembl.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IGI:ARUK-UCL.
DR GO; GO:0070304; P:positive regulation of stress-activated protein kinase signaling cascade; IDA:UniProtKB.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0002902; P:regulation of B cell apoptotic process; IBA:GO_Central.
DR GO; GO:0050855; P:regulation of B cell receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; IMP:UniProtKB.
DR GO; GO:0001817; P:regulation of cytokine production; ISS:UniProtKB.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0045646; P:regulation of erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0033003; P:regulation of mast cell activation; ISS:UniProtKB.
DR GO; GO:0043304; P:regulation of mast cell degranulation; ISS:UniProtKB.
DR GO; GO:0090025; P:regulation of monocyte chemotaxis; IMP:UniProtKB.
DR GO; GO:0090330; P:regulation of platelet aggregation; ISS:UniProtKB.
DR GO; GO:0001932; P:regulation of protein phosphorylation; TAS:UniProtKB.
DR GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; IEA:Ensembl.
DR GO; GO:0043200; P:response to amino acid; IEA:Ensembl.
DR GO; GO:0048678; P:response to axon injury; IEA:Ensembl.
DR GO; GO:0009743; P:response to carbohydrate; IEA:Ensembl.
DR GO; GO:0009725; P:response to hormone; ISS:UniProtKB.
DR GO; GO:0032868; P:response to insulin; IEA:Ensembl.
DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0006991; P:response to sterol depletion; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; TAS:Reactome.
DR GO; GO:0031295; P:T cell costimulation; TAS:Reactome.
DR GO; GO:0002513; P:tolerance induction to self antigen; ISS:UniProtKB.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IEA:Ensembl.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IMP:UniProtKB.
DR CDD; cd10364; SH2_Src_Lyn; 1.
DR CDD; cd12004; SH3_Lyn; 1.
DR DisProt; DP02545; -.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR035852; Lyn_SH2.
DR InterPro; IPR035748; Lyn_SH3.
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; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00452; SH3DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
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; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; ATP-binding;
KW Cell membrane; Cytoplasm; Golgi apparatus; Host-virus interaction;
KW Immunity; Inflammatory response; Innate immunity; Kinase; Lipoprotein;
KW Membrane; Myristate; Nucleotide-binding; Nucleus; Palmitate;
KW Phosphoprotein; Proto-oncogene; Reference proteome; SH2 domain; SH3 domain;
KW Transferase; Tyrosine-protein kinase; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:25255805"
FT CHAIN 2..512
FT /note="Tyrosine-protein kinase Lyn"
FT /id="PRO_0000088129"
FT DOMAIN 63..123
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 129..226
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 247..501
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..62
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 23..55
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 367
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 253..261
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 275
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 193
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:18577747"
FT MOD_RES 228
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 306
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 316
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 397
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:18070987,
FT ECO:0000269|PubMed:7935444"
FT MOD_RES 460
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:18577747"
FT MOD_RES 473
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 508
FT /note="Phosphotyrosine; by autocatalysis, CSK and MATK"
FT /evidence="ECO:0000269|PubMed:18070987,
FT ECO:0000269|PubMed:7935444, ECO:0000269|PubMed:9171348,
FT ECO:0007744|PubMed:15592455, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:25255805,
FT ECO:0000305|PubMed:18817770"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:18817770"
FT VAR_SEQ 23..43
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8125304"
FT /id="VSP_005002"
FT VARIANT 385
FT /note="D -> Y (in a breast pleomorphic lobular carcinoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041737"
FT MUTAGEN 2
FT /note="G->A: Loss of localization to the cell membrane;
FT when associated with A-3."
FT /evidence="ECO:0000269|PubMed:18817770"
FT MUTAGEN 3
FT /note="C->A: Loss of localization to the cell membrane;
FT when associated with A-2."
FT /evidence="ECO:0000269|PubMed:18817770"
FT MUTAGEN 275
FT /note="K->A: Loss of activity and no effect on localization
FT to the cell membrane. Abundant localization in the nucleus;
FT when associated with A-2 and A-3."
FT /evidence="ECO:0000269|PubMed:11435302,
FT ECO:0000269|PubMed:11517336, ECO:0000269|PubMed:15173188,
FT ECO:0000269|PubMed:18817770"
FT MUTAGEN 275
FT /note="K->L,R: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:11435302,
FT ECO:0000269|PubMed:11517336, ECO:0000269|PubMed:15173188,
FT ECO:0000269|PubMed:18817770"
FT MUTAGEN 346
FT /note="D->A: Impedes the trafficking from the Golgi
FT apparatus toward the cell membrane; when associated with A-
FT 353; A-498 and A-499."
FT /evidence="ECO:0000269|PubMed:15173188"
FT MUTAGEN 353
FT /note="E->A: Impedes the trafficking from the Golgi
FT apparatus toward the cell membrane; when associated with A-
FT 346; A-498 and A-499."
FT /evidence="ECO:0000269|PubMed:15173188"
FT MUTAGEN 397
FT /note="Y->F: Strongly reduced kinase activity."
FT /evidence="ECO:0000269|PubMed:16920712"
FT MUTAGEN 498
FT /note="D->A: Impedes the trafficking from the Golgi
FT apparatus toward the cell membrane; when associated with A-
FT 346; A-353 and A-499."
FT /evidence="ECO:0000269|PubMed:15173188"
FT MUTAGEN 499
FT /note="D->A: Impedes the trafficking from the Golgi
FT apparatus toward the cell membrane; when associated with A-
FT 346; A-353 and A-498."
FT /evidence="ECO:0000269|PubMed:15173188"
FT MUTAGEN 508
FT /note="Y->F: Abolishes autoinhibition and thereby increases
FT kinase activity."
FT /evidence="ECO:0000269|PubMed:16920712"
FT STRAND 67..72
FT /evidence="ECO:0007829|PDB:6NMW"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:1W1F"
FT STRAND 89..96
FT /evidence="ECO:0007829|PDB:6NMW"
FT STRAND 99..104
FT /evidence="ECO:0007829|PDB:6NMW"
FT TURN 105..107
FT /evidence="ECO:0007829|PDB:6NMW"
FT STRAND 110..114
FT /evidence="ECO:0007829|PDB:6NMW"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:6NMW"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:6NMW"
FT HELIX 244..246
FT /evidence="ECO:0007829|PDB:5XY1"
FT STRAND 247..255
FT /evidence="ECO:0007829|PDB:5XY1"
FT STRAND 260..266
FT /evidence="ECO:0007829|PDB:5XY1"
FT TURN 267..269
FT /evidence="ECO:0007829|PDB:5XY1"
FT STRAND 270..277
FT /evidence="ECO:0007829|PDB:5XY1"
FT HELIX 284..296
FT /evidence="ECO:0007829|PDB:5XY1"
FT STRAND 305..309
FT /evidence="ECO:0007829|PDB:5XY1"
FT STRAND 311..320
FT /evidence="ECO:0007829|PDB:5XY1"
FT HELIX 327..332
FT /evidence="ECO:0007829|PDB:5XY1"
FT HELIX 334..338
FT /evidence="ECO:0007829|PDB:5XY1"
FT HELIX 341..360
FT /evidence="ECO:0007829|PDB:5XY1"
FT HELIX 370..372
FT /evidence="ECO:0007829|PDB:5XY1"
FT STRAND 373..375
FT /evidence="ECO:0007829|PDB:5XY1"
FT STRAND 381..383
FT /evidence="ECO:0007829|PDB:5XY1"
FT HELIX 407..409
FT /evidence="ECO:0007829|PDB:5XY1"
FT HELIX 412..417
FT /evidence="ECO:0007829|PDB:5XY1"
FT HELIX 422..437
FT /evidence="ECO:0007829|PDB:5XY1"
FT HELIX 449..457
FT /evidence="ECO:0007829|PDB:5XY1"
FT STRAND 466..468
FT /evidence="ECO:0007829|PDB:5XY1"
FT HELIX 470..479
FT /evidence="ECO:0007829|PDB:5XY1"
FT HELIX 484..486
FT /evidence="ECO:0007829|PDB:5XY1"
FT HELIX 490..501
FT /evidence="ECO:0007829|PDB:5XY1"
SQ SEQUENCE 512 AA; 58574 MW; 408D3D461204E378 CRC64;
MGCIKSKGKD SLSDDGVDLK TQPVRNTERT IYVRDPTSNK QQRPVPESQL LPGQRFQTKD
PEEQGDIVVA LYPYDGIHPD DLSFKKGEKM KVLEEHGEWW KAKSLLTKKE GFIPSNYVAK
LNTLETEEWF FKDITRKDAE RQLLAPGNSA GAFLIRESET LKGSFSLSVR DFDPVHGDVI
KHYKIRSLDN GGYYISPRIT FPCISDMIKH YQKQADGLCR RLEKACISPK PQKPWDKDAW
EIPRESIKLV KRLGAGQFGE VWMGYYNNST KVAVKTLKPG TMSVQAFLEE ANLMKTLQHD
KLVRLYAVVT REEPIYIITE YMAKGSLLDF LKSDEGGKVL LPKLIDFSAQ IAEGMAYIER
KNYIHRDLRA ANVLVSESLM CKIADFGLAR VIEDNEYTAR EGAKFPIKWT APEAINFGCF
TIKSDVWSFG ILLYEIVTYG KIPYPGRTNA DVMTALSQGY RMPRVENCPD ELYDIMKMCW
KEKAEERPTF DYLQSVLDDF YTATEGQYQQ QP
