LYN_MOUSE
ID LYN_MOUSE Reviewed; 512 AA.
AC P25911; Q62127;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 228.
DE RecName: Full=Tyrosine-protein kinase Lyn;
DE EC=2.7.10.2;
DE AltName: Full=V-yes-1 Yamaguchi sarcoma viral related oncogene homolog;
DE AltName: Full=p53Lyn;
DE AltName: Full=p56Lyn;
GN Name=Lyn;
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), AND ALTERNATIVE SPLICING.
RX PubMed=1710766; DOI=10.1128/mcb.11.7.3399-3406.1991;
RA Stanley E., Ralph S.J., McEwen S., Boulet I., Holtzman D.A., Lock P.,
RA Dunn A.R.;
RT "Alternatively spliced murine lyn mRNAs encode distinct proteins.";
RL Mol. Cell. Biol. 11:3399-3406(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), CATALYTIC ACTIVITY,
RP AUTOPHOSPHORYLATION, AND TISSUE SPECIFICITY.
RX PubMed=2017160; DOI=10.1128/mcb.11.5.2391-2398.1991;
RA Yi T., Bolen J.B., Ihle J.N.;
RT "Hematopoietic cells express two forms of lyn kinase differing by 21 amino
RT acids in the amino terminus.";
RL Mol. Cell. Biol. 11:2391-2398(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=Czech II; TISSUE=Mammary 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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 364-432.
RX PubMed=2482828; DOI=10.1016/0378-1119(89)90465-4;
RA Wilks A.F., Kurban R.R., Hovens C.M., Ralph S.J.;
RT "The application of the polymerase chain reaction to cloning members of the
RT protein tyrosine kinase family.";
RL Gene 85:67-74(1989).
RN [5]
RP INTERACTION WITH B CELL RECEPTOR, AND AUTOPHOSPHORYLATION.
RX PubMed=1702903; DOI=10.1126/science.1702903;
RA Yamanashi Y., Kakiuchi T., Mizuguchi J., Yamamoto T., Toyoshima K.;
RT "Association of B cell antigen receptor with protein tyrosine kinase Lyn.";
RL Science 251:192-194(1991).
RN [6]
RP INTERACTION WITH CD79A.
RX PubMed=8168489; DOI=10.1002/j.1460-2075.1994.tb06460.x;
RA Clark M.R., Johnson S.A., Cambier J.C.;
RT "Analysis of Ig-alpha-tyrosine kinase interaction reveals two levels of
RT binding specificity and tyrosine phosphorylated Ig-alpha stimulation of Fyn
RT activity.";
RL EMBO J. 13:1911-1919(1994).
RN [7]
RP INTERACTION WITH CD79A AND CD79B, AND FUNCTION IN PHOSPHORYLATION OF CD79A
RP AND CD79B.
RX PubMed=15335855; DOI=10.1016/0960-9822(93)90062-s;
RA Law D.A., Chan V.W., Datta S.K., DeFranco A.L.;
RT "B-cell antigen receptor motifs have redundant signalling capabilities and
RT bind the tyrosine kinases PTK72, Lyn and Fyn.";
RL Curr. Biol. 3:645-657(1993).
RN [8]
RP FUNCTION IN SYK PHOSPHORYLATION.
RX PubMed=7513017; DOI=10.1084/jem.179.5.1725;
RA Kurosaki T., Takata M., Yamanashi Y., Inazu T., Taniguchi T., Yamamoto T.,
RA Yamamura H.;
RT "Syk activation by the Src-family tyrosine kinase in the B cell receptor
RT signaling.";
RL J. Exp. Med. 179:1725-1729(1994).
RN [9]
RP INTERACTION WITH CD79A.
RX PubMed=8183901; DOI=10.1073/pnas.91.10.4268;
RA Pleiman C.M., Abrams C., Gauen L.T., Bedzyk W., Jongstra J., Shaw A.S.,
RA Cambier J.C.;
RT "Distinct p53/56lyn and p59fyn domains associate with nonphosphorylated and
RT phosphorylated Ig-alpha.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:4268-4272(1994).
RN [10]
RP FUNCTION IN PIK3R1 ACTIVATION, AND INTERACTION WITH PIK3R1.
RX PubMed=8128248; DOI=10.1126/science.8128248;
RA Pleiman C.M., Hertz W.M., Cambier J.C.;
RT "Activation of phosphatidylinositol-3' kinase by Src-family kinase SH3
RT binding to the p85 subunit.";
RL Science 263:1609-1612(1994).
RN [11]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=7585947; DOI=10.1016/0092-8674(95)90171-x;
RA Hibbs M.L., Tarlinton D.M., Armes J., Grail D., Hodgson G., Maglitto R.,
RA Stacker S.A., Dunn A.R.;
RT "Multiple defects in the immune system of Lyn-deficient mice, culminating
RT in autoimmune disease.";
RL Cell 83:301-311(1995).
RN [12]
RP DISRUPTION PHENOTYPE, AND FUNCTION IN B CELLS AND IN PHOSPHORYLATION OF CBL
RP AND HCLS1.
RX PubMed=7584145; DOI=10.1016/1074-7613(95)90126-4;
RA Nishizumi H., Taniuchi I., Yamanashi Y., Kitamura D., Ilic D., Mori S.,
RA Watanabe T., Yamamoto T.;
RT "Impaired proliferation of peripheral B cells and indication of autoimmune
RT disease in lyn-deficient mice.";
RL Immunity 3:549-560(1995).
RN [13]
RP INTERACTION WITH CBL.
RX PubMed=7782294; DOI=10.1074/jbc.270.24.14347;
RA Tanaka S., Neff L., Baron R., Levy J.B.;
RT "Tyrosine phosphorylation and translocation of the c-cbl protein after
RT activation of tyrosine kinase signaling pathways.";
RL J. Biol. Chem. 270:14347-14351(1995).
RN [14]
RP CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, AND ACTIVITY REGULATION.
RX PubMed=8530369; DOI=10.1074/jbc.270.50.29773;
RA Sotirellis N., Johnson T.M., Hibbs M.L., Stanley I.J., Stanley E.,
RA Dunn A.R., Cheng H.C.;
RT "Autophosphorylation induces autoactivation and a decrease in the Src
RT homology 2 domain accessibility of the Lyn protein kinase.";
RL J. Biol. Chem. 270:29773-29780(1995).
RN [15]
RP FUNCTION IN TEC PHOSPHORYLATION, AND INTERACTION WITH TEC.
RX PubMed=8621063; DOI=10.1096/fasebj.10.5.8621063;
RA Mano H., Yamashita Y., Miyazato A., Miura Y., Ozawa K.;
RT "Tec protein-tyrosine kinase is an effector molecule of Lyn protein-
RT tyrosine kinase.";
RL FASEB J. 10:637-642(1996).
RN [16]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=9064343; DOI=10.1084/jem.184.3.831;
RA Wang J., Koizumi T., Watanabe T.;
RT "Altered antigen receptor signaling and impaired Fas-mediated apoptosis of
RT B cells in Lyn-deficient mice.";
RL J. Exp. Med. 184:831-838(1996).
RN [17]
RP FUNCTION IN PHOSPHORYLATION OF BTK.
RX PubMed=8629002; DOI=10.1126/science.271.5250.822;
RA Rawlings D.J., Scharenberg A.M., Park H., Wahl M.I., Lin S., Kato R.M.,
RA Fluckiger A.C., Witte O.N., Kinet J.P.;
RT "Activation of BTK by a phosphorylation mechanism initiated by SRC family
RT kinases.";
RL Science 271:822-825(1996).
RN [18]
RP DISRUPTION PHENOTYPE, FUNCTION, ALTERNATIVE SPLICING, AND PHOSPHORYLATION.
RX PubMed=9252121; DOI=10.1016/s1074-7613(00)80511-7;
RA Chan V.W., Meng F., Soriano P., DeFranco A.L., Lowell C.A.;
RT "Characterization of the B lymphocyte populations in Lyn-deficient mice and
RT the role of Lyn in signal initiation and down-regulation.";
RL Immunity 7:69-81(1997).
RN [19]
RP FUNCTION IN MAST CELLS AND IN SIGNALING DOWN-STREAM OF FCER1.
RX PubMed=9036984;
RA Nishizumi H., Yamamoto T.;
RT "Impaired tyrosine phosphorylation and Ca2+ mobilization, but not
RT degranulation, in lyn-deficient bone marrow-derived mast cells.";
RL J. Immunol. 158:2350-2355(1997).
RN [20]
RP INTERACTION WITH EPOR AND JAK2, AND FUNCTION.
RX PubMed=9573010;
RA Chin H., Arai A., Wakao H., Kamiyama R., Miyasaka N., Miura O.;
RT "Lyn physically associates with the erythropoietin receptor and may play a
RT role in activation of the Stat5 pathway.";
RL Blood 91:3734-3745(1998).
RN [21]
RP FUNCTION IN FCGR2 AND CD22 PHOSPHORYLATION AND ACTIVATION OF MAPK1/ERK2;
RP MAPK8/JNK1 AND MAPK9/JNK2.
RX PubMed=9601638; DOI=10.1016/s0960-9822(98)70223-4;
RA Chan V.W., Lowell C.A., DeFranco A.L.;
RT "Defective negative regulation of antigen receptor signaling in Lyn-
RT deficient B lymphocytes.";
RL Curr. Biol. 8:545-553(1998).
RN [22]
RP FUNCTION IN CD22 PHOSPHORYLATION.
RX PubMed=9480991; DOI=10.1084/jem.187.5.807;
RA Smith K.G., Tarlinton D.M., Doody G.M., Hibbs M.L., Fearon D.T.;
RT "Inhibition of the B cell by CD22: a requirement for Lyn.";
RL J. Exp. Med. 187:807-811(1998).
RN [23]
RP FUNCTION IN FCGR2 AND CD22 PHOSPHORYLATION.
RX PubMed=9547345; DOI=10.1084/jem.187.8.1343;
RA Nishizumi H., Horikawa K., Mlinaric-Rascan I., Yamamoto T.;
RT "A double-edged kinase Lyn: a positive and negative regulator for antigen
RT receptor-mediated signals.";
RL J. Exp. Med. 187:1343-1348(1998).
RN [24]
RP FUNCTION IN FCGR2 PHOSPHORYLATION, AND INTERACTION WITH FCGR2.
RX PubMed=9469421;
RA Malbec O., Fong D.C., Turner M., Tybulewicz V.L., Cambier J.C.,
RA Fridman W.H., Daeron M.;
RT "Fc epsilon receptor I-associated lyn-dependent phosphorylation of Fc gamma
RT receptor IIB during negative regulation of mast cell activation.";
RL J. Immunol. 160:1647-1658(1998).
RN [25]
RP FUNCTION IN CD72 PHOSPHORYLATION.
RX PubMed=9590210;
RA Adachi T., Flaswinkel H., Yakura H., Reth M., Tsubata T.;
RT "The B cell surface protein CD72 recruits the tyrosine phosphatase SHP-1
RT upon tyrosine phosphorylation.";
RL J. Immunol. 160:4662-4665(1998).
RN [26]
RP DISRUPTION PHENOTYPE, AND FUNCTION IN ERYTHROPOIESIS.
RX PubMed=10594694; DOI=10.1046/j.1365-2567.1999.00899.x;
RA Ochi H., Takeshita H., Suda T., Nisitani S., Honjo T., Watanabe T.;
RT "Regulation of B-1 cell activation and its autoantibody production by Lyn
RT kinase-regulated signallings.";
RL Immunology 98:595-603(1999).
RN [27]
RP PHOSPHORYLATION AT TYR-397 AND TYR-508, DEPHOSPHORYLATION BY PTPRC/CD45,
RP AND ACTIVITY REGULATION.
RX PubMed=10415030;
RA Katagiri T., Ogimoto M., Hasegawa K., Arimura Y., Mitomo K., Okada M.,
RA Clark M.R., Mizuno K., Yakura H.;
RT "CD45 negatively regulates lyn activity by dephosphorylating both positive
RT and negative regulatory tyrosine residues in immature B cells.";
RL J. Immunol. 163:1321-1326(1999).
RN [28]
RP FUNCTION IN PHOSPHORYLATION OF LILRB3/PIR-B.
RX PubMed=10327049; DOI=10.1038/sj.onc.1202552;
RA Maeda A., Scharenberg A.M., Tsukada S., Bolen J.B., Kinet J.P.,
RA Kurosaki T.;
RT "Paired immunoglobulin-like receptor B (PIR-B) inhibits BCR-induced
RT activation of Syk and Btk by SHP-1.";
RL Oncogene 18:2291-2297(1999).
RN [29]
RP FUNCTION IN PHOSPHORYLATION OF CSF2RB, AND INTERACTION WITH CSF2RB.
RX PubMed=10672044; DOI=10.1046/j.1365-2443.2000.00312.x;
RA Dahl M.E., Arai K.I., Watanabe S.;
RT "Association of Lyn tyrosine kinase to the GM-CSF and IL-3 receptor common
RT betac subunit and role of Src tyrosine kinases in DNA synthesis and anti-
RT apoptosis.";
RL Genes Cells 5:143-153(2000).
RN [30]
RP FUNCTION IN PHOSPHORYLATION OF DOK1.
RX PubMed=10640270;
RA Yamanashi Y., Tamura T., Kanamori T., Yamane H., Nariuchi H., Yamamoto T.,
RA Baltimore D.;
RT "Role of the rasGAP-associated docking protein p62(dok) in negative
RT regulation of B cell receptor-mediated signaling.";
RL Genes Dev. 14:11-16(2000).
RN [31]
RP FUNCTION IN CD5 PHOSPHORYLATION.
RX PubMed=11007759; DOI=10.1093/intimm/12.10.1417;
RA Ochi H., Watanabe T.;
RT "Negative regulation of B cell receptor-mediated signaling in B-1 cells
RT through CD5 and Ly49 co-receptors via Lyn kinase activity.";
RL Int. Immunol. 12:1417-1423(2000).
RN [32]
RP FUNCTION IN REGULATION OF CELL PROLIFERATION AND MIGRATION IN RESPONSE TO
RP KITLG.
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 [33]
RP DISRUPTION PHENOTYPE, FUNCTION IN PHOSPHORYLATION AND ACTIVATION OF SIRPA;
RP PTPN6/SHP-1; PTPN11/SHP-2 AND INPP5D/SHIP-1, AND MUTAGENESIS OF TYR-508.
RX PubMed=11672542; DOI=10.1016/s1074-7613(01)00208-4;
RA Harder K.W., Parsons L.M., Armes J., Evans N., Kountouri N., Clark R.,
RA Quilici C., Grail D., Hodgson G.S., Dunn A.R., Hibbs M.L.;
RT "Gain- and loss-of-function Lyn mutant mice define a critical inhibitory
RT role for Lyn in the myeloid lineage.";
RL Immunity 15:603-615(2001).
RN [34]
RP INTERACTION WITH PPP1R15A.
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 [35]
RP FUNCTION IN REGULATION OF IMMUNE RESPONSE, CATALYTIC ACTIVITY,
RP AUTOPHOSPHORYLATION, ACTIVITY REGULATION, AND MUTAGENESIS OF TYR-508.
RX PubMed=12486102; DOI=10.1084/jem.20020515;
RA Hibbs M.L., Harder K.W., Armes J., Kountouri N., Quilici C., Casagranda F.,
RA Dunn A.R., Tarlinton D.M.;
RT "Sustained activation of Lyn tyrosine kinase in vivo leads to
RT autoimmunity.";
RL J. Exp. Med. 196:1593-1604(2002).
RN [36]
RP FUNCTION IN PHOSPHORYLATING SYK.
RX PubMed=12077122; DOI=10.1074/jbc.m201362200;
RA Hong J.J., Yankee T.M., Harrison M.L., Geahlen R.L.;
RT "Regulation of signaling in B cells through the phosphorylation of Syk on
RT linker region tyrosines. A mechanism for negative signaling by the Lyn
RT tyrosine kinase.";
RL J. Biol. Chem. 277:31703-31714(2002).
RN [37]
RP FUNCTION IN PHOSPHORYLATING CLNK, AND INTERACTION WITH SKAP1 AND FYB1.
RX PubMed=12681493; DOI=10.1016/s0014-5793(03)00234-5;
RA Fujii Y., Wakahara S., Nakao T., Hara T., Ohtake H., Komurasaki T.,
RA Kitamura K., Tatsuno A., Fujiwara N., Hozumi N., Ra C., Kitamura D.,
RA Goitsuka R.;
RT "Targeting of MIST to Src-family kinases via SKAP55-SLAP-130 adaptor
RT complex in mast cells(1).";
RL FEBS Lett. 540:111-116(2003).
RN [38]
RP FUNCTION.
RX PubMed=12874221; DOI=10.4049/jimmunol.171.3.1319;
RA Pereira S., Lowell C.;
RT "The Lyn tyrosine kinase negatively regulates neutrophil integrin
RT signaling.";
RL J. Immunol. 171:1319-1327(2003).
RN [39]
RP FUNCTION IN DOWN-REGULATION OF THPO-MEDIATED CELL PROLIFERATION AND IN
RP DOWN-REGULATION OF MAPK1/ERK2 AND MAPK3/ERK1 ACTIVATION.
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 [40]
RP UBIQUITINATION.
RX PubMed=15304502; DOI=10.1074/jbc.m404082200;
RA Shao Y., Yang C., Elly C., Liu Y.C.;
RT "Differential regulation of the B cell receptor-mediated signaling by the
RT E3 ubiquitin ligase Cbl.";
RL J. Biol. Chem. 279:43646-43653(2004).
RN [41]
RP FUNCTION IN MAST CELL PROLIFERATION AND IN DOWN-REGULATION OF AKT1;
RP MAPK1/ERK2 AND MAPK3/ERK1 ACTIVATION.
RX PubMed=14525964; DOI=10.1189/jlb.0503224;
RA Hernandez-Hansen V., Mackay G.A., Lowell C.A., Wilson B.S., Oliver J.M.;
RT "The Src kinase Lyn is a negative regulator of mast cell proliferation.";
RL J. Leukoc. Biol. 75:143-151(2004).
RN [42]
RP FUNCTION AS NEGATIVE REGULATOR OF DENDRITIC CELL DIFFERENTIATION;
RP PROLIFERATION AND SURVIVAL.
RX PubMed=16116174; DOI=10.4049/jimmunol.175.5.2880;
RA Chu C.L., Lowell C.A.;
RT "The Lyn tyrosine kinase differentially regulates dendritic cell generation
RT and maturation.";
RL J. Immunol. 175:2880-2889(2005).
RN [43]
RP DISRUPTION PHENOTYPE, AND FUNCTION IN MATURATION OF DENDRITIC CELLS AND IN
RP INFLAMMATORY RESPONSE.
RX PubMed=16034130; DOI=10.4049/jimmunol.175.3.1867;
RA Beavitt S.J., Harder K.W., Kemp J.M., Jones J., Quilici C., Casagranda F.,
RA Lam E., Turner D., Brennan S., Sly P.D., Tarlinton D.M., Anderson G.P.,
RA Hibbs M.L.;
RT "Lyn-deficient mice develop severe, persistent asthma: Lyn is a critical
RT negative regulator of Th2 immunity.";
RL J. Immunol. 175:1867-1875(2005).
RN [44]
RP FUNCTION IN FCER1 SIGNALING; PHOSPHORYLATION OF SYK; MS4A2/FCER1B;
RP INPP5D/SHIP AND PTPN6/SHP-1; ACTIVATION OF AKT1; MAPK1/ERK2 AND MAPK3/ERK1,
RP PHOSPHORYLATION AT TYR-397, AND INTERACTION WITH MS4A2/FCER1B.
RX PubMed=16272347; DOI=10.4049/jimmunol.175.10.6885;
RA Xiao W., Nishimoto H., Hong H., Kitaura J., Nunomura S., Maeda-Yamamoto M.,
RA Kawakami Y., Lowell C.A., Ra C., Kawakami T.;
RT "Positive and negative regulation of mast cell activation by Lyn via the
RT FcepsilonRI.";
RL J. Immunol. 175:6885-6892(2005).
RN [45]
RP INTERACTION WITH LIME1, AND FUNCTION IN PHOSPHORYLATION OF LIME1.
RX PubMed=16249387; DOI=10.1182/blood-2005-05-1859;
RA Ahn E., Lee H., Yun Y.;
RT "LIME acts as a transmembrane adapter mediating BCR-dependent B-cell
RT activation.";
RL Blood 107:1521-1527(2006).
RN [46]
RP INTERACTION WITH FLT3.
RX PubMed=16684964; DOI=10.1182/blood-2005-07-008896;
RA Heiss E., Masson K., Sundberg C., Pedersen M., Sun J., Bengtsson S.,
RA Ronnstrand L.;
RT "Identification of Y589 and Y599 in the juxtamembrane domain of Flt3 as
RT ligand-induced autophosphorylation sites involved in binding of Src family
RT kinases and the protein tyrosine phosphatase SHP2.";
RL Blood 108:1542-1550(2006).
RN [47]
RP FUNCTION.
RX PubMed=16731527; DOI=10.1074/jbc.m604252200;
RA Udell C.M., Samayawardhena L.A., Kawakami Y., Kawakami T., Craig A.W.;
RT "Fer and Fps/Fes participate in a Lyn-dependent pathway from FcepsilonRI to
RT platelet-endothelial cell adhesion molecule 1 to limit mast cell
RT activation.";
RL J. Biol. Chem. 281:20949-20957(2006).
RN [48]
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 [49]
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 [50]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-508, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [51]
RP INTERACTION WITH ANKRD54.
RX PubMed=19064729; DOI=10.1182/blood-2008-04-153452;
RA Samuels A.L., Klinken S.P., Ingley E.;
RT "Liar, a novel Lyn-binding nuclear/cytoplasmic shuttling protein that
RT influences erythropoietin-induced differentiation.";
RL Blood 113:3845-3856(2009).
RN [52]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19; TYR-397 AND TYR-508, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [53]
RP FUNCTION.
RX PubMed=19492092; DOI=10.1371/journal.pone.0005721;
RA Kosmider O., Buet D., Gallais I., Denis N., Moreau-Gachelin F.;
RT "Erythropoietin down-regulates stem cell factor receptor (Kit) expression
RT in the leukemic proerythroblast: role of Lyn kinase.";
RL PLoS ONE 4:E5721-E5721(2009).
RN [54]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-397, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [55]
RP INTERACTION WITH THEMIS2.
RX PubMed=20644716; DOI=10.1371/journal.pone.0011465;
RA Peirce M.J., Brook M., Morrice N., Snelgrove R., Begum S., Lanfrancotti A.,
RA Notley C., Hussell T., Cope A.P., Wait R.;
RT "Themis2/ICB1 is a signaling scaffold that selectively regulates macrophage
RT Toll-like receptor signaling and cytokine production.";
RL PLoS ONE 5:E11465-E11465(2010).
RN [56]
RP FUNCTION IN PLATELET GRANULE SECRETION AND PLATELET AGGREGATION.
RX PubMed=20189992; DOI=10.1074/jbc.m109.098756;
RA Li Z., Zhang G., Liu J., Stojanovic A., Ruan C., Lowell C.A., Du X.;
RT "An important role of the SRC family kinase Lyn in stimulating platelet
RT granule secretion.";
RL J. Biol. Chem. 285:12559-12570(2010).
RN [57]
RP FUNCTION IN DOWN-REGULATION OF TLR2 AND TLR4 SIGNALING; CYTOKINE RELEASE
RP AND THE INFLAMMATORY RESPONSE TO LIPOPOLYSACCHARIDE.
RX PubMed=20385881; DOI=10.4049/jimmunol.0901423;
RA Keck S., Freudenberg M., Huber M.;
RT "Activation of murine macrophages via TLR2 and TLR4 is negatively regulated
RT by a Lyn/PI3K module and promoted by SHIP1.";
RL J. Immunol. 184:5809-5818(2010).
RN [58]
RP INTERACTION WITH CEACAM1.
RX PubMed=22496641; DOI=10.1371/journal.ppat.1002597;
RA Lu R., Pan H., Shively J.E.;
RT "CEACAM1 negatively regulates IL-1beta production in LPS activated
RT neutrophils by recruiting SHP-1 to a SYK-TLR4-CEACAM1 complex.";
RL PLoS Pathog. 8:E1002597-E1002597(2012).
RN [59]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH SCIMP, AND
RP TISSUE SPECIFICITY.
RX PubMed=28098138; DOI=10.1038/ncomms14133;
RA Luo L., Bokil N.J., Wall A.A., Kapetanovic R., Lansdaal N.M., Marceline F.,
RA Burgess B.J., Tong S.J., Guo Z., Alexandrov K., Ross I.L., Hibbs M.L.,
RA Stow J.L., Sweet M.J.;
RT "SCIMP is a transmembrane non-TIR TLR adaptor that promotes proinflammatory
RT cytokine production from macrophages.";
RL Nat. Commun. 8:14133-14133(2017).
RN [60]
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 [61]
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 [62]
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 [63]
RP REVIEW.
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 [64]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 239-512 IN COMPLEXES WITH
RP DASATINIB; PP2 AND AMP-PNP, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION,
RP ACTIVITY REGULATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18984583; DOI=10.1074/jbc.m807850200;
RA Williams N.K., Lucet I.S., Klinken S.P., Ingley E., Rossjohn J.;
RT "Crystal structures of the Lyn protein tyrosine kinase domain in its
RT Apo- and inhibitor-bound state.";
RL J. Biol. Chem. 284:284-291(2009).
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. Required for rapid phosphorylation of
CC FER in response to FCER1 activation. Mediates KIT phosphorylation. Acts
CC as an effector of EPOR (erythropoietin receptor) in controlling KIT
CC expression and may play a role in erythroid differentiation during the
CC switch between proliferation and maturation. Depending on the context,
CC activates or inhibits several signaling cascades. Regulates
CC phosphatidylinositol 3-kinase activity and AKT1 activation. Regulates
CC activation of the MAP kinase signaling cascade, including activation of
CC MAP2K1/MEK1, MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2.
CC Mediates activation of STAT5A and/or STAT5B. Phosphorylates LPXN on
CC 'Tyr-72'. Kinase activity facilitates TLR4-TLR6 heterodimerization and
CC signal initiation. Phosphorylates SCIMP on 'Tyr-96'; this enhances
CC binding of SCIMP to TLR4, promoting the phosphorylation of TLR4, and a
CC selective cytokine response to lipopolysaccharide in macrophages
CC (PubMed:28098138). Phosphorylates CLNK (PubMed:12681493).
CC {ECO:0000250|UniProtKB:P07948, ECO:0000269|PubMed:10327049,
CC ECO:0000269|PubMed:10594694, ECO:0000269|PubMed:10640270,
CC ECO:0000269|PubMed:10672044, ECO:0000269|PubMed:11007759,
CC ECO:0000269|PubMed:11435302, ECO:0000269|PubMed:11672542,
CC ECO:0000269|PubMed:12077122, ECO:0000269|PubMed:12681493,
CC ECO:0000269|PubMed:12874221, ECO:0000269|PubMed:14525964,
CC ECO:0000269|PubMed:14726379, ECO:0000269|PubMed:15335855,
CC ECO:0000269|PubMed:16034130, ECO:0000269|PubMed:16116174,
CC ECO:0000269|PubMed:16249387, ECO:0000269|PubMed:16272347,
CC ECO:0000269|PubMed:16731527, ECO:0000269|PubMed:17640867,
CC ECO:0000269|PubMed:19492092, ECO:0000269|PubMed:20189992,
CC ECO:0000269|PubMed:20385881, ECO:0000269|PubMed:28098138,
CC ECO:0000269|PubMed:7513017, ECO:0000269|PubMed:7584145,
CC ECO:0000269|PubMed:7585947, ECO:0000269|PubMed:8128248,
CC ECO:0000269|PubMed:8621063, ECO:0000269|PubMed:8629002,
CC ECO:0000269|PubMed:9036984, ECO:0000269|PubMed:9064343,
CC ECO:0000269|PubMed:9252121, ECO:0000269|PubMed:9469421,
CC ECO:0000269|PubMed:9480991, ECO:0000269|PubMed:9547345,
CC ECO:0000269|PubMed:9573010, ECO:0000269|PubMed:9590210,
CC ECO:0000269|PubMed:9601638}.
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:12486102, ECO:0000269|PubMed:18984583,
CC ECO:0000269|PubMed:2017160, ECO:0000269|PubMed:8530369};
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:10415030, ECO:0000269|PubMed:12486102,
CC ECO:0000269|PubMed:18984583, ECO:0000269|PubMed:8530369}.
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:28098138). This interaction facilitates
CC the phosphorylation of SCIMP on 'Tyr-96', which enhances binding of
CC SCIMP to TLR4, and consequently the phosphorylation of TLR4 in response
CC to stimulation by lipopolysaccharide in macrophages (PubMed:28098138).
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 (By similarity). Interacts with CD36. Interacts with LYN
CC (PubMed:22496641). Interacts with SKAP1 and FYB1; this interaction
CC promotes the phosphorylation of CLNK (PubMed:12681493).
CC {ECO:0000250|UniProtKB:P07948, ECO:0000269|PubMed:10672044,
CC ECO:0000269|PubMed:11517336, ECO:0000269|PubMed:12681493,
CC ECO:0000269|PubMed:15335855, ECO:0000269|PubMed:16249387,
CC ECO:0000269|PubMed:16272347, ECO:0000269|PubMed:16684964,
CC ECO:0000269|PubMed:1702903, ECO:0000269|PubMed:17233630,
CC ECO:0000269|PubMed:17640867, ECO:0000269|PubMed:19064729,
CC ECO:0000269|PubMed:20644716, ECO:0000269|PubMed:22496641,
CC ECO:0000269|PubMed:28098138, ECO:0000269|PubMed:7782294,
CC ECO:0000269|PubMed:8128248, ECO:0000269|PubMed:8168489,
CC ECO:0000269|PubMed:8621063, ECO:0000269|PubMed:9469421,
CC ECO:0000269|PubMed:9573010}.
CC -!- INTERACTION:
CC P25911; Q9Z1S8: Gab2; NbExp=2; IntAct=EBI-643537, EBI-641738;
CC P25911; P49710: Hcls1; NbExp=10; IntAct=EBI-643537, EBI-924601;
CC P25911; Q8CIH5: Plcg2; NbExp=2; IntAct=EBI-643537, EBI-617954;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}. Nucleus
CC {ECO:0000250}. Cytoplasm {ECO:0000250}. Cytoplasm, perinuclear region
CC {ECO:0000250}. Golgi apparatus {ECO:0000250}. Membrane
CC {ECO:0000250|UniProtKB:P07948}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P07948}. Note=Accumulates in the nucleus by
CC inhibition of Crm1-mediated nuclear export. Nuclear accumulation is
CC increased by inhibition of its kinase activity. The trafficking from
CC the Golgi apparatus to the cell membrane occurs in a kinase domain-
CC dependent but kinase activity independent manner and is mediated by
CC exocytic vesicular transport (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=LYN A, p56;
CC IsoId=P25911-1; Sequence=Displayed;
CC Name=2; Synonyms=LYN B, p53;
CC IsoId=P25911-2; Sequence=VSP_005003;
CC -!- TISSUE SPECIFICITY: Detected in bone marrow-derived monocytes and
CC macrophages (at protein level) (PubMed:28098138, PubMed:2017160).
CC Expressed predominantly in B-lymphoid and myeloid cells
CC (PubMed:2017160). {ECO:0000269|PubMed:2017160,
CC ECO:0000269|PubMed:28098138}.
CC -!- DOMAIN: The protein kinase domain plays an important role in its
CC localization in the cell membrane. {ECO:0000250}.
CC -!- PTM: Ubiquitinated by CBL, leading to its degradation.
CC {ECO:0000269|PubMed:15304502}.
CC -!- PTM: Phosphorylated on tyrosine residues in response to KIT signaling
CC (By similarity). Autophosphorylated. Phosphorylation at Tyr-397 is
CC required for optimal activity. Phosphorylation at Tyr-508 inhibits
CC kinase activity. Phosphorylated at Tyr-508 by CSK. Dephosphorylated by
CC PTPRC/CD45. Becomes rapidly phosphorylated upon activation of the B-
CC cell receptor and the immunoglobulin receptor FCGR1A. {ECO:0000250,
CC ECO:0000269|PubMed:10415030, ECO:0000269|PubMed:16272347,
CC ECO:0000269|PubMed:9252121}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype at birth. B-cell development
CC in the bone marrow proceeds normally, but mice have reduced numbers of
CC peripheral B-cells, with a greater proportion of immature cells and an
CC increased turnover rate. Dendritic cells also have a more immature
CC phenotype. Mice develop severe asthma upon exposure to airborne
CC antigen. Mice display elevated levels of serum IgM. Aging mice display
CC strongly increased levels of myeloid cells, severe extramedullary
CC hematoipoiesis and tend to develop monocyte/macrophage tumors. After
CC about 16 weeks, mice begin to develop splenomegaly and
CC glomerulonephritis, and display autoimmune antibodies. Their B-cells
CC are hypersensitive to stimulation of the B-cell receptor, and display
CC enhanced activation of the MAP kinase signaling pathway. Mice do not
CC display an allergic response upon IgE receptor engagement.
CC {ECO:0000269|PubMed:10594694, ECO:0000269|PubMed:11672542,
CC ECO:0000269|PubMed:16034130, ECO:0000269|PubMed:7584145,
CC ECO:0000269|PubMed:7585947, ECO:0000269|PubMed:9064343,
CC ECO:0000269|PubMed:9252121}.
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; M64608; AAA39470.1; -; mRNA.
DR EMBL; M57696; AAA39471.1; -; mRNA.
DR EMBL; M57697; AAA39472.1; -; mRNA.
DR EMBL; BC031547; AAH31547.1; -; mRNA.
DR EMBL; M33426; AAA40017.1; -; mRNA.
DR CCDS; CCDS17939.1; -. [P25911-2]
DR CCDS; CCDS51109.1; -. [P25911-1]
DR PIR; A39719; A39719.
DR RefSeq; NP_001104566.1; NM_001111096.1. [P25911-1]
DR PDB; 2ZV7; X-ray; 2.50 A; A=239-512.
DR PDB; 2ZV8; X-ray; 2.70 A; A=239-512.
DR PDB; 2ZV9; X-ray; 2.76 A; A=239-512.
DR PDB; 2ZVA; X-ray; 2.60 A; A=239-512.
DR PDB; 4TZI; X-ray; 2.10 A; A/B=115-229.
DR PDBsum; 2ZV7; -.
DR PDBsum; 2ZV8; -.
DR PDBsum; 2ZV9; -.
DR PDBsum; 2ZVA; -.
DR PDBsum; 4TZI; -.
DR AlphaFoldDB; P25911; -.
DR SMR; P25911; -.
DR BioGRID; 201256; 19.
DR CORUM; P25911; -.
DR DIP; DIP-37806N; -.
DR ELM; P25911; -.
DR IntAct; P25911; 18.
DR MINT; P25911; -.
DR STRING; 10090.ENSMUSP00000038838; -.
DR BindingDB; P25911; -.
DR ChEMBL; CHEMBL2258; -.
DR iPTMnet; P25911; -.
DR PhosphoSitePlus; P25911; -.
DR SwissPalm; P25911; -.
DR EPD; P25911; -.
DR jPOST; P25911; -.
DR PaxDb; P25911; -.
DR PeptideAtlas; P25911; -.
DR PRIDE; P25911; -.
DR ProteomicsDB; 295736; -. [P25911-1]
DR ProteomicsDB; 295737; -. [P25911-2]
DR Antibodypedia; 51187; 924 antibodies from 45 providers.
DR DNASU; 17096; -.
DR Ensembl; ENSMUST00000041377; ENSMUSP00000038838; ENSMUSG00000042228. [P25911-1]
DR Ensembl; ENSMUST00000103010; ENSMUSP00000100075; ENSMUSG00000042228. [P25911-2]
DR GeneID; 17096; -.
DR KEGG; mmu:17096; -.
DR UCSC; uc008rwm.2; mouse. [P25911-1]
DR CTD; 4067; -.
DR MGI; MGI:96892; Lyn.
DR VEuPathDB; HostDB:ENSMUSG00000042228; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000158011; -.
DR HOGENOM; CLU_000288_7_2_1; -.
DR InParanoid; P25911; -.
DR OMA; PKAQRPW; -.
DR PhylomeDB; P25911; -.
DR TreeFam; TF351634; -.
DR BRENDA; 2.7.10.2; 3474.
DR Reactome; R-MMU-114604; GPVI-mediated activation cascade.
DR Reactome; R-MMU-1433557; Signaling by SCF-KIT.
DR Reactome; R-MMU-1433559; Regulation of KIT signaling.
DR Reactome; R-MMU-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-MMU-2029481; FCGR activation.
DR Reactome; R-MMU-210990; PECAM1 interactions.
DR Reactome; R-MMU-2454202; Fc epsilon receptor (FCERI) signaling.
DR Reactome; R-MMU-2730905; Role of LAT2/NTAL/LAB on calcium mobilization.
DR Reactome; R-MMU-2871796; FCERI mediated MAPK activation.
DR Reactome; R-MMU-2871809; FCERI mediated Ca+2 mobilization.
DR Reactome; R-MMU-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-MMU-389356; CD28 co-stimulation.
DR Reactome; R-MMU-389513; CTLA4 inhibitory signaling.
DR Reactome; R-MMU-3928662; EPHB-mediated forward signaling.
DR Reactome; R-MMU-3928663; EPHA-mediated growth cone collapse.
DR Reactome; R-MMU-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-MMU-5621480; Dectin-2 family.
DR Reactome; R-MMU-5621575; CD209 (DC-SIGN) signaling.
DR Reactome; R-MMU-5690714; CD22 mediated BCR regulation.
DR Reactome; R-MMU-69231; Cyclin D associated events in G1.
DR Reactome; R-MMU-75892; Platelet Adhesion to exposed collagen.
DR Reactome; R-MMU-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K).
DR Reactome; R-MMU-9027284; Erythropoietin activates RAS.
DR Reactome; R-MMU-912631; Regulation of signaling by CBL.
DR Reactome; R-MMU-9674555; Signaling by CSF3 (G-CSF).
DR Reactome; R-MMU-9705462; Inactivation of CSF3 (G-CSF) signaling.
DR Reactome; R-MMU-982772; Growth hormone receptor signaling.
DR BioGRID-ORCS; 17096; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Lyn; mouse.
DR EvolutionaryTrace; P25911; -.
DR PRO; PR:P25911; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; P25911; protein.
DR Bgee; ENSMUSG00000042228; Expressed in stroma of bone marrow and 221 other tissues.
DR ExpressionAtlas; P25911; baseline and differential.
DR Genevisible; P25911; MM.
DR GO; GO:0005912; C:adherens junction; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0034666; C:integrin alpha2-beta1 complex; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0045121; C:membrane raft; IDA:ARUK-UCL.
DR GO; GO:0030061; C:mitochondrial crista; ISO:MGI.
DR GO; GO:0005758; C:mitochondrial intermembrane space; ISO:MGI.
DR GO; GO:0031966; C:mitochondrial membrane; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0099091; C:postsynaptic specialization, intracellular component; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0046875; F:ephrin receptor binding; ISO:MGI.
DR GO; GO:0005128; F:erythropoietin receptor binding; TAS:UniProtKB.
DR GO; GO:0043015; F:gamma-tubulin binding; ISO:MGI.
DR GO; GO:0043208; F:glycosphingolipid binding; ISO:MGI.
DR GO; GO:0005178; F:integrin binding; ISO:MGI.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IMP:UniProtKB.
DR GO; GO:0051219; F:phosphoprotein binding; ISO:MGI.
DR GO; GO:0140031; F:phosphorylation-dependent protein binding; ISO:MGI.
DR GO; GO:0005161; F:platelet-derived growth factor receptor binding; ISO:MGI.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:MGI.
DR GO; GO:0097110; F:scaffold protein binding; ISO:MGI.
DR GO; GO:0017124; F:SH3 domain binding; IPI:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0001782; P:B cell homeostasis; IMP:UniProtKB.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IDA:MGI.
DR GO; GO:0038159; P:C-X-C chemokine receptor CXCR4 signaling pathway; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0097028; P:dendritic cell differentiation; IMP:UniProtKB.
DR GO; GO:0030218; P:erythrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0002774; P:Fc receptor mediated inhibitory signaling pathway; IMP:UniProtKB.
DR GO; GO:0002431; P:Fc receptor mediated stimulatory signaling pathway; IMP:UniProtKB.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:0042541; P:hemoglobin biosynthetic process; TAS:UniProtKB.
DR GO; GO:0030097; P:hemopoiesis; IMP:UniProtKB.
DR GO; GO:0002553; P:histamine secretion by mast cell; ISO:MGI.
DR GO; GO:0002768; P:immune response-regulating cell surface receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:MGI.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; IMP:UniProtKB.
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; IMP:UniProtKB.
DR GO; GO:1902532; P:negative regulation of intracellular signal transduction; IMP:UniProtKB.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IMP:UniProtKB.
DR GO; GO:0070667; P:negative regulation of mast cell proliferation; IMP:UniProtKB.
DR GO; GO:0002762; P:negative regulation of myeloid leukocyte differentiation; IMP:UniProtKB.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0034136; P:negative regulation of toll-like receptor 2 signaling pathway; IMP:UniProtKB.
DR GO; GO:0034144; P:negative regulation of toll-like receptor 4 signaling pathway; IMP:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; IMP:MGI.
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; IMP:UniProtKB.
DR GO; GO:1902961; P:positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process; ISO:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:2000670; P:positive regulation of dendritic cell apoptotic process; IMP:UniProtKB.
DR GO; GO:0060369; P:positive regulation of Fc receptor mediated stimulatory signaling pathway; ISO:MGI.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; ISO:MGI.
DR GO; GO:0070668; P:positive regulation of mast cell proliferation; ISO:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:0070447; P:positive regulation of oligodendrocyte progenitor proliferation; ISO:MGI.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IMP:UniProtKB.
DR GO; GO:0042327; P:positive regulation of phosphorylation; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0070304; P:positive regulation of stress-activated protein kinase signaling cascade; ISO:MGI.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0002902; P:regulation of B cell apoptotic process; IMP:UniProtKB.
DR GO; GO:0050855; P:regulation of B cell receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; ISO:MGI.
DR GO; GO:0001817; P:regulation of cytokine production; IMP:UniProtKB.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0045646; P:regulation of erythrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:0033003; P:regulation of mast cell activation; IMP:UniProtKB.
DR GO; GO:0043304; P:regulation of mast cell degranulation; IMP:UniProtKB.
DR GO; GO:0090025; P:regulation of monocyte chemotaxis; ISO:MGI.
DR GO; GO:0090330; P:regulation of platelet aggregation; IMP:UniProtKB.
DR GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; IGI:MGI.
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; IDA: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:UniProtKB.
DR GO; GO:0002513; P:tolerance induction to self antigen; IMP:UniProtKB.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IMP:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; ISO:MGI.
DR CDD; cd10364; SH2_Src_Lyn; 1.
DR CDD; cd12004; SH3_Lyn; 1.
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; Immunity; Inflammatory response;
KW Innate immunity; Kinase; Lipoprotein; Membrane; Myristate;
KW Nucleotide-binding; Nucleus; Palmitate; Phosphoprotein; Proto-oncogene;
KW Reference proteome; SH2 domain; SH3 domain; Transferase;
KW Tyrosine-protein kinase; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P07948"
FT CHAIN 2..512
FT /note="Tyrosine-protein kinase Lyn"
FT /id="PRO_0000088130"
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..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..23
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 24..44
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:0000305"
FT BINDING 275
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 193
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P07948"
FT MOD_RES 228
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07948"
FT MOD_RES 306
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P07948"
FT MOD_RES 316
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P07948"
FT MOD_RES 397
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:10415030,
FT ECO:0000269|PubMed:16272347, ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 460
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P07948"
FT MOD_RES 473
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P07948"
FT MOD_RES 508
FT /note="Phosphotyrosine; by autocatalysis, CSK and MATK"
FT /evidence="ECO:0000269|PubMed:10415030,
FT ECO:0007744|PubMed:18034455, ECO:0007744|PubMed:19144319"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:P07948"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 25..45
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:2017160"
FT /id="VSP_005003"
FT MUTAGEN 508
FT /note="Y->F: Abolishes autoinhibition, leading to increased
FT kinase activity and constitutive phosphorylation of LYN
FT substrates."
FT /evidence="ECO:0000269|PubMed:11672542,
FT ECO:0000269|PubMed:12486102"
FT CONFLICT 77
FT /note="I -> F (in Ref. 2; AAA39471/AAA39472)"
FT /evidence="ECO:0000305"
FT CONFLICT 161
FT /note="L -> I (in Ref. 2; AAA39471/AAA39472)"
FT /evidence="ECO:0000305"
FT CONFLICT 279
FT /note="P -> L (in Ref. 2; AAA39471/AAA39472)"
FT /evidence="ECO:0000305"
FT CONFLICT 391
FT /note="V -> I (in Ref. 2; AAA39471/AAA39472)"
FT /evidence="ECO:0000305"
FT CONFLICT 415
FT /note="I -> F (in Ref. 4; AAA40017)"
FT /evidence="ECO:0000305"
FT CONFLICT 425
FT /note="D -> N (in Ref. 1; AAA39470)"
FT /evidence="ECO:0000305"
FT CONFLICT 432
FT /note="L -> P (in Ref. 4; AAA40017)"
FT /evidence="ECO:0000305"
FT HELIX 136..143
FT /evidence="ECO:0007829|PDB:4TZI"
FT STRAND 153..157
FT /evidence="ECO:0007829|PDB:4TZI"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:4TZI"
FT STRAND 165..172
FT /evidence="ECO:0007829|PDB:4TZI"
FT STRAND 174..187
FT /evidence="ECO:0007829|PDB:4TZI"
FT STRAND 193..196
FT /evidence="ECO:0007829|PDB:4TZI"
FT STRAND 199..203
FT /evidence="ECO:0007829|PDB:4TZI"
FT HELIX 204..213
FT /evidence="ECO:0007829|PDB:4TZI"
FT STRAND 218..220
FT /evidence="ECO:0007829|PDB:4TZI"
FT HELIX 244..246
FT /evidence="ECO:0007829|PDB:2ZV7"
FT STRAND 247..254
FT /evidence="ECO:0007829|PDB:2ZV7"
FT STRAND 257..266
FT /evidence="ECO:0007829|PDB:2ZV7"
FT TURN 267..269
FT /evidence="ECO:0007829|PDB:2ZV7"
FT STRAND 270..277
FT /evidence="ECO:0007829|PDB:2ZV7"
FT HELIX 284..294
FT /evidence="ECO:0007829|PDB:2ZV7"
FT STRAND 305..309
FT /evidence="ECO:0007829|PDB:2ZV7"
FT STRAND 311..314
FT /evidence="ECO:0007829|PDB:2ZV7"
FT STRAND 316..320
FT /evidence="ECO:0007829|PDB:2ZV7"
FT HELIX 327..332
FT /evidence="ECO:0007829|PDB:2ZV7"
FT HELIX 336..338
FT /evidence="ECO:0007829|PDB:2ZV7"
FT HELIX 341..360
FT /evidence="ECO:0007829|PDB:2ZV7"
FT HELIX 370..372
FT /evidence="ECO:0007829|PDB:2ZV7"
FT STRAND 373..375
FT /evidence="ECO:0007829|PDB:2ZV7"
FT STRAND 381..383
FT /evidence="ECO:0007829|PDB:2ZV7"
FT HELIX 407..409
FT /evidence="ECO:0007829|PDB:2ZV7"
FT HELIX 412..417
FT /evidence="ECO:0007829|PDB:2ZV7"
FT HELIX 422..438
FT /evidence="ECO:0007829|PDB:2ZV7"
FT HELIX 449..455
FT /evidence="ECO:0007829|PDB:2ZV7"
FT HELIX 456..458
FT /evidence="ECO:0007829|PDB:2ZV7"
FT HELIX 470..479
FT /evidence="ECO:0007829|PDB:2ZV7"
FT HELIX 484..486
FT /evidence="ECO:0007829|PDB:2ZV7"
FT HELIX 490..498
FT /evidence="ECO:0007829|PDB:2ZV7"
SQ SEQUENCE 512 AA; 58812 MW; FDA1D21CC90C50EC CRC64;
MGCIKSKRKD NLNDDEVDSK TQPVRNTDRT IYVRDPTSNK QQRPVPEFHL LPGQRFQTKD
PEEQGDIVVA LYPYDGIHPD DLSFKKGEKM KVLEEHGEWW KAKSLSSKRE GFIPSNYVAK
VNTLETEEWF FKDITRKDAE RQLLAPGNSA GAFLIRESET LKGSFSLSVR DYDPMHGDVI
KHYKIRSLDN GGYYISPRIT FPCISDMIKH YQKQSDGLCR RLEKACISPK PQKPWDKDAW
EIPRESIKLV KKLGAGQFGE VWMGYYNNST KVAVKTLKPG TMSVQAFLEE ANLMKTLQHD
KLVRLYAVVT KEEPIYIITE FMAKGSLLDF LKSDEGGKVL LPKLIDFSAQ IAEGMAYIER
KNYIHRDLRA ANVLVSESLM CKIADFGLAR VIEDNEYTAR EGAKFPIKWT APEAINFGCF
TIKSDVWSFG ILLYEIVTYG KIPYPGRTNA DVMSALSQGY RMPRMENCPD ELYDIMKMCW
KEKAEERPTF DYLQSVLDDF YTATEGQYQQ QP
