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Identification
HMDB Protein ID HMDBP13813
Secondary Accession Numbers None
Name Tyrosine-protein kinase Lyn
Synonyms
  1. V-yes-1 Yamaguchi sarcoma viral related oncogene homolog
  2. p53Lyn
  3. p56Lyn
Gene Name LYN
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending on the context. Required for the initiation of the B-cell response, but also for its down-regulation and termination. Plays an important role in the regulation of B-cell differentiation, proliferation, survival and apoptosis, and is important for immune self-tolerance. Acts downstream of several immune receptors, including the B-cell receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2 and TLR4. Plays a role in the inflammatory response to bacterial lipopolysaccharide. Mediates the responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and in mature myeloid cells, such as dendritic cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT, MPL, the chemokine receptor CXCR4, as well as the receptors for IL3, IL5 and CSF2. Plays an important role in integrin signaling. Regulates cell proliferation, survival, differentiation, migration, adhesion, degranulation, and cytokine release. Down-regulates signaling pathways by phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIM), that then serve as binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of kinases and their substrates. Phosphorylates LIME1 in response to CD22 activation. Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Required for rapid phosphorylation of FER in response to FCER1 activation. Mediates KIT phosphorylation. Acts as an effector of EPOR (erythropoietin receptor) in controlling KIT expression and may play a role in erythroid differentiation during the switch between proliferation and maturation. Depending on the context, activates or inhibits several signaling cascades. Regulates phosphatidylinositol 3-kinase activity and AKT1 activation. Regulates activation of the MAP kinase signaling cascade, including activation of MAP2K1/MEK1, MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2. Mediates activation of STAT5A and/or STAT5B. Phosphorylates LPXN on 'Tyr-72'. Kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation. Phosphorylates SCIMP on 'Tyr-96'; this enhances binding of SCIMP to TLR4, promoting the phosphorylation of TLR4, and a selective cytokine response to lipopolysaccharide in macrophages (PubMed:28098138). Phosphorylates CLNK (PubMed:12681493).
Pathways
  • B cell receptor signaling pathway
  • Chemokine signaling pathway
  • Epstein-Barr virus infection
  • Fc epsilon RI signaling pathway
  • Fc gamma R-mediated phagocytosis
  • Kaposi sarcoma-associated herpesvirus infection
  • Lipid and atherosclerosis
  • Long-term depression
  • NF-kappa B signaling pathway
  • Platelet activation
  • Viral carcinogenesis
Reactions Not Available
GO Classification
Biological Process
signal transduction
positive regulation of mast cell proliferation
regulation of cytokine production
B cell receptor signaling pathway
regulation of inflammatory response
platelet degranulation
B cell homeostasis
negative regulation of MAP kinase activity
dendritic cell differentiation
Fc receptor mediated inhibitory signaling pathway
cellular response to extracellular stimulus
Fc receptor mediated stimulatory signaling pathway
positive regulation of cell migration
histamine secretion by mast cell
response to amino acid stimulus
immune response-regulating cell surface receptor signaling pathway
positive regulation of phosphorylation
negative regulation of intracellular signal transduction
negative regulation of mast cell proliferation
oligodendrocyte development
positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process
positive regulation of cell proliferation
positive regulation of dendritic cell apoptotic process
positive regulation of Fc receptor mediated stimulatory signaling pathway
response to hormone stimulus
positive regulation of oligodendrocyte progenitor proliferation
positive regulation of stress-activated protein kinase signaling cascade
positive regulation of tyrosine phosphorylation of STAT protein
regulation of erythrocyte differentiation
regulation of mast cell degranulation
regulation of monocyte chemotaxis
negative regulation of toll-like receptor 4 signaling pathway
regulation of release of sequestered calcium ion into cytosol
response to sterol depletion
positive regulation of phosphatidylinositol 3-kinase activity
tolerance induction to self antigen
regulation of B cell apoptotic process
neuron projection development
response to insulin stimulus
response to DNA damage stimulus
response to drug
regulation of platelet aggregation
positive regulation of protein phosphorylation
regulation of cell adhesion mediated by integrin
hemopoiesis
regulation of B cell receptor signaling pathway
peptidyl-tyrosine phosphorylation
regulation of ERK1 and ERK2 cascade
negative regulation of protein phosphorylation
innate immune response
positive regulation of neuron projection development
erythrocyte differentiation
regulation of mast cell activation
hemoglobin biosynthetic process
negative regulation of myeloid leukocyte differentiation
transmembrane receptor protein tyrosine kinase signaling pathway
response to carbohydrate stimulus
cell differentiation
positive regulation of glial cell proliferation
adaptive immune response
protein phosphorylation
positive regulation of cellular component movement
cellular response to retinoic acid
negative regulation of B cell proliferation
response to toxin
response to organic cyclic compound
negative regulation of cell proliferation
negative regulation of ERK1 and ERK2 cascade
lipopolysaccharide-mediated signaling pathway
negative regulation of toll-like receptor 2 signaling pathway
protein autophosphorylation
toll-like receptor 4 signaling pathway
response to axon injury
intracellular signal transduction
cellular response to heat
Cellular Component
cytosol
mitochondrial membrane
membrane raft
integrin alpha2-beta1 complex
postsynaptic specialization, intracellular component
protein-containing complex
cytoplasm
mitochondrial crista
plasma membrane
Golgi apparatus
perinuclear region of cytoplasm
nucleus
adherens junction
glutamatergic synapse
membrane
postsynaptic density
intracellular membrane-bounded organelle
extrinsic to internal side of plasma membrane
mitochondrial intermembrane space
Molecular Function
gamma-tubulin binding
glycosphingolipid binding
phosphorylation-dependent protein binding
protein-containing complex binding
transmembrane receptor protein tyrosine kinase activity
erythropoietin receptor binding
platelet-derived growth factor receptor binding
protein tyrosine kinase activity
ATP binding
ubiquitin protein ligase binding
ion channel binding
receptor binding
SH3 domain binding
integrin binding
protein kinase activity
enzyme binding
non-membrane spanning protein tyrosine kinase activity
ephrin receptor binding
phosphoprotein binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 512
Molecular Weight 58811.795
Theoretical pI 7.157
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P25911
UniProtKB/Swiss-Prot Entry Name LYN_MOUSE
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  2. Grishin AV, Azhipa O, Semenov I, Corey SJ: Interaction between growth arrest-DNA damage protein 34 and Src kinase Lyn negatively regulates genotoxic apoptosis. Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10172-7. Epub 2001 Aug 21. [PubMed:11517336 ]
  3. Rathore VB, Okada M, Newman PJ, Newman DK: Paxillin family members function as Csk-binding proteins that regulate Lyn activity in human and murine platelets. Biochem J. 2007 Apr 15;403(2):275-81. [PubMed:17233630 ]
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  18. Wilks AF, Kurban RR, Hovens CM, Ralph SJ: The application of the polymerase chain reaction to cloning members of the protein tyrosine kinase family. Gene. 1989 Dec 21;85(1):67-74. doi: 10.1016/0378-1119(89)90465-4. [PubMed:2482828 ]
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  20. Clark MR, Johnson SA, Cambier JC: Analysis of Ig-alpha-tyrosine kinase interaction reveals two levels of binding specificity and tyrosine phosphorylated Ig-alpha stimulation of Fyn activity. EMBO J. 1994 Apr 15;13(8):1911-9. [PubMed:8168489 ]
  21. Law DA, Chan VW, Datta SK, DeFranco AL: B-cell antigen receptor motifs have redundant signalling capabilities and bind the tyrosine kinases PTK72, Lyn and Fyn. Curr Biol. 1993 Oct 1;3(10):645-57. doi: 10.1016/0960-9822(93)90062-s. [PubMed:15335855 ]
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  27. Sotirellis N, Johnson TM, Hibbs ML, Stanley IJ, Stanley E, Dunn AR, Cheng HC: Autophosphorylation induces autoactivation and a decrease in the Src homology 2 domain accessibility of the Lyn protein kinase. J Biol Chem. 1995 Dec 15;270(50):29773-80. doi: 10.1074/jbc.270.50.29773. [PubMed:8530369 ]
  28. Mano H, Yamashita Y, Miyazato A, Miura Y, Ozawa K: Tec protein-tyrosine kinase is an effector molecule of Lyn protein-tyrosine kinase. FASEB J. 1996 Apr;10(5):637-42. doi: 10.1096/fasebj.10.5.8621063. [PubMed:8621063 ]
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  30. Rawlings DJ, Scharenberg AM, Park H, Wahl MI, Lin S, Kato RM, Fluckiger AC, Witte ON, Kinet JP: Activation of BTK by a phosphorylation mechanism initiated by SRC family kinases. Science. 1996 Feb 9;271(5250):822-5. doi: 10.1126/science.271.5250.822. [PubMed:8629002 ]
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  53. Heiss E, Masson K, Sundberg C, Pedersen M, Sun J, Bengtsson S, Ronnstrand L: Identification of Y589 and Y599 in the juxtamembrane domain of Flt3 as ligand-induced autophosphorylation sites involved in binding of Src family kinases and the protein tyrosine phosphatase SHP2. Blood. 2006 Sep 1;108(5):1542-50. doi: 10.1182/blood-2005-07-008896. Epub 2006 May 9. [PubMed:16684964 ]
  54. Udell CM, Samayawardhena LA, Kawakami Y, Kawakami T, Craig AWB: Fer and Fps/Fes participate in a Lyn-dependent pathway from FcepsilonRI to platelet-endothelial cell adhesion molecule 1 to limit mast cell activation. J Biol Chem. 2006 Jul 28;281(30):20949-20957. doi: 10.1074/jbc.M604252200. Epub 2006 May 26. [PubMed:16731527 ]
  55. Samuels AL, Klinken SP, Ingley E: Liar, a novel Lyn-binding nuclear/cytoplasmic shuttling protein that influences erythropoietin-induced differentiation. Blood. 2009 Apr 16;113(16):3845-56. doi: 10.1182/blood-2008-04-153452. Epub 2008 Dec 8. [PubMed:19064729 ]
  56. Kosmider O, Buet D, Gallais I, Denis N, Moreau-Gachelin F: Erythropoietin down-regulates stem cell factor receptor (Kit) expression in the leukemic proerythroblast: role of Lyn kinase. PLoS One. 2009 May 28;4(5):e5721. doi: 10.1371/journal.pone.0005721. [PubMed:19492092 ]
  57. Li Z, Zhang G, Liu J, Stojanovic A, Ruan C, Lowell CA, Du X: An important role of the SRC family kinase Lyn in stimulating platelet granule secretion. J Biol Chem. 2010 Apr 23;285(17):12559-70. doi: 10.1074/jbc.M109.098756. Epub 2010 Feb 26. [PubMed:20189992 ]
  58. Keck S, Freudenberg M, Huber M: Activation of murine macrophages via TLR2 and TLR4 is negatively regulated by a Lyn/PI3K module and promoted by SHIP1. J Immunol. 2010 May 15;184(10):5809-18. doi: 10.4049/jimmunol.0901423. Epub 2010 Apr 12. [PubMed:20385881 ]
  59. Scapini P, Pereira S, Zhang H, Lowell CA: Multiple roles of Lyn kinase in myeloid cell signaling and function. Immunol Rev. 2009 Mar;228(1):23-40. doi: 10.1111/j.1600-065X.2008.00758.x. [PubMed:19290919 ]
  60. Williams NK, Lucet IS, Klinken SP, Ingley E, Rossjohn J: Crystal structures of the Lyn protein tyrosine kinase domain in its Apo- and inhibitor-bound state. J Biol Chem. 2009 Jan 2;284(1):284-291. doi: 10.1074/jbc.M807850200. Epub 2008 Nov 4. [PubMed:18984583 ]