======= LYN =======
== Gene Information ==
* **Official Symbol**: LYN
* **Official Name**: LYN proto-oncogene, Src family tyrosine kinase
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=4067|4067]]
* **UniProt**: [[https://www.uniprot.org/uniprot/P07948|P07948]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=LYN&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20LYN|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/165120|Open OMIM]]
== Function Summary ==
* **Entrez Summary**: This gene encodes a tyrosine protein kinase, which maybe involved in the regulation of mast cell degranulation, and erythroid differentiation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011].
* **UniProt Summary**: 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, PTK2B/PYK2, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Mediates phosphorylation of the BCR-ABL fusion protein. 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. {ECO:0000269|PubMed:10574931, ECO:0000269|PubMed:10748115, ECO:0000269|PubMed:10891478, ECO:0000269|PubMed:11435302, ECO:0000269|PubMed:11517336, ECO:0000269|PubMed:11825908, ECO:0000269|PubMed:14726379, ECO:0000269|PubMed:15795233, ECO:0000269|PubMed:16467205, ECO:0000269|PubMed:17640867, ECO:0000269|PubMed:17977829, ECO:0000269|PubMed:18056483, ECO:0000269|PubMed:18070987, ECO:0000269|PubMed:18235045, ECO:0000269|PubMed:18577747, ECO:0000269|PubMed:18802065, ECO:0000269|PubMed:19290919, ECO:0000269|PubMed:20028775, ECO:0000269|PubMed:20037584, ECO:0000269|PubMed:7687428}.
|SH2|
|Pkinase Tyr|
|SH3 1|
|Pkinase|
|SH3 2|
|negative regulation of mast cell proliferation|
|positive regulation of mast cell proliferation|
|positive regulation of dendritic cell apoptotic process|
|Fc receptor mediated inhibitory signaling pathway|
|histamine production involved in inflammatory response|
|positive regulation of oligodendrocyte progenitor proliferation|
|phosphorylation-dependent protein binding|
|histamine secretion involved in inflammatory response|
|integrin alpha2-beta1 complex|
|regulation of mast cell proliferation|
|histamine secretion by mast cell|
|postsynaptic specialization, intracellular component|
|tolerance induction to self antigen|
|negative regulation of toll-like receptor 2 signaling pathway|
|glycosphingolipid binding|
|mitochondrial crista|
|immune response-inhibiting cell surface receptor signaling pathway|
|histamine secretion|
|positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process|
|positive regulation of Fc receptor mediated stimulatory signaling pathway|
|regulation of oligodendrocyte progenitor proliferation|
|histamine transport|
|immune response-inhibiting signal transduction|
|positive regulation of aspartic-type peptidase activity|
|negative regulation of toll-like receptor 4 signaling pathway|
|regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process|
|regulation of toll-like receptor 2 signaling pathway|
|response to sterol depletion|
|regulation of dendritic cell apoptotic process|
|regulation of aspartic-type peptidase activity|
|regulation of Fc receptor mediated stimulatory signaling pathway|
|tolerance induction|
|growth hormone receptor signaling pathway via JAK-STAT|
|positive regulation of glial cell proliferation|
|platelet-derived growth factor receptor binding|
|negative regulation of B cell proliferation|
|production of molecular mediator involved in inflammatory response|
|mast cell activation involved in immune response|
|mast cell degranulation|
|regulation of B cell apoptotic process|
|regulation of platelet aggregation|
|azole transport|
|positive regulation of amyloid precursor protein catabolic process|
|mast cell mediated immunity|
|growth hormone receptor signaling pathway|
|regulation of toll-like receptor 4 signaling pathway|
|cellular response to growth hormone stimulus|
|mast cell granule|
|mast cell activation|
|regulation of monocyte chemotaxis|
|regulation of homotypic cell-cell adhesion|
|B cell homeostasis|
|gamma-tubulin binding|
|regulation of B cell receptor signaling pathway|
|ephrin receptor binding|
|positive regulation of leukocyte apoptotic process|
|negative regulation of B cell activation|
|regulation of glial cell proliferation|
|regulation of platelet activation|
|positive regulation of phosphatidylinositol 3-kinase activity|
|dendritic cell differentiation|
|peptidyl-tyrosine autophosphorylation|
|regulation of amyloid precursor protein catabolic process|
|regulation of mast cell degranulation|
|lipopolysaccharide-mediated signaling pathway|
|response to growth hormone|
|regulation of mast cell activation involved in immune response|
|phosphoprotein binding|
|positive regulation of lipid kinase activity|
|negative regulation of toll-like receptor signaling pathway|
|oligodendrocyte development|
|lysosome localization|
|regulation of mast cell activation|
|negative regulation of myeloid leukocyte differentiation|
|regulation of mononuclear cell migration|
|non-membrane spanning protein tyrosine kinase activity|
|regulation of cell adhesion mediated by integrin|
|regulation of erythrocyte differentiation|
|cytokine secretion|
|positive regulation of phospholipid metabolic process|
|response to axon injury|
|regulation of leukocyte degranulation|
|positive regulation of neural precursor cell proliferation|
|regulation of lymphocyte apoptotic process|
|ammonium transport|
|lymphocyte homeostasis|
|regulation of phosphatidylinositol 3-kinase activity|
|T cell costimulation|
|lymphocyte costimulation|
|regulation of myeloid leukocyte mediated immunity|
|extrinsic component of cytoplasmic side of plasma membrane|
|regulation of B cell proliferation|
|regulation of lipid kinase activity|
|regulation of antigen receptor-mediated signaling pathway|
|positive regulation of Ras protein signal transduction|
|negative regulation of ERK1 and ERK2 cascade|
|exocytic process|
|regulation of toll-like receptor signaling pathway|
|positive regulation of tyrosine phosphorylation of STAT protein|
|cellular response to retinoic acid|
|oligodendrocyte differentiation|
|positive regulation of gliogenesis|
|leukocyte homeostasis|
|cellular response to heat|
|positive regulation of small GTPase mediated signal transduction|
|hormone secretion|
|negative regulation of lymphocyte proliferation|
|negative regulation of MAP kinase activity|
|negative regulation of mononuclear cell proliferation|
|negative regulation of myeloid cell differentiation|
|mitochondrial intermembrane space|
|regulation of release of sequestered calcium ion into cytosol|
|regulation of tyrosine phosphorylation of STAT protein|
|negative regulation of leukocyte proliferation|
|regulation of blood coagulation|
|regulation of hemostasis|
|kinase activity|
|erythrocyte differentiation|
|hormone transport|
|regulation of leukocyte apoptotic process|
|regulation of coagulation|
|positive regulation of receptor signaling pathway via JAK-STAT|
|regulation of phospholipid metabolic process|
|positive regulation of phosphatidylinositol 3-kinase signaling|
|ephrin receptor signaling pathway|
|positive regulation of receptor signaling pathway via STAT|
|regulation of neural precursor cell proliferation|
|protein tyrosine kinase activity|
|erythrocyte homeostasis|
|regulation of calcium ion transport into cytosol|
|negative regulation of leukocyte differentiation|
|cell-cell adherens junction|
|myeloid cell homeostasis|
|glial cell development|
|response to retinoic acid|
|response to heat|
|regulation of leukocyte chemotaxis|
|stimulatory C-type lectin receptor signaling pathway|
|response to amino acid|
|regulation of myeloid leukocyte differentiation|
|innate immune response activating cell surface receptor signaling pathway|
|regulation of gliogenesis|
|regulation of phosphatidylinositol 3-kinase signaling|
|regulation of sequestering of calcium ion|
|ion channel binding|
|B cell receptor signaling pathway|
|platelet degranulation|
|regulation of receptor signaling pathway via JAK-STAT|
|SH3 domain binding|
|integrin binding|
|negative regulation of protein serine/threonine kinase activity|
|regulation of receptor signaling pathway via STAT|
|Fc-gamma receptor signaling pathway involved in phagocytosis|
|immune response-regulating cell surface receptor signaling pathway involved in phagocytosis|
|negative regulation of hemopoiesis|
|positive regulation of leukocyte proliferation|
|Fc receptor mediated stimulatory signaling pathway|
|platelet activation|
|regulation of wound healing|
|Fc-gamma receptor signaling pathway|
|positive regulation of lipid metabolic process|
|peptidyl-tyrosine phosphorylation|
|negative regulation of lymphocyte activation|
|peptidyl-tyrosine modification|
|regulation of calcium ion transmembrane transport|
|negative regulation of immune response|
|cytokine production|
|protein secretion|
|establishment of protein localization to extracellular region|
|regulation of regulated secretory pathway|
|protein localization to extracellular region|
|negative regulation of MAPK cascade|
|regulation of response to wounding|
|positive regulation of stress-activated protein kinase signaling cascade|
|signal release|
|glial cell differentiation|
|response to carbohydrate|
|positive regulation of endopeptidase activity|
|peptide secretion|
|Fc-epsilon receptor signaling pathway|
|negative regulation of leukocyte activation|
|response to temperature stimulus|
|neurotransmitter transport|
|cellular response to lipopolysaccharide|
|positive regulation of peptidyl-tyrosine phosphorylation|
|positive regulation of peptidase activity|
|cellular response to molecule of bacterial origin|
|protein autophosphorylation|
|regulation of leukocyte migration|
|negative regulation of cell activation|
|homeostasis of number of cells|
|positive regulation of T cell activation|
|regulation of cytokine secretion|
|regulation of leukocyte mediated immunity|
|regulation of B cell activation|
|cellular response to acid chemical|
|regulation of lymphocyte proliferation|
|regulation of mononuclear cell proliferation|
|regulation of chemotaxis|
|gliogenesis|
|cellular response to biotic stimulus|
|positive regulation of leukocyte cell-cell adhesion|
|positive regulation of immune effector process|
|myeloid cell differentiation|
|regulation of leukocyte proliferation|
|regulation of exocytosis|
|negative regulation of protein kinase activity|
|regulation of myeloid cell differentiation|
|membrane raft|
|response to insulin|
|innate immune response-activating signal transduction|
|regulation of stress-activated protein kinase signaling cascade|
|Fc receptor signaling pathway|
|regulation of Ras protein signal transduction|
|negative regulation of kinase activity|
|regulation of calcium ion transport|
|regulation of peptidyl-tyrosine phosphorylation|
|postsynaptic density|
|positive regulation of cell-cell adhesion|
|activation of innate immune response|
|cellular response to extracellular stimulus|
|cellular response to peptide hormone stimulus|
|regulation of leukocyte differentiation|
|negative regulation of transferase activity|
|positive regulation of neuron projection development|
|regulation of ERK1 and ERK2 cascade|
|ubiquitin protein ligase binding|
|blood coagulation|
|coagulation|
|antigen receptor-mediated signaling pathway|
|regulation of leukocyte cell-cell adhesion|
|hemostasis|
|response to lipopolysaccharide|
|regulation of T cell activation|
|response to molecule of bacterial origin|
|cellular response to peptide|
|phagocytosis|
|leukocyte differentiation|
|regulation of cation transmembrane transport|
|cellular response to external stimulus|
|signaling receptor binding|
|regulation of inflammatory response|
|positive regulation of innate immune response|
|regulation of MAP kinase activity|
|response to acid chemical|
|regulation of small GTPase mediated signal transduction|
|glutamatergic synapse|
|regulation of intracellular transport|
|positive regulation of proteolysis|
|positive regulation of lymphocyte activation|
|positive regulation of response to biotic stimulus|
|establishment of organelle localization|
|positive regulation of neuron differentiation|
|leukocyte migration|
|positive regulation of cell projection organization|
|regulation of metal ion transport|
|response to peptide hormone|
|regulation of lipid metabolic process|
|regulation of cell-cell adhesion|
|positive regulation of cell adhesion|
|positive regulation of leukocyte activation|
|negative regulation of protein phosphorylation|
|regulation of endopeptidase activity|
|positive regulation of cell activation|
|negative regulation of immune system process|
|regulation of peptidase activity|
|negative regulation of phosphorylation|
|immune response-activating cell surface receptor signaling pathway|
|regulation of hemopoiesis|
|regulation of innate immune response|
|regulation of protein secretion|
|regulation of immune effector process|
|positive regulation of neurogenesis|
|response to peptide|
|positive regulation of defense response|
|regulation of ion transmembrane transport|
|wound healing|
|immune response-regulating cell surface receptor signaling pathway|
|regulation of peptide secretion|
|regulation of body fluid levels|
|regulation of neuron projection development|
|inflammatory response|
|positive regulation of cell migration|
|negative regulation of intracellular signal transduction|
|response to toxic substance|
|positive regulation of multi-organism process|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|leukocyte degranulation|
|regulation of lymphocyte activation|
|regulation of protein serine/threonine kinase activity|
|myeloid leukocyte mediated immunity|
|cellular response to lipid|
|myeloid cell activation involved in immune response|
|positive regulation of cell motility|
|regulation of response to biotic stimulus|
|response to extracellular stimulus|
|regulation of hormone levels|
|positive regulation of nervous system development|
|positive regulation of cellular component movement|
|positive regulation of cell development|
|regulation of vesicle-mediated transport|
|positive regulation of locomotion|
|hemopoiesis|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|immune response-activating signal transduction|
|regulation of transmembrane transport|
|response to wounding|
|positive regulation of kinase activity|
|organelle localization|
|myeloid leukocyte activation|
|negative regulation of protein modification process|
|immune response-regulating signaling pathway|
|cellular response to organonitrogen compound|
|positive regulation of response to external stimulus|
|regulation of leukocyte activation|
|cellular response to hormone stimulus|
|hematopoietic or lymphoid organ development|
|adaptive immune response|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|activation of immune response|
|regulation of cell activation|
|positive regulation of apoptotic process|
|positive regulation of programmed cell death|
|immune system development|
|positive regulation of transferase activity|
|regulation of neuron differentiation|
|cellular response to nitrogen compound|
|neuron projection development|
|negative regulation of cell population proliferation|
|regulation of cell adhesion|
|intracellular membrane-bounded organelle|
|response to bacterium|
|regulation of plasma membrane bounded cell projection organization|
|regulation of cytokine production|
|perinuclear region of cytoplasm|
|positive regulation of cell death|
|regulation of ion transport|
|viral process|
|regulated exocytosis|
|regulation of protein transport|
|regulation of cell projection organization|
|negative regulation of cell differentiation|
|enzyme linked receptor protein signaling pathway|
|regulation of proteolysis|
|regulation of cellular response to stress|
|regulation of peptide transport|
|regulation of establishment of protein localization|
|regulation of secretion by cell|
|regulation of MAPK cascade|
|regulation of defense response|
|leukocyte mediated immunity|
|innate immune response|
|positive regulation of hydrolase activity|
|cellular response to DNA damage stimulus|
|regulation of multi-organism process|
|symbiotic process|
|negative regulation of catalytic activity|
|exocytosis|
|regulation of protein kinase activity|
|regulation of secretion|
|neuron development|
|regulation of neurogenesis|
|interspecies interaction between organisms|
|cation transport|
|regulation of cell migration|
|response to lipid|
|positive regulation of immune response|
|regulation of kinase activity|
|peptidyl-amino acid modification|
|response to hormone|
|regulation of cell motility|
|positive regulation of cell population proliferation|
|regulation of cellular localization|
|response to organic cyclic compound|
|regulation of nervous system development|
|leukocyte activation|
|regulation of cell development|
|negative regulation of developmental process|
|defense response to other organism|
|cell migration|
|positive regulation of cell differentiation|
|protein phosphorylation|
|regulation of transferase activity|
|central nervous system development|
|regulation of locomotion|
|Golgi apparatus|
|regulation of cellular component movement|
|response to organonitrogen compound|
|secretion by cell|
|neuron differentiation|
|positive regulation of protein phosphorylation|
|response to drug|
|positive regulation of intracellular signal transduction|
|regulation of protein localization|
|negative regulation of cellular protein metabolic process|
|export from cell|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|cell activation|
|localization of cell|
|cell motility|
|response to nitrogen compound|
|immune effector process|
|regulation of response to external stimulus|
|negative regulation of protein metabolic process|
|cell-cell signaling|
|plasma membrane bounded cell projection organization|
|secretion|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|negative regulation of molecular function|
|positive regulation of immune system process|
|regulation of immune response|
|cell projection organization|
|response to abiotic stimulus|
|negative regulation of multicellular organismal process|
|positive regulation of cellular component organization|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|negative regulation of signal transduction|
|regulation of hydrolase activity|
|phosphorylation|
|response to other organism|
|response to external biotic stimulus|
|locomotion|
|response to biotic stimulus|
|defense response|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of developmental process|
|ion transport|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|response to endogenous stimulus|
|regulation of response to stress|
|ATP binding|
|protein transport|
|intracellular transport|
|generation of neurons|
|peptide transport|
|regulation of apoptotic process|
|movement of cell or subcellular component|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|amide transport|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|establishment of protein localization|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|neurogenesis|
|homeostatic process|
|cell development|
|regulation of immune system process|
|positive regulation of signal transduction|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|positive regulation of multicellular organismal process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|establishment of localization in cell|
|nitrogen compound transport|
|regulation of protein modification process|
|regulation of transport|
|immune response|
|vesicle-mediated transport|
\\
=== CRISPR Data ===
^Screen^Score^
|[[:results:exp51|Nifuroxazide 1μM R01 exp51]]|-2.01|
|[[:results:exp372|Ibrutinib 1μM R07 exp372]]|-1.81|
|[[:results:exp312|2-Methoxyestradiol 0.55 to 1μM on day4 R07 exp312]]|1.73|
|[[:results:exp230|Epigallocatechin gallate 20μM R05 exp230]]|1.78|
|[[:results:exp455|Benzoate 10000μM R08 exp455]]|1.83|
|[[:results:exp498|Lead acetate 2000μM R08 exp498 no dilution day6]]|1.85|
No correlation found to any other genes in chemogenomics.
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 18357
* **Expression level (log2 read counts)**: 6.33
{{:chemogenomics:nalm6 dist.png?nolink |}}