LYN - Tyrosine-protein kinase Lyn - human protein (Function)
 
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LYN »  Tyrosine-protein kinase Lyn   [ EC 2.7.10.2 ]
 
Protein also known as:  V-yes-1 Yamaguchi sarcoma viral related oncogene homolog.
Gene name:  LYN
Entry whose protein(s) existence is based on evidence at protein level
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1 346 2
GENE REF ISO

Function

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Overview 
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.  
21
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
Enzyme bindingdefinition[GO:0019899]  
1
  • UniProtKB
Glycosphingolipid bindingdefinition[GO:0043208] silver  
1
  • Ortholog Compara
Integrin bindingdefinition[GO:0005178] silver  
1
  • Ortholog Compara
Ion channel bindingdefinition[GO:0044325]  
1
  • BHF-UCL
Non-membrane spanning protein tyrosine kinase activitydefinition[GO:0004715]  
1
  • RefGenome
Phosphoprotein bindingdefinition[GO:0051219] silver  
1
  • Ortholog Compara
Platelet-derived growth factor receptor bindingdefinition[GO:0005161] silver  
1
  • Ortholog Compara
Protein bindingdefinition[GO:0005515]  
23
  • IntAct
  • BHF-UCL
  • UniProtKB
Protein tyrosine kinase activitydefinition[GO:0004713]  
1
  • UniProtKB
Receptor bindingdefinition[GO:0005102]  
1
  • RefGenome
Receptor signaling protein tyrosine kinase activitydefinition[GO:0004716]  
1
  • PINC
SH3 domain bindingdefinition[GO:0017124] silver  
1
  • Ortholog Compara
Ubiquitin protein ligase bindingdefinition[GO:0031625] silver  
1
  • Ortholog Compara
GO biological process 
B cell homeostasisdefinition[GO:0001782]  
1
  • Ortholog Curator
B cell receptor signaling pathwaydefinition[GO:0050853] silver  
1
  • Ortholog Compara
Cellular response to DNA damage stimulusdefinition[GO:0006974]  
2
  • UniProtKB
Cellular response to extracellular stimulusdefinition[GO:0031668] silver  
1
  • Ortholog Compara
Cellular response to heatdefinition[GO:0034605] silver  
1
  • Ortholog Compara
Cellular response to peptide hormone stimulusdefinition[GO:0071375]  
1
  • RefGenome
Cellular response to retinoic aciddefinition[GO:0071300]  
1
  • BHF-UCL
Central nervous system developmentdefinition[GO:0007417]  
1
  • RefGenome
Cytokine secretiondefinition[GO:0050663] silver  
1
  • Ortholog Compara
Dendritic cell differentiationdefinition[GO:0097028]  
2
  • RefGenome
  • Ortholog Curator
Erythrocyte differentiationdefinition[GO:0030218]  
1
  • Ortholog Curator
Fc receptor mediated inhibitory signaling pathwaydefinition[GO:0002774]  
1
  • Ortholog Curator
Fc receptor mediated stimulatory signaling pathwaydefinition[GO:0002431]  
2
  • RefGenome
  • Ortholog Curator
Histamine secretion by mast celldefinition[GO:0002553] silver  
1
  • Ortholog Compara
Immune response-regulating cell surface receptor signaling pathwaydefinition[GO:0002768]  
2
  • UniProtKB
  • Ortholog Curator
Inflammatory responsedefinition[GO:0006954]  
1
  • RefGenome
Innate immune responsedefinition[GO:0045087]  
1
  • RefGenome
Lipopolysaccharide-mediated signaling pathwaydefinition[GO:0031663]  
1
  • Ortholog Curator
Negative regulation of B cell proliferationdefinition[GO:0030889]  
1
  • RefGenome
Negative regulation of cell proliferationdefinition[GO:0008285]  
1
  • UniProtKB
Negative regulation of ERK1 and ERK2 cascadedefinition[GO:0070373]  
1
  • Ortholog Curator
Negative regulation of immune responsedefinition[GO:0050777]  
1
  • UniProtKB
Negative regulation of intracellular signal transductiondefinition[GO:1902532]  
1
  • Ortholog Curator
Negative regulation of MAP kinase activitydefinition[GO:0043407]  
1
  • Ortholog Curator
Negative regulation of mast cell proliferationdefinition[GO:0070667]  
2
  • Ortholog Curator
  • RefGenome
Negative regulation of myeloid leukocyte differentiationdefinition[GO:0002762] silver  
1
  • Ortholog Compara
Negative regulation of protein phosphorylationdefinition[GO:0001933]  
1
  • Ortholog Curator
Negative regulation of toll-like receptor 2 signaling pathwaydefinition[GO:0034136]  
1
  • Ortholog Curator
Negative regulation of toll-like receptor 4 signaling pathwaydefinition[GO:0034144]  
1
  • Ortholog Curator
Neuron projection developmentdefinition[GO:0031175] silver  
1
  • Ortholog Compara
Oligodendrocyte developmentdefinition[GO:0014003] silver  
1
  • Ortholog Compara
Peptidyl-tyrosine autophosphorylationdefinition[GO:0038083]  
1
  • RefGenome
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
1
  • UniProtKB
Platelet degranulationdefinition[GO:0002576]  
2
  • Ortholog Curator
  • RefGenome
Positive regulation of B cell receptor signaling pathwaydefinition[GO:0050861] silver  
1
  • Ortholog Compara
Positive regulation of cell migrationdefinition[GO:0030335] silver  
1
  • Ortholog Compara
Positive regulation of cell proliferationdefinition[GO:0008284]  
1
  • Ortholog Curator
Positive regulation of cellular component movementdefinition[GO:0051272]  
1
  • UniProtKB
Positive regulation of dendritic cell apoptotic processdefinition[GO:2000670]  
2
  • Ortholog Curator
  • RefGenome
Positive regulation of Fc receptor mediated stimulatory signaling pathwaydefinition[GO:0060369] silver  
1
  • Ortholog Compara
Positive regulation of glial cell proliferationdefinition[GO:0060252] silver  
1
  • Ortholog Compara
Positive regulation of mast cell proliferationdefinition[GO:0070668]  
1
  • UniProtKB
Positive regulation of neuron projection developmentdefinition[GO:0010976]  
1
  • BHF-UCL
Positive regulation of oligodendrocyte progenitor proliferationdefinition[GO:0070447] silver  
1
  • Ortholog Compara
Positive regulation of phosphatidylinositol 3-kinase activitydefinition[GO:0043552] silver  
1
  • Ortholog Compara
Positive regulation of stress-activated protein kinase signaling cascadedefinition[GO:0070304]  
1
  • UniProtKB
Positive regulation of tyrosine phosphorylation of STAT proteindefinition[GO:0042531]  
1
  • Ortholog Curator
Protein autophosphorylationdefinition[GO:0046777]  
1
  • UniProtKB
Protein phosphorylationdefinition[GO:0006468]  
1
  • UniProtKB
Regulation of B cell apoptotic processdefinition[GO:0002902]  
1
  • RefGenome
Regulation of B cell receptor signaling pathwaydefinition[GO:0050855]  
2
  • RefGenome
  • Ortholog Curator
Regulation of cell adhesion mediated by integrindefinition[GO:0033628]  
1
  • UniProtKB
Regulation of cytokine productiondefinition[GO:0001817]  
1
  • Ortholog Curator
Regulation of cytokine secretiondefinition[GO:0050707] silver  
1
  • Ortholog Compara
Regulation of ERK1 and ERK2 cascadedefinition[GO:0070372]  
1
  • Ortholog Curator
Regulation of erythrocyte differentiationdefinition[GO:0045646]  
1
  • Ortholog Curator
Regulation of inflammatory responsedefinition[GO:0050727] silver  
1
  • Ortholog Compara
Regulation of mast cell activationdefinition[GO:0033003]  
1
  • Ortholog Curator
Regulation of mast cell degranulationdefinition[GO:0043304]  
2
  • RefGenome
  • Ortholog Curator
Regulation of monocyte chemotaxisdefinition[GO:0090025]  
1
  • UniProtKB
Regulation of platelet aggregationdefinition[GO:0090330]  
2
  • Ortholog Curator
  • RefGenome
Regulation of protein phosphorylationdefinition[GO:0001932]  
1
  • UniProtKB
Regulation of release of sequestered calcium ion into cytosoldefinition[GO:0051279] silver  
1
  • Ortholog Compara
Response to amino aciddefinition[GO:0043200] silver  
1
  • Ortholog Compara
Response to axon injurydefinition[GO:0048678] silver  
1
  • Ortholog Compara
Response to carbohydratedefinition[GO:0009743] silver  
1
  • Ortholog Compara
Response to drugdefinition[GO:0042493] silver  
1
  • Ortholog Compara
Response to hormonedefinition[GO:0009725]  
1
  • Ortholog Curator
Response to insulindefinition[GO:0032868] silver  
1
  • Ortholog Compara
Response to organic cyclic compounddefinition[GO:0014070] silver  
1
  • Ortholog Compara
Response to sterol depletiondefinition[GO:0006991] silver  
1
  • Ortholog Compara
Response to toxic substancedefinition[GO:0009636] silver  
1
  • Ortholog Compara
Signal transductiondefinition[GO:0007165]  
1
  • PINC
Signal transduction by phosphorylationdefinition[GO:0023014]  
1
  • GOC
Tolerance induction to self antigendefinition[GO:0002513]  
3
  • UniProtKB
  • RefGenome
  • Ortholog Curator
Transmembrane receptor protein tyrosine kinase signaling pathwaydefinition[GO:0007169]  
1
  • UniProtKB
Viral processdefinition[GO:0016032]  
1
  • UniProtKB KW
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.2: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
6
  • UniProtKB
  • PROSITE-ProRule
It is regulated in the following manner
Subject to autoinhibition, mediated by intramolecular interactions between the SH2 domain and the C-terminal phosphotyrosine. Phosphorylation at Tyr-397 is required for optimal activity. Phosphorylated by CSK at Tyr-508; phosphorylation at Tyr-508 inhibits kinase activity. Kinase activity is modulated by dephosphorylation by PTPRC/CD45. Inhibited by Dasatinib, PP2, and SU6656.  
3
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
B cell receptor signaling pathway  hsa04662+4067  
Chemokine signaling pathway  hsa04062+4067  
Epithelial cell signaling in Helicobacter pylori infection  hsa05120+4067  
Fc epsilon RI signaling pathway  hsa04664+4067  
Fc gamma R-mediated phagocytosis  hsa04666+4067  
Long-term depression  hsa04730+4067  
According to Reactome, this protein belongs to the following pathways:
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers  REACT_118700  
CD28 co-stimulation  REACT_19183  
Cell surface interactions at the vascular wall  REACT_12051  
CTLA4 inhibitory signaling  REACT_19405  
EPH-ephrin mediated repulsion of cells  REACT_228189  
EPH-Ephrin signaling  REACT_228170  
EPHA-mediated growth cone collapse  REACT_228063  
EPHB-mediated forward signaling  REACT_228085  
Fc epsilon receptor (FCERI) signaling  REACT_163936  
FCERI mediated Ca+2 mobilization  REACT_163834  
FCERI mediated MAPK activation  REACT_163701  
FCERI mediated NF-kB activation  REACT_163994  
FCGR activation  REACT_160274  
GPVI-mediated activation cascade  REACT_1695  
Growth hormone receptor signaling  REACT_111133  
PECAM1 interactions  REACT_12519  
Platelet Adhesion to exposed collagen  REACT_1230  
Regulation of KIT signaling  REACT_111225  
Regulation of signaling by CBL  REACT_23787  
Role of LAT2/NTAL/LAB on calcium mobilization  REACT_163769  
Signaling by SCF-KIT  REACT_111040  
 

Keywords

Biological process 
Adaptive immunity  definition   [KW-1064]
Host-virus interaction  definition   [KW-0945]
Immunity  definition   [KW-0391]
Inflammatory response  definition   [KW-0395]
Innate immunity  definition   [KW-0399]
Molecular function 
Kinase  definition   [KW-0418]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: LYN
GenomeRNAi: 4067
PRO: PR:P07948
Chemistry
GuidetoPHARMACOLOGY: 2060