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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1 172 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'.  
19
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Enzyme bindingdefinition[GO:0019899]  
1
  • IPIUniProtKB
Glycosphingolipid bindingdefinition[GO:0043208] silver  
  • IEAOrtholog Compara
Integrin bindingdefinition[GO:0005178] silver  
  • IEAOrtholog Compara
Ion channel bindingdefinition[GO:0044325]  
1
  • IPIBHF-UCL
Phosphoprotein bindingdefinition[GO:0051219] silver  
  • IEAOrtholog Compara
Platelet-derived growth factor receptor bindingdefinition[GO:0005161] silver  
  • IEAOrtholog Compara
Protein bindingdefinition[GO:0005515]  
21
  • IPIIntAct
  • IPIBHF-UCL
  • IPIUniProtKB
Protein tyrosine kinase activitydefinition[GO:0004713]  
1
  • IDAUniProtKB
Receptor signaling protein tyrosine kinase activitydefinition[GO:0004716]  
1
  • TASPINC
SH3 domain bindingdefinition[GO:0017124] silver  
  • IEAOrtholog Compara
Ubiquitin protein ligase bindingdefinition[GO:0031625] silver  
  • IEAOrtholog Compara
GO biological process 
B cell homeostasisdefinition[GO:0001782]  
  • ISSOrtholog Curator
B cell receptor signaling pathwaydefinition[GO:0050853] silver  
  • IEAOrtholog Compara
Cellular response to DNA damage stimulusdefinition[GO:0006974]  
2
  • IDAUniProtKB
Cellular response to extracellular stimulusdefinition[GO:0031668] silver  
  • IEAOrtholog Compara
Cellular response to heatdefinition[GO:0034605] silver  
  • IEAOrtholog Compara
Cellular response to retinoic aciddefinition[GO:0071300]  
1
  • IMPBHF-UCL
Cytokine secretiondefinition[GO:0050663] silver  
  • IEAOrtholog Compara
Dendritic cell differentiationdefinition[GO:0097028]  
  • ISSOrtholog Curator
Erythrocyte differentiationdefinition[GO:0030218]  
  • ISSOrtholog Curator
Fc receptor mediated inhibitory signaling pathwaydefinition[GO:0002774]  
  • ISSOrtholog Curator
Fc receptor mediated stimulatory signaling pathwaydefinition[GO:0002431]  
  • ISSOrtholog Curator
Histamine secretion by mast celldefinition[GO:0002553] silver  
  • IEAOrtholog Compara
Immune response-regulating cell surface receptor signaling pathwaydefinition[GO:0002768]  
1
  • TASUniProtKB
  • ISSOrtholog Curator
Intrinsic apoptotic signaling pathway in response to DNA damagedefinition[GO:0008630]  
1
  • ICUniProtKB
Lipopolysaccharide-mediated signaling pathwaydefinition[GO:0031663]  
  • ISSOrtholog Curator
Negative regulation of B cell proliferationdefinition[GO:0030889] silver  
  • IEAOrtholog Compara
Negative regulation of cell proliferationdefinition[GO:0008285]  
1
  • IMPUniProtKB
Negative regulation of ERK1 and ERK2 cascadedefinition[GO:0070373]  
  • ISSOrtholog Curator
Negative regulation of immune responsedefinition[GO:0050777]  
1
  • TASUniProtKB
Negative regulation of intracellular signal transductiondefinition[GO:1902532]  
  • ISSOrtholog Curator
Negative regulation of MAP kinase activitydefinition[GO:0043407]  
  • ISSOrtholog Curator
Negative regulation of mast cell proliferationdefinition[GO:0070667]  
  • ISSOrtholog Curator
Negative regulation of myeloid leukocyte differentiationdefinition[GO:0002762] silver  
  • IEAOrtholog Compara
Negative regulation of protein phosphorylationdefinition[GO:0001933]  
  • ISSOrtholog Curator
Negative regulation of toll-like receptor 2 signaling pathwaydefinition[GO:0034136]  
  • ISSOrtholog Curator
Negative regulation of toll-like receptor 4 signaling pathwaydefinition[GO:0034144]  
  • ISSOrtholog Curator
Neuron projection developmentdefinition[GO:0031175] silver  
  • IEAOrtholog Compara
Oligodendrocyte developmentdefinition[GO:0014003] silver  
  • IEAOrtholog Compara
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
1
  • IDAUniProtKB
Platelet degranulationdefinition[GO:0002576]  
  • ISSOrtholog Curator
Positive regulation of cell migrationdefinition[GO:0030335] silver  
  • IEAOrtholog Compara
Positive regulation of cell proliferationdefinition[GO:0008284]  
  • ISSOrtholog Curator
Positive regulation of cellular component movementdefinition[GO:0051272]  
1
  • IDAUniProtKB
Positive regulation of dendritic cell apoptotic processdefinition[GO:2000670]  
  • ISSOrtholog Curator
Positive regulation of Fc receptor mediated stimulatory signaling pathwaydefinition[GO:0060369] silver  
  • IEAOrtholog Compara
Positive regulation of glial cell proliferationdefinition[GO:0060252] silver  
  • IEAOrtholog Compara
Positive regulation of mast cell proliferationdefinition[GO:0070668]  
1
  • IMPUniProtKB
Positive regulation of neuron projection developmentdefinition[GO:0010976]  
1
  • IMPBHF-UCL
Positive regulation of oligodendrocyte progenitor proliferationdefinition[GO:0070447] silver  
  • IEAOrtholog Compara
Positive regulation of phosphatidylinositol 3-kinase activitydefinition[GO:0043552] silver  
  • IEAOrtholog Compara
Positive regulation of stress-activated protein kinase signaling cascadedefinition[GO:0070304]  
1
  • IDAUniProtKB
Positive regulation of tyrosine phosphorylation of STAT proteindefinition[GO:0042531]  
  • ISSOrtholog Curator
Protein autophosphorylationdefinition[GO:0046777]  
1
  • IDAUniProtKB
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDAUniProtKB
Regulation of B cell apoptotic processdefinition[GO:0002902] silver  
  • IEAOrtholog Compara
Regulation of B cell receptor signaling pathwaydefinition[GO:0050855]  
  • ISSOrtholog Curator
Regulation of cell adhesion mediated by integrindefinition[GO:0033628]  
1
  • IMPUniProtKB
Regulation of cytokine productiondefinition[GO:0001817]  
  • ISSOrtholog Curator
Regulation of cytokine secretiondefinition[GO:0050707] silver  
  • IEAOrtholog Compara
Regulation of ERK1 and ERK2 cascadedefinition[GO:0070372]  
  • ISSOrtholog Curator
Regulation of erythrocyte differentiationdefinition[GO:0045646]  
  • ISSOrtholog Curator
Regulation of inflammatory responsedefinition[GO:0050727] silver  
  • IEAOrtholog Compara
Regulation of mast cell activationdefinition[GO:0033003]  
  • ISSOrtholog Curator
Regulation of mast cell degranulationdefinition[GO:0043304]  
  • ISSOrtholog Curator
Regulation of monocyte chemotaxisdefinition[GO:0090025]  
1
  • IMPUniProtKB
Regulation of platelet aggregationdefinition[GO:0090330]  
  • ISSOrtholog Curator
Regulation of protein phosphorylationdefinition[GO:0001932]  
1
  • TASUniProtKB
Regulation of release of sequestered calcium ion into cytosoldefinition[GO:0051279] silver  
  • IEAOrtholog Compara
Response to amino aciddefinition[GO:0043200] silver  
  • IEAOrtholog Compara
Response to axon injurydefinition[GO:0048678] silver  
  • IEAOrtholog Compara
Response to carbohydratedefinition[GO:0009743] silver  
  • IEAOrtholog Compara
Response to drugdefinition[GO:0042493] silver  
  • IEAOrtholog Compara
Response to hormonedefinition[GO:0009725]  
  • ISSOrtholog Curator
Response to insulindefinition[GO:0032868] silver  
  • IEAOrtholog Compara
Response to organic cyclic compounddefinition[GO:0014070] silver  
  • IEAOrtholog Compara
Response to sterol depletiondefinition[GO:0006991] silver  
  • IEAOrtholog Compara
Response to toxic substancedefinition[GO:0009636] silver  
  • IEAOrtholog Compara
Signal transductiondefinition[GO:0007165]  
1
  • TASPINC
Signal transduction by phosphorylationdefinition[GO:0023014]  
1
  • TASGOC
Tolerance induction to self antigendefinition[GO:0002513]  
1
  • TASUniProtKB
  • ISSOrtholog Curator
Transmembrane receptor protein tyrosine kinase signaling pathwaydefinition[GO:0007169]  
1
  • IMPUniProtKB
Viral processdefinition[GO:0016032]  
  • IEAUniProtKB 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.  
4
  • CuratedUniProtKB
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.  
2
  • CuratedUniProtKB
 
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:
Hemostasis  REACT_604  
Immune System  REACT_6900  
Signal Transduction  REACT_111102  
 

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