ID:LYN_HUMAN DESCRIPTION: RecName: Full=Tyrosine-protein kinase Lyn; EC=2.7.10.2; AltName: Full=Lck/Yes-related novel protein tyrosine kinase; AltName: Full=V-yes-1 Yamaguchi sarcoma viral related oncogene homolog; AltName: Full=p53Lyn; AltName: Full=p56Lyn; 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, 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'. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ENZYME REGULATION: 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. SUBUNIT: Interacts with TEC (By similarity). Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with LIME1 and with CD79A upon activation of the B-cell antigen receptor. Interacts with the B-cell receptor complex. Interacts with phosphorylated THEMIS2. Interacts with EPOR (By similarity). Interacts with MS4A2/FCER1B. Interaction (via the SH2 and SH3 domains) with MUC1 is stimulated by IL7 and the subsequent phosphorylation increases the binding between MUC1 and CTNNB1/beta-catenin. Interacts with Epstein-Barr virus LMP2A. Interacts with Herpes virus saimiri tyrosine kinase interacting protein (Tip). Interacts with ADAM15. Interacts with NDFIP2 and more weakly with NDFIP1. Interacts with FASLG. Interacts with KIT. Interacts with HCLS1. Interacts with FCGR2B. Interacts with FCGR1A; the interaction may be indirect. Interacts with CD19, CD22, CD79A and CD79B. Interacts (via SH3 domain) with PPP1R15A and PDE4A. Interacts with TGFB1I1. Interacts (via SH3 domain) with PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase; this interaction enhances phosphatidylinositol 3-kinase activity. Interacts with CSF2RB, the common subunit of the IL3, IL5 and CSF2 receptors. Interacts with PAG1; identified in a complex with PAG1 and STAT3. Interacts with ABL1. Interacts with PTPN6/SHP-1. Interacts (via SH3 domain) with SCIMP (via prolin-rich region). Interacts with LPXN (via LD motif 3) and the interaction is induced upon B-cell antigen receptor (BCR) activation. Interacts (via ankyrin repeat region) with LYN (via SH3-domain) in an activation-independent status of LYN (By similarity). Forms a multiprotein complex with LYN and HS1 (By similarity). INTERACTION: O92972:- (xeno); NbExp=2; IntAct=EBI-79452, EBI-710506; P27958:- (xeno); NbExp=5; IntAct=EBI-79452, EBI-706378; Q9WMX2:- (xeno); NbExp=3; IntAct=EBI-79452, EBI-710918; Q8R5G7:Arap3 (xeno); NbExp=2; IntAct=EBI-79452, EBI-621463; P20273:CD22; NbExp=2; IntAct=EBI-79452, EBI-78277; P25063:CD24; NbExp=6; IntAct=EBI-79452, EBI-6267018; P11049:CD37; NbExp=5; IntAct=EBI-79452, EBI-6139068; P46527:CDKN1B; NbExp=2; IntAct=EBI-79452, EBI-519280; Q9HCN6:GP6; NbExp=2; IntAct=EBI-79452, EBI-515278; P05556:ITGB1; NbExp=4; IntAct=EBI-79452, EBI-703066; SUBCELLULAR LOCATION: Cell membrane. Nucleus. Cytoplasm. Cytoplasm, perinuclear region. Golgi apparatus. Note=Accumulates in the nucleus by inhibition of CRM1-mediated nuclear export. Nuclear accumulation is increased by inhibition of its kinase activity. The trafficking from the Golgi apparatus to the plasma membrane occurs in a kinase domain-dependent but kinase activity independent manner and is mediated by exocytic vesicular transport. Detected on plasma membrane lipid rafts. TISSUE SPECIFICITY: Detected in monocytes (at protein level). Detected in placenta, and in fetal brain, lung, liver and kidney. Widely expressed in a variety of organs, tissues, and cell types such as epidermoid, hematopoietic, and neuronal cells. Expressed in primary neuroblastoma tumors. DOMAIN: The protein kinase domain plays an important role in its localization in the cell membrane. PTM: Ubiquitinated by CBL, leading to its degradation. Ubiquitination is SH3-dependent. PTM: Autophosphorylated. Phosphorylated on tyrosine residues in response to KIT signaling. Phosphorylation at Tyr-397 is required for optimal activity. Phosphorylation at Tyr-508 inhibits kinase activity. Phosphorylated at Tyr-508 by CSK. Dephosphorylated by PTPRC/CD45. Becomes rapidly phosphorylated upon activation of the B-cell receptor and the immunoglobulin receptor FCGR1A. DISEASE: Note=Constitutively phosphorylated and activated in cells from a number of chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML) patients. Mediates phosphorylation of the BCR-ABL fusion protein. Abnormally elevated expression levels or activation of LYN signaling may play a role in survival and proliferation of some types of cancer cells. SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 1 SH2 domain. SIMILARITY: Contains 1 SH3 domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P07948
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0001782 B cell homeostasis GO:0001817 regulation of cytokine production GO:0001932 regulation of protein phosphorylation GO:0001933 negative regulation of protein phosphorylation GO:0001934 positive regulation of protein phosphorylation GO:0002223 stimulatory C-type lectin receptor signaling pathway GO:0002250 adaptive immune response GO:0002376 immune system process GO:0002431 Fc receptor mediated stimulatory signaling pathway GO:0002513 tolerance induction to self antigen GO:0002553 histamine secretion by mast cell GO:0002576 platelet degranulation GO:0002762 negative regulation of myeloid leukocyte differentiation GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0002774 Fc receptor mediated inhibitory signaling pathway GO:0002902 regulation of B cell apoptotic process GO:0006468 protein phosphorylation GO:0006954 inflammatory response GO:0006974 cellular response to DNA damage stimulus GO:0006991 response to sterol depletion GO:0007165 signal transduction GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway GO:0007417 central nervous system development GO:0007596 blood coagulation GO:0008284 positive regulation of cell proliferation GO:0008285 negative regulation of cell proliferation GO:0009636 response to toxic substance GO:0009725 response to hormone GO:0009743 response to carbohydrate GO:0010976 positive regulation of neuron projection development GO:0014003 oligodendrocyte development GO:0014070 response to organic cyclic compound GO:0016032 viral process GO:0016310 phosphorylation GO:0018108 peptidyl-tyrosine phosphorylation GO:0023014 signal transduction by protein phosphorylation GO:0030097 hemopoiesis GO:0030168 platelet activation GO:0030218 erythrocyte differentiation GO:0030335 positive regulation of cell migration GO:0030889 negative regulation of B cell proliferation GO:0031175 neuron projection development GO:0031295 T cell costimulation GO:0031663 lipopolysaccharide-mediated signaling pathway GO:0031668 cellular response to extracellular stimulus GO:0032868 response to insulin GO:0033003 regulation of mast cell activation GO:0033628 regulation of cell adhesion mediated by integrin GO:0034136 negative regulation of toll-like receptor 2 signaling pathway GO:0034144 negative regulation of toll-like receptor 4 signaling pathway GO:0034605 cellular response to heat GO:0035556 intracellular signal transduction GO:0038083 peptidyl-tyrosine autophosphorylation GO:0038095 Fc-epsilon receptor signaling pathway GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis GO:0042327 positive regulation of phosphorylation GO:0042493 response to drug GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein GO:0043200 response to amino acid GO:0043304 regulation of mast cell degranulation GO:0043407 negative regulation of MAP kinase activity GO:0043434 response to peptide hormone GO:0043552 positive regulation of phosphatidylinositol 3-kinase activity GO:0045087 innate immune response GO:0045646 regulation of erythrocyte differentiation GO:0046777 protein autophosphorylation GO:0048013 ephrin receptor signaling pathway GO:0048678 response to axon injury GO:0050663 cytokine secretion GO:0050707 regulation of cytokine secretion GO:0050727 regulation of inflammatory response GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation GO:0050777 negative regulation of immune response GO:0050853 B cell receptor signaling pathway GO:0050855 regulation of B cell receptor signaling pathway GO:0050861 positive regulation of B cell receptor signaling pathway GO:0050900 leukocyte migration GO:0051272 positive regulation of cellular component movement GO:0051279 regulation of release of sequestered calcium ion into cytosol GO:0060252 positive regulation of glial cell proliferation GO:0060369 positive regulation of Fc receptor mediated stimulatory signaling pathway GO:0060397 JAK-STAT cascade involved in growth hormone signaling pathway GO:0070304 positive regulation of stress-activated protein kinase signaling cascade GO:0070372 regulation of ERK1 and ERK2 cascade GO:0070373 negative regulation of ERK1 and ERK2 cascade GO:0070447 positive regulation of oligodendrocyte progenitor proliferation GO:0070667 negative regulation of mast cell proliferation GO:0070668 positive regulation of mast cell proliferation GO:0071300 cellular response to retinoic acid GO:0090025 regulation of monocyte chemotaxis GO:0090330 regulation of platelet aggregation GO:0097028 dendritic cell differentiation GO:1902532 negative regulation of intracellular signal transduction GO:1902961 positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process GO:2000670 positive regulation of dendritic cell apoptotic process
M16038 - Human lyn mRNA encoding a tyrosine kinase. BC126456 - Homo sapiens v-yes-1 Yamaguchi sarcoma viral related oncogene homolog, mRNA (cDNA clone MGC:161734 IMAGE:8992172), complete cds. BC126458 - Homo sapiens v-yes-1 Yamaguchi sarcoma viral related oncogene homolog, mRNA (cDNA clone MGC:161736 IMAGE:8992174), complete cds. BC059394 - Homo sapiens v-yes-1 Yamaguchi sarcoma viral related oncogene homolog, mRNA (cDNA clone IMAGE:30332044), partial cds. BC068551 - Homo sapiens v-yes-1 Yamaguchi sarcoma viral related oncogene homolog, mRNA (cDNA clone IMAGE:30334379), partial cds. AK290494 - Homo sapiens cDNA FLJ75641 complete cds, highly similar to Homo sapiens v-yes-1 Yamaguchi sarcoma viral related oncogene homolog (LYN), mRNA. BC075001 - Homo sapiens v-yes-1 Yamaguchi sarcoma viral related oncogene homolog, mRNA (cDNA clone MGC:103991 IMAGE:30915399), complete cds. BC075002 - Homo sapiens v-yes-1 Yamaguchi sarcoma viral related oncogene homolog, mRNA (cDNA clone MGC:104151 IMAGE:30915611), complete cds. M79321 - Human Lyn B protein mRNA, complete cds. AB527528 - Synthetic construct DNA, clone: pF1KB5955, Homo sapiens LYN gene for v-yes-1 Yamaguchi sarcoma viral related oncogene homolog, without stop codon, in Flexi system. HQ258300 - Synthetic construct Homo sapiens clone IMAGE:100072609 Unknown protein gene, encodes complete protein. KJ891560 - Synthetic construct Homo sapiens clone ccsbBroadEn_00954 LYN gene, encodes complete protein. KJ897152 - Synthetic construct Homo sapiens clone ccsbBroadEn_06546 LYN gene, encodes complete protein. AK298677 - Homo sapiens cDNA FLJ56471 complete cds, highly similar to Tyrosine-protein kinase Lyn (EC 2.7.10.2). AK130135 - Homo sapiens cDNA FLJ26625 fis, clone MPC03823, highly similar to Tyrosine-protein kinase LYN (EC 2.7.1.112). JD460338 - Sequence 441362 from Patent EP1572962. JD382310 - Sequence 363334 from Patent EP1572962. JD103353 - Sequence 84377 from Patent EP1572962. JD057362 - Sequence 38386 from Patent EP1572962. JD405340 - Sequence 386364 from Patent EP1572962. JD083678 - Sequence 64702 from Patent EP1572962. JD493559 - Sequence 474583 from Patent EP1572962. JD560454 - Sequence 541478 from Patent EP1572962. JD447626 - Sequence 428650 from Patent EP1572962. JD292270 - Sequence 273294 from Patent EP1572962. JD248588 - Sequence 229612 from Patent EP1572962. JD424477 - Sequence 405501 from Patent EP1572962. JD352328 - Sequence 333352 from Patent EP1572962. JD358389 - Sequence 339413 from Patent EP1572962. JD326905 - Sequence 307929 from Patent EP1572962. JD430901 - Sequence 411925 from Patent EP1572962. JD558719 - Sequence 539743 from Patent EP1572962. JD442894 - Sequence 423918 from Patent EP1572962. JD335279 - Sequence 316303 from Patent EP1572962. JD335280 - Sequence 316304 from Patent EP1572962. JD254675 - Sequence 235699 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_bcrPathway - BCR Signaling Pathway h_ephA4Pathway - Eph Kinases and ephrins support platelet aggregation h_fcer1Pathway - Fc Epsilon Receptor I Signaling in Mast Cells h_ptdinsPathway - Phosphoinositides and their downstream targets.
Reactome (by CSHL, EBI, and GO)
Protein P07948 (Reactome details) participates in the following event(s):
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
