CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-002569
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Tyrosine-protein kinase Lyn 
Protein Synonyms/Alias
 Lck/Yes-related novel protein tyrosine kinase; V-yes-1 Yamaguchi sarcoma viral related oncogene homolog; p53Lyn; p56Lyn 
Gene Name
 LYN 
Gene Synonyms/Alias
 JTK8 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
9GCIKSKGKDSLSDDGubiquitination[1]
20SDDGVDLKTQPVRNTubiquitination[1, 2]
101EEHGEWWKAKSLLTKubiquitination[3]
213DMIKHYQKQADGLCRubiquitination[4]
477DELYDIMKMCWKEKAubiquitination[3, 4]
Reference
 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [4] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094] 
Functional Description
 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'. 
Sequence Annotation
 DOMAIN 63 123 SH3.
 DOMAIN 129 226 SH2.
 DOMAIN 247 501 Protein kinase.
 NP_BIND 253 261 ATP (By similarity).
 ACT_SITE 367 367 Proton acceptor (By similarity).
 BINDING 275 275 ATP (By similarity).
 MOD_RES 6 6 Phosphoserine.
 MOD_RES 11 11 Phosphoserine.
 MOD_RES 13 13 Phosphoserine.
 MOD_RES 30 30 Phosphothreonine.
 MOD_RES 32 32 Phosphotyrosine.
 MOD_RES 37 37 Phosphothreonine.
 MOD_RES 193 193 Phosphotyrosine.
 MOD_RES 194 194 Phosphotyrosine.
 MOD_RES 228 228 Phosphoserine.
 MOD_RES 265 265 Phosphotyrosine.
 MOD_RES 306 306 Phosphotyrosine.
 MOD_RES 316 316 Phosphotyrosine.
 MOD_RES 397 397 Phosphotyrosine; by autocatalysis.
 MOD_RES 460 460 Phosphotyrosine.
 MOD_RES 473 473 Phosphotyrosine.
 MOD_RES 489 489 Phosphothreonine.
 MOD_RES 502 502 Phosphothreonine.
 MOD_RES 508 508 Phosphotyrosine; by autocatalysis, CSK
 LIPID 2 2 N-myristoyl glycine (Probable).
 LIPID 3 3 S-palmitoyl cysteine (Probable).  
Keyword
 3D-structure; Adaptive immunity; Alternative splicing; ATP-binding; Cell membrane; Complete proteome; Cytoplasm; Golgi apparatus; Host-virus interaction; Immunity; Inflammatory response; Innate immunity; Kinase; Lipoprotein; Membrane; Myristate; Nucleotide-binding; Nucleus; Palmitate; Phosphoprotein; Polymorphism; Proto-oncogene; Reference proteome; SH2 domain; SH3 domain; Transferase; Tyrosine-protein kinase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 512 AA 
Protein Sequence
MGCIKSKGKD SLSDDGVDLK TQPVRNTERT IYVRDPTSNK QQRPVPESQL LPGQRFQTKD 60
PEEQGDIVVA LYPYDGIHPD DLSFKKGEKM KVLEEHGEWW KAKSLLTKKE GFIPSNYVAK 120
LNTLETEEWF FKDITRKDAE RQLLAPGNSA GAFLIRESET LKGSFSLSVR DFDPVHGDVI 180
KHYKIRSLDN GGYYISPRIT FPCISDMIKH YQKQADGLCR RLEKACISPK PQKPWDKDAW 240
EIPRESIKLV KRLGAGQFGE VWMGYYNNST KVAVKTLKPG TMSVQAFLEE ANLMKTLQHD 300
KLVRLYAVVT REEPIYIITE YMAKGSLLDF LKSDEGGKVL LPKLIDFSAQ IAEGMAYIER 360
KNYIHRDLRA ANVLVSESLM CKIADFGLAR VIEDNEYTAR EGAKFPIKWT APEAINFGCF 420
TIKSDVWSFG ILLYEIVTYG KIPYPGRTNA DVMTALSQGY RMPRVENCPD ELYDIMKMCW 480
KEKAEERPTF DYLQSVLDDF YTATEGQYQQ QP 512 
Gene Ontology
 GO:0034666; C:alpha2-beta1 integrin complex; IEA:Compara.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
 GO:0045121; C:membrane raft; IDA:UniProtKB.
 GO:0030061; C:mitochondrial crista; IEA:Compara.
 GO:0005758; C:mitochondrial intermembrane space; IEA:Compara.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
 GO:0005886; C:plasma membrane; IDA:UniProtKB.
 GO:0014069; C:postsynaptic density; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0043208; F:glycosphingolipid binding; IEA:Compara.
 GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; TAS:Reactome.
 GO:0004716; F:receptor signaling protein tyrosine kinase activity; TAS:ProtInc.
 GO:0030262; P:apoptotic nuclear changes; IDA:UniProtKB.
 GO:0001782; P:B cell homeostasis; ISS:UniProtKB.
 GO:0050853; P:B cell receptor signaling pathway; IEA:Compara.
 GO:0031668; P:cellular response to extracellular stimulus; IEA:Compara.
 GO:0034605; P:cellular response to heat; IEA:Compara.
 GO:0071300; P:cellular response to retinoic acid; IMP:BHF-UCL.
 GO:0050663; P:cytokine secretion; IEA:Compara.
 GO:0097028; P:dendritic cell differentiation; ISS:UniProtKB.
 GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
 GO:0002774; P:Fc receptor mediated inhibitory signaling pathway; ISS:UniProtKB.
 GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
 GO:0002553; P:histamine secretion by mast cell; IEA:Compara.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IC:UniProtKB.
 GO:0060397; P:JAK-STAT cascade involved in growth hormone signaling pathway; TAS:Reactome.
 GO:0050900; P:leukocyte migration; TAS:Reactome.
 GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISS:UniProtKB.
 GO:0030889; P:negative regulation of B cell proliferation; IEA:Compara.
 GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
 GO:0050777; P:negative regulation of immune response; TAS:UniProtKB.
 GO:0043407; P:negative regulation of MAP kinase activity; ISS:UniProtKB.
 GO:0070667; P:negative regulation of mast cell proliferation; ISS:UniProtKB.
 GO:0002762; P:negative regulation of myeloid leukocyte differentiation; IEA:Compara.
 GO:0034136; P:negative regulation of toll-like receptor 2 signaling pathway; ISS:UniProtKB.
 GO:0034144; P:negative regulation of toll-like receptor 4 signaling pathway; ISS:UniProtKB.
 GO:0031175; P:neuron projection development; IEA:Compara.
 GO:0014003; P:oligodendrocyte development; IEA:Compara.
 GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
 GO:0030168; P:platelet activation; TAS:Reactome.
 GO:0002576; P:platelet degranulation; ISS:UniProtKB.
 GO:0030335; P:positive regulation of cell migration; IEA:Compara.
 GO:0051272; P:positive regulation of cellular component movement; IDA:UniProtKB.
 GO:2000670; P:positive regulation of dendritic cell apoptotic process; ISS:UniProtKB.
 GO:0060369; P:positive regulation of Fc receptor mediated stimulatory signaling pathway; IEA:Compara.
 GO:0060252; P:positive regulation of glial cell proliferation; IEA:Compara.
 GO:0070668; P:positive regulation of mast cell proliferation; IMP:UniProtKB.
 GO:0010976; P:positive regulation of neuron projection development; IMP:BHF-UCL.
 GO:0070447; P:positive regulation of oligodendrocyte progenitor proliferation; IEA:Compara.
 GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IEA:Compara.
 GO:0070304; P:positive regulation of stress-activated protein kinase signaling cascade; IDA:UniProtKB.
 GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISS:UniProtKB.
 GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
 GO:0002902; P:regulation of B cell apoptotic process; IEA:Compara.
 GO:0050855; P:regulation of B cell receptor signaling pathway; ISS:UniProtKB.
 GO:0033628; P:regulation of cell adhesion mediated by integrin; IMP:UniProtKB.
 GO:0001817; P:regulation of cytokine production; ISS:UniProtKB.
 GO:0050707; P:regulation of cytokine secretion; IEA:Compara.
 GO:0045646; P:regulation of erythrocyte differentiation; ISS:UniProtKB.
 GO:0050727; P:regulation of inflammatory response; IEA:Compara.
 GO:0043304; P:regulation of mast cell degranulation; ISS:UniProtKB.
 GO:0090025; P:regulation of monocyte chemotaxis; IMP:UniProtKB.
 GO:0090330; P:regulation of platelet aggregation; ISS:UniProtKB.
 GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; IEA:Compara.
 GO:0043200; P:response to amino acid stimulus; IEA:Compara.
 GO:0048678; P:response to axon injury; IEA:Compara.
 GO:0009743; P:response to carbohydrate stimulus; IEA:Compara.
 GO:0032868; P:response to insulin stimulus; IEA:Compara.
 GO:0014070; P:response to organic cyclic compound; IEA:Compara.
 GO:0006991; P:response to sterol depletion; IEA:Compara.
 GO:0009636; P:response to toxic substance; IEA:Compara.
 GO:0031295; P:T cell costimulation; TAS:Reactome.
 GO:0002513; P:tolerance induction to self antigen; ISS:UniProtKB.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 
Interpro
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
 IPR000980; SH2.
 IPR001452; SH3_domain.
 IPR008266; Tyr_kinase_AS.
 IPR020635; Tyr_kinase_cat_dom. 
Pfam
 PF07714; Pkinase_Tyr
 PF00017; SH2
 PF00018; SH3_1 
SMART
 SM00252; SH2
 SM00326; SH3
 SM00219; TyrKc 
PROSITE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR
 PS50001; SH2
 PS50002; SH3 
PRINTS
 PR00401; SH2DOMAIN.
 PR00452; SH3DOMAIN.
 PR00109; TYRKINASE.