LipidDB ID

LipidDB-10090-01476

Entry Name

UniProt Accession

P25911; Q62127;

Theoretical PI

6.74

Molecular Weight

58812.28

Genbank Protein ID

AAA39470.1; AAA39471.1; AAA39472.1; AAH31547.1; AAA40017.1;

Genbank Nucleotide ID

M64608; M57696; M57697; BC031547; M33426;

Protein Name

Tyrosine-protein kinase Lyn

Protein Synonyms/Alias

2.7.10.2; V-yes-1 Yamaguchi sarcoma viral related oncogene homolog; p53Lyn; p56Lyn;

Gene Name

Lyn

Gene Synonyms/Alias

Created Date

01-MAY-1992

Organism

Mus musculus (Mouse)

NCBI Taxa ID

10090

Reference

[1] Resh MD. Fatty acylation of proteins: new insights into membrane targeting of myristoylated and palmitoylated proteins. Biochim Biophys Acta. 1999 Aug12;1451(1):1-16. Review.[PMID:10446384]

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. 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.

Sequence Annotation

Domain: 63 123 SH3.
Domain: 129 226 SH2.
Domain: 247 501 Protein kinase.
Nucleotide-binding: 253 261 ATP.
Active site: 367 367 Proton acceptor.
Binding site: 275 275 ATP.
Modified residue: 6 6 Phosphoserine.
Modified residue: 19 19 Phosphoserine.
Modified residue: 30 30 Phosphothreonine.
Modified residue: 32 32 Phosphotyrosine.
Modified residue: 37 37 Phosphothreonine.
Modified residue: 193 193 Phosphotyrosine.
Modified residue: 194 194 Phosphotyrosine.
Modified residue: 228 228 Phosphoserine.
Modified residue: 265 265 Phosphotyrosine.
Modified residue: 306 306 Phosphotyrosine.
Modified residue: 316 316 Phosphotyrosine.
Modified residue: 397 397 Phosphotyrosine; by autocatalysis.
Modified residue: 460 460 Phosphotyrosine.
Modified residue: 473 473 Phosphotyrosine.
Modified residue: 489 489 Phosphothreonine.
Modified residue: 502 502 Phosphothreonine.
Modified residue: 508 508 Phosphotyrosine; by autocatalysis, CSKand MATK.

Protein Length

512 AA.

Protein Sequence
(Canonical)

FASTA
(Canonical)

Gene Ontology

GO:0005737; C:cytoplasm; IDA:UniProtKB
GO:0005829; C:cytosol; TAS:Reactome
GO:0070062; C:extracellular vesicular exosome; IEA:Ensembl
GO:0005794; C:Golgi apparatus; IEA:UniProtKB-KW
GO:0034666; C:integrin alpha2-beta1 complex; IEA:Ensembl
GO:0042629; C:mast cell granule; IEA:GOC
GO:0045121; C:membrane raft; IEA:Ensembl
GO:0030061; C:mitochondrial crista; IEA:Ensembl
GO:0005758; C:mitochondrial intermembrane space; IEA:Ensembl
GO:0005634; C:nucleus; IDA:UniProtKB
GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl
GO:0005886; C:plasma membrane; IDA:MGI
GO:0014069; C:postsynaptic density; IEA:Ensembl
GO:0005524; F:ATP binding; IEA:UniProtKB-KW
GO:0005128; F:erythropoietin receptor binding; TAS:UniProtKB
GO:0043208; F:glycosphingolipid binding; IEA:Ensembl
GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:UniProtKB-EC
GO:0032403; F:protein complex binding; IPI:MGI
GO:0004672; F:protein kinase activity; IDA:MGI
GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB
GO:0017124; F:SH3 domain binding; IPI:MGI
GO:0001782; P:B cell homeostasis; IMP:UniProtKB
GO:0050853; P:B cell receptor signaling pathway; IDA:MGI
GO:0006974; P:cellular response to DNA damage stimulus; IEA:Ensembl
GO:0031668; P:cellular response to extracellular stimulus; IEA:Ensembl
GO:0034605; P:cellular response to heat; IEA:Ensembl
GO:0071300; P:cellular response to retinoic acid; IEA:Ensembl
GO:0050663; P:cytokine secretion; IEA:Ensembl
GO:0097028; P:dendritic cell differentiation; IMP:UniProtKB
GO:0030218; P:erythrocyte differentiation; IMP:UniProtKB
GO:0002774; P:Fc receptor mediated inhibitory signaling pathway; IMP:UniProtKB
GO:0002431; P:Fc receptor mediated stimulatory signaling pathway; IMP:UniProtKB
GO:0042541; P:hemoglobin biosynthetic process; TAS:UniProtKB
GO:0030097; P:hemopoiesis; IMP:UniProtKB
GO:0002553; P:histamine secretion by mast cell; IEA:Ensembl
GO:0002768; P:immune response-regulating cell surface receptor signaling pathway; IMP:UniProtKB
GO:0045087; P:innate immune response; IEA:UniProtKB-KW
GO:0035556; P:intracellular signal transduction; IDA:MGI
GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IMP:UniProtKB
GO:0030889; P:negative regulation of B cell proliferation; IMP:UniProtKB
GO:0008285; P:negative regulation of cell proliferation; IMP:UniProtKB
GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IMP:UniProtKB
GO:1902532; P:negative regulation of intracellular signal transduction; IMP:UniProtKB
GO:0043407; P:negative regulation of MAP kinase activity; IMP:UniProtKB
GO:0070667; P:negative regulation of mast cell proliferation; IMP:UniProtKB
GO:0002762; P:negative regulation of myeloid leukocyte differentiation; IMP:UniProtKB
GO:0001933; P:negative regulation of protein phosphorylation; IMP:UniProtKB
GO:0034136; P:negative regulation of toll-like receptor 2 signaling pathway; IMP:UniProtKB
GO:0034144; P:negative regulation of toll-like receptor 4 signaling pathway; IMP:UniProtKB
GO:0031175; P:neuron projection development; IMP:MGI
GO:0014003; P:oligodendrocyte development; IEA:Ensembl
GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB
GO:0002576; P:platelet degranulation; IMP:UniProtKB
GO:0050861; P:positive regulation of B cell receptor signaling pathway; IGI:MGI
GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB
GO:0008284; P:positive regulation of cell proliferation; IMP:UniProtKB
GO:2000670; P:positive regulation of dendritic cell apoptotic process; IMP:UniProtKB
GO:0060369; P:positive regulation of Fc receptor mediated stimulatory signaling pathway; IEA:Ensembl
GO:0060252; P:positive regulation of glial cell proliferation; IEA:Ensembl
GO:0070668; P:positive regulation of mast cell proliferation; IEA:Ensembl
GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl
GO:0070447; P:positive regulation of oligodendrocyte progenitor proliferation; IEA:Ensembl
GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:MGI
GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IMP:UniProtKB
GO:0070304; P:positive regulation of stress-activated protein kinase signaling cascade; IEA:Ensembl
GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IMP:UniProtKB
GO:0046777; P:protein autophosphorylation; IDA:UniProtKB
GO:0002902; P:regulation of B cell apoptotic process; IMP:UniProtKB
GO:0050855; P:regulation of B cell receptor signaling pathway; IMP:UniProtKB
GO:0033628; P:regulation of cell adhesion mediated by integrin; IEA:Ensembl
GO:0001817; P:regulation of cytokine production; IMP:UniProtKB
GO:0050707; P:regulation of cytokine secretion; IMP:UniProtKB
GO:0070372; P:regulation of ERK1 and ERK2 cascade; IMP:UniProtKB
GO:0045646; P:regulation of erythrocyte differentiation; IMP:UniProtKB
GO:0050727; P:regulation of inflammatory response; IMP:UniProtKB
GO:0033003; P:regulation of mast cell activation; IMP:UniProtKB
GO:0043304; P:regulation of mast cell degranulation; IMP:UniProtKB
GO:0090025; P:regulation of monocyte chemotaxis; IEA:Ensembl
GO:0090330; P:regulation of platelet aggregation; IMP:UniProtKB
GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; IGI:MGI
GO:0043200; P:response to amino acid; IEA:Ensembl
GO:0048678; P:response to axon injury; IEA:Ensembl
GO:0009743; P:response to carbohydrate; IEA:Ensembl
GO:0042493; P:response to drug; IEA:Ensembl
GO:0009725; P:response to hormone; IDA:UniProtKB
GO:0032868; P:response to insulin; IEA:Ensembl
GO:0014070; P:response to organic cyclic compound; IEA:Ensembl
GO:0006991; P:response to sterol depletion; IEA:Ensembl
GO:0009636; P:response to toxic substance; IEA:Ensembl
GO:0007165; P:signal transduction; TAS:UniProtKB
GO:0002513; P:tolerance induction to self antigen; IMP:UniProtKB
GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IEA:Ensembl

Interpro

InterPro; IPR011009; Kinase-like_dom
InterPro; IPR000719; Prot_kinase_dom
InterPro; IPR017441; Protein_kinase_ATP_BS
InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom
InterPro; IPR000980; SH2
InterPro; IPR001452; SH3_domain
InterPro; IPR008266; Tyr_kinase_AS
InterPro; IPR020635; Tyr_kinase_cat_dom

Pfam

Pfam; PF07714; Pkinase_Tyr;
Pfam; PF00017; SH2;
Pfam; PF00018; SH3_1;

SMART

SMART; SM00252; SH2;
SMART; SM00326; SH3;
SMART; SM00219; TyrKc;

PROSITE

PROSITE; PS00107; PROTEIN_KINASE_ATP;
PROSITE; PS50011; PROTEIN_KINASE_DOM;
PROSITE; PS00109; PROTEIN_KINASE_TYR;
PROSITE; PS50001; SH2;
PROSITE; PS50002; SH3;

PRINTS

PRINTS; PR00401; SH2DOMAIN;
PRINTS; PR00452; SH3DOMAIN;
PRINTS; PR00109; TYRKINASE;