InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Lyn

Summary

InnateDB Protein

IDBP-128369.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Lyn

Protein Name

Yamaguchi sarcoma viral (v-yes-1) oncogene homolog

Synonyms

AA407514; Hck-2; p53Lyn; p56Lyn;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000100075

InnateDB Gene

IDBG-128365 (Lyn)

Protein Structure

UniProt Annotation

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. 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'. {ECO:0000269PubMed:10327049, ECO:0000269PubMed:10594694, ECO:0000269PubMed:10640270, ECO:0000269PubMed:10672044, ECO:0000269PubMed:11007759, ECO:0000269PubMed:11435302, ECO:0000269PubMed:11672542, ECO:0000269PubMed:12077122, ECO:0000269PubMed:12874221, ECO:0000269PubMed:14525964, ECO:0000269PubMed:14726379, ECO:0000269PubMed:15335855, ECO:0000269PubMed:16034130, ECO:0000269PubMed:16116174, ECO:0000269PubMed:16249387, ECO:0000269PubMed:16272347, ECO:0000269PubMed:16731527, ECO:0000269PubMed:17640867, ECO:0000269PubMed:19492092, ECO:0000269PubMed:20189992, ECO:0000269PubMed:20385881, ECO:0000269PubMed:7513017, ECO:0000269PubMed:7584145, ECO:0000269PubMed:7585947, ECO:0000269PubMed:8128248, ECO:0000269PubMed:8621063, ECO:0000269PubMed:8629002, ECO:0000269PubMed:9036984, ECO:0000269PubMed:9064343, ECO:0000269PubMed:9252121, ECO:0000269PubMed:9469421, ECO:0000269PubMed:9480991, ECO:0000269PubMed:9547345, ECO:0000269PubMed:9573010, ECO:0000269PubMed:9590210, ECO:0000269PubMed:9601638}.

Subcellular Localization

Cell membrane {ECO:0000250}. Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}. Cytoplasm, perinuclear region {ECO:0000250}. Golgi apparatus {ECO:0000250}. 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 cell membrane occurs in a kinase domain-dependent but kinase activity independent manner and is mediated by exocytic vesicular transport (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Detected in bone marrow-derived monocytes (at protein level). Expressed predominantly in B-lymphoid and myeloid cells. {ECO:0000269PubMed:2017160}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 74 experimentally validated interaction(s) in this database.
They are also associated with 103 interaction(s) predicted by orthology.

Experimentally validated
Total	74 [view]
Protein-Protein	74 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	103 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004715	non-membrane spanning protein tyrosine kinase activity
GO:0005128	erythropoietin receptor binding
GO:0005161	platelet-derived growth factor receptor binding
GO:0005178	integrin binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0017124	SH3 domain binding
GO:0031625	ubiquitin protein ligase binding
GO:0032403	protein complex binding
GO:0043208	glycosphingolipid binding
GO:0044325	ion channel binding
GO:0051219	phosphoprotein binding

Biological Process

GO:0001782	B cell homeostasis
GO:0001817	regulation of cytokine production
GO:0001933	negative regulation of protein phosphorylation
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: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: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:0018108	peptidyl-tyrosine phosphorylation
GO:0030097	hemopoiesis
GO:0030218	erythrocyte differentiation
GO:0030262	apoptotic nuclear changes
GO:0030335	positive regulation of cell migration
GO:0030889	negative regulation of B cell proliferation
GO:0031175	neuron projection development
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:0042493	response to drug
GO:0042531	positive regulation of tyrosine phosphorylation of STAT protein
GO:0042541	hemoglobin biosynthetic process
GO:0043200	response to amino acid
GO:0043304	regulation of mast cell degranulation
GO:0043407	negative regulation of MAP kinase activity
GO:0043552	positive regulation of phosphatidylinositol 3-kinase activity
GO:0045087	innate immune response (InnateDB)
GO:0045646	regulation of erythrocyte differentiation
GO:0046777	protein autophosphorylation
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: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: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: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:2000670	positive regulation of dendritic cell apoptotic process

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005758	mitochondrial intermembrane space
GO:0005794	Golgi apparatus
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0014069	postsynaptic density
GO:0030061	mitochondrial crista
GO:0034666	alpha2-beta1 integrin complex
GO:0042629	mast cell granule
GO:0045121	membrane raft
GO:0048471	perinuclear region of cytoplasm

Protein Structure and Domains

PDB ID

MGI:96892

InterPro

IPR000719 Protein kinase domain
IPR000980 SH2 domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR001452 SH3 domain
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR011511 Variant SH3 domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM