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 (updated: April 1, 2015)

Protein identification was indicated in the following studies:

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

Publication	Identification ¹	Uniprot mapping ²	Not mapped / Obsolete	TrEMBL	Swiss-Prot
Goodman (2013)	2289 (gene list)	2278	53	20599	2269
Lange (2014)	1234	1234	7	28	1224
Hegedus (2015)	2638	2622	0	235	2387
Wilson (2016)	1658	1528	170	291	1068
d'Alessandro (2017)	1826	1817	2	0	1815
Bryk (2017)	2090	2060	10	108	1942
Chu (2018)	1853	1804	55	362	1387

¹ as available in the article and/or in supplementary material
² uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Protein sequence (FASTA)

Protein coevolution profile (FreeContact)

Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.

Total structural coverage: 100%

Model score: 0

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Variant	Description
	a breast pleomorphic lobular carcinoma sample; somatic mutation

Biological Process

Adaptive immune response

Axon guidance

B cell homeostasis

B cell receptor signaling pathway

Blood coagulation

Cell differentiation

Cellular response to DNA damage stimulus

Cellular response to extracellular stimulus

Cellular response to heat

Cellular response to peptide hormone stimulus

Cellular response to retinoic acid

Central nervous system development

Cytokine secretion

Dendritic cell differentiation

Ephrin receptor signaling pathway

Erythrocyte differentiation

Fc receptor mediated inhibitory signaling pathway

Fc receptor mediated stimulatory signaling pathway

Fc-epsilon receptor signaling pathway

Fc-gamma receptor signaling pathway involved in phagocytosis

Growth hormone receptor signaling pathway via JAK-STAT

Histamine secretion by mast cell

Immune response-regulating cell surface receptor signaling pathway

Inflammatory response

Innate immune response

Intracellular signal transduction

Leukocyte migration

Lipopolysaccharide-mediated signaling pathway

Negative regulation of B cell proliferation

Negative regulation of cell population proliferation

Negative regulation of ERK1 and ERK2 cascade

Negative regulation of immune response

Negative regulation of inflammatory response to antigenic stimulus

Negative regulation of intracellular signal transduction

Negative regulation of MAP kinase activity

Negative regulation of mast cell proliferation

Negative regulation of myeloid leukocyte differentiation

Negative regulation of protein phosphorylation

Negative regulation of toll-like receptor 2 signaling pathway

Negative regulation of toll-like receptor 4 signaling pathway

Neuron projection development

Oligodendrocyte development

Peptidyl-tyrosine autophosphorylation

Peptidyl-tyrosine phosphorylation

Platelet activation

Platelet degranulation

Positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process

Positive regulation of B cell receptor signaling pathway

Positive regulation of cell migration

Positive regulation of cell population proliferation

Positive regulation of cellular component movement

Positive regulation of dendritic cell apoptotic process

Positive regulation of Fc receptor mediated stimulatory signaling pathway

Positive regulation of glial cell proliferation

Positive regulation of mast cell proliferation

Positive regulation of neuron projection development

Positive regulation of oligodendrocyte progenitor proliferation

Positive regulation of phosphatidylinositol 3-kinase activity

Positive regulation of phosphatidylinositol 3-kinase signaling

Positive regulation of protein phosphorylation

Positive regulation of Ras protein signal transduction

Positive regulation of stress-activated protein kinase signaling cascade

Positive regulation of tyrosine phosphorylation of STAT protein

Protein autophosphorylation

Protein phosphorylation

Regulation of B cell apoptotic process

Regulation of B cell receptor signaling pathway

Regulation of cell adhesion mediated by integrin

Regulation of cell population proliferation

Regulation of cytokine production

Regulation of cytokine secretion

Regulation of ERK1 and ERK2 cascade

Regulation of erythrocyte differentiation

Regulation of inflammatory response

Regulation of mast cell activation

Regulation of mast cell degranulation

Regulation of monocyte chemotaxis

Regulation of platelet aggregation

Regulation of protein phosphorylation

Regulation of release of sequestered calcium ion into cytosol

Response to amino acid

Response to axon injury

Response to carbohydrate

Response to drug

Response to hormone

Response to insulin

Response to organic cyclic compound

Response to sterol depletion

Response to toxic substance

Signal transduction

Signal transduction by protein phosphorylation

Stimulatory C-type lectin receptor signaling pathway

T cell costimulation

Tolerance induction to self antigen

Toll-like receptor 4 signaling pathway

Transmembrane receptor protein tyrosine kinase signaling pathway

Viral process

Cellular Component

Adherens junction

Cell-cell adherens junction

Cytoplasm

Cytosol

Extracellular exosome

Extrinsic component of cytoplasmic side of plasma membrane

Glutamatergic synapse

Golgi apparatus

Integrin alpha2-beta1 complex

Intracellular membrane-bounded organelle

Mast cell granule

Membrane raft

Mitochondrial crista

Mitochondrial intermembrane space

Nucleus

Perinuclear region of cytoplasm

Plasma membrane

Postsynaptic density

Postsynaptic specialization, intracellular component

Molecular Function

ATP binding

Enzyme binding

Ephrin receptor binding

Gamma-tubulin binding

Glycosphingolipid binding

Integrin binding

Ion channel binding

Kinase activity

Non-membrane spanning protein tyrosine kinase activity

Obsolete signal transducer, downstream of receptor, with protein tyrosine kinase activity

Phosphoprotein binding

Phosphorylation-dependent protein binding

Platelet-derived growth factor receptor binding

Protein tyrosine kinase activity

SH3 domain binding

Signaling receptor binding

Transmembrane receptor protein tyrosine kinase activity

Ubiquitin protein ligase binding

The reference OMIM entry for this protein is 165120

V-yes-1 yamaguchi sarcoma viral related oncogene homolog; lyn
Oncogene lyn

CLONING

Using a v-yes DNA as the probe, Yamanashi et al. (1987) screened a human cDNA library made from placental RNA and derived DNA clones representing a novel genetic locus termed LYN. Nucleotide sequencing showed that LYN encodes a novel tyrosine kinase. Northern hybridization analysis showed that a 3.2-kb LYN mRNA was expressed in a variety of tissues of the human fetus. The pattern of expression was different from those of related genes such as YES (164880).

GENE FUNCTION

Parravicini et al. (2002) noted that Lyn deficiency impairs some mast cell functions, but degranulation and cytokine production are intact. In Gab2 (606203)-deficient mice, on the other hand, degranulation and cytokine production are impaired. Using immunoblot analysis, they showed that although Lyn is essential for Syk (600085) activation and Lat (602354) phosphorylation after Fcer1 (see FCER1G; 147139) aggregation, neither Lyn nor Lat are necessary for Gab2 phosphorylation. RT-PCR and coimmunoprecipitation analyses demonstrated abundant Fyn (137025) expression in mast cells and an association with Gab2. In cells lacking Fyn, neither Gab2 nor Akt (164730) were phosphorylated. Functional analysis showed that Lyn -/- mast cells exhibited hyperdegranulation and enhanced PI3K (see 601232) activity and Akt phosphorylation, whereas in Fyn -/- mast cells the degranulation response was inhibited. The inhibition was associated with decreased binding of PI3K with Gab2. Parravicini et al. (2002) observed that the degranulation response was independent of Fcer1 stimulation in Fyn-deficient mast cells and that degranulation was dependent on PI3K in wildtype and mutant cell lines. The degranulation response was dependent on a rise in intracellular calcium that was inhibited in Lyn-deficient mast cells but intact in Fyn-deficient cells. Degranulation proceeded in Lyn -/- cells due to increased activation and constitutive phosphorylation of the calcium-independent protein kinase C delta isoform (PRKCD; 176977). Parravicini et al. (2002) concluded that Fyn- and Lyn-initiated pathways synergize in late events at the level of protein kinase C and calcium, respectively, to regulate mast cell degranulation. Yoo et al. (2011) identified Lyn as a redox sensor that mediates initial neutrophil recruitment to wounds in zebrafish larvae. Lyn activation in neutrophils is dependent on wound-derived H2O2 after tissue injury, and inhibition of Lyn attenuates neutrophil wound recruitment. Inhibition of Src family kinase (SFK) also disrupted H2O2-mediated chemotaxis of primary human neutrophils. In vitro analysis identified a single cysteine residue, C466, as being responsible for direct oxidation-mediated activation of Lyn. Furthermore, transgenic tissue-specific reconstitution with wildtype Lyn and a cysteine mutant revealed that Lyn C466 is important for the neutrophil wound response and downstream signaling in vivo. Yoo et al. (2011) concluded that this was the first identification of a physiologic redox sensor that mediates leukocyte wound attraction in multicellular organisms.

MAPPING

By hybridization analysis of DNA from sorted chromosomes, Yamanashi et al. (1987) mapped the LYN gene to chromosome 8q13-qter.

ANIMAL MODEL

Hibbs et al. (1995) demonstrated that mice homozygous for a disruption of the Lyn locus display abnormalities associated with the B-lymphocyte lineage and in mast cell function. Despite reduced numbers of recirculating B lympho ... More on the omim web site

Subscribe to this protein entry history

May 13, 2019: Protein entry updated
Automatic update: model status changed

Nov. 17, 2018: Protein entry updated
Automatic update: model status changed

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Oct. 27, 2017: Protein entry updated
Automatic update: model status changed

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 165120 was added.

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed

Tyrosine-protein kinase Lyn (LYN)