Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance. Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain. Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions. Involved in the regulation of cell adhesion and motility through phosphorylation of CTNNB1 (beta-catenin) and CTNND1 (delta-catenin). Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT. Promotes cell survival by phosphorylating AGAP2/PIKE-A and preventing its apoptotic cleavage. Participates in signal transduction pathways that regulate the integrity of the glomerular slit diaphragm (an essential part of the glomerular filter of the kidney) by phosphorylating several slit diaphragm components including NPHS1, KIRREL1 and TRPC6. Plays a role in neural processes by phosphorylating DPYSL2, a multifunctional adapter protein within the central nervous system, ARHGAP32, a regulator for Rho family GTPases implicated in various neural functions, and SNCA, a small pre-synaptic protein. Participates in the downstream signaling pathways that lead to T-cell differentiation and proliferation fo (updated: Oct. 10, 2018)

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: 71%

Model score: 0

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Variant	Description
	a lung squamous cell carcinoma sample; somatic mutation
	a metastatic melanoma sample; somatic mutation
	dbSNP:rs1801121
	dbSNP:rs28763975

No binding partner found

Biological Process

Activated T cell proliferation

Adaptive immune response

Axon guidance

Blood coagulation

Calcium ion transport

Cell differentiation

Cellular response to amyloid-beta

Cellular response to glycine

Cellular response to L-glutamate

Cellular response to peptide hormone stimulus

Cellular response to platelet-derived growth factor stimulus

Cellular response to transforming growth factor beta stimulus

Cytokine-mediated signaling pathway

Dendrite morphogenesis

Dendritic spine maintenance

Detection of mechanical stimulus involved in sensory perception of pain

Ephrin receptor signaling pathway

Fc-gamma receptor signaling pathway involved in phagocytosis

Feeding behavior

Forebrain development

Heart process

Innate immune response

Intracellular signal transduction

Learning

Leukocyte migration

MAPK cascade

Modulation of chemical synaptic transmission

Negative regulation of dendritic spine maintenance

Negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

Negative regulation of gene expression

Negative regulation of hydrogen peroxide biosynthetic process

Negative regulation of inflammatory response to antigenic stimulus

Negative regulation of neuron apoptotic process

Negative regulation of oxidative stress-induced cell death

Negative regulation of protein catabolic process

Negative regulation of protein ubiquitination

Neuron migration

Peptidyl-tyrosine autophosphorylation

Peptidyl-tyrosine phosphorylation

Platelet activation

Positive regulation of cysteine-type endopeptidase activity

Positive regulation of I-kappaB kinase/NF-kappaB signaling

Positive regulation of neuron death

Positive regulation of neuron projection development

Positive regulation of non-membrane spanning protein tyrosine kinase activity

Positive regulation of phosphatidylinositol 3-kinase signaling

Positive regulation of protein kinase B signaling

Positive regulation of protein localization to membrane

Positive regulation of protein localization to nucleus

Positive regulation of protein targeting to membrane

Positive regulation of tyrosine phosphorylation of STAT protein

Protein autophosphorylation

Protein phosphorylation

Regulation of calcium ion import across plasma membrane

Regulation of cell population proliferation

Regulation of cell shape

Regulation of defense response to virus by virus

Regulation of glutamate receptor signaling pathway

Regulation of peptidyl-tyrosine phosphorylation

Response to amyloid-beta

Response to drug

Response to ethanol

Response to hydrogen peroxide

Response to singlet oxygen

Stimulatory C-type lectin receptor signaling pathway

T cell costimulation

T cell receptor signaling pathway

Transmembrane receptor protein tyrosine kinase signaling pathway

Vascular endothelial growth factor receptor signaling pathway

Cellular Component

Actin filament

Cell body

Cytosol

Dendrite

Endosome

Extrinsic component of cytoplasmic side of plasma membrane

Glial cell projection

Glutamatergic synapse

Membrane raft

Mitochondrion

Nucleus

Perinuclear endoplasmic reticulum

Perinuclear region of cytoplasm

Plasma membrane

Postsynaptic density

Postsynaptic density, intracellular component

Schaffer collateral - CA1 synapse

Molecular Function

Alpha-tubulin binding

ATP binding

CD4 receptor binding

CD8 receptor binding

Disordered domain specific binding

Enzyme binding

Ephrin receptor binding

Growth factor receptor binding

Identical protein binding

Ion channel binding

Metal ion binding

Non-membrane spanning protein tyrosine kinase activity

Peptide hormone receptor binding

Phosphatidylinositol 3-kinase binding

Phospholipase activator activity

Phospholipase binding

Protein tyrosine kinase activity

Signaling receptor binding

T cell receptor binding

Tau protein binding

Tau-protein kinase activity

Transmembrane receptor protein tyrosine kinase activity

Type 5 metabotropic glutamate receptor binding

The reference OMIM entry for this protein is 137025

Fyn oncogene related to src, fgr, yes; fyn
Fyn tyrosine kinase protooncogene
Src-like kinase; slk
Syn

CLONING

By screening a genomic library with a YES1 (164880) gene probe, Semba et al. (1986) identified a related gene, which they called SYN (src/yes-related novel gene). Northern blot analysis revealed that the 2.8-kb SYN mRNA was expressed in various cell types. The tyrosine kinase domain of the predicted 537-amino acid SYN protein is 77 to 80% identical to those of the YES1, FGR (164940), and chicken SRC (190090) tyrosine kinase oncogenes. Therefore, Semba et al. (1986) concluded that SYN is a new member of the tyrosine kinase oncogene family.

GENE FUNCTION

PrPc, the cellular, nonpathogenic isoform of prion protein (Prp; 176640), is a ubiquitous glycoprotein expressed strongly in neurons. Mouillet-Richard et al. (2000) used the murine 1C11 neuronal differentiation model to search for PrPc-dependent signal transduction through antibody-mediated crosslinking. The 1C11 clone is a committed neuroectodermal progenitor with an epithelial morphology that lacks neuron-associated functions. Upon induction, 1C11 cells develop a neural-like morphology, and may differentiate either into serotonergic or noradrenergic cells. The choice between the 2 differentiation pathways depends on the set of inducers used. Ligation of PrPc with specific antibodies induced a marked decrease in the phosphorylation level of the tyrosine kinase FYN in both serotonergic and noradrenergic cells. The coupling of PrPc to FYN was dependent upon caveolin-1 (601047). Mouillet-Richard et al. (2000) suggested that clathrin (see 118960) might also contribute to this coupling. The ability of the 1C11 cell line to trigger PrPc-dependent FYN activation was restricted to its fully differentiated serotonergic or noradrenergic progenies. Moreover, the signaling activity of PrPc occurred mainly at neurites. Mouillet-Richard et al. (2000) suggested that PrPc may be a signal transduction protein. Parravicini et al. (2002) noted that Lyn (165120) 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 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 ... More on the omim web site

Subscribe to this protein entry history

July 1, 2020: Protein entry updated
Automatic update: OMIM entry 137025 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).

Tyrosine-protein kinase Fyn (FYN)