InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Fyn

Summary

InnateDB Protein

IDBP-533519.4

Last Modified

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

Gene Symbol

Fyn

Protein Name

Fyn proto-oncogene

Synonyms

AI448320; AW552119;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000115233

InnateDB Gene

IDBG-144629 (Fyn)

Protein Structure

UniProt Annotation

Function

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, KIRREL 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 following T-cell receptor (TCR) stimulation. Also participates in negative feedback regulation of TCR signaling through phosphorylation of PAG1, thereby promoting interaction between PAG1 and CSK and recruitment of CSK to lipid rafts. CSK maintains LCK and FYN in an inactive form. Promotes CD28-induced phosphorylation of VAV1 (By similarity). {ECO:0000250}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. Cell membrane {ECO:0000250}. Note=Present and active in lipid rafts. Palmitoylation is crucial for proper trafficking (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Isoform 1 is highly expressed in the brain, isoform 2 is expressed in cells of hemopoietic lineages, especially T-lymphocytes. {ECO:0000269PubMed:1361685, ECO:0000269PubMed:8007959}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 84 experimentally validated interaction(s) in this database.
They are also associated with 270 interaction(s) predicted by orthology.

Experimentally validated
Total	84 [view]
Protein-Protein	84 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	270 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001664	G-protein coupled receptor binding
GO:0001948	glycoprotein binding
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004715	non-membrane spanning protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0015631	tubulin binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0042608	T cell receptor binding
GO:0042609	CD4 receptor binding
GO:0042610	CD8 receptor binding
GO:0043548	phosphatidylinositol 3-kinase binding
GO:0044325	ion channel binding
GO:0046872	metal ion binding
GO:0046875	ephrin receptor binding
GO:0051428	peptide hormone receptor binding
GO:0070851	growth factor receptor binding

Biological Process

GO:0001764	neuron migration
GO:0006468	protein phosphorylation
GO:0007166	cell surface receptor signaling pathway
GO:0008360	regulation of cell shape
GO:0010629	negative regulation of gene expression
GO:0010976	positive regulation of neuron projection development
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0030900	forebrain development
GO:0042177	negative regulation of protein catabolic process
GO:0042493	response to drug
GO:0042552	myelination
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0045471	response to ethanol
GO:0046777	protein autophosphorylation
GO:0048813	dendrite morphogenesis
GO:0050798	activated T cell proliferation
GO:0050852	T cell receptor signaling pathway
GO:0050966	detection of mechanical stimulus involved in sensory perception of pain
GO:0071363	cellular response to growth factor stimulus
GO:0071375	cellular response to peptide hormone stimulus
GO:1900182	positive regulation of protein localization to nucleus
GO:2001240	negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

Cellular Component

GO:0005634	nucleus
GO:0005739	mitochondrion
GO:0005768	endosome
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0014069	postsynaptic density

Protein Structure and Domains

PDB ID

MGI:95602

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