InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: FYN

Summary

InnateDB Protein

IDBP-584112.3

Last Modified

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

Gene Symbol

FYN

Protein Name

FYN oncogene related to SRC, FGR, YES

Synonyms

p59-FYN; SLK; SYN;

Species

Homo sapiens

Ensembl Protein

ENSP00000440646

InnateDB Gene

IDBG-95463 (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. {ECO:0000269PubMed:11005864, ECO:0000269PubMed:11162638, ECO:0000269PubMed:11536198, ECO:0000269PubMed:12788081, ECO:0000269PubMed:14707117, ECO:0000269PubMed:14761972, ECO:0000269PubMed:15536091, ECO:0000269PubMed:15557120, ECO:0000269PubMed:16387660, ECO:0000269PubMed:16841086, ECO:0000269PubMed:17194753, ECO:0000269PubMed:18056706, ECO:0000269PubMed:18258597, ECO:0000269PubMed:19179337, ECO:0000269PubMed:19652227, ECO:0000269PubMed:20100835, ECO:0000269PubMed:22080863, ECO:0000269PubMed:7568038, ECO:0000269PubMed:7822789}.

Subcellular Localization

Cytoplasm. Nucleus. Cell membrane. Note=Present and active in lipid rafts. Palmitoylation is crucial for proper trafficking.

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:10196263}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 253 experimentally validated interaction(s) in this database.
They are also associated with 39 interaction(s) predicted by orthology.

Experimentally validated
Total	253 [view]
Protein-Protein	252 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	39 [view]

Gene Ontology

Molecular Function

Accession	GO Term
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:0016772	transferase activity, transferring phosphorus-containing groups
GO:0046872	metal ion binding
GO:0046875	ephrin receptor binding
GO:0070851	growth factor receptor binding

Biological Process

GO:0006468	protein phosphorylation
GO:0006816	calcium ion transport
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007411	axon guidance
GO:0007596	blood coagulation
GO:0007612	learning
GO:0007631	feeding behavior
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0016032	viral process
GO:0030168	platelet activation
GO:0031295	T cell costimulation
GO:0035556	intracellular signal transduction
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0038096	Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0045087	innate immune response
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling
GO:0050690	regulation of defense response to virus by virus
GO:0050852	T cell receptor signaling pathway
GO:0050900	leukocyte migration

Cellular Component

GO:0005634	nucleus
GO:0005768	endosome
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0045121	membrane raft

Protein Structure and Domains

PDB ID

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