FYN / TRP channels
Name: Tyrosine-protein kinase Fyn
(FYN)
Official Symbol: FYN
provided by HGNC
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.
Source: Reorganizing the protein space at the Universal Protein Resource (UniProt)
Nucleic Acids Res. 40: D71-D75 (2012).
Species | External DB | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Entrez Gene | UniprotKB | DIP | IntAct | MINT | BioGRID | STRING | IUPHAR-DB | KEGG | OMIM | |
Human
|
2534 | P06241 | DIP-33876N | P06241 | MINT-93594 | 108810 | P06241 | hsa:2534 | 137025 | |
Mouse
|
14360 | P39688 | DIP-198N | P39688 | MINT-85422 | 199773 | P39688 | mmu:14360 | ||
Rat
|
25150 | Q62844 | DIP-47815N | UNK-5463756 | 247215 | Q62844 | rno:25150 |
Biological Process:
- GO:0050798 : activated T cell proliferation
- GO:0007411 : axon guidance
- GO:0006816 : calcium ion transport
- GO:0071363 : cellular response to growth factor stimulus
- GO:0071375 : cellular response to peptide hormone stimulus
- GO:0048813 : dendrite morphogenesis
- GO:0050966 : detection of mechanical stimulus involved in sensory perception of pain
- GO:0007631 : feeding behavior
- GO:0030900 : forebrain development
- GO:0007243 : intracellular protein kinase cascade
- GO:0007612 : learning
- GO:0050900 : leukocyte migration
- GO:0010629 : negative regulation of gene expression
- GO:0042177 : negative regulation of protein catabolic process
- GO:0001764 : neuron migration
- GO:0018108 : peptidyl-tyrosine phosphorylation
- GO:0030168 : platelet activation
- GO:0046777 : protein autophosphorylation
- GO:0008360 : regulation of cell shape
- GO:0050690 : regulation of defense response to virus by virus
- GO:0042493 : response to drug
- GO:0045471 : response to ethanol
- GO:0031295 : T cell costimulation
- GO:0050852 : T cell receptor signaling pathway
- GO:0016032 : viral reproduction
- GO:0019048 : virus-host interaction
Source: The Gene Ontology Consortium. Gene ontology: tool for the unification of biology. Nat. Genet.. May 2000;25(1):25-9.
World Wide Web URL: http://www.geneontology.org/
World Wide Web URL: http://www.geneontology.org/
Disease:
No information in OMIM
Source: Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine,
Johns Hopkins University (Baltimore, MD), May, 2012.
World Wide Web URL: http://omim.org/
World Wide Web URL: http://omim.org/
Screening Validation: In vitro validation Validation: In vivo validation Characterization Functional consequence | top |
Screening | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
Experimental screening | Non-experimental screening | Reference | ||||||||
TRP channel construct | Interactor source | |||||||||
TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
TRPC4 | FYN | Inference | Prediction | 16144838 | ||||||
TRPC6 | FYN | Inference | Prediction | 14761972 | ||||||
TRPV4 | FYN | Inference | Prediction | 12538589 | ||||||
TRPV6 | FYN | Inference | Prediction | 17197020 |
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Screening Validation: In vitro validation Validation: In vivo validation Characterization Functional consequence | top |
Validation: In vitro validation | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
Assay with recombinant proteins | Reference | |||||||||
TRP channel construct | Interactor construct | |||||||||
TRP channel | Interactor | Method | Species | Region | Expression system | Species | Region | Expression system | ||
TRPC6 | FYN | Fusion protein-pull down assay | Mouse | Full-length | HEK293 lysates | Human | 149-257 | E. coli | 14761972 |
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Screening Validation: In vitro validation Validation: In vivo validation Characterization Functional consequence | top |
Validation: In vivo validation | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
Assay with endogenous proteins | Assay with overexpressed proteins | Reference | ||||||||
Cell or tissue | Cell or tissue | TRP channel construct | Interactor construct | |||||||
TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
TRPC4 | FYN | Co-immunoprecipitation | Rat brain microsome | 18048348 | ||||||
TRPC4 | FYN | Co-immunoprecipitation | COS-7 | 16144838 | ||||||
TRPC4 | FYN | Co-immunoprecipitation | COS-7 | Human | Full-length | Not specifed | Full-length | 16144838 | ||
TRPC6 | FYN | Co-immunofluorescence staining | CHO-K1 | Mouse | Full-length | Human | Full-length | 14761972 | ||
TRPC6 | FYN | Co-immunoprecipitation | Rat brain microsome | 14761972 | ||||||
TRPC6 | FYN | Co-immunoprecipitation | COS-7 | Mouse | Full-length | Human | Full-length | 14761972 | ||
TRPV4 | FYN | Co-immunoprecipitation | HEK293 | Mouse | Full-length | Not used | 12538589 |
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Screening Validation: In vitro validation Validation: In vivo validation Characterization Functional consequence | top |
Characterization | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
Binding region mapping | Stoichiometry | Affinity (Kd) | Reference | |||||||
TRP channel | Interactor | |||||||||
TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
TRPC6 | FYN | Fusion protein-pull down assay | Mouse | 1-388 | Human | 149-257 | 14761972 | |||
TRPV4 | FYN | Co-immunoprecipitation | Mouse | Not determined | Mouse | 145-247 | 12538589 |
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Screening Validation: In vitro validation Validation: In vivo validation Characterization Functional consequence | top |
Functional consequence | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
TRP channel | Interactor | Method | Post-translational modification | Subcellular trafficking | Activity | Reference | ||||||
TRPC6 | FYN | In vivo PTM assay | Phosphorylation | 14761972 | ||||||||
TRPC6 | FYN | Patch clamp | Activation | 14761972 | ||||||||
TRPV4 | FYN | Calcium measurement | Activation | 12538589 | ||||||||
TRPV4 | FYN | In vitro PTM assay | Phosphorylation (Tyr-273) | 12538589 | ||||||||
TRPV6 | FYN | In vitro PTM assay | Phosphorylation | 17197020 |
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)