P39688 · FYN_MOUSE
- ProteinTyrosine-protein kinase Fyn
- GeneFyn
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids537 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain (By similarity).
Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions (By similarity).
Involved in the regulation of cell adhesion and motility through phosphorylation of CTNNB1 (beta-catenin) and CTNND1 (delta-catenin) (PubMed:12640114).
Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT (By similarity).
Promotes cell survival by phosphorylating AGAP2/PIKE-A and preventing its apoptotic cleavage (By similarity).
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 (By similarity).
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 (By similarity).
Involved in reelin signaling by mediating phosphorylation of DAB1 following reelin (RELN)-binding to its receptor (PubMed:12526739).
Participates in the downstream signaling pathways that lead to T-cell differentiation and proliferation following T-cell receptor (TCR) stimulation (By similarity).
Phosphorylates PTK2B/PYK2 in response to T-cell receptor activation (By similarity).
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 (By similarity).
CSK maintains LCK and FYN in an inactive form (PubMed:12218089).
Promotes CD28-induced phosphorylation of VAV1 (By similarity).
In mast cells, phosphorylates CLNK after activation of immunoglobulin epsilon receptor signaling (PubMed:12681493).
Catalytic activity
- ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein]
Cofactor
Activity regulation
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTyrosine-protein kinase Fyn
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP39688
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Palmitoylation is crucial for proper trafficking (By similarity).
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 2 | Abolishes myristoylation and palmitoylation. | ||||
Sequence: G → A | ||||||
Mutagenesis | 3 | Abolishes palmitoylation and plasma membrane association; when associated with A-6. | ||||
Sequence: C → A | ||||||
Mutagenesis | 3 | Abolishes palmitoylation and plasma membrane association; when associated with S-6. Abolishes plasma membrane association. | ||||
Sequence: C → S | ||||||
Mutagenesis | 6 | Abolishes palmitoylation and plasma membrane association; when associated with A-3. | ||||
Sequence: C → A | ||||||
Mutagenesis | 6 | Abolishes palmitoylation and plasma membrane association; when associated with S-3. | ||||
Sequence: C → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 16 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Chemistry
PTM/Processing
Features
Showing features for initiator methionine, lipidation, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Lipidation | 2 | N-myristoyl glycine | ||||
Sequence: G | ||||||
Chain | PRO_0000088100 | 2-537 | Tyrosine-protein kinase Fyn | |||
Sequence: GCVQCKDKEAAKLTEERDGSLNQSSGYRYGTDPTPQHYPSFGVTSIPNYNNFHAAGGQGLTVFGGVNSSSHTGTLRTRGGTGVTLFVALYDYEARTEDDLSFHKGEKFQILNSSEGDWWEARSLTTGETGYIPSNYVAPVDSIQAEEWYFGKLGRKDAERQLLSFGNPRGTFLIRESETTKGAYSLSIRDWDDMKGDHVKHYKIRKLDNGGYYITTRAQFETLQQLVQHYSERAAGLCCRLVVPCHKGMPRLTDLSVKTKDVWEIPRESLQLIKRLGNGQFGEVWMGTWNGNTKVAIKTLKPGTMSPESFLEEAQIMKKLKHDKLVQLYAVVSEEPIYIVTEYMSKGSLLDFLKDGEGRALKLPNLVDMAAQVAAGMAYIERMNYIHRDLRSANILVGNGLICKIADFGLARLIEDNEYTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPQDCPISLHELMIHCWKKDPEERPTFEYLQGFLEDYFTATEPQYQPGENL | ||||||
Lipidation | 3 | S-palmitoyl cysteine | ||||
Sequence: C | ||||||
Lipidation | 6 | S-palmitoyl cysteine | ||||
Sequence: C | ||||||
Modified residue | 21 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 26 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 185 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 420 | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | ||||||
Modified residue | 531 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 531 | Phosphotyrosine; by CSK | ||||
Sequence: Y |
Post-translational modification
Phosphorylation on the C-terminal tail at Tyr-531 by CSK maintains the enzyme in an inactive state (PubMed:8441403).
PTPRC/CD45 dephosphorylates Tyr-531 leading to activation. Ultraviolet B (UVB) strongly increase phosphorylation at Thr-15 and kinase activity, and promotes translocation from the cytoplasm to the nucleus. Dephosphorylation at Tyr-420 by PTPN2 negatively regulates T-cell receptor signaling (By similarity).
Phosphorylated at tyrosine residues, which can be enhanced by NTN1 (PubMed:22685302).
Palmitoylation at Cys-3 and Cys-6, probably by ZDHHC21, regulates subcellular location (PubMed:19956733, PubMed:7980442, PubMed:8413237, PubMed:9201723).
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Interacts with FYB1, PAG1, and SH2D1A (By similarity).
Interacts with CD79A (tyrosine-phosphorylated form); the interaction increases FYN activity (PubMed:8168489).
Interacts with TOM1L1 (phosphorylated form) (PubMed:11711534).
Interacts with SH2D1A and SLAMF1 (By similarity).
Interacts with and phosphorylates ITCH, down-regulating its activity (By similarity).
Interacts with FASLG (By similarity).
Interacts with RUNX3 (By similarity).
Interacts with KIT (By similarity).
Interacts with EPHA8; possible downstream effector of EPHA8 in regulation of cell adhesion (By similarity).
Interacts with PTK2/FAK1; this interaction leads to PTK2/FAK1 phosphorylation and activation (By similarity).
Interacts with CAV1; this interaction couples integrins to the Ras-ERK pathway (By similarity).
Interacts (via SH3 domain) with KLHL2 (via N-terminus) (By similarity).
Interacts with KDR (tyrosine phosphorylated) (PubMed:16966330).
Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) (PubMed:7681396, PubMed:9312046).
Interacts with UNC119 (By similarity).
Interacts (via SH2 domain) with PTPRH (phosphorylated form) (PubMed:20398064).
Interacts with PTPRO (phosphorylated form) (PubMed:20398064).
Interacts with PTPRB (phosphorylated form) (PubMed:20398064).
Interacts with FYB2 (By similarity).
Interacts with DSCAM (PubMed:22685302).
Interacts with SKAP1 and FYB1; this interaction promotes the phosphorylation of CLNK (PubMed:12681493).
Interacts with NEDD9; in the presence of PTK2 (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P39688 | Cbl P22682 | 5 | EBI-524514, EBI-640919 | |
XENO | P39688 | CBL P22681 | 3 | EBI-524514, EBI-518228 | |
BINARY | P39688 | Dynlt1 P51807 | 3 | EBI-524514, EBI-642797 | |
XENO | P39688 | FZD2 Q14332 | 4 | EBI-524514, EBI-6254477 | |
XENO | P39688 | Irs1 P35570 | 4 | EBI-524514, EBI-520230 | |
BINARY | P39688 | Khdrbs1 Q60749 | 15 | EBI-524514, EBI-519077 | |
BINARY | P39688 | Khdrbs2 Q9WU01 | 2 | EBI-524514, EBI-8339046 | |
BINARY | P39688 | Pdgfrb P05622 | 3 | EBI-524514, EBI-1554855 | |
XENO | P39688 | PLXNA2 O75051 | 3 | EBI-524514, EBI-308264 | |
XENO | P39688 | PTPRA P18433 | 2 | EBI-524514, EBI-2609645 | |
BINARY | P39688 | Slamf1 Q9QUM4 | 4 | EBI-524514, EBI-7910086 | |
BINARY | P39688 | Sphk2 Q9JIA7 | 2 | EBI-524514, EBI-985434 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 14-35 | Disordered | ||||
Sequence: LTEERDGSLNQSSGYRYGTDPT | ||||||
Compositional bias | 18-35 | Polar residues | ||||
Sequence: RDGSLNQSSGYRYGTDPT | ||||||
Domain | 82-143 | SH3 | ||||
Sequence: TGVTLFVALYDYEARTEDDLSFHKGEKFQILNSSEGDWWEARSLTTGETGYIPSNYVAPVDS | ||||||
Domain | 149-246 | SH2 | ||||
Sequence: WYFGKLGRKDAERQLLSFGNPRGTFLIRESETTKGAYSLSIRDWDDMKGDHVKHYKIRKLDNGGYYITTRAQFETLQQLVQHYSERAAGLCCRLVVPC | ||||||
Domain | 271-524 | Protein kinase | ||||
Sequence: LQLIKRLGNGQFGEVWMGTWNGNTKVAIKTLKPGTMSPESFLEEAQIMKKLKHDKLVQLYAVVSEEPIYIVTEYMSKGSLLDFLKDGEGRALKLPNLVDMAAQVAAGMAYIERMNYIHRDLRSANILVGNGLICKIADFGLARLIEDNEYTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPQDCPISLHELMIHCWKKDPEERPTFEYLQGFLEDYF |
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
P39688-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- SynonymsB
- Length537
- Mass (Da)60,675
- Last updated2013-04-03 v4
- Checksum99558702596DAEE0
P39688-2
- Name2
- SynonymsT
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Features
Showing features for compositional bias, sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 18-35 | Polar residues | ||||
Sequence: RDGSLNQSSGYRYGTDPT | ||||||
Sequence conflict | 179 | in Ref. 1; AAA37644 and 2; AAB09568 | ||||
Sequence: E → Q | ||||||
Alternative sequence | VSP_024111 | 234-236 | in isoform 2 | |||
Sequence: RAA → KAD | ||||||
Alternative sequence | VSP_024112 | 240-287 | in isoform 2 | |||
Sequence: CRLVVPCHKGMPRLTDLSVKTKDVWEIPRESLQLIKRLGNGQFGEVWM → FNLTVVSSSCTPQTSGLAKDAWEVARDSLFLEKKLGQGCFAEVWL | ||||||
Sequence conflict | 432 | in Ref. 3; BAE42585 | ||||
Sequence: W → R |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M27266 EMBL· GenBank· DDBJ | AAA37644.1 EMBL· GenBank· DDBJ | mRNA | ||
U70324 EMBL· GenBank· DDBJ | AAB09568.1 EMBL· GenBank· DDBJ | mRNA | ||
AK156584 EMBL· GenBank· DDBJ | BAE33766.1 EMBL· GenBank· DDBJ | mRNA | ||
AK171646 EMBL· GenBank· DDBJ | BAE42585.1 EMBL· GenBank· DDBJ | mRNA | ||
BC032149 EMBL· GenBank· DDBJ | AAH32149.1 EMBL· GenBank· DDBJ | mRNA | ||
BC092217 EMBL· GenBank· DDBJ | AAH92217.1 EMBL· GenBank· DDBJ | mRNA |