A1Y2K1 (FYN_PIG) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 66. History...
Names and origin
|Protein names||Recommended name:|
Tyrosine-protein kinase Fyn
|Organism||Sus scrofa (Pig) [Reference proteome]|
|Taxonomic identifier||9823 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Suina › Suidae › Sus|
|Sequence length||537 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at transcript level|
General annotation (Comments)
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.
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. UniProtKB P06241
Manganese By similarity. UniProtKB P06241
Inhibited by phosphorylation of Tyr-531 by leukocyte common antigen and activated by dephosphorylation of this site By similarity.
Interacts (via its SH3 domain) with PIK3R1 and PRMT8. Interacts with FYB, PAG1, and SH2D1A. Interacts with CD79A (tyrosine-phosphorylated form); the interaction increases FYN activity. Interacts with TOM1L1 (phosphorylated form). Interacts with SH2D1A and SLAMF1. Interacts with and phosphorylates ITCH, down-regulating its activity. Interacts with FASLG. Interacts with RUNX3. Interacts with KIT. Interacts with KDR (tyrosine phosphorylated). Interacts with EPHA8; possible downstream effector of EPHA8 in regulation of cell adhesion. Interacts with PTK2/FAK1; this interaction leads to PTK2/FAK1 phosphorylation and activation. Interacts with CAV1; this interaction couples integrins to the Ras-ERK pathway. Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated). Interacts (via SH3 domain) with KLHL2 (via N-terminus) By similarity.
Autophosphorylated at Tyr-420. Phosphorylation on the C-terminal tail at Tyr-531 by CSK maintains the enzyme in an inactive state. PTPRC/CD45 dephosphorylates Tyr-531 leading to activation. Ultraviolet B (UVB) strongly increase phosphorylation at Thr-12 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.
Palmitoylation at Cys-3 and Cys-6 regulate subcellular location By similarity.
Contains 1 protein kinase domain.
Contains 1 SH2 domain.
Contains 1 SH3 domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed By similarity UniProtKB P06241|
|Chain||2 – 537||536||Tyrosine-protein kinase Fyn UniProtKB P06241||PRO_0000282943|
|Domain||82 – 143||62||SH3|
|Domain||149 – 246||98||SH2|
|Domain||271 – 524||254||Protein kinase|
|Nucleotide binding||277 – 285||9||ATP By similarity UniProtKB P28523|
|Active site||390||1||Proton acceptor By similarity UniProtKB P28523|
|Binding site||299||1||ATP By similarity UniProtKB Q62844|
Amino acid modifications
|Modified residue||12||1||Phosphothreonine; by PKC By similarity UniProtKB P06241|
|Modified residue||15||1||Phosphothreonine By similarity|
|Modified residue||21||1||Phosphoserine By similarity UniProtKB P06241|
|Modified residue||25||1||Phosphoserine By similarity|
|Modified residue||185||1||Phosphotyrosine By similarity|
|Modified residue||213||1||Phosphotyrosine By similarity|
|Modified residue||214||1||Phosphotyrosine By similarity|
|Modified residue||257||1||Phosphoserine By similarity|
|Modified residue||420||1||Phosphotyrosine; by autocatalysis By similarity UniProtKB P06241|
|Modified residue||440||1||Phosphotyrosine By similarity|
|Modified residue||512||1||Phosphothreonine By similarity|
|Modified residue||531||1||Phosphotyrosine; by CSK By similarity UniProtKB P39688|
|Lipidation||2||1||N-myristoyl glycine By similarity UniProtKB P39688|
|Lipidation||3||1||S-palmitoyl cysteine By similarity UniProtKB P39688|
|Lipidation||6||1||S-palmitoyl cysteine By similarity UniProtKB P39688|
|DQ836055 mRNA. Translation: ABI33874.2.|
|RefSeq||NP_001073675.2. NM_001080206.2. |
3D structure databases
|SMR||A1Y2K1. Positions 81-537. |
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSSSCT00000004884; ENSSSCP00000004769; ENSSSCG00000004421. |
Family and domain databases
|Gene3D||3.30.505.10. 1 hit. |
|InterPro||IPR011009. Kinase-like_dom. |
|Pfam||PF07714. Pkinase_Tyr. 1 hit. |
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
|PRINTS||PR00401. SH2DOMAIN. |
|SMART||SM00252. SH2. 1 hit. |
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
|SUPFAM||SSF50044. SSF50044. 1 hit. |
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
|PROSITE||PS00107. PROTEIN_KINASE_ATP. 1 hit. |
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
|Accession||Primary (citable) accession number: A1Y2K1|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families