P06241

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. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. COFACTOR: Manganese. ENZYME REGULATION: Inhibited by phosphorylation of Tyr-531 by leukocyte common antigen and activated by dephosphorylation of this site. SUBUNIT: 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 (via SH2 domain) with CSF1R (tyrosine phosphorylated) (By similarity). Interacts with TOM1L1 (phosphorylated form). Interacts with KDR (tyrosine phosphorylated) (By similarity). Interacts with SH2D1A and SLAMF1. Interacts (via its SH3 domain) with HEV ORF3 protein. Interacts with ITCH; the interaction phosphorylates ITCH and negatively regulates its activity. Interacts with FASLG. Interacts with RUNX3. Interacts with KIT. 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. SUBCELLULAR LOCATION: Cell membrane. Note=Present and active in lipid rafts. Palmitoylation is crucial for proper trafficking. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=3; Name=1; Synonyms=B; IsoId=P06241-1; Sequence=Displayed; Name=2; Synonyms=T; IsoId=P06241-2; Sequence=VSP_024110; Name=3; IsoId=P06241-3; Sequence=VSP_024108; Note=No experimental confirmation available; TISSUE SPECIFICITY: Isoform 1 is highly expressed in the brain. Isoform 2 is expressed in cells of hemopoietic lineages, especially T-lymphocytes. PTM: Autophosphorylated at Tyr-420. Phosphorylation on the C- terminal tail at Tyr-531 by CSK maintains the enzyme in an inactive state (By similarity). PTPRC/CD45 dephosphorylates Tyr- 531 leading to activation. PTM: Palmitoylation at Cys-3 and Cys-6 regulates subcellular location (By similarity). SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 1 SH2 domain. SIMILARITY: Contains 1 SH3 domain. GENE SYNONYMS:FYN. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License., SEQUENCE 537 AA; 60762 MW; 4A1E443A4B5A0977 CRC64;

FYN_HUMAN

urn:biopax:ModificationFeature:FYN_HUMAN_1, urn:biopax:ModificationFeature:FYN_HUMAN_10, urn:biopax:ModificationFeature:FYN_HUMAN_11, urn:biopax:ModificationFeature:FYN_HUMAN_12, urn:biopax:ModificationFeature:FYN_HUMAN_13, urn:biopax:ModificationFeature:FYN_HUMAN_2, urn:biopax:ModificationFeature:FYN_HUMAN_3, urn:biopax:ModificationFeature:FYN_HUMAN_4, urn:biopax:ModificationFeature:FYN_HUMAN_5, urn:biopax:ModificationFeature:FYN_HUMAN_6, urn:biopax:ModificationFeature:FYN_HUMAN_7, urn:biopax:ModificationFeature:FYN_HUMAN_8, urn:biopax:ModificationFeature:FYN_HUMAN_9

MGCVQCKDKEATKLTEERDGSLNQSSGYRYGTDPTPQHYPSFGVTSIPNYNNFHAAGGQGLTVFGGVNSSSHTGTLRTRGGTGVTLFVALYDYEARTEDDLSFHKGEKFQILNSSEGDWWEARSLTTGETGYIPSNYVAPVDSIQAEEWYFGKLGRKDAERQLLSFGNPRGTFLIRESETTKGAYSLSIRDWDDMKGDHVKHYKIRKLDNGGYYITTRAQFETLQQLVQHYSERAAGLCCRLVVPCHKGMPRLTDLSVKTKDVWEIPRESLQLIKRLGNGQFGEVWMGTWNGNTKVAIKTLKPGTMSPESFLEEAQIMKKLKHDKLVQLYAVVSEEPIYIVTEYMNKGSLLDFLKDGEGRALKLPNLVDMAAQVAAGMAYIERMNYIHRDLRSANILVGNGLICKIADFGLARLIEDNEYTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPQDCPISLHELMIHCWKKDPEERPTFEYLQSFLEDYFTATEPQYQPGENL