CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-002330
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Tyrosine-protein kinase Fyn 
Protein Synonyms/Alias
 Proto-oncogene Syn; Proto-oncogene c-Fyn; Src-like kinase; SLK; p59-Fyn 
Gene Name
 FYN 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
182IRESETTKGAYSLSIubiquitination[1]
355GSLLDFLKDGEGRALubiquitination[1]
405VGNGLICKIADFGLAubiquitination[1]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 82 143 SH3.
 DOMAIN 149 246 SH2.
 DOMAIN 271 524 Protein kinase.
 NP_BIND 277 285 ATP (By similarity).
 ACT_SITE 390 390 Proton acceptor (By similarity).
 BINDING 299 299 ATP (By similarity).
 MOD_RES 12 12 Phosphothreonine; by PKC.
 MOD_RES 15 15 Phosphothreonine.
 MOD_RES 21 21 Phosphoserine.
 MOD_RES 25 25 Phosphoserine.
 MOD_RES 185 185 Phosphotyrosine (By similarity).
 MOD_RES 213 213 Phosphotyrosine.
 MOD_RES 214 214 Phosphotyrosine.
 MOD_RES 254 254 Phosphothreonine (By similarity).
 MOD_RES 257 257 Phosphoserine.
 MOD_RES 420 420 Phosphotyrosine; by autocatalysis.
 MOD_RES 440 440 Phosphotyrosine.
 MOD_RES 512 512 Phosphothreonine.
 MOD_RES 531 531 Phosphotyrosine; by CSK.
 LIPID 2 2 N-myristoyl glycine.
 LIPID 3 3 S-palmitoyl cysteine (By similarity).
 LIPID 6 6 S-palmitoyl cysteine (By similarity).  
Keyword
 3D-structure; Adaptive immunity; Alternative splicing; ATP-binding; Cell membrane; Complete proteome; Cytoplasm; Developmental protein; Host-virus interaction; Immunity; Kinase; Lipoprotein; Manganese; Membrane; Metal-binding; Myristate; Nucleotide-binding; Nucleus; Palmitate; Phosphoprotein; Polymorphism; Proto-oncogene; Reference proteome; SH2 domain; SH3 domain; Transferase; Tyrosine-protein kinase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 537 AA 
Protein Sequence
MGCVQCKDKE ATKLTEERDG SLNQSSGYRY GTDPTPQHYP SFGVTSIPNY NNFHAAGGQG 60
LTVFGGVNSS SHTGTLRTRG GTGVTLFVAL YDYEARTEDD LSFHKGEKFQ ILNSSEGDWW 120
EARSLTTGET GYIPSNYVAP VDSIQAEEWY FGKLGRKDAE RQLLSFGNPR GTFLIRESET 180
TKGAYSLSIR DWDDMKGDHV KHYKIRKLDN GGYYITTRAQ FETLQQLVQH YSERAAGLCC 240
RLVVPCHKGM PRLTDLSVKT KDVWEIPRES LQLIKRLGNG QFGEVWMGTW NGNTKVAIKT 300
LKPGTMSPES FLEEAQIMKK LKHDKLVQLY AVVSEEPIYI VTEYMNKGSL LDFLKDGEGR 360
ALKLPNLVDM AAQVAAGMAY IERMNYIHRD LRSANILVGN GLICKIADFG LARLIEDNEY 420
TARQGAKFPI KWTAPEAALY GRFTIKSDVW SFGILLTELV TKGRVPYPGM NNREVLEQVE 480
RGYRMPCPQD CPISLHELMI HCWKKDPEER PTFEYLQSFL EDYFTATEPQ YQPGENL 537 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005768; C:endosome; IDA:HGNC.
 GO:0005739; C:mitochondrion; IEA:Compara.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0005886; C:plasma membrane; IDA:HGNC.
 GO:0014069; C:postsynaptic density; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; NAS:UniProtKB.
 GO:0050798; P:activated T cell proliferation; IEA:Compara.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0006816; P:calcium ion transport; NAS:UniProtKB.
 GO:0071375; P:cellular response to peptide hormone stimulus; IEA:Compara.
 GO:0048813; P:dendrite morphogenesis; IEA:Compara.
 GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; IEA:Compara.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
 GO:0007631; P:feeding behavior; TAS:ProtInc.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0030900; P:forebrain development; IEA:Compara.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0007243; P:intracellular protein kinase cascade; TAS:ProtInc.
 GO:0007612; P:learning; TAS:ProtInc.
 GO:0050900; P:leukocyte migration; TAS:Reactome.
 GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IEA:Compara.
 GO:0010629; P:negative regulation of gene expression; IEA:Compara.
 GO:0042177; P:negative regulation of protein catabolic process; IEA:Compara.
 GO:0001764; P:neuron migration; IEA:Compara.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0018108; P:peptidyl-tyrosine phosphorylation; IEA:Compara.
 GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
 GO:0030168; P:platelet activation; TAS:Reactome.
 GO:0010976; P:positive regulation of neuron projection development; IEA:Compara.
 GO:0046777; P:protein autophosphorylation; IEA:Compara.
 GO:0008360; P:regulation of cell shape; IEA:Compara.
 GO:0050690; P:regulation of defense response to virus by virus; TAS:Reactome.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0045471; P:response to ethanol; IEA:Compara.
 GO:0031295; P:T cell costimulation; TAS:Reactome.
 GO:0050852; P:T cell receptor signaling pathway; IDA:UniProtKB.
 GO:0016032; P:viral reproduction; TAS:Reactome.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 
Interpro
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
 IPR000980; SH2.
 IPR001452; SH3_domain.
 IPR008266; Tyr_kinase_AS.
 IPR020635; Tyr_kinase_cat_dom. 
Pfam
 PF07714; Pkinase_Tyr
 PF00017; SH2
 PF00018; SH3_1 
SMART
 SM00252; SH2
 SM00326; SH3
 SM00219; TyrKc 
PROSITE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR
 PS50001; SH2
 PS50002; SH3 
PRINTS
 PR00401; SH2DOMAIN.
 PR00452; SH3DOMAIN.
 PR00109; TYRKINASE.