CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-004480
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Tyrosine-protein kinase Fer 
Protein Synonyms/Alias
 Feline encephalitis virus-related kinase FER; Fujinami poultry sarcoma/Feline sarcoma-related protein Fer; Proto-oncogene c-Fer; Tyrosine kinase 3; p94-Fer 
Gene Name
 FER 
Gene Synonyms/Alias
 TYK3 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
476EAQELLKKQGDFLVRubiquitination[1]
594SVAVKTCKEDLPQELubiquitination[1]
602EDLPQELKIKFLQEAubiquitination[1]
610IKFLQEAKILKQYDHubiquitination[1, 2, 3]
613LQEAKILKQYDHPNIubiquitination[1]
699VGENNVLKISDFGMSubiquitination[1]
720VYSSSGLKQIPIKWTubiquitination[3]
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]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983] 
Functional Description
 Tyrosine-protein kinase that acts downstream of cell surface receptors for growth factors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, lamellipodia formation, cell adhesion, cell migration and chemotaxis. Acts downstream of EGFR, KIT, PDGFRA and PDGFRB. Acts downstream of EGFR to promote activation of NF-kappa-B and cell proliferation. May play a role in the regulation of the mitotic cell cycle. Plays a role in the insulin receptor signaling pathway and in activation of phosphatidylinositol 3-kinase. Acts downstream of the activated FCER1 receptor and plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Plays a role in the regulation of mast cell degranulation. Plays a role in leukocyte recruitment and diapedesis in response to bacterial lipopolysaccharide (LPS). Plays a role in synapse organization, trafficking of synaptic vesicles, the generation of excitatory postsynaptic currents and neuron-neuron synaptic transmission. Plays a role in neuronal cell death after brain damage. Phosphorylates CTTN, CTNND1, PTK2/FAK1, GAB1, PECAM1 and PTPN11. May phosphorylate JUP and PTPN1. Can phosphorylate STAT3, but the biological relevance of this depends on cell type and stimulus. 
Sequence Annotation
 DOMAIN 1 58 FCH.
 DOMAIN 460 550 SH2.
 DOMAIN 563 816 Protein kinase.
 NP_BIND 569 577 ATP (By similarity).
 REGION 1 300 Important for interaction with membranes
 ACT_SITE 684 684 Proton acceptor (By similarity).
 BINDING 591 591 ATP (By similarity).
 MOD_RES 402 402 Phosphotyrosine.
 MOD_RES 434 434 Phosphoserine.
 MOD_RES 615 615 Phosphotyrosine; by autocatalysis (By
 MOD_RES 714 714 Phosphotyrosine; by autocatalysis.  
Keyword
 3D-structure; Alternative promoter usage; Alternative splicing; ATP-binding; Cell junction; Cell membrane; Cell projection; Coiled coil; Complete proteome; Cytoplasm; Cytoskeleton; Kinase; Lipid-binding; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Proto-oncogene; Reference proteome; SH2 domain; Transferase; Tyrosine-protein kinase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 822 AA 
Protein Sequence
MGFGSDLKNS HEAVLKLQDW ELRLLETVKK FMALRIKSDK EYASTLQNLC NQVDKESTVQ 60
MNYVSNVSKS WLLMIQQTEQ LSRIMKTHAE DLNSGPLHRL TMMIKDKQQV KKSYIGVHQQ 120
IEAEMIKVTK TELEKLKCSY RQLIKEMNSA KEKYKEALAK GKETEKAKER YDKATMKLHM 180
LHNQYVLALK GAQLHQNQYY DITLPLLLDS LQKMQEEMIK ALKGIFDEYS QITSLVTEEI 240
VNVHKEIQMS VEQIDPSTEY NNFIDVHRTT AAKEQEIEFD TSLLEENENL QANEIMWNNL 300
TAESLQVMLK TLAEELMQTQ QMLLNKEEAV LELEKRIEES SETCEKKSDI VLLLSQKQAL 360
EELKQSVQQL RCTEAKFSAQ KELLEQKVQE NDGKEPPPVV NYEEDARSVT SMERKERLSK 420
FESIRHSIAG IIRSPKSALG SSALSDMISI SEKPLAEQDW YHGAIPRIEA QELLKKQGDF 480
LVRESHGKPG EYVLSVYSDG QRRHFIIQYV DNMYRFEGTG FSNIPQLIDH HYTTKQVITK 540
KSGVVLLNPI PKDKKWILSH EDVILGELLG KGNFGEVYKG TLKDKTSVAV KTCKEDLPQE 600
LKIKFLQEAK ILKQYDHPNI VKLIGVCTQR QPVYIIMELV SGGDFLTFLR RKKDELKLKQ 660
LVKFSLDAAA GMLYLESKNC IHRDLAARNC LVGENNVLKI SDFGMSRQED GGVYSSSGLK 720
QIPIKWTAPE ALNYGRYSSE SDVWSFGILL WETFSLGVCP YPGMTNQQAR EQVERGYRMS 780
APQHCPEDIS KIMMKCWDYK PENRPKFSEL QKELTIIKRK LT 822 
Gene Ontology
 GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
 GO:0030054; C:cell junction; IEA:UniProtKB-SubCell.
 GO:0042995; C:cell projection; IEA:UniProtKB-SubCell.
 GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0031234; C:extrinsic to internal side of plasma membrane; IDA:UniProtKB.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0005154; F:epidermal growth factor receptor binding; IDA:UniProtKB.
 GO:0008289; F:lipid binding; IDA:UniProtKB.
 GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB.
 GO:0031532; P:actin cytoskeleton reorganization; ISS:UniProtKB.
 GO:0008283; P:cell proliferation; IMP:UniProtKB.
 GO:0044331; P:cell-cell adhesion mediated by cadherin; ISS:UniProtKB.
 GO:0036006; P:cellular response to macrophage colony-stimulating factor stimulus; IMP:UniProtKB.
 GO:0034614; P:cellular response to reactive oxygen species; ISS:UniProtKB.
 GO:0006935; P:chemotaxis; IEA:Compara.
 GO:0050904; P:diapedesis; ISS:UniProtKB.
 GO:0035426; P:extracellular matrix-cell signaling; ISS:UniProtKB.
 GO:0038095; P:Fc-epsilon receptor signaling pathway; ISS:UniProtKB.
 GO:0038028; P:insulin receptor signaling pathway via phosphatidylinositol 3-kinase cascade; ISS:UniProtKB.
 GO:0070102; P:interleukin-6-mediated signaling pathway; IMP:UniProtKB.
 GO:0038109; P:Kit signaling pathway; ISS:UniProtKB.
 GO:0000226; P:microtubule cytoskeleton organization; IMP:UniProtKB.
 GO:0000278; P:mitotic cell cycle; IMP:UniProtKB.
 GO:0033007; P:negative regulation of mast cell activation involved in immune response; ISS:UniProtKB.
 GO:0048008; P:platelet-derived growth factor receptor signaling pathway; ISS:UniProtKB.
 GO:0030838; P:positive regulation of actin filament polymerization; IMP:UniProtKB.
 GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB.
 GO:0008284; P:positive regulation of cell proliferation; TAS:UniProtKB.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
 GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
 GO:0042058; P:regulation of epidermal growth factor receptor signaling pathway; IMP:UniProtKB.
 GO:0010762; P:regulation of fibroblast migration; IEA:Compara.
 GO:0010591; P:regulation of lamellipodium assembly; IDA:UniProtKB.
 GO:0001932; P:regulation of protein phosphorylation; ISS:UniProtKB.
 GO:0032496; P:response to lipopolysaccharide; ISS:UniProtKB.
 GO:0036119; P:response to platelet-derived growth factor stimulus; ISS:UniProtKB.
 GO:0034446; P:substrate adhesion-dependent cell spreading; ISS:UniProtKB.
 GO:0042503; P:tyrosine phosphorylation of Stat3 protein; IDA:UniProtKB. 
Interpro
 IPR001060; FCH_dom.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
 IPR000980; SH2.
 IPR008266; Tyr_kinase_AS.
 IPR020635; Tyr_kinase_cat_dom.
 IPR016250; Tyr_kinase_non-rcpt_Fes_subgr. 
Pfam
 PF00611; FCH
 PF07714; Pkinase_Tyr
 PF00017; SH2 
SMART
 SM00055; FCH
 SM00252; SH2
 SM00219; TyrKc 
PROSITE
 PS50133; FCH
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR
 PS50001; SH2 
PRINTS
 PR00401; SH2DOMAIN.
 PR00109; TYRKINASE.