CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-001785
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Epidermal growth factor receptor 
Protein Synonyms/Alias
 Proto-oncogene c-ErbB-1; Receptor tyrosine-protein kinase erbB-1 
Gene Name
 EGFR 
Gene Synonyms/Alias
 ERBB; ERBB1; HER1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
708QALLRILKETEFKKIacetylation[1]
716ETEFKKIKVLGSGAFubiquitination[2]
737LWIPEGEKVKIPVAIubiquitination[2, 3, 4]
754LREATSPKANKEILDubiquitination[2]
860ITDFGLAKLLGAEEKacetylation[1]
860ITDFGLAKLLGAEEKubiquitination[3, 4, 5]
867KLLGAEEKEYHAEGGacetylation[1]
867KLLGAEEKEYHAEGGubiquitination[2]
929EISSILEKGERLPQPubiquitination[2, 4]
970ELIIEFSKMARDPQRubiquitination[2]
1179YQQDFFPKEAKPNGIacetylation[6]
1182DFFPKEAKPNGIFKGacetylation[6]
1188AKPNGIFKGSTAENAacetylation[6]
Reference
 [1] Acetylation of EGF receptor contributes to tumor cell resistance to histone deacetylase inhibitors.
 Song H, Li CW, Labaff AM, Lim SO, Li LY, Kan SF, Chen Y, Zhang K, Lang J, Xie X, Wang Y, Huo LF, Hsu SC, Chen X, Zhao Y, Hung MC.
 Biochem Biophys Res Commun. 2011 Jan 7;404(1):68-73. [PMID: 21094134]
 [2] Computational identification of ubiquitylation sites from protein sequences.
 Tung CW, Ho SY.
 BMC Bioinformatics. 2008 Jul 15;9:310. [PMID: 18625080]
 [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]
 [4] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [5] 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]
 [6] Multiple mechanisms collectively regulate clathrin-mediated endocytosis of the epidermal growth factor receptor.
 Goh LK, Huang F, Kim W, Gygi S, Sorkin A.
 J Cell Biol. 2010 May 31;189(5):871-83. [PMID: 20513767] 
Functional Description
 Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS- RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin. 
Sequence Annotation
 REPEAT 75 300 Approximate.
 REPEAT 390 600 Approximate.
 DOMAIN 712 979 Protein kinase.
 NP_BIND 718 726 ATP.
 NP_BIND 790 791 ATP.
 REGION 688 704 Important for dimerization,
 ACT_SITE 837 837 Proton acceptor (By similarity).
 BINDING 745 745 ATP.
 BINDING 855 855 ATP.
 MOD_RES 229 229 Phosphoserine.
 MOD_RES 678 678 Phosphothreonine; by PKC and PKD/PRKD1.
 MOD_RES 693 693 Phosphothreonine; by PKD/PRKD1.
 MOD_RES 695 695 Phosphoserine.
 MOD_RES 991 991 Phosphoserine.
 MOD_RES 995 995 Phosphoserine.
 MOD_RES 998 998 Phosphotyrosine; by autocatalysis.
 MOD_RES 1016 1016 Phosphotyrosine; by autocatalysis.
 MOD_RES 1026 1026 Phosphoserine.
 MOD_RES 1039 1039 Phosphoserine.
 MOD_RES 1041 1041 Phosphothreonine.
 MOD_RES 1042 1042 Phosphoserine.
 MOD_RES 1064 1064 Phosphoserine.
 MOD_RES 1070 1070 Phosphoserine.
 MOD_RES 1071 1071 Phosphoserine.
 MOD_RES 1081 1081 Phosphoserine.
 MOD_RES 1092 1092 Phosphotyrosine; by autocatalysis.
 MOD_RES 1110 1110 Phosphotyrosine; by autocatalysis.
 MOD_RES 1166 1166 Phosphoserine.
 MOD_RES 1172 1172 Phosphotyrosine; by autocatalysis.
 MOD_RES 1197 1197 Phosphotyrosine; by autocatalysis.
 MOD_RES 1199 1199 Omega-N-methylated arginine.
 CARBOHYD 56 56 N-linked (GlcNAc...) (complex); partial;
 CARBOHYD 73 73 N-linked (GlcNAc...); atypical.
 CARBOHYD 128 128 N-linked (GlcNAc...).
 CARBOHYD 175 175 N-linked (GlcNAc...).
 CARBOHYD 196 196 N-linked (GlcNAc...).
 CARBOHYD 352 352 N-linked (GlcNAc...).
 CARBOHYD 361 361 N-linked (GlcNAc...).
 CARBOHYD 413 413 N-linked (GlcNAc...).
 CARBOHYD 444 444 N-linked (GlcNAc...).
 CARBOHYD 528 528 N-linked (GlcNAc...).
 CARBOHYD 568 568 N-linked (GlcNAc...); partial.
 CARBOHYD 603 603 N-linked (GlcNAc...); partial.
 DISULFID 31 58
 DISULFID 157 187
 DISULFID 190 199
 DISULFID 194 207
 DISULFID 215 223
 DISULFID 219 231
 DISULFID 232 240
 DISULFID 236 248
 DISULFID 251 260
 DISULFID 264 291
 DISULFID 295 307
 DISULFID 311 326
 DISULFID 329 333
 DISULFID 337 362
 DISULFID 470 499
 DISULFID 506 515
 DISULFID 510 523
 DISULFID 526 535
 DISULFID 539 555
 DISULFID 558 571
 DISULFID 562 579
 DISULFID 582 591
 DISULFID 595 617
 DISULFID 620 628
 DISULFID 624 636
 CROSSLNK 716 716 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 737 737 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 754 754 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 867 867 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 929 929 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 970 970 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Alternative splicing; ATP-binding; Cell membrane; Complete proteome; Developmental protein; Direct protein sequencing; Disease mutation; Disulfide bond; Endoplasmic reticulum; Endosome; Glycoprotein; Golgi apparatus; Isopeptide bond; Kinase; Membrane; Methylation; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Receptor; Reference proteome; Repeat; Secreted; Signal; Transferase; Transmembrane; Transmembrane helix; Tumor suppressor; Tyrosine-protein kinase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1210 AA 
Protein Sequence
MRPSGTAGAA LLALLAALCP ASRALEEKKV CQGTSNKLTQ LGTFEDHFLS LQRMFNNCEV 60
VLGNLEITYV QRNYDLSFLK TIQEVAGYVL IALNTVERIP LENLQIIRGN MYYENSYALA 120
VLSNYDANKT GLKELPMRNL QEILHGAVRF SNNPALCNVE SIQWRDIVSS DFLSNMSMDF 180
QNHLGSCQKC DPSCPNGSCW GAGEENCQKL TKIICAQQCS GRCRGKSPSD CCHNQCAAGC 240
TGPRESDCLV CRKFRDEATC KDTCPPLMLY NPTTYQMDVN PEGKYSFGAT CVKKCPRNYV 300
VTDHGSCVRA CGADSYEMEE DGVRKCKKCE GPCRKVCNGI GIGEFKDSLS INATNIKHFK 360
NCTSISGDLH ILPVAFRGDS FTHTPPLDPQ ELDILKTVKE ITGFLLIQAW PENRTDLHAF 420
ENLEIIRGRT KQHGQFSLAV VSLNITSLGL RSLKEISDGD VIISGNKNLC YANTINWKKL 480
FGTSGQKTKI ISNRGENSCK ATGQVCHALC SPEGCWGPEP RDCVSCRNVS RGRECVDKCN 540
LLEGEPREFV ENSECIQCHP ECLPQAMNIT CTGRGPDNCI QCAHYIDGPH CVKTCPAGVM 600
GENNTLVWKY ADAGHVCHLC HPNCTYGCTG PGLEGCPTNG PKIPSIATGM VGALLLLLVV 660
ALGIGLFMRR RHIVRKRTLR RLLQERELVE PLTPSGEAPN QALLRILKET EFKKIKVLGS 720
GAFGTVYKGL WIPEGEKVKI PVAIKELREA TSPKANKEIL DEAYVMASVD NPHVCRLLGI 780
CLTSTVQLIT QLMPFGCLLD YVREHKDNIG SQYLLNWCVQ IAKGMNYLED RRLVHRDLAA 840
RNVLVKTPQH VKITDFGLAK LLGAEEKEYH AEGGKVPIKW MALESILHRI YTHQSDVWSY 900
GVTVWELMTF GSKPYDGIPA SEISSILEKG ERLPQPPICT IDVYMIMVKC WMIDADSRPK 960
FRELIIEFSK MARDPQRYLV IQGDERMHLP SPTDSNFYRA LMDEEDMDDV VDADEYLIPQ 1020
QGFFSSPSTS RTPLLSSLSA TSNNSTVACI DRNGLQSCPI KEDSFLQRYS SDPTGALTED 1080
SIDDTFLPVP EYINQSVPKR PAGSVQNPVY HNQPLNPAPS RDPHYQDPHS TAVGNPEYLN 1140
TVQPTCVNST FDSPAHWAQK GSHQISLDNP DYQQDFFPKE AKPNGIFKGS TAENAEYLRV 1200
APQSSEFIGA 1210 
Gene Ontology
 GO:0016323; C:basolateral plasma membrane; IDA:BHF-UCL.
 GO:0030139; C:endocytic vesicle; IEA:Compara.
 GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
 GO:0005768; C:endosome; IDA:UniProtKB.
 GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
 GO:0005615; C:extracellular space; NAS:UniProtKB.
 GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
 GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
 GO:0045121; C:membrane raft; IDA:UniProtKB.
 GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0048471; C:perinuclear region of cytoplasm; IEA:Compara.
 GO:0070435; C:Shc-EGFR complex; ISS:BHF-UCL.
 GO:0051015; F:actin filament binding; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0003690; F:double-stranded DNA binding; NAS:UniProtKB.
 GO:0005006; F:epidermal growth factor-activated receptor activity; IDA:UniProtKB.
 GO:0004709; F:MAP kinase kinase kinase activity; NAS:UniProtKB.
 GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
 GO:0004716; F:receptor signaling protein tyrosine kinase activity; IEA:InterPro.
 GO:0043006; P:activation of phospholipase A2 activity by calcium-mediated signaling; TAS:UniProtKB.
 GO:0007202; P:activation of phospholipase C activity; TAS:UniProtKB.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0008283; P:cell proliferation; IDA:UniProtKB.
 GO:0016337; P:cell-cell adhesion; IMP:UniProtKB.
 GO:0021795; P:cerebral cortex cell migration; IEA:Compara.
 GO:0048546; P:digestive tract morphogenesis; IEA:Compara.
 GO:0001892; P:embryonic placenta development; IEA:Compara.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0001942; P:hair follicle development; IEA:Compara.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0060571; P:morphogenesis of an epithelial fold; IEA:Compara.
 GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
 GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0042177; P:negative regulation of protein catabolic process; IDA:UniProtKB.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0001503; P:ossification; NAS:UniProtKB.
 GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
 GO:0035413; P:positive regulation of catenin import into nucleus; IMP:BHF-UCL.
 GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB.
 GO:0031659; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle; IDA:BHF-UCL.
 GO:0045739; P:positive regulation of DNA repair; IDA:UniProtKB.
 GO:0045740; P:positive regulation of DNA replication; IDA:UniProtKB.
 GO:0050679; P:positive regulation of epithelial cell proliferation; IDA:UniProtKB.
 GO:0048146; P:positive regulation of fibroblast proliferation; IEA:Compara.
 GO:0043406; P:positive regulation of MAP kinase activity; IDA:UniProtKB.
 GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IDA:UniProtKB.
 GO:0051897; P:positive regulation of protein kinase B signaling cascade; IMP:BHF-UCL.
 GO:0046777; P:protein autophosphorylation; IMP:UniProtKB.
 GO:0051205; P:protein insertion into membrane; TAS:UniProtKB.
 GO:0050999; P:regulation of nitric-oxide synthase activity; IDA:UniProtKB.
 GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IMP:UniProtKB.
 GO:0070141; P:response to UV-A; IDA:BHF-UCL.
 GO:0007435; P:salivary gland morphogenesis; IEA:Compara. 
Interpro
 IPR000494; EGF_rcpt_L.
 IPR006211; Furin-like_Cys-rich_dom.
 IPR006212; Furin_repeat.
 IPR009030; Growth_fac_rcpt_N_dom.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
 IPR008266; Tyr_kinase_AS.
 IPR020635; Tyr_kinase_cat_dom.
 IPR016245; Tyr_kinase_EGF/ERB/XmrK_rcpt. 
Pfam
 PF00757; Furin-like
 PF07714; Pkinase_Tyr
 PF01030; Recep_L_domain 
SMART
 SM00261; FU
 SM00219; TyrKc 
PROSITE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR 
PRINTS
 PR00109; TYRKINASE.