CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-010841
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Epidermal growth factor receptor 
Protein Synonyms/Alias
  
Gene Name
 Egfr 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
454SLGLRSLKEISDGDVubiquitination[1]
487LFGTPNQKTKIMNNRubiquitination[1]
710QAHLRILKETEFKKIubiquitination[1]
730GAFGTVYKGLWIPEGubiquitination[1]
739LWIPEGEKVKIPVAIubiquitination[1]
741IPEGEKVKIPVAIKEubiquitination[1]
747VKIPVAIKELREATSubiquitination[1]
759ATSPKANKEILDEAYubiquitination[1]
848AARNVLVKTPQHVKIubiquitination[1]
854VKTPQHVKITDFGLAubiquitination[1]
862ITDFGLAKLLGAEEKubiquitination[1]
869KLLGAEEKEYHAEGGubiquitination[1]
877EYHAEGGKVPIKWMAubiquitination[1]
931DISSILEKGERLPQPubiquitination[1]
972ELILEFSKMARDPQRubiquitination[1]
1061RNGSCRVKEDAFLQRubiquitination[1]
1179YQQDFFPKETKPNGIubiquitination[1]
1182DFFPKETKPNGIFKGubiquitination[1]
1188TKPNGIFKGPTAENAubiquitination[1]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 
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 714 981 Protein kinase.
 NP_BIND 720 728 ATP (By similarity).
 NP_BIND 792 793 ATP (By similarity).
 REGION 690 706 Important for dimerization,
 ACT_SITE 839 839 Proton acceptor (By similarity).
 BINDING 747 747 ATP (By similarity).
 BINDING 857 857 ATP (By similarity).
 MOD_RES 229 229 Phosphoserine (By similarity).
 MOD_RES 680 680 Phosphothreonine; by PKC and PKD/PRKD1
 MOD_RES 695 695 Phosphothreonine; by PKD/PRKD1 (By
 MOD_RES 697 697 Phosphoserine (By similarity).
 MOD_RES 993 993 Phosphoserine (By similarity).
 MOD_RES 997 997 Phosphoserine (By similarity).
 MOD_RES 1000 1000 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1018 1018 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1028 1028 Phosphoserine (By similarity).
 MOD_RES 1041 1041 Phosphoserine (By similarity).
 MOD_RES 1043 1043 Phosphothreonine (By similarity).
 MOD_RES 1044 1044 Phosphoserine (By similarity).
 MOD_RES 1070 1070 Phosphoserine (By similarity).
 MOD_RES 1071 1071 Phosphoserine (By similarity).
 MOD_RES 1092 1092 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1110 1110 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1166 1166 Phosphoserine (By similarity).
 MOD_RES 1172 1172 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1197 1197 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1199 1199 Omega-N-methylated arginine (By
 CARBOHYD 128 128 N-linked (GlcNAc...) (Potential).
 CARBOHYD 175 175 N-linked (GlcNAc...).
 CARBOHYD 196 196 N-linked (GlcNAc...) (Potential).
 CARBOHYD 352 352 N-linked (GlcNAc...).
 CARBOHYD 413 413 N-linked (GlcNAc...) (Potential).
 CARBOHYD 444 444 N-linked (GlcNAc...).
 CARBOHYD 528 528 N-linked (GlcNAc...) (Potential).
 CARBOHYD 568 568 N-linked (GlcNAc...) (Potential).
 CARBOHYD 603 603 N-linked (GlcNAc...) (Potential).
 CARBOHYD 623 623 N-linked (GlcNAc...) (Potential).
 DISULFID 190 199 By similarity.
 DISULFID 194 207 By similarity.
 DISULFID 215 223 By similarity.
 DISULFID 219 231 By similarity.
 DISULFID 232 240 By similarity.
 DISULFID 236 248 By similarity.
 DISULFID 251 260 By similarity.
 DISULFID 264 291 By similarity.
 DISULFID 295 307 By similarity.
 DISULFID 311 326 By similarity.
 DISULFID 329 333 By similarity.
 DISULFID 506 515 By similarity.
 DISULFID 510 523 By similarity.
 DISULFID 526 535 By similarity.
 DISULFID 539 555 By similarity.
 DISULFID 558 571 By similarity.
 DISULFID 562 579 By similarity.
 DISULFID 582 591 By similarity.
 DISULFID 595 617 By similarity.
 DISULFID 620 628 By similarity.
 DISULFID 624 636 By similarity.
 CROSSLNK 718 718 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 739 739 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 756 756 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 869 869 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 931 931 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 972 972 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 ATP-binding; Cell membrane; Complete proteome; Developmental protein; Disulfide bond; Endoplasmic reticulum; Endosome; Glycoprotein; Golgi apparatus; Isopeptide bond; Kinase; Membrane; Methylation; Nucleotide-binding; Nucleus; Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1210 AA 
Protein Sequence
MRPSGTARTT LLVLLTALCA AGGALEEKKV CQGTSNRLTQ LGTFEDHFLS LQRMYNNCEV 60
VLGNLEITYV QRNYDLSFLK TIQEVAGYVL IALNTVERIP LENLQIIRGN ALYENTYALA 120
ILSNYGTNRT GLRELPMRNL QEILIGAVRF SNNPILCNMD TIQWRDIVQN VFMSNMSMDL 180
QSHPSSCPKC DPSCPNGSCW GGGEENCQKL TKIICAQQCS HRCRGRSPSD CCHNQCAAGC 240
TGPRESDCLV CQKFQDEATC KDTCPPLMLY NPTTYQMDVN PEGKYSFGAT CVKKCPRNYV 300
VTDHGSCVRA CGPDYYEVEE DGIRKCKKCD GPCRKVCNGI GIGEFKDTLS INATNIKHFK 360
YCTAISGDLH ILPVAFKGDS FTRTPPLDPR ELEILKTVKE ITGFLLIQAW PDNWTDLHAF 420
ENLEIIRGRT KQHGQFSLAV VGLNITSLGL RSLKEISDGD VIISGNRNLC YANTINWKKL 480
FGTPNQKTKI MNNRAEKDCK AVNHVCNPLC SSEGCWGPEP RDCVSCQNVS RGRECVEKCN 540
ILEGEPREFV ENSECIQCHP ECLPQAMNIT CTGRGPDNCI QCAHYIDGPH CVKTCPAGIM 600
GENNTLVWKY ADANNVCHLC HANCTYGCAG PGLQGCEVWP SGPKIPSIAT GIVGGLLFIV 660
VVALGIGLFM RRRHIVRKRT LRRLLQEREL VEPLTPSGEA PNQAHLRILK ETEFKKIKVL 720
GSGAFGTVYK GLWIPEGEKV KIPVAIKELR EATSPKANKE ILDEAYVMAS VDNPHVCRLL 780
GICLTSTVQL ITQLMPYGCL LDYVREHKDN IGSQYLLNWC VQIAKGMNYL EDRRLVHRDL 840
AARNVLVKTP QHVKITDFGL AKLLGAEEKE YHAEGGKVPI KWMALESILH RIYTHQSDVW 900
SYGVTVWELM TFGSKPYDGI PASDISSILE KGERLPQPPI CTIDVYMIMV KCWMIDADSR 960
PKFRELILEF SKMARDPQRY LVIQGDERMH LPSPTDSNFY RALMDEEDME DVVDADEYLI 1020
PQQGFFNSPS TSRTPLLSSL SATSNNSTVA CINRNGSCRV KEDAFLQRYS SDPTGAVTED 1080
NIDDAFLPVP EYVNQSVPKR PAGSVQNPVY HNQPLHPAPG RDLHYQNPHS NAVGNPEYLN 1140
TAQPTCLSSG FNSPALWIQK GSHQMSLDNP DYQQDFFPKE TKPNGIFKGP TAENAEYLRV 1200
APPSSEFIGA 1210 
Gene Ontology
 GO:0016323; C:basolateral plasma membrane; IDA:MGI.
 GO:0030139; C:endocytic vesicle; IDA:MGI.
 GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
 GO:0005768; C:endosome; ISS:UniProtKB.
 GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
 GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
 GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
 GO:0045121; C:membrane raft; IEA:Compara.
 GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; IDA:BHF-UCL.
 GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0005006; F:epidermal growth factor-activated receptor activity; IDA:MGI.
 GO:0030235; F:nitric-oxide synthase regulator activity; IEA:Compara.
 GO:0004716; F:receptor signaling protein tyrosine kinase activity; IEA:InterPro.
 GO:0000902; P:cell morphogenesis; IGI:MGI.
 GO:0008283; P:cell proliferation; IEA:Compara.
 GO:0016337; P:cell-cell adhesion; IEA:Compara.
 GO:0021795; P:cerebral cortex cell migration; IMP:MGI.
 GO:0048546; P:digestive tract morphogenesis; IMP:MGI.
 GO:0001892; P:embryonic placenta development; IMP:MGI.
 GO:0001942; P:hair follicle development; IMP:MGI.
 GO:0060571; P:morphogenesis of an epithelial fold; IMP:MGI.
 GO:0043066; P:negative regulation of apoptotic process; IEA:Compara.
 GO:0042177; P:negative regulation of protein catabolic process; IEA:Compara.
 GO:0035413; P:positive regulation of catenin import into nucleus; IEA:Compara.
 GO:0030335; P:positive regulation of cell migration; IEA:Compara.
 GO:0031659; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle; IEA:Compara.
 GO:0045739; P:positive regulation of DNA repair; IEA:Compara.
 GO:0045740; P:positive regulation of DNA replication; IEA:Compara.
 GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:MGI.
 GO:0048146; P:positive regulation of fibroblast proliferation; IMP:BHF-UCL.
 GO:0043406; P:positive regulation of MAP kinase activity; IEA:Compara.
 GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IEA:Compara.
 GO:0051897; P:positive regulation of protein kinase B signaling cascade; IEA:Compara.
 GO:0046777; P:protein autophosphorylation; IDA:MGI.
 GO:0050999; P:regulation of nitric-oxide synthase activity; IEA:Compara.
 GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IMP:MGI.
 GO:0070141; P:response to UV-A; IEA:Compara.
 GO:0007435; P:salivary gland morphogenesis; IMP:MGI.
 GO:0023014; P:signal transduction by phosphorylation; IEA:GOC. 
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.