CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-002136
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Receptor tyrosine-protein kinase erbB-2 
Protein Synonyms/Alias
 Metastatic lymph node gene 19 protein; MLN 19; Proto-oncogene Neu; Proto-oncogene c-ErbB-2; Tyrosine kinase-type cell surface receptor HER2; p185erbB2; CD340 
Gene Name
 ERBB2 
Gene Synonyms/Alias
 HER2; MLN19; NEU; NGL 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
126GAFGTVYKGIWIPDGubiquitination[1]
137IPDGENVKIPVAIKVubiquitination[1]
Reference
 [1] 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] 
Functional Description
 Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization. 
Sequence Annotation
 DOMAIN 720 987 Protein kinase.
 NP_BIND 726 734 ATP (By similarity).
 REGION 676 689 Nuclear localization signal.
 REGION 676 689 Required for interaction with KPNB1 and
 REGION 1195 1197 Interaction with PIK3C2B (Probable).
 ACT_SITE 845 845 Proton acceptor (By similarity).
 BINDING 753 753 ATP (By similarity).
 MOD_RES 1054 1054 Phosphoserine.
 MOD_RES 1107 1107 Phosphoserine.
 MOD_RES 1139 1139 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1196 1196 Phosphotyrosine (Potential).
 MOD_RES 1248 1248 Phosphotyrosine; by autocatalysis.
 CARBOHYD 68 68 N-linked (GlcNAc...).
 CARBOHYD 124 124 N-linked (GlcNAc...) (Potential).
 CARBOHYD 187 187 N-linked (GlcNAc...) (Potential).
 CARBOHYD 259 259 N-linked (GlcNAc...).
 CARBOHYD 530 530 N-linked (GlcNAc...).
 CARBOHYD 571 571 N-linked (GlcNAc...).
 CARBOHYD 629 629 N-linked (GlcNAc...) (Potential).
 DISULFID 26 53
 DISULFID 162 192
 DISULFID 195 204
 DISULFID 199 212
 DISULFID 220 227
 DISULFID 224 235
 DISULFID 236 244
 DISULFID 240 252
 DISULFID 255 264
 DISULFID 268 295
 DISULFID 299 311
 DISULFID 315 331
 DISULFID 334 338
 DISULFID 342 367
 DISULFID 475 504
 DISULFID 511 520
 DISULFID 515 528
 DISULFID 531 540
 DISULFID 544 560
 DISULFID 563 576
 DISULFID 567 584
 DISULFID 587 596
 DISULFID 600 623
 DISULFID 626 634 By similarity.
 DISULFID 630 642 By similarity.  
Keyword
 3D-structure; Activator; Alternative initiation; Alternative splicing; ATP-binding; Cell membrane; Chromosomal rearrangement; Complete proteome; Cytoplasm; Disulfide bond; Glycoprotein; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Receptor; Reference proteome; Signal; Transcription; Transcription regulation; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1255 AA 
Protein Sequence
MPIWKFPDEE GACQPCPINC THSCVDLDDK GCPAEQRASP LTSIISAVVG ILLVVVLGVV 60
FGILIKRRQQ KIRKYTMRRL LQETELVEPL TPSGAMPNQA QMRILKETEL RKVKVLGSGA 120
FGTVYKGIWI PDGENVKIPV AIKVLRENTS PKANKEILDE AYVMAGVGSP YVSRLLGICL 180
TSTVQLVTQL MPYGCLLDHV RENRGRLGSQ DLLNWCMQIA KGMSYLEDVR LVHRDLAARN 240
VLVKSPNHVK ITDFGLARLL DIDETEYHAD GGKVPIKWMA LESILRRRFT HQSDVWSYGV 300
TVWELMTFGA KPYDGIPARE IPDLLEKGER LPQPPICTID VYMIMVKCWM IDSECRPRFR 360
ELVSEFSRMA RDPQRFVVIQ NEDLGPASPL DSTFYRSLLE DDDMGDLVDA EEYLVPQQGF 420
FCPDPAPGAG GMVHHRHRSS STRSGGGDLT LGLEPSEEEA PRSPLAPSEG AGSDVFDGDL 480
GMGAAKGLQS LPTHDPSPLQ RYSEDPTVPL PSETDGYVAP LTCSPQPEYV NQPDVRPQPP 540
SPREGPLPAA RPAGATLERP KTLSPGKNGV VKDVFAFGGA VENPEYLTPQ GGAAPQPHPP 600
PAFSPAFDNL YYWDQDPPER GAPPSTFKGT PTAENPEYLG LDVPV 645 
Gene Ontology
 GO:0016324; C:apical plasma membrane; IEA:Compara.
 GO:0016323; C:basolateral plasma membrane; IDA:BHF-UCL.
 GO:0010008; C:endosome membrane; IDA:UniProtKB.
 GO:0016021; C:integral to membrane; NAS:UniProtKB.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
 GO:0043235; C:receptor complex; IDA:BHF-UCL.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0005006; F:epidermal growth factor-activated receptor activity; NAS:UniProtKB.
 GO:0043125; F:ErbB-3 class receptor binding; TAS:ProtInc.
 GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
 GO:0004716; F:receptor signaling protein tyrosine kinase activity; TAS:ProtInc.
 GO:0001042; F:RNA polymerase I core binding; IDA:UniProtKB.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0008283; P:cell proliferation; TAS:ProtInc.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0007507; P:heart development; TAS:UniProtKB.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0030879; P:mammary gland development; TAS:UniProtKB.
 GO:0008045; P:motor neuron axon guidance; IEA:Compara.
 GO:0042552; P:myelination; IEA:Compara.
 GO:0033088; P:negative regulation of immature T cell proliferation in thymus; IEA:Compara.
 GO:0007528; P:neuromuscular junction development; IEA:Compara.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0007422; P:peripheral nervous system development; IEA:Compara.
 GO:0014065; P:phosphatidylinositol 3-kinase cascade; IDA:BHF-UCL.
 GO:0045785; P:positive regulation of cell adhesion; IDA:BHF-UCL.
 GO:0030307; P:positive regulation of cell growth; IMP:UniProtKB.
 GO:0050679; P:positive regulation of epithelial cell proliferation; IDA:UniProtKB.
 GO:0043406; P:positive regulation of MAP kinase activity; IDA:UniProtKB.
 GO:0032321; P:positive regulation of Rho GTPase activity; ISS:BHF-UCL.
 GO:0045943; P:positive regulation of transcription from RNA polymerase I promoter; IMP:UniProtKB.
 GO:0045945; P:positive regulation of transcription from RNA polymerase III promoter; IDA:UniProtKB.
 GO:0045727; P:positive regulation of translation; IMP:UniProtKB.
 GO:0046777; P:protein autophosphorylation; IDA:BHF-UCL.
 GO:0045765; P:regulation of angiogenesis; NAS:UniProtKB.
 GO:0070372; P:regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
 GO:0032886; P:regulation of microtubule-based process; IDA:UniProtKB.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0042060; P:wound healing; IDA:BHF-UCL. 
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.