Protein detail

ERBB2

Receptor tyrosine-protein kinase erbB-2 (EC 2.7.10.1) (Metastatic lymph node gene 19 protein) (MLN 19) (Proto-oncogene Neu) (Proto-oncogene c-ErbB-2) (Tyrosine kinase-type cell surface receptor HER2) (p185erbB2) (CD antigen CD340)

Entry name
ERBB2
UniProt ID
EVMP confidence score
0.50
Supporting publications (n)
8
Transmembrane count
1
Protein classification
Cancer-related genesCD markersDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteinsTransporters
EVMP confidence score

Annotation confidence score; open for threshold definitions.

Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40
Basic Information13
Protein Names
Receptor tyrosine-protein kinase erbB-2 (EC 2.7.10.1) (Metastatic lymph node gene 19 protein) (MLN 19) (Proto-oncogene Neu) (Proto-oncogene c-ErbB-2) (Tyrosine kinase-type cell surface receptor HER2) (p185erbB2) (CD antigen CD340)
Protein Class (10)
Cancer-related genesCD markersDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteinsTransporters
Protein Function (17)
  • Cancer-related genes:Mutational cancer driver genes
  • Human disease related genes:Cancers:Head and neck cancers
  • Human disease related genes:Cancers:Cancers of the digestive system
  • Human disease related genes:Cancers:Cancers of eye, brain, and central nervous system
  • Predicted intracellular proteins
  • ENZYME proteins:Transferases
  • Human disease related genes:Cancers:Cancers of the breast and female genital organs
  • Cancer-related genes:Mutated cancer genes
  • CD markers
  • Enzymes
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Transmembrane
653..675; Helical
Transmembrane Count
1
Entrez Gene Symbol
Gene Synonym (9)
c-ERB-2c-ERB2CD340HER-2HER2MLN-19NEUNGLp185(erbB2)
Gene Description
Erb-b2 receptor tyrosine kinase 2
Chromosome
17
Position
39687914-39730426
Supporting publications (n)
8
EVMP confidence score
0.50
Fluorescence & Localization4
ERBB2 fluorescence
Tissue Specificchoroid plexusCell SpecificChoroid plexus epithelial cellsSingle-Nuclei Brain Specificchoroid plexus epithelial cell
Function & Pathway7
Protein Function (17)
  • Cancer-related genes:Mutational cancer driver genes
  • Human disease related genes:Cancers:Head and neck cancers
  • Human disease related genes:Cancers:Cancers of the digestive system
  • Human disease related genes:Cancers:Cancers of eye, brain, and central nervous system
  • Predicted intracellular proteins
  • ENZYME proteins:Transferases
  • Human disease related genes:Cancers:Cancers of the breast and female genital organs
  • Cancer-related genes:Mutated cancer genes
  • CD markers
  • Enzymes
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Mediation Categories (5)
Adhesion and uptake mediationClinical-translation mediationFusion and delivery mediationImmune mediationReceptor-signaling mediation
Relations & Evidence177

Enzyme-Mediated Modification (50)

50 records.

Substrate Gene SymbolEnzyme Gene SymbolEnzyme UniProt IDResidue TypeResidue OffsetModificationDatabaseReferences
ERBB2PRKACAP17612T686phosphorylationphosphoELM_MIMPPhosphoSite_MIMPMIMPNCI-PID_ProtMapperSIGNORProtMapperKEASIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapperSIGNOR:18799465ProtMapper:18799465KEA:9855018
ERBB2EGFRP00533Y1,248phosphorylationBEL-Large-Corpus_ProtMapperphosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperHPRDRLIMS-P_ProtMapperKEASIGNOR_ProtMapperHPRD:1706616KEA:17426253HPRD:12354693KEA:11500516HPRD:17426253ProtMapper:12354693SIGNOR:12354693KEA:1706616KEA:17081983ProtMapper:15951569ProtMapper:24355130HPRD:17389395KEA:12354693
ERBB2EGFRP00533Y1,218phosphorylationHPRDKEAHPRD:11500516KEA:17426253KEA:11500516HPRD:17426253KEA:1706616KEA:17081983HPRD:17389395KEA:12354693
ERBB2EGFRP00533Y1,139phosphorylationLi2012
ERBB2EGFRP00533Y1,221phosphorylationLi2012
ERBB2EGFRP00533Y1,222phosphorylationLi2012
ERBB2PTPRGP23470Y1,248dephosphorylationSIGNORSIGNOR:25624455
ERBB2PTPRGP23470Y1,248phosphorylationSIGNOR_ProtMapperProtMapperProtMapper:25624455
ERBB2ACP3P15309Y1,248dephosphorylationHPRDHPRD:10851066HPRD:11067847HPRD:9705354
ERBB2ACP3P15309Y1,218dephosphorylationHPRDHPRD:10851066HPRD:11067847HPRD:9705354
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Ligand-Receptor Signaling (70)

70 records.

CategoryParentDatabaseTransmitterReceiverSecretedPlasma Membrane (Transmembrane)Plasma Membrane (Peripheral)
receptorreceptorCellPhoneDBNoYesNoYesNo
receptorreceptorHPMRNoYesNoYesNo
receptorreceptorICELLNETNoYesNoYesNo
receptorreceptorCellTalkDBNoYesNoYesNo
receptorreceptorSurfaceomeNoYesNoYesNo
receptorreceptorRamilowski2015NoYesNoYesNo
receptorreceptorLRdbNoYesNoYesNo
receptorreceptorBaccin2019NoYesNoYesNo
receptorreceptorSignaLink_functionNoYesNoYesNo
egfreceptorAlmen2009NoYesNoYesNo
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Regulatory Interaction Network (44)

44 records.

Source Protein SymbolSource UniProt IDTarget Protein SymbolTarget UniProt IDIs DirectedIs StimulationIs InhibitionDatabaseReferences
AREGP15514ERBB2P04626YesYesNoSIGNORSignaLink3SignaLink3:7679104SignaLink3:23331499SIGNOR:7679104
EGFP01133ERBB2P04626YesYesNoiTALKSIGNORProtMapperSignaLink3HPRD_LRdbtalklrHPRDRamilowski2015_Baccin2019WangRamilowski2015Reactome_LRdbHPRD_talklrBaccin2019STRING_talklrEMBRACECellCallFantom5_LRdbCellTalkDBSparser_ProtMapperconnectomeDB2020LRdbBaccin2019:12093292HPRD:12093292connectomeDB2020:12093292ProtMapper:15748904ProtMapper:34025398SIGNOR:11279155CellTalkDB:12093292SignaLink3:23331499SignaLink3:11279155LRdb:12093292
ERBB2P04626PLCG1P19174YesYesNoDOMINOWangPhosphoPointSIGNORHPRDCui2007HINTSignaLink3BioGRIDSPIKE_LCLit-BM-17Lit-BM-17:16273093SignaLink3:1683701SPIKE_LC:16273093HPRD:1683701DOMINO:16273093HINT:22973453SIGNOR:1676673Lit-BM-17:1676673SignaLink3:1676673SignaLink3:23331499BioGRID:1683701BioGRID:1676673HPRD:1676673
ERBB2P04626ESR1P03372YesYesNoPhosphoPointSIGNORProtMapperHPRDSignaLink3REACH_ProtMapperSignaLink3:15173068ProtMapper:22419892HPRD:15173068SignaLink3:23331499SIGNOR:15173068
ERBB2P04626SHC3Q92529YesYesNoDOMINOWangPhosphoPointSIGNORHINTSPIKE_LCSIGNOR:16729043SPIKE_LC:16273093DOMINO:16273093HINT:22973453
PTN11Q06124ERBB2P04626YesNoYesDOMINOWangSIGNORProtMapperHPRDHINTIntActSIGNOR_ProtMapperLit-BM-17SPIKE_LCSIGNOR:32024694IntAct:35512704Lit-BM-17:16273093SPIKE_LC:16273093Lit-BM-17:16729043ProtMapper:32024694DOMINO:16273093HINT:22973453IntAct:16273093HINT:28065597Lit-BM-17:9756944HPRD:16729043IntAct:28065597
ERBB2P04626BBC3Q9BXH1YesNoYesPhosphoSite_norefSIGNORiPTMnetProtMapperPhosphoSitePhosphoSite_ProtMapperSIGNOR:24236056PhosphoSite:24236056
ERBB2P04626BBC3BQ96PG8YesNoYesPhosphoSite_norefSIGNORiPTMnetProtMapperPhosphoSitePhosphoSite_ProtMapperSIGNOR:24236056PhosphoSite:24236056
KAPCAP17612ERBB2P04626YesYesNoWangphosphoELM_MIMPPhosphoSite_MIMPMIMPNCI-PID_ProtMapperiPTMnetSIGNORProtMapperKinexus_KEAKEASIGNOR_ProtMapperPhosphoSite_ProtMapperSIGNOR:18799465ProtMapper:18799465KEA:9855018
CBLP22681ERBB2P04626YesNoYesSIGNORProtMapperHINTACSNREACH_ProtMapperHINT:12574167ACSN:10514377ACSN:17635922HINT:25081058ProtMapper:25102001SIGNOR:20332299
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Protein Complex Composition (12)

12 records.

Component NameComponent Gene SymbolsComponent UniProt IDStoichiometryDatabaseDatabase IDsReferences
ERBB2Q7Z3Y4P04626Q7Z3Y42:2PDBPDB:1s78
ERBB2PTPN18P04626Q999524:4PDBPDB:4gfuPDB:4nnd
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Isolation & Detection Technology (1)

1 record.

EV Isolation MethodDetection MethodNumber of ReferencesReferences
NANA0
Sequence, Structure & Domains15

Sequences

Length
1,255
Mass
137,910
Sequence
MELAALCRWGLLLALLPPGAASTQVCTGTDMKLRLPASPETHLDMLRHLYQGCQVVQGNLELTYLPTNASLSFLQDIQEVQGYVLIAHNQVRQVPLQRLRIVRGTQLFEDNYALAVLDNGDPLNNTTPVTGASPGGLRELQLRSLTEILKGGVLIQRNPQLCYQDTILWKDIFHKNNQLALTLIDTNRSRACHPCSPMCKGSRCWGESSEDCQSLTRTVCAGGCARCKGPLPTDCCHEQCAAGCTGPKHSDCLACLHFNHSGICELHCPALVTYNTDTFESMPNPEGRYTFGASCVTACPYNYLSTDVGSCTLVCPLHNQEVTAEDGTQRCEKCSKPCARVCYGLGMEHLREVRAVTSANIQEFAGCKKIFGSLAFLPESFDGDPASNTAPLQPEQLQVFETLEEITGYLYISAWPDSLPDLSVFQNLQVIRGRILHNGAYSLTLQGLGISWLGLRSLRELGSGLALIHHNTHLCFVHTVPWDQLFRNPHQALLHTANRPEDECVGEGLACHQLCARGHCWGPGPTQCVNCSQFLRGQECVEECRVLQGLPREYVNARHCLPCHPECQPQNGSVTCFGPEADQCVACAHYKDPPFCVARCPSGVKPDLSYMPIWKFPDEEGACQPCPINCTHSCVDLDDKGCPAEQRASPLTSIISAVVGILLVVVLGVVFGILIKRRQQKIRKYTMRRLLQETELVEPLTPSGAMPNQAQMRILKETELRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFVVIQNEDLGPASPLDSTFYRSLLEDDDMGDLVDAEEYLVPQQGFFCPDPAPGAGGMVHHRHRSSSTRSGGGDLTLGLEPSEEEAPRSPLAPSEGAGSDVFDGDLGMGAAKGLQSLPTHDPSPLQRYSEDPTVPLPSETDGYVAPLTCSPQPEYVNQPDVRPQPPSPREGPLPAARPAGATLERPKTLSPGKNGVVKDVFAFGGAVENPEYLTPQGGAAPQPHPPPAFSPAFDNLYYWDQDPPERGAPPSTFKGTPTAENPEYLGLDVPV
Alternative Products
Event=Alternative splicing, Alternative initiation; Named isoforms=6; Name=1; Synonyms=ERBB2, HER2; IsoId=P04626-1; Sequence=Displayed; Name=2; Synonyms=CTF-611; IsoId=P04626-2; Sequence=VSP_039249; Name=3; Synonyms=CTF-687; IsoId=P04626-3; Sequence=VSP_039250; Name=4; IsoId=P04626-4; Sequence=VSP_039248; Name=5; IsoId=P04626-5; Sequence=VSP_054787; Name=6; Synonyms=B; IsoId=P04626-6; Sequence=VSP_055902, VSP_055903, VSP_055904
Alternative Sequence
1..686; Missing (in isoform 3); 1..610; Missing (in isoform 2); 1..30; Missing (in isoform 5); 1..23; MELAALCRWGLLLALLPPGAAST -> MPRGSWKP (in isoform 4); 633..648; Missing (in isoform 6); 771..883; AYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGK -> TISNLFSNFAPRGPSACCEPTCWCHSGKGQDSLPREEWGRQRRFCLWGCRGEPRVLDTPGRSCPSAPPSSCLQPSLRQPLLLGPGPTRAGGSTQHLQRDTYGREPRVPGSGRASVNQKAKSAEALMCPQGAGKA (in isoform 6); 884..1255; Missing (in isoform 6)

3D Structural Models

Turn
109..111; 130..132; 276..278; 284..286; 358..360; 438..440; 476..479; 507..509; 762..765; 922..925; 1008..1011
Helix
39..50; 72..74; 164..166; 169..171; 175..177; 200..202; 209..211; 221..223; 232..234; 348..350; 361..364; 378..382; 385..387; 394..400; 423..425; 482..485; 501..506; 516..518; 525..527; 651..678; 684..690; 691..697; 717..719; 770..775; 806..813; 814..816; 819..838; 848..850; 866..870; 874..876; 878..880; 886..888; 891..896; 901..916; 928..930; 931..936; 949..958; 963..965; 969..980; 983..985; 989..992; 1003..1007; 1020..1022
Beta Strand
25..27; 55..64; 79..82; 84..88; 92..95; 112..117; 123..125; 139..141; 147..150; 152..156; 182..184; 204..208; 217..219; 227..231; 240..248; 251..260; 263..267; 271..274; 281..283; 289..291; 294..298; 303..305; 309..314; 319..323; 325..327; 329..333; 335..337; 368..376; 405..408; 410..413; 417..421; 430..435; 441..447; 463..469; 488..490; 493..499; 520..524; 532..536; 539..542; 545..551; 553..556; 559..562; 565..567; 571..573; 575..580; 583..592; 595..599; 602..604; 605..608; 613..616; 621..625; 630..632; 635..637; 720..729; 732..739; 748..755; 787..799; 851..855; 858..861; 1140..1142
3D Structure
Electron microscopy (14); NMR spectroscopy (6); X-ray crystallography (36)

Domain & Motif Annotations

Compositional Bias
1146..1155; Pro residues
Motif
676..689; Nuclear localization signal
Domain (FT)
720..987; Protein kinase
Region
676..689; Required for interaction with KPNB1 and EEA1; 1035..1179; Disordered; 1195..1197; Interaction with PIK3C2B; 1196..1255; Disordered
Protein Families (3)
  • Protein kinase superfamily
  • Tyr protein kinase family
  • EGF receptor subfamily
Sequence Similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.
Clinical Relevance7
Disease Involvement (3)
Cancer-related genesDisease variantFDA approved drug targets
Drug Targets
FDA approved drug targets
Drugs (152)
BMS-599626NERATINIBCHLORAMBUCILRITUXIMABNULLERTUMAXOMABGEFITINIBPD-98059CUDC-101POZIOTINIBMDX-210ZENOCUTUZUMABADO-TRASTUZUMAB EMTANSINEROCILETINIBRIBOCICLIBCENISERTIBNELIPEPIMUT-SNAKIJIQUINONES GCETUXIMABKADCYLABDTX189CRIZOTINIBSACITUZUMAB GOVITECANTUCATINIBMM-111OSIMERTINIBDACOMITINIB ANHYDROUSPACLITAXELAFATINIBMETHYLCURCUMINAFATINIB DIMALEATEALISERTIBALPELISIBCANERTINIBTAK-285IRINOTECAN HYDROCHLORIDEIBRUTINIBTRASTUZUMAB DUOCARMAZINEANTHRAQUINONEVACCINE ADJUVANTAKT INHIBITOR MK2206TRIFLURIDINEEMODINMARGETUXIMAB-CMKBLAPATINIBEVEROLIMUSNAKIJIQUINONE IABEMACICLIBTAMOXIFENVORINOSTATNIVOLUMABPAN-HER KINASE INHIBITOR AC480CP-724714LETROZOLEPEMBROLIZUMABMUBRITINIBEXEMESTANEGO-6976PALBOCICLIBMOMELOTINIBVARLITINIBAV-412NERATINIB MALEATEPYROTINIBROMIDEPSINGEMCITABINETALAZOPARIBHER2-TARGETED LIPOSOMAL DOXORUBICIN HYDROCHLORIDE MM-302ANTI-HER2 ANTIBODY-DRUG CONJUGATE MEDI4276AEE-788TARLOXOTINIBKN-026SOTRASTAURINHER2 ECD+TM VIRUS-LIKE REPLICON PARTICLES VACCINE AVX901BLARCAMESINEDOCETAXEL ANHYDROUSCAPECITABINE(R)-STU104SIROLIMUST-DM1FULVESTRANTTBO-FILGRASTIMARX-788ZOLEDRONIC ACID ANHYDROUSPELITINIBIL-12NVP-TAE684EPIGALLOCATECHIN-3-GALLATEALITRETINOINCIMAGLERMIN ALFACANERTINIB DIHYDROCHLORIDECURCUMINGLYCOOPTIMIZED TRASTUZUMAB-GEXTESEVATINIBMEK INHIBITOR IPROTEASE INHIBITORFAM-TRASTUZUMAB DERUXTECAN-NXKIURACILIXABEPILONECAPIVASERTIBLAPULEUCEL-TMASOPROCOLMP-412ANTI-EGFR/HER2/HER3 MONOCLONAL ANTIBODY MIXTURE SYM013PLATINUM COMPOUNDNAKIJIQUINONES HGANCICLOVIRTIPIFARNIBTYRPHOSTIN AG 879MECHLORETHAMINEVITAMIN ETAMATINIBPLUMBAGINS-222611HSP90 INHIBITOROLAPARIBEPIRUBICINFLOXURIDINEBMS-690514NONSTEROIDAL ANTIINFLAMMATORY DRUGCARBOPLATINANTINEOPLASTIC AGENTVANDETANIBINSM-18ERIBULIN MESYLATEERLOTINIBKBP5209DASATINIB ANHYDROUSELACESTRANTPICTILISIBJNJ-26483327ANASTROZOLEDIMETHYLCURCUMINPILARALISIBALLITINIBSAPITINIBTHERAPEUTIC AUTOLOGOUS DENDRITIC CELLSILORASERTIBHEMAY-022CIPATINIBGREEN TEA EXTRACTZANIDATAMABGW843682XADJUVANTHYDROCORTISONE BUTYRATETAS-102CEDIRANIBAEE788MULTIKINASE INHIBITOR AEE788MULTI-NEO-EPITOPE VACCINE OSE 2101GANCOTAMABDIETHYLSTILBESTROL
Interaction Protein (32)
ENSG00000007264ENSG00000044574ENSG00000065361ENSG00000075624ENSG00000080824ENSG00000082898ENSG00000094631ENSG00000096384ENSG00000100351ENSG00000100938ENSG00000101213ENSG00000105401ENSG00000105647ENSG00000105701ENSG00000115415ENSG00000116285ENSG00000117461ENSG00000121653ENSG00000141738ENSG00000144749ENSG00000145675ENSG00000145715ENSG00000146648ENSG00000153233ENSG00000160691ENSG00000168610ENSG00000169398ENSG00000177885ENSG00000178568ENSG00000179295ENSG00000197122ENSG00000197943
Interaction Count
32
Interaction Dataset
intact_biogrid
Supporting Publications8
PMIDTitleAbstract
26775013Proteomic characterization of circulating extracellular vesicles identifies novel serum myeloma associated markers.No abstract available
29242380Insights into the Proteome of Gastrointestinal Stromal Tumors-Derived Exosomes Reveals New Potential Diagnostic Biomarkers.No abstract available
31320591Exosomes regulate neurogenesis and circuit assembly.No abstract available
32795414Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers.
38731868The Deep Proteomics Approach Identified Extracellular Vesicular Proteins Correlated to Extracellular Matrix in Type One and Two Endometrial Cancer.No abstract available
39290459Urinary extracellular vesicles as a monitoring tool for renal damage in patients not meeting criteria for chronic kidney disease.No abstract available
40091455Potential Role of Menstrual Fluid-Derived Small Extracellular Vesicle Proteins in Endometriosis Pathogenesiss.No abstract available
41201090Identification of molecular markers and exploration of the oncogenic role of exomeres in hepatocellular carcinoma.No abstract available