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 >= 0.40Basic 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
Ensembl
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
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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Cellular Component (18)
- GO:0002116 semaphorin receptor complex
- GO:0005634 nucleus
- GO:0005654 nucleoplasm
- GO:0005769 early endosome
- GO:0005829 cytosol
- GO:0005886 plasma membrane
- GO:0009925 basal plasma membrane
- GO:0010008 endosome membrane
- GO:0016020 membrane
- GO:0016323 basolateral plasma membrane
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Molecular Function (13)
- GO:0001042 RNA polymerase I core binding
- GO:0004713 protein tyrosine kinase activity
- GO:0004714 transmembrane receptor protein tyrosine kinase activity
- GO:0004888 transmembrane signaling receptor activity
- GO:0005102 signaling receptor binding
- GO:0005515 protein binding
- GO:0005524 ATP binding
- GO:0015026 coreceptor activity
- GO:0019838 growth factor binding
- GO:0030971 receptor tyrosine kinase binding
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Biological Process (3)
KEGG (24)
- hsa01521 EGFR tyrosine kinase inhibitor resistance
- KEGG:hsa01522 Endocrine resistance
- KEGG:hsa01524 Platinum drug resistance
- KEGG:hsa04010 MAPK signaling pathway
- KEGG:hsa04012 ErbB signaling pathway
- KEGG:hsa04020 Calcium signaling pathway
- KEGG:hsa04066 HIF-1 signaling pathway
- KEGG:hsa04151 PI3K-Akt signaling pathway
- KEGG:hsa04510 Focal adhesion
- KEGG:hsa04518 Integrin signaling
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Reactome (34)
- R-hsa-2219530 constitutive signaling by aberrant pi3k in cancer
- R-hsa-9634285 constitutive signaling by overexpressed erbb2
- R-hsa-9734767 developmental cell lineages
- R-hsa-9734779 developmental cell lineages of the integumentary system
- R-hsa-9924644 developmental lineages of the mammary gland
- R-hsa-9927418 developmental lineage of mammary gland luminal epithelial cells
- R-hsa-9927432 developmental lineage of mammary gland myoepithelial cells
- R-hsa-9938206 developmental lineage of mammary stem cells
- R-hsa-5663202 diseases of signal transduction by growth factor receptors and second messengers
- R-hsa-1358803 downregulation of erbb2 erbb3 signaling
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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 Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| ERBB2 | PRKACA | P17612 | T | 686 | phosphorylation | phosphoELM_MIMPPhosphoSite_MIMPMIMPNCI-PID_ProtMapperSIGNORProtMapperKEASIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper | SIGNOR:18799465ProtMapper:18799465KEA:9855018 |
| ERBB2 | EGFR | P00533 | Y | 1,248 | phosphorylation | BEL-Large-Corpus_ProtMapperphosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperHPRDRLIMS-P_ProtMapperKEASIGNOR_ProtMapper | HPRD:1706616KEA:17426253HPRD:12354693KEA:11500516HPRD:17426253ProtMapper:12354693SIGNOR:12354693KEA:1706616KEA:17081983ProtMapper:15951569ProtMapper:24355130HPRD:17389395KEA:12354693 |
| ERBB2 | EGFR | P00533 | Y | 1,218 | phosphorylation | HPRDKEA | HPRD:11500516KEA:17426253KEA:11500516HPRD:17426253KEA:1706616KEA:17081983HPRD:17389395KEA:12354693 |
| ERBB2 | EGFR | P00533 | Y | 1,139 | phosphorylation | Li2012 | |
| ERBB2 | EGFR | P00533 | Y | 1,221 | phosphorylation | Li2012 | |
| ERBB2 | EGFR | P00533 | Y | 1,222 | phosphorylation | Li2012 | |
| ERBB2 | PTPRG | P23470 | Y | 1,248 | dephosphorylation | SIGNOR | SIGNOR:25624455 |
| ERBB2 | PTPRG | P23470 | Y | 1,248 | phosphorylation | SIGNOR_ProtMapperProtMapper | ProtMapper:25624455 |
| ERBB2 | ACP3 | P15309 | Y | 1,248 | dephosphorylation | HPRD | HPRD:10851066HPRD:11067847HPRD:9705354 |
| ERBB2 | ACP3 | P15309 | Y | 1,218 | dephosphorylation | HPRD | HPRD:10851066HPRD:11067847HPRD:9705354 |
Ligand-Receptor Signaling (70)
70 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| receptor | receptor | CellPhoneDB | No | Yes | No | Yes | No |
| receptor | receptor | HPMR | No | Yes | No | Yes | No |
| receptor | receptor | ICELLNET | No | Yes | No | Yes | No |
| receptor | receptor | CellTalkDB | No | Yes | No | Yes | No |
| receptor | receptor | Surfaceome | No | Yes | No | Yes | No |
| receptor | receptor | Ramilowski2015 | No | Yes | No | Yes | No |
| receptor | receptor | LRdb | No | Yes | No | Yes | No |
| receptor | receptor | Baccin2019 | No | Yes | No | Yes | No |
| receptor | receptor | SignaLink_function | No | Yes | No | Yes | No |
| egf | receptor | Almen2009 | No | Yes | No | Yes | No |
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Regulatory Interaction Network (44)
44 records.
Protein Complex Composition (12)
12 records.
| Component Name | Component Gene Symbols | Component UniProt ID | Stoichiometry | Database | Database IDs | References |
|---|---|---|---|---|---|---|
| ERBB2-MEMO-SHC complex | ERBB2MEMO1SHC1 | P04626P29353Q9Y316 | 1:1:1 | CompleatCORUM | CORUM:2528Compleat:HC107 | 15156151 |
| GDF15-ERBB2 complex | ERBB2GDF15 | P04626Q99988 | 0:0 | CORUM | CORUM:7351 | 29636108 |
| ERBB2PLXNB1 | O43157P04626 | 0:0 | ICELLNET | 15210733 | ||
| ERBB2IGKCP0DOX5Q6GMX6 | P01834P04626P0DOX5Q6GMX6 | 2:1:1:1 | PDB | PDB:6oge | ||
| ERBB2IGHG1 | P01857P04626 | 1:1 | PDB | PDB:5kwgPDB:5k33 | ||
| ERBB2 | P04626 | 2 | PDB | PDB:4hrmPDB:3wlwPDB:3pp0PDB:4hrnPDB:3rcdPDB:2jwaPDB:5ob4PDB:9iutPDB:7jxhPDB:3h3bPDB:8vqePDB:8jyqPDB:2n2a | ||
| ERBB2P0DOX5Q7Z3Y4 | P04626P0DOX5Q7Z3Y4 | 1:1:1 | PDB | PDB:6bgt | ||
| BTCERBB2ERBB4 | P04626P35070Q15303 | 1:1:1 | PDB | PDB:8u4k | ||
| ERBB2ERBB4NRG1 | P04626Q02297Q15303 | 1:1:1 | PDB | PDB:8u4l | ||
| ERBB2ERBB4 | P04626Q15303 | 0:0 | CellinkerICELLNETCellChatDB | 10214951 |
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Isolation & Detection Technology (1)
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| NA | NA | 0 |
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
| PMID | Title | Abstract |
|---|---|---|
| 26775013 | Proteomic characterization of circulating extracellular vesicles identifies novel serum myeloma associated markers. | No abstract available |
| 29242380 | Insights into the Proteome of Gastrointestinal Stromal Tumors-Derived Exosomes Reveals New Potential Diagnostic Biomarkers. | No abstract available |
| 31320591 | Exosomes regulate neurogenesis and circuit assembly. | No abstract available |
| 32795414 | Extracellular 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. |
| 38731868 | The Deep Proteomics Approach Identified Extracellular Vesicular Proteins Correlated to Extracellular Matrix in Type One and Two Endometrial Cancer. | No abstract available |
| 39290459 | Urinary extracellular vesicles as a monitoring tool for renal damage in patients not meeting criteria for chronic kidney disease. | No abstract available |
| 40091455 | Potential Role of Menstrual Fluid-Derived Small Extracellular Vesicle Proteins in Endometriosis Pathogenesiss. | No abstract available |
| 41201090 | Identification of molecular markers and exploration of the oncogenic role of exomeres in hepatocellular carcinoma. | No abstract available |