ERBB2


Summary: This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized. [provided by RefSeq, Jul 2008].

NameOMIM IDEnsembl IDHGNC IDPHARMGKB IDMap Location
erb-b2 receptor tyrosine kinase 2MIM:164870Ensembl:ENSG00000141736HGNC:HGNC:3430PA2784417q12

GO terms in ERBB2


Term TypeEvidence TypeGO Term IDGO Des.
BPTASGO:0000165MAPK cascade
BPISSGO:0001934positive regulation of protein phosphorylation
BPIEAGO:0006351transcription, DNA-templated
BPTASGO:0006357regulation of transcription by RNA polymerase II
BPTASGO:0006468protein phosphorylation
BPIDAGO:0007165signal transduction
BPIDAGO:0007166cell surface receptor signaling pathway
BPTASGO:0007167enzyme linked receptor protein signaling pathway
BPIDAGO:0007169transmembrane receptor protein tyrosine kinase signaling pathway
BPTASGO:0007169transmembrane receptor protein tyrosine kinase signaling pathway
BPIBAGO:0007275multicellular organism development
BPIEAGO:0007422peripheral nervous system development
BPIEAGO:0007507heart development
BPIEAGO:0007528neuromuscular junction development
BPIEAGO:0008045motor neuron axon guidance
BPTASGO:0008283cell proliferation
BPIBAGO:0009968negative regulation of signal transduction
BPIDAGO:0014065phosphatidylinositol 3-kinase signaling
BPIEAGO:0018108peptidyl-tyrosine phosphorylation
BPIBAGO:0030154cell differentiation
BPIMPGO:0030307positive regulation of cell growth
BPIDAGO:0032886regulation of microtubule-based process
BPIEAGO:0033088negative regulation of immature T cell proliferation in thymus
BPIBAGO:0033674positive regulation of kinase activity
BPTASGO:0038128ERBB2 signaling pathway
BPIDAGO:0042060wound healing
BPIEAGO:0042552myelination
BPIBAGO:0043066negative regulation of apoptotic process
BPIDAGO:0043406positive regulation of MAP kinase activity
BPIBAGO:0043410positive regulation of MAPK cascade
BPISSGO:0043547positive regulation of GTPase activity
BPIMPGO:0045727positive regulation of translation
BPNASGO:0045765regulation of angiogenesis
BPIDAGO:0045785positive regulation of cell adhesion
BPIMPGO:0045943positive regulation of transcription by RNA polymerase I
BPIDAGO:0045945positive regulation of transcription by RNA polymerase III
BPIDAGO:0046777protein autophosphorylation
BPIEAGO:0046854phosphatidylinositol phosphorylation
BPIEAGO:0048709oligodendrocyte differentiation
BPIDAGO:0050679positive regulation of epithelial cell proliferation
BPTASGO:0051897positive regulation of protein kinase B signaling
BPIMPGO:0070372regulation of ERK1 and ERK2 cascade
BPIBAGO:0070374positive regulation of ERK1 and ERK2 cascade
BPIDAGO:0071363cellular response to growth factor stimulus
BPIMPGO:0071364cellular response to epidermal growth factor stimulus
BPIDAGO:0090314positive regulation of protein targeting to membrane
BPTASGO:1901185negative regulation of ERBB signaling pathway
BPTASGO:2000145regulation of cell motility
CCIDAGO:0005634nucleus
CCIBAGO:0005737cytoplasm
CCIDAGO:0005829cytosol
CCIDAGO:0005886plasma membrane
CCNASGO:0005886plasma membrane
CCTASGO:0005886plasma membrane
CCIBAGO:0005887integral component of plasma membrane
CCIBAGO:0009925basal plasma membrane
CCIDAGO:0010008endosome membrane
CCNASGO:0016021integral component of membrane
CCIDAGO:0016323basolateral plasma membrane
CCIEAGO:0016324apical plasma membrane
CCIEAGO:0043209myelin sheath
CCIBAGO:0043235receptor complex
CCIDAGO:0043235receptor complex
CCTASGO:0043235receptor complex
CCIEAGO:0048471perinuclear region of cytoplasm
MFIDAGO:0001042RNA polymerase I core binding
MFIBAGO:0004709MAP kinase kinase kinase activity
MFIBAGO:0004713protein tyrosine kinase activity
MFIDAGO:0004713protein tyrosine kinase activity
MFIGIGO:0004713protein tyrosine kinase activity
MFTASGO:0004713protein tyrosine kinase activity
MFIBAGO:0004714transmembrane receptor protein tyrosine kinase activity
MFIDAGO:0004714transmembrane receptor protein tyrosine kinase activity
MFIBAGO:0004888transmembrane signaling receptor activity
MFIDAGO:0004888transmembrane signaling receptor activity
MFTASGO:0005088Ras guanyl-nucleotide exchange factor activity
MFIPIGO:0005515protein binding
MFIEAGO:0005524ATP binding
MFIPIGO:0008022protein C-terminus binding
MFIDAGO:0019838growth factor binding
MFIPIGO:0019903protein phosphatase binding
MFIBAGO:0031434mitogen-activated protein kinase kinase binding
MFIPIGO:0042802identical protein binding
MFTASGO:0043125ErbB-3 class receptor binding
MFTASGO:0046934phosphatidylinositol-4,5-bisphosphate 3-kinase activity
MFIDAGO:0046982protein heterodimerization activity
MFIPIGO:0046982protein heterodimerization activity
MFNASGO:0046983protein dimerization activity

Gene expression in normal tissue: ERBB2

Gene-model tissue-cancer distribution: Bubble Plot

Gene-drug pathway distribution

Pathways in ERBB2


DatabasePathway IDPathway Des.
kegghsa04010MAPK signaling pathway - Homo sapiens (human)
kegghsa04012ErbB signaling pathway - Homo sapiens (human)
kegghsa04020Calcium signaling pathway - Homo sapiens (human)
kegghsa04066HIF-1 signaling pathway - Homo sapiens (human)
kegghsa04151PI3K-Akt signaling pathway - Homo sapiens (human)
kegghsa04510Focal adhesion - Homo sapiens (human)
kegghsa04520Adherens junction - Homo sapiens (human)
kegghsa04530Tight junction - Homo sapiens (human)
kegghsa05200Pathways in cancer - Homo sapiens (human)
kegghsa05205Proteoglycans in cancer - Homo sapiens (human)
kegghsa05206MicroRNAs in cancer - Homo sapiens (human)
kegghsa05212Pancreatic cancer - Homo sapiens (human)
kegghsa05213Endometrial cancer - Homo sapiens (human)
kegghsa05215Prostate cancer - Homo sapiens (human)
kegghsa05219Bladder cancer - Homo sapiens (human)
kegghsa05223Non-small cell lung cancer - Homo sapiens (human)
kegghsa05224Breast cancer - Homo sapiens (human)
kegghsa05226Gastric cancer - Homo sapiens (human)
kegghsa05230Central carbon metabolism in cancer - Homo sapiens (human)
netpathPathway_Alpha6Beta4IntegrinAlpha6Beta4Integrin
netpathPathway_EGFR1EGFR1
netpathPathway_IL6IL6
netpathPathway_LeptinLeptin
netpathPathway_Oncostatin_MOncostatin_M
netpathPathway_ProlactinProlactin
reactomeR-HSA-1227986Signaling by ERBB2
reactomeR-HSA-1227986Signaling by ERBB2
reactomeR-HSA-1250196SHC1 events in ERBB2 signaling
reactomeR-HSA-1250196SHC1 events in ERBB2 signaling
reactomeR-HSA-1251932PLCG1 events in ERBB2 signaling
reactomeR-HSA-1257604PIP3 activates AKT signaling
reactomeR-HSA-1266738Developmental Biology
reactomeR-HSA-1306955GRB7 events in ERBB2 signaling
reactomeR-HSA-1358803Downregulation of ERBB2:ERBB3 signaling
reactomeR-HSA-162582Signal Transduction
reactomeR-HSA-162582Signal Transduction
reactomeR-HSA-1643685Disease
reactomeR-HSA-1963640GRB2 events in ERBB2 signaling
reactomeR-HSA-1963640GRB2 events in ERBB2 signaling
reactomeR-HSA-1963642PI3K events in ERBB2 signaling
reactomeR-HSA-199418Negative regulation of the PI3K/AKT network
reactomeR-HSA-212436Generic Transcription Pathway
reactomeR-HSA-2219528PI3K/AKT Signaling in Cancer
reactomeR-HSA-2219530Constitutive Signaling by Aberrant PI3K in Cancer
reactomeR-HSA-373755Semaphorin interactions
reactomeR-HSA-400685Sema4D in semaphorin signaling
reactomeR-HSA-416572Sema4D induced cell migration and growth-cone collapse
reactomeR-HSA-422475Axon guidance
reactomeR-HSA-5663202Diseases of signal transduction
reactomeR-HSA-5673001RAF/MAP kinase cascade
reactomeR-HSA-5683057MAPK family signaling cascades
reactomeR-HSA-5684996MAPK1/MAPK3 signaling
reactomeR-HSA-6785631ERBB2 Regulates Cell Motility
reactomeR-HSA-6811558PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
reactomeR-HSA-73857RNA Polymerase II Transcription
reactomeR-HSA-74160Gene expression (Transcription)
reactomeR-HSA-8847993ERBB2 Activates PTK6 Signaling
reactomeR-HSA-8848021Signaling by PTK6
reactomeR-HSA-8863795Downregulation of ERBB2 signaling
reactomeR-HSA-8864260Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors
reactomeR-HSA-8866910TFAP2 (AP-2) family regulates transcription of growth factors and their receptors
reactomeR-HSA-9006925Intracellular signaling by second messengers
reactomeR-HSA-9006927Signaling by Non-Receptor Tyrosine Kinases
reactomeR-HSA-9006934Signaling by Receptor Tyrosine Kinases
reactomeR-HSA-9006934Signaling by Receptor Tyrosine Kinases
biocartaher2pathwayrole of erbb2 in signal transduction and oncology
biocartatffpathwaytrefoil factors initiate mucosal healing
pida6b1_a6b4_integrin_pathwaya6b1 and a6b4 Integrin signaling
piderbb2erbb3pathwayErbB2/ErbB3 signaling events
piderbb4_pathwayErbB4 signaling events
piderbb_network_pathwayErbB receptor signaling network
pidmyc_represspathwayValidated targets of C-MYC transcriptional repression
pharmgkbPA162356267EGFR Inhibitor Pathway, Pharmacodynamics
wikipathwaysWP2005miR-targeted genes in muscle cell - TarBase
wikipathwaysWP2034Leptin signaling pathway
wikipathwaysWP2037Prolactin Signaling Pathway
wikipathwaysWP2261Signaling Pathways in Glioblastoma
wikipathwaysWP2512Integrated Lung Cancer Pathway
wikipathwaysWP2828Bladder Cancer
wikipathwaysWP2870Extracellular vesicle-mediated signaling in recipient cells
wikipathwaysWP306Focal Adhesion
wikipathwaysWP3303Rac1-Pak1-p38-MMP-2 pathway
wikipathwaysWP3651Pathways Affected in Adenoid Cystic Carcinoma
wikipathwaysWP3680Association Between Physico-Chemical Features and Toxicity Associated Pathways
wikipathwaysWP4086Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors
wikipathwaysWP4155Endometrial cancer
wikipathwaysWP437EGF-EGFR Signaling Pathway
wikipathwaysWP673ErbB Signaling Pathway
wikipathwaysWP710DNA Damage Response (only ATM dependent)
smpdbSMP00463Phosphatidylinositol Phosphate Metabolism
smpdbSMP00582Joubert syndrome

Gene-Drug: Aster Plot


Drug IDDrug NameModel Num.
iGMDRD872BRD71377
iGMDRD80Irinotecan1
iGMDRD300Tozasertib3
iGMDRD353PD03259011
iGMDRD894EGFR inhibitor1
iGMDRD62Platinum1
iGMDRD459RO-33061
iGMDRD35PD1530351
iGMDRD904ERBB2 inhibitor7
iGMDRD368Oxaliplatin1
iGMDRD725Pilaralisib1
iGMDRD178MG-1321
iGMDRD382CEP-7013
iGMDRD1020Trastuzumab139
iGMDRD898EGFR mAb inhibitor2
iGMDRD456Crizotinib2
iGMDRD345Compound 10b [PMID: 11504634]4
iGMDRD577BIX012942
iGMDRD562Navitoclax4
iGMDRD183CDK4/6 inhibitor2
iGMDRD364CP-7247141
iGMDRD131Erlotinib3
iGMDRD60Quinoclamine11
iGMDRD491TAE-6841
iGMDRD255SB2250024
iGMDRD109Gefitinib1
iGMDRD573GSK-1904529A1
iGMDRD318PAC-16
iGMDRD608Refametinib1
iGMDRD201SKI II3
iGMDRD673LSM-12151
iGMDRD401Afatinib31
iGMDRD83Capecitabine3
iGMDRD136Nutlin-31
iGMDRD112Methotrexate1
iGMDRD387CHIR-990211
iGMDRD659Avagacestat (BMS-708163)1
iGMDRD1008SR-II-138A3
iGMDRD772BRD47701
iGMDRD979Pertuzumab23
iGMDRD63Camptothecin2
iGMDRD70LHRH analogues or antagonist1
iGMDRD286Nsc 6328396
iGMDRD658CHEMBL16730391
iGMDRD366PI-1032
iGMDRD28Letrozole1
iGMDRD101Fulvestrant1
iGMDRD402AKT Inhibitor VIII2
iGMDRD396AS6012451
iGMDRD184IPA-31
iGMDRD605AZD64821
iGMDRD821TAK-7882
iGMDRD330BRD41321
iGMDRD324CI-10401
iGMDRD248BRD43543
iGMDRD520Pictilisib1
iGMDRD738PP-2421
iGMDRD1036X17AAG1
iGMDRD188Piperlongumine5
iGMDRD399Selumetinib2
iGMDRD74Idarubicin1
iGMDRD506Fedratinib11
iGMDRD391OSU-030121
iGMDRD190Nilotinib1
iGMDRD513BML-2593
iGMDRD474Avrainvillamide5
iGMDRD171Pemetrexed1
iGMDRD117Docetaxel2
iGMDRD284Palbociclib3
iGMDRD52Rotenone3
iGMDRD918HER2 inhibitor1
iGMDRD152179324-69-77
iGMDRD394BX-7953
iGMDRD427ABT7376
iGMDRD8Anastrozole1
iGMDRD967Panitumumab1
iGMDRD650Abemaciclib1
iGMDRD886Compound 1541A2
iGMDRD695FR-1802041
iGMDRD42Vorinostat7
iGMDRD384EHT-18641
iGMDRD783BRD-K93923542-001-01-91
iGMDRD310Everolimus7
iGMDRD434BMS-5369243
iGMDRD807Ado-trastuzumab emtansine18
iGMDRD551Ponatinib1
iGMDRD1026Trastuzumab-based chemotherapy1
iGMDRD1027Trastuzumab-based therapy1
iGMDRD85Ursolic acid2
iGMDRD689EX-86781
iGMDRD536PLX-47203
iGMDRD735CO-1686 (AVL-301)1
iGMDRD792Cetuximab3
iGMDRD160Cis-Platin1
iGMDRD887Compound 23 citrate3
iGMDRD185DMOG1
iGMDRD447Dacomitinib7
iGMDRD270Ciclosporin3
iGMDRD134Sorafenib1
iGMDRD30917AAG2
iGMDRD498GW441756X2
iGMDRD280CYTOCHALASIN B8
iGMDRD375GW-4058331
iGMDRD763Osimertinib1
iGMDRD6011166227-08-21
iGMDRD354Midostaurin1
iGMDRD871BRD63685
iGMDRD119Temsirolimus1
iGMDRD699Neratinib plus temsirolimus1
iGMDRD421AZD77621
iGMDRD322FK 8661
iGMDRD439KW-24492
iGMDRD221Tamoxifen1
iGMDRD372TGX 2211
iGMDRD77Itraconazole1
iGMDRD698Neratinib47
iGMDRD352PD-03259011
iGMDRD219Bax channel blocker3
iGMDRD879chemotherapy8
iGMDRD1002rTRAIL1
iGMDRD560MK-22062
iGMDRD50Cytarabine1
iGMDRD79Gemcitabine3
iGMDRD133Lapatinib82
iGMDRD888Compound 442
iGMDRD23Gossypol2
iGMDRD920HSP90 inhibitor2
iGMDRD816anti-EGFR mAbs2
iGMDRD1023Trastuzumab Emtansine5
iGMDRD748PHA-6657522
iGMDRD61Kinetin riboside3
iGMDRD470Trametinib1
iGMDRD679Bistramide A3
iGMDRD778SCHEMBL135867082
iGMDRD466Chaetocin8
iGMDRD409Saracatinib3
iGMDRD12Bicalutamide1
iGMDRD670ML 2103
iGMDRD546BMS-7548071
iGMDRD403BAY 61-36061

Gene in drug-gene network: Network Plot

Gene-drug targets distribution

Gene Structure: PDB

Models in ERBB2

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