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].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| erb-b2 receptor tyrosine kinase 2 | MIM:164870 | Ensembl:ENSG00000141736 | HGNC:HGNC:3430 | PA27844 | 17q12 |
GO terms in ERBB2
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| BP | TAS | GO:0000165 | MAPK cascade |
| BP | ISS | GO:0001934 | positive regulation of protein phosphorylation |
| BP | IEA | GO:0006351 | transcription, DNA-templated |
| BP | TAS | GO:0006357 | regulation of transcription by RNA polymerase II |
| BP | TAS | GO:0006468 | protein phosphorylation |
| BP | IDA | GO:0007165 | signal transduction |
| BP | IDA | GO:0007166 | cell surface receptor signaling pathway |
| BP | TAS | GO:0007167 | enzyme linked receptor protein signaling pathway |
| BP | IDA | GO:0007169 | transmembrane receptor protein tyrosine kinase signaling pathway |
| BP | TAS | GO:0007169 | transmembrane receptor protein tyrosine kinase signaling pathway |
| BP | IBA | GO:0007275 | multicellular organism development |
| BP | IEA | GO:0007422 | peripheral nervous system development |
| BP | IEA | GO:0007507 | heart development |
| BP | IEA | GO:0007528 | neuromuscular junction development |
| BP | IEA | GO:0008045 | motor neuron axon guidance |
| BP | TAS | GO:0008283 | cell proliferation |
| BP | IBA | GO:0009968 | negative regulation of signal transduction |
| BP | IDA | GO:0014065 | phosphatidylinositol 3-kinase signaling |
| BP | IEA | GO:0018108 | peptidyl-tyrosine phosphorylation |
| BP | IBA | GO:0030154 | cell differentiation |
| BP | IMP | GO:0030307 | positive regulation of cell growth |
| BP | IDA | GO:0032886 | regulation of microtubule-based process |
| BP | IEA | GO:0033088 | negative regulation of immature T cell proliferation in thymus |
| BP | IBA | GO:0033674 | positive regulation of kinase activity |
| BP | TAS | GO:0038128 | ERBB2 signaling pathway |
| BP | IDA | GO:0042060 | wound healing |
| BP | IEA | GO:0042552 | myelination |
| BP | IBA | GO:0043066 | negative regulation of apoptotic process |
| BP | IDA | GO:0043406 | positive regulation of MAP kinase activity |
| BP | IBA | GO:0043410 | positive regulation of MAPK cascade |
| BP | ISS | GO:0043547 | positive regulation of GTPase activity |
| BP | IMP | GO:0045727 | positive regulation of translation |
| BP | NAS | GO:0045765 | regulation of angiogenesis |
| BP | IDA | GO:0045785 | positive regulation of cell adhesion |
| BP | IMP | GO:0045943 | positive regulation of transcription by RNA polymerase I |
| BP | IDA | GO:0045945 | positive regulation of transcription by RNA polymerase III |
| BP | IDA | GO:0046777 | protein autophosphorylation |
| BP | IEA | GO:0046854 | phosphatidylinositol phosphorylation |
| BP | IEA | GO:0048709 | oligodendrocyte differentiation |
| BP | IDA | GO:0050679 | positive regulation of epithelial cell proliferation |
| BP | TAS | GO:0051897 | positive regulation of protein kinase B signaling |
| BP | IMP | GO:0070372 | regulation of ERK1 and ERK2 cascade |
| BP | IBA | GO:0070374 | positive regulation of ERK1 and ERK2 cascade |
| BP | IDA | GO:0071363 | cellular response to growth factor stimulus |
| BP | IMP | GO:0071364 | cellular response to epidermal growth factor stimulus |
| BP | IDA | GO:0090314 | positive regulation of protein targeting to membrane |
| BP | TAS | GO:1901185 | negative regulation of ERBB signaling pathway |
| BP | TAS | GO:2000145 | regulation of cell motility |
| CC | IDA | GO:0005634 | nucleus |
| CC | IBA | GO:0005737 | cytoplasm |
| CC | IDA | GO:0005829 | cytosol |
| CC | IDA | GO:0005886 | plasma membrane |
| CC | NAS | GO:0005886 | plasma membrane |
| CC | TAS | GO:0005886 | plasma membrane |
| CC | IBA | GO:0005887 | integral component of plasma membrane |
| CC | IBA | GO:0009925 | basal plasma membrane |
| CC | IDA | GO:0010008 | endosome membrane |
| CC | NAS | GO:0016021 | integral component of membrane |
| CC | IDA | GO:0016323 | basolateral plasma membrane |
| CC | IEA | GO:0016324 | apical plasma membrane |
| CC | IEA | GO:0043209 | myelin sheath |
| CC | IBA | GO:0043235 | receptor complex |
| CC | IDA | GO:0043235 | receptor complex |
| CC | TAS | GO:0043235 | receptor complex |
| CC | IEA | GO:0048471 | perinuclear region of cytoplasm |
| MF | IDA | GO:0001042 | RNA polymerase I core binding |
| MF | IBA | GO:0004709 | MAP kinase kinase kinase activity |
| MF | IBA | GO:0004713 | protein tyrosine kinase activity |
| MF | IDA | GO:0004713 | protein tyrosine kinase activity |
| MF | IGI | GO:0004713 | protein tyrosine kinase activity |
| MF | TAS | GO:0004713 | protein tyrosine kinase activity |
| MF | IBA | GO:0004714 | transmembrane receptor protein tyrosine kinase activity |
| MF | IDA | GO:0004714 | transmembrane receptor protein tyrosine kinase activity |
| MF | IBA | GO:0004888 | transmembrane signaling receptor activity |
| MF | IDA | GO:0004888 | transmembrane signaling receptor activity |
| MF | TAS | GO:0005088 | Ras guanyl-nucleotide exchange factor activity |
| MF | IPI | GO:0005515 | protein binding |
| MF | IEA | GO:0005524 | ATP binding |
| MF | IPI | GO:0008022 | protein C-terminus binding |
| MF | IDA | GO:0019838 | growth factor binding |
| MF | IPI | GO:0019903 | protein phosphatase binding |
| MF | IBA | GO:0031434 | mitogen-activated protein kinase kinase binding |
| MF | IPI | GO:0042802 | identical protein binding |
| MF | TAS | GO:0043125 | ErbB-3 class receptor binding |
| MF | TAS | GO:0046934 | phosphatidylinositol-4,5-bisphosphate 3-kinase activity |
| MF | IDA | GO:0046982 | protein heterodimerization activity |
| MF | IPI | GO:0046982 | protein heterodimerization activity |
| MF | NAS | GO:0046983 | protein dimerization activity |
Gene expression in normal tissue: ERBB2
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in ERBB2
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| kegg | hsa04010 | MAPK signaling pathway - Homo sapiens (human) |
| kegg | hsa04012 | ErbB signaling pathway - Homo sapiens (human) |
| kegg | hsa04020 | Calcium signaling pathway - Homo sapiens (human) |
| kegg | hsa04066 | HIF-1 signaling pathway - Homo sapiens (human) |
| kegg | hsa04151 | PI3K-Akt signaling pathway - Homo sapiens (human) |
| kegg | hsa04510 | Focal adhesion - Homo sapiens (human) |
| kegg | hsa04520 | Adherens junction - Homo sapiens (human) |
| kegg | hsa04530 | Tight junction - Homo sapiens (human) |
| kegg | hsa05200 | Pathways in cancer - Homo sapiens (human) |
| kegg | hsa05205 | Proteoglycans in cancer - Homo sapiens (human) |
| kegg | hsa05206 | MicroRNAs in cancer - Homo sapiens (human) |
| kegg | hsa05212 | Pancreatic cancer - Homo sapiens (human) |
| kegg | hsa05213 | Endometrial cancer - Homo sapiens (human) |
| kegg | hsa05215 | Prostate cancer - Homo sapiens (human) |
| kegg | hsa05219 | Bladder cancer - Homo sapiens (human) |
| kegg | hsa05223 | Non-small cell lung cancer - Homo sapiens (human) |
| kegg | hsa05224 | Breast cancer - Homo sapiens (human) |
| kegg | hsa05226 | Gastric cancer - Homo sapiens (human) |
| kegg | hsa05230 | Central carbon metabolism in cancer - Homo sapiens (human) |
| netpath | Pathway_Alpha6Beta4Integrin | Alpha6Beta4Integrin |
| netpath | Pathway_EGFR1 | EGFR1 |
| netpath | Pathway_IL6 | IL6 |
| netpath | Pathway_Leptin | Leptin |
| netpath | Pathway_Oncostatin_M | Oncostatin_M |
| netpath | Pathway_Prolactin | Prolactin |
| reactome | R-HSA-1227986 | Signaling by ERBB2 |
| reactome | R-HSA-1227986 | Signaling by ERBB2 |
| reactome | R-HSA-1250196 | SHC1 events in ERBB2 signaling |
| reactome | R-HSA-1250196 | SHC1 events in ERBB2 signaling |
| reactome | R-HSA-1251932 | PLCG1 events in ERBB2 signaling |
| reactome | R-HSA-1257604 | PIP3 activates AKT signaling |
| reactome | R-HSA-1266738 | Developmental Biology |
| reactome | R-HSA-1306955 | GRB7 events in ERBB2 signaling |
| reactome | R-HSA-1358803 | Downregulation of ERBB2:ERBB3 signaling |
| reactome | R-HSA-162582 | Signal Transduction |
| reactome | R-HSA-162582 | Signal Transduction |
| reactome | R-HSA-1643685 | Disease |
| reactome | R-HSA-1963640 | GRB2 events in ERBB2 signaling |
| reactome | R-HSA-1963640 | GRB2 events in ERBB2 signaling |
| reactome | R-HSA-1963642 | PI3K events in ERBB2 signaling |
| reactome | R-HSA-199418 | Negative regulation of the PI3K/AKT network |
| reactome | R-HSA-212436 | Generic Transcription Pathway |
| reactome | R-HSA-2219528 | PI3K/AKT Signaling in Cancer |
| reactome | R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer |
| reactome | R-HSA-373755 | Semaphorin interactions |
| reactome | R-HSA-400685 | Sema4D in semaphorin signaling |
| reactome | R-HSA-416572 | Sema4D induced cell migration and growth-cone collapse |
| reactome | R-HSA-422475 | Axon guidance |
| reactome | R-HSA-5663202 | Diseases of signal transduction |
| reactome | R-HSA-5673001 | RAF/MAP kinase cascade |
| reactome | R-HSA-5683057 | MAPK family signaling cascades |
| reactome | R-HSA-5684996 | MAPK1/MAPK3 signaling |
| reactome | R-HSA-6785631 | ERBB2 Regulates Cell Motility |
| reactome | R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling |
| reactome | R-HSA-73857 | RNA Polymerase II Transcription |
| reactome | R-HSA-74160 | Gene expression (Transcription) |
| reactome | R-HSA-8847993 | ERBB2 Activates PTK6 Signaling |
| reactome | R-HSA-8848021 | Signaling by PTK6 |
| reactome | R-HSA-8863795 | Downregulation of ERBB2 signaling |
| reactome | R-HSA-8864260 | Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors |
| reactome | R-HSA-8866910 | TFAP2 (AP-2) family regulates transcription of growth factors and their receptors |
| reactome | R-HSA-9006925 | Intracellular signaling by second messengers |
| reactome | R-HSA-9006927 | Signaling by Non-Receptor Tyrosine Kinases |
| reactome | R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases |
| reactome | R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases |
| biocarta | her2pathway | role of erbb2 in signal transduction and oncology |
| biocarta | tffpathway | trefoil factors initiate mucosal healing |
| pid | a6b1_a6b4_integrin_pathway | a6b1 and a6b4 Integrin signaling |
| pid | erbb2erbb3pathway | ErbB2/ErbB3 signaling events |
| pid | erbb4_pathway | ErbB4 signaling events |
| pid | erbb_network_pathway | ErbB receptor signaling network |
| pid | myc_represspathway | Validated targets of C-MYC transcriptional repression |
| pharmgkb | PA162356267 | EGFR Inhibitor Pathway, Pharmacodynamics |
| wikipathways | WP2005 | miR-targeted genes in muscle cell - TarBase |
| wikipathways | WP2034 | Leptin signaling pathway |
| wikipathways | WP2037 | Prolactin Signaling Pathway |
| wikipathways | WP2261 | Signaling Pathways in Glioblastoma |
| wikipathways | WP2512 | Integrated Lung Cancer Pathway |
| wikipathways | WP2828 | Bladder Cancer |
| wikipathways | WP2870 | Extracellular vesicle-mediated signaling in recipient cells |
| wikipathways | WP306 | Focal Adhesion |
| wikipathways | WP3303 | Rac1-Pak1-p38-MMP-2 pathway |
| wikipathways | WP3651 | Pathways Affected in Adenoid Cystic Carcinoma |
| wikipathways | WP3680 | Association Between Physico-Chemical Features and Toxicity Associated Pathways |
| wikipathways | WP4086 | Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors |
| wikipathways | WP4155 | Endometrial cancer |
| wikipathways | WP437 | EGF-EGFR Signaling Pathway |
| wikipathways | WP673 | ErbB Signaling Pathway |
| wikipathways | WP710 | DNA Damage Response (only ATM dependent) |
| smpdb | SMP00463 | Phosphatidylinositol Phosphate Metabolism |
| smpdb | SMP00582 | Joubert syndrome |
Gene-Drug: Aster Plot
| Drug ID | Drug Name | Model Num. |
|---|---|---|
| iGMDRD872 | BRD7137 | 7 |
| iGMDRD80 | Irinotecan | 1 |
| iGMDRD300 | Tozasertib | 3 |
| iGMDRD353 | PD0325901 | 1 |
| iGMDRD894 | EGFR inhibitor | 1 |
| iGMDRD62 | Platinum | 1 |
| iGMDRD459 | RO-3306 | 1 |
| iGMDRD35 | PD153035 | 1 |
| iGMDRD904 | ERBB2 inhibitor | 7 |
| iGMDRD368 | Oxaliplatin | 1 |
| iGMDRD725 | Pilaralisib | 1 |
| iGMDRD178 | MG-132 | 1 |
| iGMDRD382 | CEP-701 | 3 |
| iGMDRD1020 | Trastuzumab | 139 |
| iGMDRD898 | EGFR mAb inhibitor | 2 |
| iGMDRD456 | Crizotinib | 2 |
| iGMDRD345 | Compound 10b [PMID: 11504634] | 4 |
| iGMDRD577 | BIX01294 | 2 |
| iGMDRD562 | Navitoclax | 4 |
| iGMDRD183 | CDK4/6 inhibitor | 2 |
| iGMDRD364 | CP-724714 | 1 |
| iGMDRD131 | Erlotinib | 3 |
| iGMDRD60 | Quinoclamine | 11 |
| iGMDRD491 | TAE-684 | 1 |
| iGMDRD255 | SB225002 | 4 |
| iGMDRD109 | Gefitinib | 1 |
| iGMDRD573 | GSK-1904529A | 1 |
| iGMDRD318 | PAC-1 | 6 |
| iGMDRD608 | Refametinib | 1 |
| iGMDRD201 | SKI II | 3 |
| iGMDRD673 | LSM-1215 | 1 |
| iGMDRD401 | Afatinib | 31 |
| iGMDRD83 | Capecitabine | 3 |
| iGMDRD136 | Nutlin-3 | 1 |
| iGMDRD112 | Methotrexate | 1 |
| iGMDRD387 | CHIR-99021 | 1 |
| iGMDRD659 | Avagacestat (BMS-708163) | 1 |
| iGMDRD1008 | SR-II-138A | 3 |
| iGMDRD772 | BRD4770 | 1 |
| iGMDRD979 | Pertuzumab | 23 |
| iGMDRD63 | Camptothecin | 2 |
| iGMDRD70 | LHRH analogues or antagonist | 1 |
| iGMDRD286 | Nsc 632839 | 6 |
| iGMDRD658 | CHEMBL1673039 | 1 |
| iGMDRD366 | PI-103 | 2 |
| iGMDRD28 | Letrozole | 1 |
| iGMDRD101 | Fulvestrant | 1 |
| iGMDRD402 | AKT Inhibitor VIII | 2 |
| iGMDRD396 | AS601245 | 1 |
| iGMDRD184 | IPA-3 | 1 |
| iGMDRD605 | AZD6482 | 1 |
| iGMDRD821 | TAK-788 | 2 |
| iGMDRD330 | BRD4132 | 1 |
| iGMDRD324 | CI-1040 | 1 |
| iGMDRD248 | BRD4354 | 3 |
| iGMDRD520 | Pictilisib | 1 |
| iGMDRD738 | PP-242 | 1 |
| iGMDRD1036 | X17AAG | 1 |
| iGMDRD188 | Piperlongumine | 5 |
| iGMDRD399 | Selumetinib | 2 |
| iGMDRD74 | Idarubicin | 1 |
| iGMDRD506 | Fedratinib | 11 |
| iGMDRD391 | OSU-03012 | 1 |
| iGMDRD190 | Nilotinib | 1 |
| iGMDRD513 | BML-259 | 3 |
| iGMDRD474 | Avrainvillamide | 5 |
| iGMDRD171 | Pemetrexed | 1 |
| iGMDRD117 | Docetaxel | 2 |
| iGMDRD284 | Palbociclib | 3 |
| iGMDRD52 | Rotenone | 3 |
| iGMDRD918 | HER2 inhibitor | 1 |
| iGMDRD152 | 179324-69-7 | 7 |
| iGMDRD394 | BX-795 | 3 |
| iGMDRD427 | ABT737 | 6 |
| iGMDRD8 | Anastrozole | 1 |
| iGMDRD967 | Panitumumab | 1 |
| iGMDRD650 | Abemaciclib | 1 |
| iGMDRD886 | Compound 1541A | 2 |
| iGMDRD695 | FR-180204 | 1 |
| iGMDRD42 | Vorinostat | 7 |
| iGMDRD384 | EHT-1864 | 1 |
| iGMDRD783 | BRD-K93923542-001-01-9 | 1 |
| iGMDRD310 | Everolimus | 7 |
| iGMDRD434 | BMS-536924 | 3 |
| iGMDRD807 | Ado-trastuzumab emtansine | 18 |
| iGMDRD551 | Ponatinib | 1 |
| iGMDRD1026 | Trastuzumab-based chemotherapy | 1 |
| iGMDRD1027 | Trastuzumab-based therapy | 1 |
| iGMDRD85 | Ursolic acid | 2 |
| iGMDRD689 | EX-8678 | 1 |
| iGMDRD536 | PLX-4720 | 3 |
| iGMDRD735 | CO-1686 (AVL-301) | 1 |
| iGMDRD792 | Cetuximab | 3 |
| iGMDRD160 | Cis-Platin | 1 |
| iGMDRD887 | Compound 23 citrate | 3 |
| iGMDRD185 | DMOG | 1 |
| iGMDRD447 | Dacomitinib | 7 |
| iGMDRD270 | Ciclosporin | 3 |
| iGMDRD134 | Sorafenib | 1 |
| iGMDRD309 | 17AAG | 2 |
| iGMDRD498 | GW441756X | 2 |
| iGMDRD280 | CYTOCHALASIN B | 8 |
| iGMDRD375 | GW-405833 | 1 |
| iGMDRD763 | Osimertinib | 1 |
| iGMDRD601 | 1166227-08-2 | 1 |
| iGMDRD354 | Midostaurin | 1 |
| iGMDRD871 | BRD6368 | 5 |
| iGMDRD119 | Temsirolimus | 1 |
| iGMDRD699 | Neratinib plus temsirolimus | 1 |
| iGMDRD421 | AZD7762 | 1 |
| iGMDRD322 | FK 866 | 1 |
| iGMDRD439 | KW-2449 | 2 |
| iGMDRD221 | Tamoxifen | 1 |
| iGMDRD372 | TGX 221 | 1 |
| iGMDRD77 | Itraconazole | 1 |
| iGMDRD698 | Neratinib | 47 |
| iGMDRD352 | PD-0325901 | 1 |
| iGMDRD219 | Bax channel blocker | 3 |
| iGMDRD879 | chemotherapy | 8 |
| iGMDRD1002 | rTRAIL | 1 |
| iGMDRD560 | MK-2206 | 2 |
| iGMDRD50 | Cytarabine | 1 |
| iGMDRD79 | Gemcitabine | 3 |
| iGMDRD133 | Lapatinib | 82 |
| iGMDRD888 | Compound 44 | 2 |
| iGMDRD23 | Gossypol | 2 |
| iGMDRD920 | HSP90 inhibitor | 2 |
| iGMDRD816 | anti-EGFR mAbs | 2 |
| iGMDRD1023 | Trastuzumab Emtansine | 5 |
| iGMDRD748 | PHA-665752 | 2 |
| iGMDRD61 | Kinetin riboside | 3 |
| iGMDRD470 | Trametinib | 1 |
| iGMDRD679 | Bistramide A | 3 |
| iGMDRD778 | SCHEMBL13586708 | 2 |
| iGMDRD466 | Chaetocin | 8 |
| iGMDRD409 | Saracatinib | 3 |
| iGMDRD12 | Bicalutamide | 1 |
| iGMDRD670 | ML 210 | 3 |
| iGMDRD546 | BMS-754807 | 1 |
| iGMDRD403 | BAY 61-3606 | 1 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in ERBB2
CLASSFICATION
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