Protein:ERBB2 |
Protein Summary |
 Gene summary |
| Gene name: ERBB2 | ASpdb.0 ID: 2064 | Gene | Gene symbol | ERBB2 | Gene ID | 2064 |
| Gene name | erb-b2 receptor tyrosine kinase 2 |
| Synonyms | CD340|HER-2|HER-2/neu|HER2|MLN 19|MLN-19|NEU|NGL|TKR1|VSCN2|c-ERB-2|c-ERB2|p185(erbB2) |
| Cytomap | 17q12 |
| Type of gene | protein-coding |
| Description | receptor tyrosine-protein kinase erbB-2c-erb B2/neu proteinherstatinhuman epidermal growth factor receptor 2metastatic lymph node gene 19 proteinneuro/glioblastoma derived oncogene homologneuroblastoma/glioblastoma derived oncogene homologproto-onc |
| Modification date | 20240416 |
| UniProtAcc | P04626 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | ERBB2 | GO:0001042 | RNA polymerase I core binding | 21555369 |
| Gene | ERBB2 | GO:0004713 | protein tyrosine kinase activity | 7556068|12000754 |
| Gene | ERBB2 | GO:0004714 | transmembrane receptor protein tyrosine kinase activity | 7514177 |
| Gene | ERBB2 | GO:0004888 | transmembrane signaling receptor activity | 7514177 |
| Gene | ERBB2 | GO:0005634 | nucleus | 16314522|21555369 |
| Gene | ERBB2 | GO:0005654 | nucleoplasm | - |
| Gene | ERBB2 | GO:0005829 | cytosol | - |
| Gene | ERBB2 | GO:0005886 | plasma membrane | 20010870 |
| Gene | ERBB2 | GO:0007165 | signal transduction | 10572067 |
| Gene | ERBB2 | GO:0007166 | cell surface receptor signaling pathway | 9685399 |
| Gene | ERBB2 | GO:0007169 | cell surface receptor protein tyrosine kinase signaling pathway | 7514177|7556068 |
| Gene | ERBB2 | GO:0010008 | endosome membrane | 16314522 |
| Gene | ERBB2 | GO:0016323 | basolateral plasma membrane | 12646923 |
| Gene | ERBB2 | GO:0018108 | peptidyl-tyrosine phosphorylation | 12000754 |
| Gene | ERBB2 | GO:0019838 | growth factor binding | 7514177 |
| Gene | ERBB2 | GO:0032886 | regulation of microtubule-based process | 20937854 |
| Gene | ERBB2 | GO:0035556 | intracellular signal transduction | 19372587 |
| Gene | ERBB2 | GO:0038134 | ERBB2-EGFR signaling pathway | 8702723 |
| Gene | ERBB2 | GO:0038143 | ERBB3:ERBB2 complex | 12000754 |
| Gene | ERBB2 | GO:0042060 | wound healing | 12646923 |
| Gene | ERBB2 | GO:0043235 | receptor complex | 7514177|23382219 |
| Gene | ERBB2 | GO:0043406 | positive regulation of MAP kinase activity | 10572067 |
| Gene | ERBB2 | GO:0043491 | phosphatidylinositol 3-kinase/protein kinase B signal transduction | 7556068 |
| Gene | ERBB2 | GO:0045785 | positive regulation of cell adhesion | 7556068 |
| Gene | ERBB2 | GO:0050679 | positive regulation of epithelial cell proliferation | 10572067 |
| Gene | ERBB2 | GO:0071363 | cellular response to growth factor stimulus | 20010870 |
| Gene | ERBB2 | GO:0090314 | positive regulation of protein targeting to membrane | 20010870 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P04626-1 | P04626-1_6oge_A.pdb | 6OGE | EM | 4.36 | A | 23 | 644 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P04626 | ERBB2 | P04626-1 | P04626-2 | 1255 | 645 | 1 | 610 | Deletion | none | none | 0 | 0 |
| P04626 | ERBB2 | P04626-1 | P04626-3 | 1255 | 569 | 1 | 686 | Deletion | none | none | 0 | 0 |
| P04626 | ERBB2 | P04626-1 | P04626-6 | 1255 | 888 | 633 | 648 | Deletion | none | none | 632 | 632 |
| P04626 | ERBB2 | P04626-1 | P04626-6 | 1255 | 888 | 771 | 883 | Substitution | AYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGK | TISNLFSNFAPRGPSACCEPTCWCHSGKGQDSLPREEWGRQRRFCLWGCRGEPRVLDTPGRSCPSAPPSSCLQPSLRQPLLLGPGPTRAGGSTQHLQRDTYGREPRVPGSGRASVNQKAKSAEALMCPQGAGKA | 755 | 888 |
| P04626 | ERBB2 | P04626-1 | P04626-6 | 1255 | 888 | 884 | 1255 | Deletion | none | none | 888 | 888 |
| Multiple sequence alignment of our canonical and alternatively spliced ERBB2 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of ERBB2 |
| UniProt-id | ENSG | ENST | ENSP |
| P04626-1 | ENSG00000141736.14 | ENST00000269571.10 | ENSP00000269571.4 |
| UniProt-id | NM ID | NP ID |
| P04626-1 | NM_004448.3 | NP_004439.2 |
| Amino acid sequences of our canonical and alternatively spliced ERBB2 |
| accession_id | Protein sequence |
| P04626-1 | MELAALCRWGLLLALLPPGAASTQVCTGTDMKLRLPASPETHLDMLRHLYQGCQVVQGNLELTYLPTNASLSFLQDIQEVQGYVLIAHNQ VRQVPLQRLRIVRGTQLFEDNYALAVLDNGDPLNNTTPVTGASPGGLRELQLRSLTEILKGGVLIQRNPQLCYQDTILWKDIFHKNNQLA LTLIDTNRSRACHPCSPMCKGSRCWGESSEDCQSLTRTVCAGGCARCKGPLPTDCCHEQCAAGCTGPKHSDCLACLHFNHSGICELHCPA LVTYNTDTFESMPNPEGRYTFGASCVTACPYNYLSTDVGSCTLVCPLHNQEVTAEDGTQRCEKCSKPCARVCYGLGMEHLREVRAVTSAN IQEFAGCKKIFGSLAFLPESFDGDPASNTAPLQPEQLQVFETLEEITGYLYISAWPDSLPDLSVFQNLQVIRGRILHNGAYSLTLQGLGI SWLGLRSLRELGSGLALIHHNTHLCFVHTVPWDQLFRNPHQALLHTANRPEDECVGEGLACHQLCARGHCWGPGPTQCVNCSQFLRGQEC VEECRVLQGLPREYVNARHCLPCHPECQPQNGSVTCFGPEADQCVACAHYKDPPFCVARCPSGVKPDLSYMPIWKFPDEEGACQPCPINC THSCVDLDDKGCPAEQRASPLTSIISAVVGILLVVVLGVVFGILIKRRQQKIRKYTMRRLLQETELVEPLTPSGAMPNQAQMRILKETEL RKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHV RENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILRRRFT HQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFVVIQ NEDLGPASPLDSTFYRSLLEDDDMGDLVDAEEYLVPQQGFFCPDPAPGAGGMVHHRHRSSSTRSGGGDLTLGLEPSEEEAPRSPLAPSEG AGSDVFDGDLGMGAAKGLQSLPTHDPSPLQRYSEDPTVPLPSETDGYVAPLTCSPQPEYVNQPDVRPQPPSPREGPLPAARPAGATLERP |
| P04626-2 | MPIWKFPDEEGACQPCPINCTHSCVDLDDKGCPAEQRASPLTSIISAVVGILLVVVLGVVFGILIKRRQQKIRKYTMRRLLQETELVEPL TPSGAMPNQAQMRILKETELRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL TSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHAD GGKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFR ELVSEFSRMARDPQRFVVIQNEDLGPASPLDSTFYRSLLEDDDMGDLVDAEEYLVPQQGFFCPDPAPGAGGMVHHRHRSSSTRSGGGDLT LGLEPSEEEAPRSPLAPSEGAGSDVFDGDLGMGAAKGLQSLPTHDPSPLQRYSEDPTVPLPSETDGYVAPLTCSPQPEYVNQPDVRPQPP SPREGPLPAARPAGATLERPKTLSPGKNGVVKDVFAFGGAVENPEYLTPQGGAAPQPHPPPAFSPAFDNLYYWDQDPPERGAPPSTFKGT |
| P04626-3 | MRRLLQETELVEPLTPSGAMPNQAQMRILKETELRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAG VGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGL ARLLDIDETEYHADGGKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMV KCWMIDSECRPRFRELVSEFSRMARDPQRFVVIQNEDLGPASPLDSTFYRSLLEDDDMGDLVDAEEYLVPQQGFFCPDPAPGAGGMVHHR HRSSSTRSGGGDLTLGLEPSEEEAPRSPLAPSEGAGSDVFDGDLGMGAAKGLQSLPTHDPSPLQRYSEDPTVPLPSETDGYVAPLTCSPQ PEYVNQPDVRPQPPSPREGPLPAARPAGATLERPKTLSPGKNGVVKDVFAFGGAVENPEYLTPQGGAAPQPHPPPAFSPAFDNLYYWDQD |
| P04626-6 | MELAALCRWGLLLALLPPGAASTQVCTGTDMKLRLPASPETHLDMLRHLYQGCQVVQGNLELTYLPTNASLSFLQDIQEVQGYVLIAHNQ VRQVPLQRLRIVRGTQLFEDNYALAVLDNGDPLNNTTPVTGASPGGLRELQLRSLTEILKGGVLIQRNPQLCYQDTILWKDIFHKNNQLA LTLIDTNRSRACHPCSPMCKGSRCWGESSEDCQSLTRTVCAGGCARCKGPLPTDCCHEQCAAGCTGPKHSDCLACLHFNHSGICELHCPA LVTYNTDTFESMPNPEGRYTFGASCVTACPYNYLSTDVGSCTLVCPLHNQEVTAEDGTQRCEKCSKPCARVCYGLGMEHLREVRAVTSAN IQEFAGCKKIFGSLAFLPESFDGDPASNTAPLQPEQLQVFETLEEITGYLYISAWPDSLPDLSVFQNLQVIRGRILHNGAYSLTLQGLGI SWLGLRSLRELGSGLALIHHNTHLCFVHTVPWDQLFRNPHQALLHTANRPEDECVGEGLACHQLCARGHCWGPGPTQCVNCSQFLRGQEC VEECRVLQGLPREYVNARHCLPCHPECQPQNGSVTCFGPEADQCVACAHYKDPPFCVARCPSGVKPDLSYMPIWKFPDEEGACQPCPINC THSPLTSIISAVVGILLVVVLGVVFGILIKRRQQKIRKYTMRRLLQETELVEPLTPSGAMPNQAQMRILKETELRKVKVLGSGAFGTVYK GIWIPDGENVKIPVAIKVLRENTSPKANKEILDETISNLFSNFAPRGPSACCEPTCWCHSGKGQDSLPREEWGRQRRFCLWGCRGEPRVL |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| ERBB2 (go to UniProt):P04626 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P04626 | Topological domain | 23 | 652 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=1;End=610 |
| P04626 | Topological domain | 23 | 652 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=1;End=686 |
| P04626 | Topological domain | 23 | 652 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=633;End=648 |
| P04626 | Transmembrane | 653 | 675 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=1;End=686 |
| P04626 | Topological domain | 676 | 1255 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=1;End=686 |
| P04626 | Topological domain | 676 | 1255 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=771;End=883 |
| P04626 | Topological domain | 676 | 1255 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=884;End=1255 |
| P04626 | Domain | 720 | 987 | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 | Type=Substitution;Start=771;End=883 |
| P04626 | Domain | 720 | 987 | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 | Type=Deletion;Start=884;End=1255 |
| P04626 | Region | 676 | 689 | Note=Required for interaction with KPNB1 and EEA1;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:16314522;Dbxref=PMID:16314522 | Type=Deletion;Start=1;End=686 |
| P04626 | Region | 1035 | 1179 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=884;End=1255 |
| P04626 | Region | 1195 | 1197 | Note=Interaction with PIK3C2B;Ontology_term=ECO:0000305;evidence=ECO:0000305 | Type=Deletion;Start=884;End=1255 |
| P04626 | Region | 1196 | 1255 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=884;End=1255 |
| P04626 | Motif | 676 | 689 | Note=Nuclear localization signal | Type=Deletion;Start=1;End=686 |
| P04626 | Compositional bias | 1142 | 1157 | Note=Pro residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=884;End=1255 |
Gene Isoform Structures and Expression Levels for ERBB2 |
| Gene structures of our canonical and alternative spliced genes of ERBB2 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P04626-1 |
| 3D view using mol* of P04626-2 |
| 3D view using mol* of P04626-3 |
| 3D view using mol* of P04626-6 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P04626-1 |
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| pLDDT distribution across the protein length of P04626-2 |
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| pLDDT distribution across the protein length of P04626-3 |
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| pLDDT distribution across the protein length of P04626-6 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P04626-1 |
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| Ramachandran plot of P04626-6 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P04626-1 | 1.067 | 173 | 1.102 | 808.451 | 0.616 | 0.755 | 0.92 | 0.651 | 0.894 | 0.728 | 1.138 | 726,727,728,729,730,731,732,734,751,753,774,796,79 8,799,800,801,803,804,805,807,808,811,812,845,849, 850,852,862,863,866,882,883,884,885,921,1004,1242, 1243,1244,1245,1248 |
| P04626-2 | 1.062 | 592 | 1.088 | 1454.663 | 0.497 | 0.767 | 0.981 | 0.919 | 0.956 | 0.961 | 0.916 | 114,115,116,117,118,119,120,121,122,124,141,143,14 5,146,148,149,150,152,153,156,157,160,164,173,175, 186,188,190,191,193,194,195,197,198,199,202,230,23 1,232,234,235,239,240,242,252,253,254,256,257,258, 259,260,261,262,267,269,270,271,272,273,274,275,27 6,277,278,287,288,289,290,311,314,315,316,317,318, 393,394,397,398,580,581,582,583,586,587,629,631,63 2,633,634,635,638,639,640 |
| P04626-3 | 1.077 | 77 | 0.847 | 145.775 | 0.417 | 0.947 | 1.377 | 1.07 | 1.676 | 0.639 | 0.84 | 42,43,44,45,48,67,158,159,163,164,177,181,182,184, 186,197,198,199,202,203,213,425,426,427,429,431 |
| P04626-6 | 1.042 | 258 | 1.113 | 983.724 | 0.66 | 0.656 | 0.808 | 0.834 | 0.675 | 1.235 | 1.355 | 670,671,674,675,678,679,684,685,686,687,688,689,69 0,691,692,693,695,696,697,698,699,704,710,718,720, 723,725,728,730,731,732,733,734,735,737,739,748,74 9,751,752,753,755,756,759,760,875,876,877,878,879, 880,881,882,883 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P04626-1_P04626-1_6oge_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P04626-1_6oge_A_P04626-2.pdb |
| 3D view using mol* of P04626-1_6oge_A_P04626-3.pdb |
| 3D view using mol* of P04626-1_6oge_A_P04626-6.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P04626-1_P04626-2.pdb |
| 3D view using mol* of P04626-1_P04626-3.pdb |
| 3D view using mol* of P04626-1_P04626-6.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P04626-1_vs_P04626-2.png |
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| ./stats/secondary_structure/figure/P04626-1_vs_P04626-3.png |
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| ./stats/secondary_structure/figure/P04626-1_vs_P04626-6.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P04626-1_vs_P04626-2.png |
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| ./stats/relative_asa/P04626-1_vs_P04626-3.png |
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| ./stats/relative_asa/P04626-1_vs_P04626-6.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P04626 | Region | 676 | 689 | Note=Required for interaction with KPNB1 and EEA1;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:16314522;Dbxref=PMID:16314522 | Type=Deletion;Start=1;End=686 |
| P04626 | Region | 1195 | 1197 | Note=Interaction with PIK3C2B;Ontology_term=ECO:0000305;evidence=ECO:0000305 | Type=Deletion;Start=884;End=1255 |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to ERBB2 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P04626 | ERBB2 | DB01259 | Lapatinib | approved, investigational | antagonist |
| P04626 | ERBB2 | DB06366 | Pertuzumab | approved | binder, antibody |
| P04626 | ERBB2 | DB15035 | Zanubrutinib | approved, investigational | inhibitor |
| P04626 | ERBB2 | DB08916 | Afatinib | approved | inhibitor |
| P04626 | ERBB2 | DB05773 | Trastuzumab emtansine | approved, investigational | antibody |
| P04626 | ERBB2 | DB12267 | Brigatinib | approved, investigational | inhibitor |
| P04626 | ERBB2 | DB14967 | Margetuximab | approved, investigational | antagonist |
| P04626 | ERBB2 | DB11652 | Tucatinib | approved, investigational | inhibitor |
| P04626 | ERBB2 | DB11973 | Tesevatinib | investigational | |
| P04626 | ERBB2 | DB05944 | Varlitinib | investigational | |
| P04626 | ERBB2 | DB04988 | IGN311 | investigational | |
| P04626 | ERBB2 | DB12010 | Fostamatinib | approved, investigational | inhibitor |
| P04626 | ERBB2 | DB00072 | Trastuzumab | approved, investigational | binder, antibody |
| P04626 | ERBB2 | DB06021 | AV-412 | investigational |
Related Diseases to ERBB2 |
| Previous studies relating to the alternative splicing of ERBB2 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| ERBB2 | 15014023 | Association between HER-2/neu and vascular endothelial growth factor expression predicts clinical outcome in primary breast cancer patients. | Activation or overexpression of HER-2/neu is associated with up-regulation of vascular endothelial growth factor (VEGF) in human breast cancer cells in vitro. Preclinical experiments indicate that increased expression of VEGF may in part mediate the biologically aggressive phenotype of HER-2/neu-overexpressing human breast cancer. It was the purpose of this study to: (a). evaluate the association between HER-2/neu and VEGF expression in a large clinical cohort of primary breast cancer patients; (b). compare the prognostic significance of VEGF isoforms; and (c). analyze the combined effects of HER-2/neu and VEGF on clinical outcome. | D001943 | Breast Neoplasms |
| ERBB2 | 15014023 | Association between HER-2/neu and vascular endothelial growth factor expression predicts clinical outcome in primary breast cancer patients. | Activation or overexpression of HER-2/neu is associated with up-regulation of vascular endothelial growth factor (VEGF) in human breast cancer cells in vitro. Preclinical experiments indicate that increased expression of VEGF may in part mediate the biologically aggressive phenotype of HER-2/neu-overexpressing human breast cancer. It was the purpose of this study to: (a). evaluate the association between HER-2/neu and VEGF expression in a large clinical cohort of primary breast cancer patients; (b). compare the prognostic significance of VEGF isoforms; and (c). analyze the combined effects of HER-2/neu and VEGF on clinical outcome. | D008207 | Lymphatic Metastasis |
| ERBB2 | 19035464 | Modification of HER2 pre-mRNA alternative splicing and its effects on breast cancer cells. | The oncogene HER2 is overexpressed in a variety of human tumors, providing a target for anti-cancer molecular therapies. Here, we employed a 2'-O-methoxyethyl (MOE) splice switching oligonucleotide, SSO111, to induce skipping of exon 15 in HER2 pre-mRNA, leading to significant downregulation of full-length HER2 mRNA, and simultaneous upregulation of Delta15HER2 mRNA. SSO111 treatment of SK-BR-3 cells, which highly overexpress HER2, led to inhibition of cell proliferation and induction of apoptosis. The novel Delta15HER2 mRNA encodes a soluble, secreted form of the receptor. Treating SK-BR-3 cells with exogenous Delta15HER2 protein reduced membrane-bound HER2 and decreased HER3 transphosphorylation. Delta15HER2 protein thus has similar activity to an autoinhibitory, natural splice variant of HER2, Herstatin, and to the breast cancer drug Herceptin. Both SSO111 and Delta15HER2 may be potential candidates for the development of novel HER2-targeted cancer therapeutics. | D001943 | Breast Neoplasms |
| ERBB2 | 24802673 | A new class of protein cancer biomarker candidates: differentially expressed splice variants of ERBB2 (HER2/neu) and ERBB1 (EGFR) in breast cancer cell lines. | Combined RNA-Seq and proteomics analyses reveal striking differential expression of splice isoforms of key proteins in important cancer pathways and networks. Even between primary tumor cell lines from histologically similar inflammatory breast cancers, we find striking differences in hormone receptor-negative cell lines that are ERBB2 (Her2/neu)-amplified versus ERBB1 (EGFR) over-expressed with low ERBB2 activity. We have related these findings to protein-protein interaction networks, signaling and metabolic pathways, and methods for predicting functional variants among multiple alternative isoforms. Understanding the upstream ligands and regulators and the downstream pathways and interaction networks for ERBB receptors is certain to be important for explanation and prediction of the variable levels of expression and therapeutic responses of ERBB+tumors in the breast and in other organ sites. Alternative splicing is a remarkable evolutionary development that increases protein diversity from multi-exonic genes without requiring expansion of the genome. It is no longer sufficient to report the up- or down-expression of genes and proteins without dissecting the complexity due to alternative splicing. This article is part of a Special Issue entitled: 20Years of Proteomics in memory of Viatliano Pallini. Guest Editors: Luca Bini , Juan J. Calvete, Natacha Turck, Denis Hochstrasser and Jean-Charles Sanchez. | D001943 | Breast Neoplasms |
Clinically important variants in ERBB2 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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