Protein:ERBB3 |
Protein Summary |
 Gene summary |
| Gene name: ERBB3 | ASpdb.0 ID: 2065 | Gene | Gene symbol | ERBB3 | Gene ID | 2065 |
| Gene name | erb-b2 receptor tyrosine kinase 3 |
| Synonyms | ErbB-3|FERLK|HER3|LCCS2|MDA-BF-1|VSCN1|c-erbB-3|c-erbB3|erbB3-S|p180-ErbB3|p45-sErbB3|p85-sErbB3 |
| Cytomap | 12q13.2 |
| Type of gene | protein-coding |
| Description | receptor tyrosine-protein kinase erbB-3human epidermal growth factor receptor 3proto-oncogene-like protein c-ErbB-3tyrosine kinase-type cell surface receptor HER3v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3 |
| Modification date | 20240411 |
| UniProtAcc | P21860 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | ERBB3 | GO:0004713 | protein tyrosine kinase activity | 7556068 |
| Gene | ERBB3 | GO:0005615 | extracellular space | 11389077 |
| Gene | ERBB3 | GO:0007162 | negative regulation of cell adhesion | 7556068 |
| Gene | ERBB3 | GO:0007165 | signal transduction | 10572067 |
| Gene | ERBB3 | GO:0007169 | cell surface receptor protein tyrosine kinase signaling pathway | 7556068 |
| Gene | ERBB3 | GO:0009968 | negative regulation of signal transduction | 11389077 |
| Gene | ERBB3 | GO:0016323 | basolateral plasma membrane | 12646923 |
| Gene | ERBB3 | GO:0030296 | protein tyrosine kinase activator activity | 7556068 |
| Gene | ERBB3 | GO:0038132 | neuregulin binding | 20682778 |
| Gene | ERBB3 | GO:0038143 | ERBB3:ERBB2 complex | 12000754 |
| Gene | ERBB3 | GO:0042127 | regulation of cell population proliferation | 11389077 |
| Gene | ERBB3 | GO:0043235 | receptor complex | 23382219 |
| Gene | ERBB3 | GO:0043491 | phosphatidylinositol 3-kinase/protein kinase B signal transduction | 7556068 |
| Gene | ERBB3 | GO:0051048 | negative regulation of secretion | 10559227 |
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 |
| P21860-1 | P21860-1_6kbi_B.pdb | 6KBI | X-ray | 3.0 | B | 24 | 630 |
| 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 |
| P21860 | ERBB3 | P21860-1 | P21860-2 | 1342 | 183 | 141 | 183 | Substitution | EILSGGVYIEKNDKLCHMDTIDWRDIVRDRDAEIVVKDNGRSC | GQFPMVPSGLTPQPAQDWYLLDDDPRLLTLSASSKVPVTLAAV | 141 | 183 |
| P21860 | ERBB3 | P21860-1 | P21860-2 | 1342 | 183 | 184 | 1342 | Deletion | none | none | 183 | 183 |
| P21860 | ERBB3 | P21860-1 | P21860-3 | 1342 | 331 | 331 | 331 | Substitution | C | F | 331 | 331 |
| P21860 | ERBB3 | P21860-1 | P21860-3 | 1342 | 331 | 332 | 1342 | Deletion | none | none | 331 | 331 |
| P21860 | ERBB3 | P21860-1 | P21860-5 | 1342 | 699 | 1 | 643 | Deletion | none | none | 0 | 0 |
| Multiple sequence alignment of our canonical and alternatively spliced ERBB3 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of ERBB3 |
| UniProt-id | ENSG | ENST | ENSP |
| P21860-1 | ENSG00000065361.17 | ENST00000267101.8 | ENSP00000267101.4 |
| P21860-2 | ENSG00000065361.17 | ENST00000411731.6 | ENSP00000415753.2 |
| P21860-3 | ENSG00000065361.17 | ENST00000551242.5 | ENSP00000447510.1 |
| UniProt-id | NM ID | NP ID |
| P21860-1 | NM_001982.3 | NP_001973.2 |
| P21860-2 | NM_001005915.1 | NP_001005915.1 |
| Amino acid sequences of our canonical and alternatively spliced ERBB3 |
| accession_id | Protein sequence |
| P21860-1 | MRANDALQVLGLLFSLARGSEVGNSQAVCPGTLNGLSVTGDAENQYQTLYKLYERCEVVMGNLEIVLTGHNADLSFLQWIREVTGYVLVA MNEFSTLPLPNLRVVRGTQVYDGKFAIFVMLNYNTNSSHALRQLRLTQLTEILSGGVYIEKNDKLCHMDTIDWRDIVRDRDAEIVVKDNG RSCPPCHEVCKGRCWGPGSEDCQTLTKTICAPQCNGHCFGPNPNQCCHDECAGGCSGPQDTDCFACRHFNDSGACVPRCPQPLVYNKLTF QLEPNPHTKYQYGGVCVASCPHNFVVDQTSCVRACPPDKMEVDKNGLKMCEPCGGLCPKACEGTGSGSRFQTVDSSNIDGFVNCTKILGN LDFLITGLNGDPWHKIPALDPEKLNVFRTVREITGYLNIQSWPPHMHNFSVFSNLTTIGGRSLYNRGFSLLIMKNLNVTSLGFRSLKEIS AGRIYISANRQLCYHHSLNWTKVLRGPTEERLDIKHNRPRRDCVAEGKVCDPLCSSGGCWGPGPGQCLSCRNYSRGGVCVTHCNFLNGEP REFAHEAECFSCHPECQPMEGTATCNGSGSDTCAQCAHFRDGPHCVSSCPHGVLGAKGPIYKYPDVQNECRPCHENCTQGCKGPELQDCL GQTLVLIGKTHLTMALTVIAGLVVIFMMLGGTFLYWRGRRIQNKRAMRRYLERGESIEPLDPSEKANKVLARIFKETELRKLKVLGSGVF GTVHKGVWIPEGESIKIPVCIKVIEDKSGRQSFQAVTDHMLAIGSLDHAHIVRLLGLCPGSSLQLVTQYLPLGSLLDHVRQHRGALGPQL LLNWGVQIAKGMYYLEEHGMVHRNLAARNVLLKSPSQVQVADFGVADLLPPDDKQLLYSEAKTPIKWMALESIHFGKYTHQSDVWSYGVT VWELMTFGAEPYAGLRLAEVPDLLEKGERLAQPQICTIDVYMVMVKCWMIDENIRPTFKELANEFTRMARDPPRYLVIKRESGPGIAPGP EPHGLTNKKLEEVELEPELDLDLDLEAEEDNLATTTLGSALSLPVGTLNRPRGSQSLLSPSSGYMPMNQGNLGESCQESAVSGSSERCPR PVSLHPMPRGCLASESSEGHVTGSEAELQEKVSMCRSRSRSRSPRPRGDSAYHSQRHSLLTPVTPLSPPGLEEEDVNGYVMPDTHLKGTP SSREGTLSSVGLSSVLGTEEEDEDEEYEYMNRRRRHSPPHPPRPSSLEELGYEYMDVGSDLSASLGSTQSCPLHPVPIMPTAGTTPDEDY |
| P21860-2 | MRANDALQVLGLLFSLARGSEVGNSQAVCPGTLNGLSVTGDAENQYQTLYKLYERCEVVMGNLEIVLTGHNADLSFLQWIREVTGYVLVA MNEFSTLPLPNLRVVRGTQVYDGKFAIFVMLNYNTNSSHALRQLRLTQLTGQFPMVPSGLTPQPAQDWYLLDDDPRLLTLSASSKVPVTL |
| P21860-3 | MRANDALQVLGLLFSLARGSEVGNSQAVCPGTLNGLSVTGDAENQYQTLYKLYERCEVVMGNLEIVLTGHNADLSFLQWIREVTGYVLVA MNEFSTLPLPNLRVVRGTQVYDGKFAIFVMLNYNTNSSHALRQLRLTQLTEILSGGVYIEKNDKLCHMDTIDWRDIVRDRDAEIVVKDNG RSCPPCHEVCKGRCWGPGSEDCQTLTKTICAPQCNGHCFGPNPNQCCHDECAGGCSGPQDTDCFACRHFNDSGACVPRCPQPLVYNKLTF |
| P21860-5 | MALTVIAGLVVIFMMLGGTFLYWRGRRIQNKRAMRRYLERGESIEPLDPSEKANKVLARIFKETELRKLKVLGSGVFGTVHKGVWIPEGE SIKIPVCIKVIEDKSGRQSFQAVTDHMLAIGSLDHAHIVRLLGLCPGSSLQLVTQYLPLGSLLDHVRQHRGALGPQLLLNWGVQIAKGMY YLEEHGMVHRNLAARNVLLKSPSQVQVADFGVADLLPPDDKQLLYSEAKTPIKWMALESIHFGKYTHQSDVWSYGVTVWELMTFGAEPYA GLRLAEVPDLLEKGERLAQPQICTIDVYMVMVKCWMIDENIRPTFKELANEFTRMARDPPRYLVIKRESGPGIAPGPEPHGLTNKKLEEV ELEPELDLDLDLEAEEDNLATTTLGSALSLPVGTLNRPRGSQSLLSPSSGYMPMNQGNLGESCQESAVSGSSERCPRPVSLHPMPRGCLA SESSEGHVTGSEAELQEKVSMCRSRSRSRSPRPRGDSAYHSQRHSLLTPVTPLSPPGLEEEDVNGYVMPDTHLKGTPSSREGTLSSVGLS SVLGTEEEDEDEEYEYMNRRRRHSPPHPPRPSSLEELGYEYMDVGSDLSASLGSTQSCPLHPVPIMPTAGTTPDEDYEYMNRQRDGGGPG |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| ERBB3 (go to UniProt):P21860 |
| 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 |
| P21860 | Topological domain | 20 | 643 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=141;End=183 |
| P21860 | Topological domain | 20 | 643 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=184;End=1342 |
| P21860 | Topological domain | 20 | 643 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=331;End=331 |
| P21860 | Topological domain | 20 | 643 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=332;End=1342 |
| P21860 | Topological domain | 20 | 643 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=1;End=643 |
| P21860 | Transmembrane | 644 | 664 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=184;End=1342 |
| P21860 | Transmembrane | 644 | 664 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=332;End=1342 |
| P21860 | Topological domain | 665 | 1342 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=184;End=1342 |
| P21860 | Topological domain | 665 | 1342 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=332;End=1342 |
| P21860 | Domain | 709 | 966 | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 | Type=Deletion;Start=184;End=1342 |
| P21860 | Domain | 709 | 966 | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 | Type=Deletion;Start=332;End=1342 |
| P21860 | Region | 980 | 999 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=184;End=1342 |
| P21860 | Region | 980 | 999 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=332;End=1342 |
| P21860 | Region | 1033 | 1152 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=184;End=1342 |
| P21860 | Region | 1033 | 1152 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=332;End=1342 |
| P21860 | Compositional bias | 1033 | 1076 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=184;End=1342 |
| P21860 | Compositional bias | 1033 | 1076 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=332;End=1342 |
| P21860 | Compositional bias | 1111 | 1132 | Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=184;End=1342 |
| P21860 | Compositional bias | 1111 | 1132 | Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=332;End=1342 |
Gene Isoform Structures and Expression Levels for ERBB3 |
| Gene structures of our canonical and alternative spliced genes of ERBB3 * 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 P21860-1 |
| 3D view using mol* of P21860-2 |
| 3D view using mol* of P21860-3 |
| 3D view using mol* of P21860-5 |
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 P21860-1 |
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| pLDDT distribution across the protein length of P21860-2 |
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| pLDDT distribution across the protein length of P21860-3 |
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| pLDDT distribution across the protein length of P21860-5 |
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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 P21860-1 |
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| Ramachandran plot of P21860-2 |
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| Ramachandran plot of P21860-3 |
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| Ramachandran plot of P21860-5 |
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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 |
| P21860-1 | 1.124 | 123 | 1.159 | 335.454 | 0.448 | 0.832 | 1.075 | 1.192 | 0.86 | 1.386 | 0.992 | 715,716,718,719,720,723,740,742,763,766,772,773,77 4,785,786,787,789,790,791,793,794,834,838,839,841, 851,852,853,855 |
| P21860-2 | 0.853 | 71 | 0.853 | 202.37 | 0.673 | 0.632 | 0.894 | 0.338 | 0.977 | 0.346 | 1.965 | 104,105,106,107,110,116,139,140,141,142,143,144,14 5,146,152,153,154,155,156,158 |
| P21860-3 | 0.988 | 152 | 1.016 | 399.252 | 0.589 | 0.666 | 0.848 | 0.388 | 0.993 | 0.391 | 0.642 | 23,24,25,26,28,57,58,60,81,82,84,101,103,104,106,1 38,241,243,244,245,246,250,251,252,253,255,279,282 ,283,284,285,286,287,288,289,291 |
| P21860-5 | 1.077 | 170 | 1.099 | 447.615 | 0.483 | 0.796 | 1.031 | 1.04 | 0.978 | 1.063 | 0.687 | 72,73,74,75,76,77,78,80,97,98,99,120,129,131,142,1 44,146,147,148,150,191,195,196,198,208,209,210,212 ,227,231,234 |
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 P21860-1_P21860-1_6kbi_B.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P21860-1_6kbi_B_P21860-2.pdb |
| 3D view using mol* of P21860-1_6kbi_B_P21860-3.pdb |
| 3D view using mol* of P21860-1_6kbi_B_P21860-5.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P21860-1_P21860-2.pdb |
| 3D view using mol* of P21860-1_P21860-3.pdb |
| 3D view using mol* of P21860-1_P21860-5.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P21860-1_vs_P21860-2.png |
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| ./stats/secondary_structure/figure/P21860-1_vs_P21860-3.png |
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| ./stats/secondary_structure/figure/P21860-1_vs_P21860-5.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P21860-1_vs_P21860-2.png |
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| ./stats/relative_asa/P21860-1_vs_P21860-3.png |
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| ./stats/relative_asa/P21860-1_vs_P21860-5.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to ERBB3 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P21860 | ERBB3 | DB11652 | Tucatinib | approved, investigational | inhibitor |
Related Diseases to ERBB3 |
| Previous studies relating to the alternative splicing of ERBB3 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| ERBB3 | 7685162 | c-erbB3 gene encodes secreted as well as transmembrane receptor tyrosine kinase. | c-erbB3 product is moderately expressed in gastric mucosa, especially in parietal cells. Northern blot analysis revealed that 6.2-kb c-erbB3 transcript was expressed in all gastric cancer cell lines examined, and that 1.4-kb c-erbB3 transcript was expressed as highly as 6.2-kb transcript in MKN45 cells. erbB3-S cDNA, corresponding to 1.4-kb c-erbB3 transcript, was cloned by rapid amplification of cDNA ends. Sequence analysis of erbB3-S cDNA showed that this 1.4-kb c-erbB3 mRNA encoded a secreted receptor. Analysis of partial genomic structure of c-erbB3 gene revealed that the exon specific to secreted receptor was identical with the 5' portion of the intron in c-erbB3 gene. c-erbB3 gene encodes secreted as well as transmembrane receptor tyrosine kinase due to alternative splicing. | D013274 | Stomach Neoplasms |
Clinically important variants in ERBB3 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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