Protein detail
ERBB3
Receptor tyrosine-protein kinase erbB-3 (EC 2.7.10.1) (Proto-oncogene-like protein c-ErbB-3) (Tyrosine kinase-type cell surface receptor HER3)
Entry name ERBB3 | UniProt ID | EVMP score 0.38 |
Frequency 1 | Transmembrane count 1 | Protein classification Cancer-related genesDisease related genesEnzymesHuman disease related genesPlasma proteinsPotential drug targetsPredicted intracellular proteinsPredicted membrane proteinsPredicted secreted proteinsTransporters |
EVMP score: annotation confidence score.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40
Basic Information
Protein Names
Receptor tyrosine-protein kinase erbB-3 (EC 2.7.10.1) (Proto-oncogene-like protein c-ErbB-3) (Tyrosine kinase-type cell surface receptor HER3)
Protein Class
Cancer-related genesDisease related genesEnzymesHuman disease related genesPlasma proteinsPotential drug targetsPredicted intracellular proteinsPredicted membrane proteinsPredicted secreted proteinsTransporters
Protein Function
- Predicted intracellular proteins
- Human disease related genes:Congenital malformations:Congenital malformations of the musculoskeletal system
- Human disease related genes:Endocrine and metabolic diseases:Diabetes
- ENZYME proteins:Transferases
- Cancer-related genes:Mutated cancer genes
- Potential drug targets
- Enzymes
- Cancer-related genes:Candidate cancer biomarkers
- Predicted secreted proteins
- Transporters:Accessory Factors Involved in Transport
- Kinases:Tyr protein kinases
- Disease related genes
Transmembrane
644..664; Helical
Transmembrane Count
1
Ensembl
Entrez Gene Symbol
Gene Synonym
HER3LCCS2
Gene Description
Erb-b2 receptor tyrosine kinase 3
Chromosome
12
Position
56076799-56103505
Frequency
1
EVMP Score
0.38
Fluorescence & Localization
Tissue Specificheart muscleBrain Regional SpecificmidbrainCell SpecificT-cellsSingle-Nuclei Brain SpecificleukocyteBlood Cell SpecificgdT-cellBlood Lineage SpecificT-cells
Function & Pathway
Protein Function
- Predicted intracellular proteins
- Human disease related genes:Congenital malformations:Congenital malformations of the musculoskeletal system
- Human disease related genes:Endocrine and metabolic diseases:Diabetes
- ENZYME proteins:Transferases
- Cancer-related genes:Mutated cancer genes
- Potential drug targets
- Enzymes
- Cancer-related genes:Candidate cancer biomarkers
- Predicted secreted proteins
- Transporters:Accessory Factors Involved in Transport
- Kinases:Tyr protein kinases
- Disease related genes
Cellular Component
Molecular Function
- GO:0004888 transmembrane signaling receptor activity
- GO:0005515 protein binding
- GO:0005524 ATP binding
- GO:0019838 growth factor binding
- GO:0030296 protein tyrosine kinase activator activity
- GO:0031625 ubiquitin protein ligase binding
- GO:0038131 neuregulin receptor activity
- GO:0038132 neuregulin binding
- GO:0042802 identical protein binding
- GO:0043125 ErbB-3 class receptor binding
- GO:0046982 protein heterodimerization activity
Biological Process
KEGG
Reactome
- R-hsa-2219530 constitutive signaling by aberrant pi3k in cancer
- R-hsa-5663202 diseases of signal transduction by growth factor receptors and second messengers
- R-hsa-1358803 downregulation of erbb2 erbb3 signaling
- R-hsa-8863795 downregulation of erbb2 signaling
- R-hsa-8847993 erbb2 activates ptk6 signaling
- R-hsa-6785631 erbb2 regulates cell motility
- R-hsa-1306955 grb7 events in erbb2 signaling
- R-hsa-9006925 intracellular signaling by second messengers
- R-hsa-5684996 mapk1 mapk3 signaling
- R-hsa-5683057 mapk family signaling cascades
- R-hsa-199418 negative regulation of the pi3k akt network
- R-hsa-2219528 pi3k akt signaling in cancer
- R-hsa-1963642 pi3k events in erbb2 signaling
- R-hsa-1250196 shc1 events in erbb2 signaling
- R-hsa-1227986 signaling by erbb2
- R-hsa-1227990 signaling by erbb2 in cancer
- R-hsa-1236394 signaling by erbb4
- R-hsa-8848021 signaling by ptk6
- R-hsa-9006934 signaling by receptor tyrosine kinases
Mediation Categories
Adhesion and uptake mediationClinical-translation mediationFusion and delivery mediationReceptor-signaling mediation
Relations & Evidence
Enzyme-Mediated Modification
18 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| ERBB3 | ERBB2 | P04626 | Y | 1,199 | phosphorylation | KEA | KEA:17570479 |
| ERBB3 | HRG | P04196 | Y | 1,289 | phosphorylation | REACH_ProtMapperProtMapper | ProtMapper:26148232 |
| ERBB3 | HRG | P04196 | S | 686 | phosphorylation | REACH_ProtMapperProtMapper | ProtMapper:24036211 |
| ERBB3 | ROR1 | Q01973 | Y | 1,307 | phosphorylation | RLIMS-P_ProtMapperREACH_ProtMapperSparser_ProtMapperProtMapper | ProtMapper:28114269 |
| ERBB3 | RORA | P35398 | Y | 1,307 | phosphorylation | Sparser_ProtMapperProtMapper | ProtMapper:28114269 |
| ERBB3 | FYN | P06241 | Y | 1,262 | phosphorylation | KEA | KEA:17570479 |
| ERBB3 | INSR | P06213 | Y | 1,262 | phosphorylation | KEA | KEA:17570479 |
| ERBB3 | LCK | P06239 | Y | 1,199 | phosphorylation | KEA | KEA:17570479 |
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Ligand-Receptor Signaling
77 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| cell_surface | cell_surface | OmniPath | No | No | Yes | Yes | No |
| receptor | receptor | talklr | No | Yes | Yes | Yes | No |
| receptor | receptor | Cellinker | No | Yes | Yes | Yes | No |
| receptor | receptor | scConnect | No | Yes | Yes | Yes | No |
| receptor | receptor | connectomeDB2020 | No | Yes | Yes | Yes | No |
| receptor | receptor | CellCall | No | Yes | Yes | Yes | No |
| receptor | receptor | iTALK | No | Yes | Yes | Yes | No |
| growth_factor | receptor | iTALK | No | Yes | Yes | Yes | No |
| receptor | receptor | Almen2009 | No | Yes | Yes | Yes | No |
| receptor | receptor | CellCellInteractions | No | Yes | Yes | Yes | No |
Regulatory Interaction Network
17 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| RNF41 | Q9H4P4 | ERBB3 | P21860 | Yes | No | Yes | SIGNORHPRDHINTBioGRIDWang | BioGRID:17384230HPRD:12411582HINT:11867753SIGNOR:12411582HINT:12411582BioGRID:27353365 |
| CDK5 | Q00535 | ERBB3 | P21860 | Yes | Yes | No | MIMPHPRD_MIMPiPTMnetPhosphoPointSIGNORProtMapperHPRDPhosphoSite_KEAKEAHPRD_KEASIGNOR_ProtMapper | KEA:12824184HPRD:12824184ProtMapper:12824184SIGNOR:12824184 |
| EREG | O14944 | ERBB3 | P21860 | Yes | Yes | No | Fantom5_LRdbCellTalkDBiTALKtalklrSIGNORLRdbSTRING_talklrCellCall | SIGNOR:16829981SIGNOR:22891299CellTalkDB:32196115 |
| ERBB3 | P21860 | PK3CA | P42336 | Yes | Yes | No | SIGNORHINTACSNIntActWang | IntAct:19411071SIGNOR:16729043HINT:34591642HINT:19411071IntAct:34591642ACSN:17496910 |
| ERBB3 | P21860 | PK3CG | P48736 | Yes | Yes | No | WangSIGNORACSN | SIGNOR:16729043ACSN:17496910 |
| ERBB3 | P21860 | PK3CB | P42338 | Yes | Yes | No | WangSIGNORACSN | SIGNOR:16729043ACSN:17496910 |
| ERBB3 | P21860 | PK3CD | O00329 | Yes | Yes | No | WangSIGNORACSN | SIGNOR:16729043ACSN:17496910 |
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Protein Complex Composition
Isolation & Detection Technology
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| Protein Organic Solvent Precipitation | Mass spectrometry | 1 | 32384937 |
Sequence, Structure & Domains
Sequences
Length
1,342
Mass
148,098
Sequence
MRANDALQVLGLLFSLARGSEVGNSQAVCPGTLNGLSVTGDAENQYQTLYKLYERCEVVMGNLEIVLTGHNADLSFLQWIREVTGYVLVAMNEFSTLPLPNLRVVRGTQVYDGKFAIFVMLNYNTNSSHALRQLRLTQLTEILSGGVYIEKNDKLCHMDTIDWRDIVRDRDAEIVVKDNGRSCPPCHEVCKGRCWGPGSEDCQTLTKTICAPQCNGHCFGPNPNQCCHDECAGGCSGPQDTDCFACRHFNDSGACVPRCPQPLVYNKLTFQLEPNPHTKYQYGGVCVASCPHNFVVDQTSCVRACPPDKMEVDKNGLKMCEPCGGLCPKACEGTGSGSRFQTVDSSNIDGFVNCTKILGNLDFLITGLNGDPWHKIPALDPEKLNVFRTVREITGYLNIQSWPPHMHNFSVFSNLTTIGGRSLYNRGFSLLIMKNLNVTSLGFRSLKEISAGRIYISANRQLCYHHSLNWTKVLRGPTEERLDIKHNRPRRDCVAEGKVCDPLCSSGGCWGPGPGQCLSCRNYSRGGVCVTHCNFLNGEPREFAHEAECFSCHPECQPMEGTATCNGSGSDTCAQCAHFRDGPHCVSSCPHGVLGAKGPIYKYPDVQNECRPCHENCTQGCKGPELQDCLGQTLVLIGKTHLTMALTVIAGLVVIFMMLGGTFLYWRGRRIQNKRAMRRYLERGESIEPLDPSEKANKVLARIFKETELRKLKVLGSGVFGTVHKGVWIPEGESIKIPVCIKVIEDKSGRQSFQAVTDHMLAIGSLDHAHIVRLLGLCPGSSLQLVTQYLPLGSLLDHVRQHRGALGPQLLLNWGVQIAKGMYYLEEHGMVHRNLAARNVLLKSPSQVQVADFGVADLLPPDDKQLLYSEAKTPIKWMALESIHFGKYTHQSDVWSYGVTVWELMTFGAEPYAGLRLAEVPDLLEKGERLAQPQICTIDVYMVMVKCWMIDENIRPTFKELANEFTRMARDPPRYLVIKRESGPGIAPGPEPHGLTNKKLEEVELEPELDLDLDLEAEEDNLATTTLGSALSLPVGTLNRPRGSQSLLSPSSGYMPMNQGNLGESCQESAVSGSSERCPRPVSLHPMPRGCLASESSEGHVTGSEAELQEKVSMCRSRSRSRSPRPRGDSAYHSQRHSLLTPVTPLSPPGLEEEDVNGYVMPDTHLKGTPSSREGTLSSVGLSSVLGTEEEDEDEEYEYMNRRRRHSPPHPPRPSSLEELGYEYMDVGSDLSASLGSTQSCPLHPVPIMPTAGTTPDEDYEYMNRQRDGGGPGGDYAAMGACPASEQGYEEMRAFQGPGHQAPHVHYARLKTLRSLEATDSAFDNPDYWHSRLFPKANAQRT
Alternative Products
Event=Alternative splicing; Named isoforms=5; Name=1; Synonyms=long form; IsoId=P21860-1; Sequence=Displayed; Name=2; Synonyms=short form; IsoId=P21860-2; Sequence=VSP_002893, VSP_002894; Name=3; IsoId=P21860-3; Sequence=VSP_041663, VSP_041664; Name=4; IsoId=P21860-4; Sequence=VSP_041662; Name=5; IsoId=P21860-5; Sequence=VSP_041661
Alternative Sequence
1..643; Missing (in isoform 5); 1..59; Missing (in isoform 4); 141..183; EILSGGVYIEKNDKLCHMDTIDWRDIVRDRDAEIVVKDNGRSC -> GQFPMVPSGLTPQPAQDWYLLDDDPRLLTLSASSKVPVTLAAV (in isoform 2); 184..1342; Missing (in isoform 2); 331; C -> F (in isoform 3); 332..1342; Missing (in isoform 3)
3D Structural Models
Turn
112..114; 158..160; 267..269; 345..347; 372..375; 425..427; 747..749; 870..872; 911..914; 952..954
Helix
43..53; 75..79; 163..166; 188..190; 199..201; 223..225; 240..242; 348..351; 365..369; 381..389; 410..412; 465..467; 470..474; 490..495; 514..516; 626..628; 641..670; 706..708; 758..764; 795..802; 803..806; 808..827; 837..839; 856..858; 865..868; 875..877; 880..885; 890..905; 917..919; 920..925; 938..947; 958..969; 972..974
Beta Strand
28..30; 38..41; 58..61; 63..67; 82..85; 87..91; 95..98; 115..120; 125..128; 133..135; 141..144; 146..150; 174..178; 194..198; 214..216; 218..222; 231..233; 235..239; 243..251; 254..258; 262..265; 270..274; 280..282; 285..289; 295..297; 300..304; 309..314; 317..322; 324..326; 330..332; 338..342; 355..363; 392..395; 397..399; 428..433; 451..457; 481..488; 509..513; 517..522; 528..531; 534..540; 542..545; 548..551; 560..562; 564..569; 572..581; 584..588; 591..595; 598..604; 608..612; 621..625; 709..717; 722..728; 731..733; 737..744; 753..755; 774..778; 780..788; 840..846; 848..850; 980..983
3D Structure
Electron microscopy (4); NMR spectroscopy (1); X-ray crystallography (17)
Domain & Motif Annotations
Compositional Bias
1042..1075; Polar residues
Domain (CC)
The cytoplasmic part of the receptor may interact with the SH2 or SH3 domains of many signal-transducing proteins.
Domain (FT)
709..966; Protein kinase
Region
980..999; Disordered; 1033..1152; Disordered
Protein Families
- 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 Relevance
Disease Involvement
Cancer-related genesDisease variant
Drugs
PATRITUMABMM-111CDX-3379METHYLCURCUMINPAN-HER KINASE INHIBITOR AC480ELGEMTUMABNULLTRAMETINIB DIMETHYL SULFOXIDESELUMETINIBMARGETUXIMAB-CMKBPATRITUMAB DERUXTECANAV-203LUMRETUZUMABGEFITINIBCETUXIMABLAPATINIBMM-121RITUXIMABMOMELOTINIBANTI-HER3 MONOCLONAL ANTIBODY GSK2849330ELISIDEPSINMM-151ANTI-ERBB3 MONOCLONAL ANTIBODY REGN1400ANTI-ERBB3 MONOCLONAL ANTIBODY AV-203DULIGOTUZUMABCOMPOUND 11 [PMID: 26431428]AFATINIBDARIZMETINIBSERIBANTUMABCIMAGLERMIN ALFACURCUMINMEK INHIBITOR IAMG-888ISTIRATUMABTARLOXOTINIBDACOMITINIB ANHYDROUSANTI-EGFR/HER2/HER3 MONOCLONAL ANTIBODY MIXTURE SYM013SAPITINIBPOZIOTINIBDOCETAXEL ANHYDROUSHER2 INHIBITOR CP-724,714DIMETHYLCURCUMINVANDETANIBKBP5209ERLOTINIBCARBOPLATINANTI-ERBB3 MONOCLONAL ANTIBODY CDX-3379ZENOCUTUZUMABSTAUROSPORINE
Interaction Protein
ENSG00000094631ENSG00000105647ENSG00000117461ENSG00000121879ENSG00000138032ENSG00000141736ENSG00000141738ENSG00000145675ENSG00000146648ENSG00000160691ENSG00000174791ENSG00000177885ENSG00000179295ENSG00000183386ENSG00000197747
Interaction Count
15
Interaction Dataset
intact_biogrid