ERBB3 Gene (Protein Coding)

Erb-B2 Receptor Tyrosine Kinase 3

GC12P056086
GIFtS:
55
This gene encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family mem... See more...

Aliases for ERBB3 Gene

Aliases for ERBB3 Gene

  • Erb-B2 Receptor Tyrosine Kinase 3 2 3 5
  • V-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 3 2 3
  • Tyrosine Kinase-Type Cell Surface Receptor HER3 3 4
  • Human Epidermal Growth Factor Receptor 3 2 3
  • Receptor Tyrosine-Protein Kinase ErbB-3 3 4
  • Proto-Oncogene-Like Protein C-ErbB-3 3 4
  • EC 2.7.10.1 4 52
  • HER3 3 4
  • Lethal Congenital Contracture Syndrome 2 2
  • P180-ErbB3 3
  • P45-SErbB3 3
  • P85-SErbB3 3
  • EC 2.7.10 52
  • MDA-BF-1 3
  • C-ErbB-3 3
  • C-ErbB3 3
  • ErbB3-S 3
  • ErbB-3 3
  • FERLK 3
  • LCCS2 3

External Ids for ERBB3 Gene

Previous HGNC Symbols for ERBB3 Gene

  • LCCS2

Previous GeneCards Identifiers for ERBB3 Gene

  • GC12M056386
  • GC12M056841
  • GC12P056190
  • GC12P054760
  • GC12P056473
  • GC12P053512
  • GC12P056079
  • GC12P056080

Summaries for ERBB3 Gene

Entrez Gene Summary for ERBB3 Gene

  • This gene encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers, including prostate, bladder, and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. One isoform lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported, but they have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

CIViC Summary for ERBB3 Gene

GeneCards Summary for ERBB3 Gene

ERBB3 (Erb-B2 Receptor Tyrosine Kinase 3) is a Protein Coding gene. Diseases associated with ERBB3 include Lethal Congenital Contracture Syndrome 2 and Erythroleukemia, Familial. Among its related pathways are RET signaling and Downstream signaling events of B Cell Receptor (BCR). Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and transferase activity, transferring phosphorus-containing groups. An important paralog of this gene is ERBB4.

UniProtKB/Swiss-Prot Summary for ERBB3 Gene

  • Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. Binds to neuregulin-1 (NRG1) and is activated by it; ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase (PubMed:20682778). May also be activated by CSPG5 (PubMed:15358134). Involved in the regulation of myeloid cell differentiation (PubMed:27416908).

Tocris Summary for ERBB3 Gene

  • The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase of the ErbB family. Four members of the ErbB family have been identified; EGFR (ErbB1, HER1), ErbB2 (HER2), ErbB3 (HER3) and ErbB4 (HER4). EGFR signaling drives many cellular responses.

Gene Wiki entry for ERBB3 Gene

Additional gene information for ERBB3 Gene

No data available for PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ERBB3 Gene

Genomics for ERBB3 Gene

GeneHancer (GH) Regulatory Elements for ERBB3 Gene

Promoters and enhancers for ERBB3 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ERBB3 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ERBB3

Top Transcription factor binding sites by QIAGEN in the ERBB3 gene promoter:
  • AP-2alpha
  • AP-2alpha isoform 2
  • AP-2alpha isoform 3
  • AP-2alpha isoform 4
  • AP-2alphaA

Genomic Locations for ERBB3 Gene

Genomic Locations for ERBB3 Gene
chr12:56,076,799-56,103,507
(GRCh38/hg38)
Size:
26,709 bases
Orientation:
Plus strand
chr12:56,473,641-56,497,291
(GRCh37/hg19)
Size:
23,651 bases
Orientation:
Plus strand

Genomic View for ERBB3 Gene

Genes around ERBB3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ERBB3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ERBB3 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for ERBB3 Gene

Proteins for ERBB3 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for ERBB3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P21860-ERBB3_HUMAN
    Recommended name:
    Receptor tyrosine-protein kinase erbB-3
    Protein Accession:
    P21860
    Secondary Accessions:
    • A8K6L6
    • B4DIK7
    • B4DV32
    • E9PDT8
    • Q9BUD7

    Protein attributes for ERBB3 Gene

    Size:
    1342 amino acids
    Molecular mass:
    148098 Da
    Quaternary structure:
    • Monomer and homodimer. Heterodimer with each of the other ERBB receptors (Potential). Interacts with CSPG5 (PubMed:15358134). Interacts with GRB7 (PubMed:9516479). Interacts with MUC1 (PubMed:12939402). Interacts with MYOC (By similarity). Interacts with isoform 2 of PA2G4 (PubMed:11325528, PubMed:16832058). Found in a ternary complex with NRG1 and ITGAV:ITGB3 or ITGA6:ITGB4 (PubMed:20682778).

    Three dimensional structures from OCA and Proteopedia for ERBB3 Gene

    Alternative splice isoforms for ERBB3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ERBB3 Gene

Protein Expression for ERBB3 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Selected DME Specific Peptides for ERBB3 Gene

P21860:
  • CPHNFVVD
  • QTVDSSNID
  • MVKCWMID
  • SLQLVTQ
  • SDVWSYGVT
  • DTDCFAC
  • CFSCHPEC
  • CEVVMGNLEI
  • FNDSGACVPRCP
  • AARNVLL
  • VCDPLCS
  • SLKEISAG
  • MARDPPRYLVI
  • YGVTVWE
  • REVTGYVLVA
  • KETELRK
  • PLVYNKLTFQLEPNPH
  • YTHQSDVWS
  • AFDNPDYW
  • TCNGSGS
  • LNIQSWPP
  • ECAGGCSGP

Post-translational modifications for ERBB3 Gene

  • Autophosphorylated (PubMed:20351256). Ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase (PubMed:20682778).
  • Glycosylation at Asn126, Asn250, Asn353, Asn408, Asn414, Asn437, Asn469, Asn522, Asn566, and Asn616
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • ERBB3_HUMAN (1711)

Other Protein References for ERBB3 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Abcam antibodies for ERBB3

Domains & Families for ERBB3 Gene

Gene Families for ERBB3 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Enzymes
  • Plasma proteins
  • Potential drug targets
  • Predicted intracellular proteins
  • Predicted membrane proteins
  • Predicted secreted proteins

Protein Domains for ERBB3 Gene

Blocks:
  • Tyrosine protein kinase, active site
  • Furin-like repeat
  • Epidermal growth-factor receptor (EGFR), L domain
  • Furin-like cysteine rich region
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for ERBB3 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ43038 fis, clone BRTHA3002955, highly similar to Receptor tyrosine-protein kinase erbB-3 (EC 2.7.10.1) (B3KWG5_HUMAN)
  • cDNA FLJ59207, highly similar to Receptor tyrosine-protein kinase erbB-3 (EC 2.7.10.1) (B4DGQ7_HUMAN)
  • Tyrosine kinase-type cell surface receptor HER3 (ERBB3_HUMAN)
  • ErbB-3 R1 (O75810_HUMAN)
  • ErbB-3 R2 (O75811_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P21860

UniProtKB/Swiss-Prot:

ERBB3_HUMAN :
  • The cytoplasmic part of the receptor may interact with the SH2 or SH3 domains of many signal-transducing proteins.
  • Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.
Domain:
  • The cytoplasmic part of the receptor may interact with the SH2 or SH3 domains of many signal-transducing proteins.
Family:
  • Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.
genes like me logo Genes that share domains with ERBB3: view

Function for ERBB3 Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for ERBB3 Gene

UniProtKB/Swiss-Prot Function:
Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. Binds to neuregulin-1 (NRG1) and is activated by it; ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase (PubMed:20682778). May also be activated by CSPG5 (PubMed:15358134). Involved in the regulation of myeloid cell differentiation (PubMed:27416908).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence=. ;.
GENATLAS Biochemistry:
avian erythroblastic leukemia,viral (v-erb-b) oncogene homolog 3,heregulin beta 1 receptor,signal transducer receptor,heterodimerizing with the ligand less recetpor ERBB2

Enzyme Numbers (IUBMB) for ERBB3 Gene

Phenotypes From GWAS Catalog for ERBB3 Gene

Gene Ontology (GO) - Molecular Function for ERBB3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0004672 protein kinase activity IEA --
GO:0004713 NOT protein tyrosine kinase activity IEA,IDA 7556068
GO:0004714 transmembrane receptor protein tyrosine kinase activity IBA,IEA 21873635
GO:0004888 transmembrane signaling receptor activity ISS 7514177
genes like me logo Genes that share ontologies with ERBB3: view
genes like me logo Genes that share phenotypes with ERBB3: view

Human Phenotype Ontology for ERBB3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for ERBB3 Gene

MGI Knock Outs for ERBB3:

Animal Model Products

Clone Products

  • Addgene plasmids for ERBB3

No data available for Transcription Factor Targets and HOMER Transcription for ERBB3 Gene

Localization for ERBB3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ERBB3 Gene

[Isoform 1]: Cell membrane; Single-pass type I membrane protein.
[Isoform 2]: Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ERBB3 gene
Compartment Confidence
plasma membrane 5
extracellular 5
cytoskeleton 3
nucleus 3
mitochondrion 2
endoplasmic reticulum 2
endosome 2
cytosol 2
lysosome 2
peroxisome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (3)
  • Actin filaments (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ERBB3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IDA 11389077
GO:0005886 plasma membrane TAS 17701904
GO:0005887 integral component of plasma membrane IBA,TAS 21873635
GO:0009925 basal plasma membrane IBA 21873635
genes like me logo Genes that share ontologies with ERBB3: view

Pathways & Interactions for ERBB3 Gene

PathCards logo

SuperPathways for ERBB3 Gene

SuperPathway Contained pathways
1 RET signaling
Frs2-mediated activation
.95
GRB2 events in EGFR signaling
.95
MAPK1/MAPK3 signaling
.95
Prolonged ERK activation events
.95
RAF/MAP kinase cascade
.95
SHC1 events in EGFR signaling
.95
Signaling by Leptin
.95
SOS-mediated signalling
.95
VEGFR2 mediated cell proliferation
.95
ARMS-mediated activation
.95
Signalling to ERKs
.95
Signalling to p38 via RIT and RIN
.95
Signalling to RAS
.95
Interleukin receptor SHC signaling
.95
Interleukin-3, 5 and GM-CSF signaling
.94
Interleukin-2 signaling
.94
Downstream signal transduction
.94
Signaling by PDGF
.94
DAP12 signaling
.92
RET signaling
.92
Insulin receptor signalling cascade
.92
Signaling by Insulin receptor
.92
IRS-mediated signalling
.91
Signaling by EGFR
.90
FCERI mediated MAPK activation
.90
IGF1R signaling cascade
.90
IRS-related events triggered by IGF1R
.90
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
.90
DAP12 interactions
.89
NCAM signaling for neurite out-growth
.89
NGF signalling via TRKA from the plasma membrane
.87
MAPK family signaling cascades
.87
Signaling by SCF-KIT
.85
Signalling by NGF
.81
Fc epsilon receptor (FCERI) signaling
.79
VEGFA-VEGFR2 Pathway
.78
Signaling by VEGF
.76
Gastrin-CREB signalling pathway via PKC and MAPK
.55
2 GPCR Pathway
Paxillin Interactions
.73
Ras Pathway
.73
GPCR Pathway
.62
Pancreatic Adenocarcinoma
.59
Breast Cancer Regulation by Stathmin1
.58
NFAT in Immune Response
.58
Estrogen Pathway
.55
P2Y Receptor Signaling
.38
3 GAB1 signalosome
Negative regulation of the PI3K/AKT network
.93
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
.93
PIP3 activates AKT signaling
.91
Role of LAT2/NTAL/LAB on calcium mobilization
.91
GAB1 signalosome
.89
PI3K/AKT activation
.89
Constitutive Signaling by Aberrant PI3K in Cancer
.75
PI3K/AKT Signaling in Cancer
.72
4 Signaling by ERBB2
Downregulation of ERBB2 signaling
.59
Signaling by ERBB2
.59
SHC1 events in ERBB2 signaling
.43
Downregulation of ERBB2-ERBB3 signaling
.01
ERBB2 Activates PTK6 Signaling
.01
ERBB2 Regulates Cell Motility
.01
PI3K events in ERBB2 signaling
.01
5 ERK Signaling
ERK Signaling
.61
Rho Family GTPases
.61
MAPK Signaling
.58
Molecular Mechanisms of Cancer
.51
ILK Signaling
.49
genes like me logo Genes that share pathways with ERBB3: view

Pathways by source for ERBB3 Gene

1 PharmGKB pathway for ERBB3 Gene
3 GeneGo (Thomson Reuters) pathways for ERBB3 Gene
  • Apoptosis and survival Role of CDK5 in neuronal death and survival
  • Development ERBB-family signaling
  • Development Ligand-independent activation of ESR1 and ESR2
4 Tocris pathways for ERBB3 Gene
35 Qiagen pathways for ERBB3 Gene
  • 14-3-3 Induced Intracellular Signaling
  • Actin Nucleation and Branching
  • Actin Nucleation by ARP-WASP Complex
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
1 Cell Signaling Technology pathway for ERBB3 Gene

SIGNOR curated interactions for ERBB3 Gene

Activates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for ERBB3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade TAS --
GO:0003197 endocardial cushion development IEA --
GO:0006468 protein phosphorylation IEA --
GO:0007162 negative regulation of cell adhesion IDA 7556068
GO:0007165 signal transduction IDA 10572067
genes like me logo Genes that share ontologies with ERBB3: view

Drugs & Compounds for ERBB3 Gene

Products:

  1. Drug

(58) Drugs for ERBB3 Gene - From: PharmGKB, ClinicalTrials, ApexBio, DGIdb, IUPHAR, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Gefitinib Approved, Investigational Pharma Biomarker, inhibitor EGFR Inhibitors, Kinase Inhibitors, Epidermal growth factor receptor (EGFR) inhibitors 401
Trastuzumab Approved, Investigational Pharma HER2 antagonist, HER2 Inhibitors, Therapeutic Antibodies, Epidermal growth factor receptor (EGFR) inhibitors 960
Tyrosine Approved, Investigational Nutra 985
Carboplatin Approved Pharma Antitumor agent that forms platinum-DNA adducts., Platinum 2480
Docetaxel Approved, Investigational Pharma Microtubulin disassembly inhibitor, Tubulin and VEGF inhibitor, Taxanes 2273

(19) Additional Compounds for ERBB3 Gene - From: Novoseek, HMDB, and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
 Full agonist, Agonist, Partial agonist, Antagonist, Gating inhibitor 58-64-0
AG 490
133550-30-8
CP 724714
383432-38-0

(4) Tocris Compounds for ERBB3 Gene

Compound Action Cas Number
AG 490 EGFR-kinase inhibitor. Also JAK2, JAK3 inhibitor 133550-30-8
CGP 52411 EGFR inhibitor. Also inhibits Abeta42 fibril formation 145915-58-8
CP 724714 Potent and selective ErbB2 inhibitor 383432-38-0
Genistein EGFR kinase inhibitor. Also estrogen and PPARgamma ligand 446-72-0

(3) ApexBio Compounds for ERBB3 Gene

Compound Action Cas Number
AZD8931 (Sapitinib) ErbB inhibitor 848942-61-0
Poziotinib irreversible pan-HER inhibitor 1092364-38-9
Varlitinib (ARRY334543) ErbB inhibitor 845272-21-1
genes like me logo Genes that share compounds with ERBB3: view

Transcripts for ERBB3 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for ERBB3 Gene

2 REFSEQ mRNAs :
24 NCBI additional mRNA sequence :
23 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Clone Products

  • Addgene plasmids for ERBB3

Alternative Splicing Database (ASD) splice patterns (SP) for ERBB3 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7a · 7b ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13a · 13b ^ 14a · 14b ^ 15 ^ 16a · 16b · 16c ^ 17 ^
SP1: - - - -
SP2: - -
SP3:
SP4: - - - - - - - - - - - - - -
SP5:
SP6:
SP7:
SP8: -
SP9:
SP10: -
SP11:
SP12:

ExUns: 18 ^ 19a · 19b · 19c ^ 20 ^ 21 ^ 22a · 22b ^ 23a · 23b ^ 24a · 24b ^ 25 ^ 26 ^ 27a · 27b ^ 28 ^ 29
SP1: - - -
SP2: - - - - - - -
SP3: - -
SP4: - - - - - - - - - - - - - - -
SP5:
SP6:
SP7:
SP8:
SP9: -
SP10:
SP11:
SP12:

Relevant External Links for ERBB3 Gene

GeneLoc Exon Structure for
ERBB3

Expression for ERBB3 Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ERBB3 Gene

mRNA expression in normal human tissues for ERBB3 Gene
mRNA expression by BioGPS for ERBB3 GenemRNA expression by GTEx for ERBB3 Gene