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Aliases for ERBB2 Gene

Aliases for ERBB2 Gene

  • Erb-B2 Receptor Tyrosine Kinase 2 2 3 5
  • V-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 2 2 3
  • Tyrosine Kinase-Type Cell Surface Receptor HER2 3 4
  • Neuro/Glioblastoma Derived Oncogene Homolog 2 3
  • Human Epidermal Growth Factor Receptor 2 2 3
  • Metastatic Lymph Node Gene 19 Protein 3 4
  • Proto-Oncogene C-ErbB-2 3 4
  • Proto-Oncogene Neu 3 4
  • P185erbB2 3 4
  • MLN 19 3 4
  • HER2 3 4
  • NGL 3 4
  • NEU 3 4
  • V-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 2 (Neuro/Glioblastoma Derived Oncogene Homolog) 2
  • V-Erb-B2 Erythroblastic Leukemia Viral Oncogene Homolog 2, Neuro/Glioblastoma Derived Oncogene Homolog 3
  • V-Erb-B2 Avian Erythroblastic Leukemia Viral Oncoprotein 2 3
  • Neuroblastoma/Glioblastoma Derived Oncogene Homolog 3
  • Receptor Tyrosine-Protein Kinase ErbB-2 3
  • C-Erb B2/Neu Protein 3
  • CD340 Antigen 4
  • EC 2.7.10.1 4
  • HER-2/Neu 3
  • Herstatin 3
  • CD340 3
  • HER-2 3
  • MLN19 4
  • TKR1 3

External Ids for ERBB2 Gene

Previous HGNC Symbols for ERBB2 Gene

  • NGL

Previous GeneCards Identifiers for ERBB2 Gene

  • GC17P037262
  • GC17P039854
  • GC17P037766
  • GC17P038231
  • GC17P035109
  • GC17P037844
  • GC17P033638

Summaries for ERBB2 Gene

Entrez Gene Summary for ERBB2 Gene

  • 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]

CIViC summary for ERBB2 Gene

  • ERBB2, commonly referred to as HER2, is amplified and/or overexpressed in 20-30% of invasive breast carcinomas. HER2-positive breast cancer is treated in a separate manner from other subtypes of breast cancer and commonly presents as more aggressive disease. Metastatic HER2-positive breast cancer is now commonly treated with HER2-targeted therapy. Apart from being amplified/overexpressed, ERBB2 activating mutations have been shown to have clinical importance in HER2-negative breast cancer. These mutations have shown sensitivity to the tyrosine kinase inhibitor neratinib, and highlight the importance of clinical sequencing efforts in treating breast cancer.

GeneCards Summary for ERBB2 Gene

ERBB2 (Erb-B2 Receptor Tyrosine Kinase 2) is a Protein Coding gene. Diseases associated with ERBB2 include Glioma Susceptibility 1 and Lung Cancer. Among its related pathways are ERK Signaling and Gene Expression. Gene Ontology (GO) annotations related to this gene include identical protein binding and protein kinase activity. An important paralog of this gene is EGFR.

UniProtKB/Swiss-Prot for ERBB2 Gene

  • Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization.

  • In the nucleus is involved in transcriptional regulation. Associates with the 5-TCAAATTC-3 sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth.

Tocris Summary for ERBB2 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 ERBB2 Gene

PharmGKB "VIP" Summary for ERBB2 Gene

Additional gene information for ERBB2 Gene

No data available for fRNAdb sequence ontologies and piRNA Summary for ERBB2 Gene

Genomics for ERBB2 Gene

GeneHancer (GH) Regulatory Elements for ERBB2 Gene

Promoters and enhancers for ERBB2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH17J039698 Promoter/Enhancer 2.7 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 657.3 +15.5 15460 8.8 PKNOX1 FOXA2 ARID4B SIN3A DMAP1 ZBTB7B YY1 FOS SP3 SP5 ERBB2 GRB7 PGAP3 MIEN1 NEUROD2 THRA ORMDL3 GSDMB MIR4728
GH17J039686 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 650.7 +0.3 316 3 PKNOX1 SMAD1 FOXA2 MLX ARID4B SIN3A DMAP1 YY1 POLR2B E2F8 PGAP3 ERBB2 MED1 LOC105371762 MIEN1 GRB7 STARD3 SNORA21 MED24 GC17P039685
GH17J039766 Enhancer 1.7 FANTOM5 Ensembl ENCODE dbSUPER 11.5 +87.0 86973 17.2 HDGF PKNOX1 CLOCK FOXA2 SMAD1 FEZF1 ZNF2 IRF4 ZNF213 FOS GC17P039774 GSDMB MED1 ORMDL3 GSDMA SNORD124 MED24 CDK12 ERBB2 MIEN1
GH17J039812 Enhancer 1.4 FANTOM5 Ensembl ENCODE dbSUPER 10.8 +125.8 125810 2.7 PKNOX1 ZBTB21 MZF1 FEZF1 ZIC2 YY1 ZNF121 GATA3 RXRA ZNF10 GC17P039815 ORMDL3 GSDMB PGAP3 ERBB2 GSDMA IKZF3 FBXL20 CASC3 WIPF2
GH17J039631 Enhancer 1.2 Ensembl ENCODE dbSUPER 11.1 -54.9 -54919 4 ELF3 PKNOX1 RAD21 ETS1 ZNF121 GLIS2 SCRT2 ZNF143 ZNF654 REST PGAP3 STARD3 PNMT TCAP NEUROD2 RNU6-233P ERBB2 PPP1R1B
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ERBB2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the ERBB2 gene promoter:
  • AP-2alpha isoform 3
  • AP-2alpha
  • AP-2alpha isoform 2
  • AP-2alphaA
  • AP-2alpha isoform 4

Genomic Locations for ERBB2 Gene

Genomic Locations for ERBB2 Gene
chr17:39,687,914-39,730,426
(GRCh38/hg38)
Size:
42,513 bases
Orientation:
Plus strand
chr17:37,844,167-37,886,679
(GRCh37/hg19)
Size:
42,513 bases
Orientation:
Plus strand

Genomic View for ERBB2 Gene

Genes around ERBB2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ERBB2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ERBB2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ERBB2 Gene

Proteins for ERBB2 Gene

  • Protein details for ERBB2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P04626-ERBB2_HUMAN
    Recommended name:
    Receptor tyrosine-protein kinase erbB-2
    Protein Accession:
    P04626
    Secondary Accessions:
    • B2RZG3
    • B4DHN3
    • Q14256
    • Q6LDV1
    • Q9UMK4
    • X5D2V5

    Protein attributes for ERBB2 Gene

    Size:
    1255 amino acids
    Molecular mass:
    137910 Da
    Quaternary structure:
    • Homodimer (PubMed:21454582). Heterodimer with EGFR, ERBB3 and ERBB4 (PubMed:10358079, PubMed:15093539, PubMed:21190959, PubMed:16978839). Part of a complex with EGFR and either PIK3C2A or PIK3C2B. May interact with PIK3C2B when phosphorylated on Tyr-1196 (PubMed:10805725). Interacts with PLXNB1 (PubMed:15210733). Interacts (when phosphorylated on Tyr-1248) with MEMO1 (PubMed:15156151). Interacts with MUC1; the interaction is enhanced by heregulin (HRG) (PubMed:12939402). Interacts (when phosphorylated on Tyr-1139) with GRB7 (via SH2 domain) (PubMed:12975581). Interacts (when phosphorylated on Tyr-1248) with ERBIN (PubMed:12444095). Interacts with KPNB1, RANBP2, EEA1, CRM1 and CLTC (PubMed:16314522). Interacts with PTK6 (PubMed:18719096). Interacts with RPA194 and ACTB (PubMed:21555369). Interacts with PRKCABP, SRC and MYOC (By similarity). Interacts (preferentially with the tyrosine phosphorylated form) with CPNE3; this interaction occurs at the cell membrane and is increased in a growth factor heregulin-dependent manner (PubMed:20010870). Interacts with HSP90AA1 and HSP90AB1 in an ATP-dependent manner; the interaction suppresses ERBB2 kinase activity (PubMed:26517842).

    Three dimensional structures from OCA and Proteopedia for ERBB2 Gene

    Alternative splice isoforms for ERBB2 Gene

neXtProt entry for ERBB2 Gene

Post-translational modifications for ERBB2 Gene

  • Autophosphorylated. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit (Probable). Ligand-binding increases phosphorylation on tyrosine residues (PubMed:27134172). Signaling via SEMA4C promotes phosphorylation at Tyr-1248 (PubMed:17554007). Dephosphorylated by PTPN12 (PubMed:27134172).
  • Glycosylation at isoforms=2, 4, 5, 6629, isoforms=4, 5, 6571, isoforms=4, 5, 6530, isoforms=4, 5, 6259, Asn187, Asn124, and Asn68
  • Ubiquitination at Lys753, Lys747, and isoforms=2, 3, 4, 5, 6736
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Abcam antibodies for ERBB2

No data available for DME Specific Peptides for ERBB2 Gene

Domains & Families for ERBB2 Gene

Gene Families for ERBB2 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Cancer-related genes
  • CD markers
  • Disease related genes
  • Enzymes
  • FDA approved drug targets
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted membrane proteins

Graphical View of Domain Structure for InterPro Entry

P04626

UniProtKB/Swiss-Prot:

ERBB2_HUMAN :
  • Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.
Family:
  • Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.
genes like me logo Genes that share domains with ERBB2: view

Function for ERBB2 Gene

Molecular function for ERBB2 Gene

UniProtKB/Swiss-Prot Function:
Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization.
UniProtKB/Swiss-Prot Function:
In the nucleus is involved in transcriptional regulation. Associates with the 5-TCAAATTC-3 sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth.
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated by dimerization. Not activated by EGF, TGF-alpha and amphiregulin. Interaction with PTK6 increases its intrinsic kinase activity.
GENATLAS Biochemistry:
avian erythroblastic leukemia viral (v-erb-b) oncogene homolog 2,HERC2/neu receptor tyrosine kinase,neuroglioblastoma derived,constitutively acting as a coreceptor for multiple stroma-derived growth factors i.e EGF-like ligands and neuregulins after heterodimerization with other ERBBs,involved in androgen receptor transactivation of inducing prostate-specific antigen (PSA) through the MAP kinase pathway,signal transducer,also presenting as a secreted transcript herstatin,expressed in normal fetal kidney and liver,potential inhibitor of ERBB2,commonly amplified in primary breast cancer and in endometrial cancer,coamplified with GRB7 in primary gastric cancer,and in prostate carcinoma with metastasis and poor prognosis

Enzyme Numbers (IUBMB) for ERBB2 Gene

Phenotypes From GWAS Catalog for ERBB2 Gene

Gene Ontology (GO) - Molecular Function for ERBB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0001042 RNA polymerase I core binding IDA 21555369
GO:0004672 protein kinase activity IEA --
GO:0004709 MAP kinase kinase kinase activity IBA --
GO:0004713 protein tyrosine kinase activity TAS,IGI --
genes like me logo Genes that share ontologies with ERBB2: view
genes like me logo Genes that share phenotypes with ERBB2: view

Human Phenotype Ontology for ERBB2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for ERBB2 Gene

MGI Knock Outs for ERBB2:

Animal Model Products

miRNA for ERBB2 Gene

miRTarBase miRNAs that target ERBB2

Clone Products

  • Addgene plasmids for ERBB2

No data available for Transcription Factor Targets and HOMER Transcription for ERBB2 Gene

Localization for ERBB2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ERBB2 Gene

Isoform 1: Cell membrane; Single-pass type I membrane protein. Cytoplasm, perinuclear region. Nucleus. Note=Translocation to the nucleus requires endocytosis, probably endosomal sorting and is mediated by importin beta-1/KPNB1.
Isoform 2: Cytoplasm. Nucleus.
Isoform 3: Cytoplasm. Nucleus.

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 ERBB2 gene
Compartment Confidence
plasma membrane 5
nucleus 5
cytosol 5
endosome 5
extracellular 3
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
lysosome 2
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Plasma membrane (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ERBB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular IEA --
GO:0005634 nucleus IEA,IDA 16314522
GO:0005737 cytoplasm IBA,IEA --
GO:0005829 cytosol IDA --
GO:0005886 plasma membrane TAS --
genes like me logo Genes that share ontologies with ERBB2: view

Pathways & Interactions for ERBB2 Gene

SuperPathways for ERBB2 Gene

SuperPathway Contained pathways
1 RET signaling
2 Signaling by ERBB2
3 GPCR Pathway
4 PI3K/AKT activation
5 ERK Signaling
genes like me logo Genes that share pathways with ERBB2: view

SIGNOR curated interactions for ERBB2 Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for ERBB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade TAS --
GO:0001934 positive regulation of protein phosphorylation ISS --
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006357 regulation of transcription by RNA polymerase II TAS --
genes like me logo Genes that share ontologies with ERBB2: view

Drugs & Compounds for ERBB2 Gene

(165) Drugs for ERBB2 Gene - From: DrugBank, PharmGKB, ClinicalTrials, ApexBio, DGIdb, FDA Approved Drugs, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Lapatinib Approved March 2007, Investigational Pharma Inhibition, inhibitor, Biomarker, Target, antagonist EGFR/HER2 inhibitor,potent,selective and reversible, HER2 and EGFR kinase inhibitor, HER2 Inhibitors, Kinase Inhibitors, Epidermal growth factor receptor (EGFR) inhibitors 306
Trastuzumab Approved, Investigational Pharma antagonist, Biomarker, antibody, inhibitor, Target HER2 antagonist, HER2 Inhibitors, Therapeutic Antibodies, Epidermal growth factor receptor (EGFR) inhibitors 848
Pertuzumab Approved Pharma Biomarker, antibody, inhibitor, Target HER2 Inhibitors, Therapeutic Antibodies, Epidermal growth factor receptor (EGFR) inhibitors, HER2 Dimerization Inhibitor 143
trastuzumab emtansine Approved, Investigational Pharma Target, antibody 0
afatinib Approved Pharma inhibitor, Target Kinase Inhibitors, Epidermal growth factor receptor (EGFR) inhibitors 0

(49) Additional Compounds for ERBB2 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 ERBB2 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
genes like me logo Genes that share compounds with ERBB2: view

Transcripts for ERBB2 Gene

Unigene Clusters for ERBB2 Gene

V-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian):
Representative Sequences:

Clone Products

  • Addgene plasmids for ERBB2

Alternative Splicing Database (ASD) splice patterns (SP) for ERBB2 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15a · 15b · 15c ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^
SP1: - -
SP2: -
SP3: -
SP4: -
SP5:
SP6:

ExUns: 22 ^ 23a · 23b ^ 24 ^ 25 ^ 26 ^ 27a · 27b
SP1:
SP2:
SP3:
SP4:
SP5:
SP6: -

Relevant External Links for ERBB2 Gene

GeneLoc Exon Structure for
ERBB2
ECgene alternative splicing isoforms for
ERBB2

Expression for ERBB2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for ERBB2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for ERBB2 Gene

This gene is overexpressed in Lung (28.2), Skin (14.6), and Placenta (6.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ERBB2 Gene



Protein tissue co-expression partners for ERBB2 Gene

NURSA nuclear receptor signaling pathways regulating expression of ERBB2 Gene:

ERBB2

SOURCE GeneReport for Unigene cluster for ERBB2 Gene:

Hs.446352

mRNA Expression by UniProt/SwissProt for ERBB2 Gene:

P04626-ERBB2_HUMAN
Tissue specificity: Expressed in a variety of tumor tissues including primary breast tumors and tumors from small bowel, esophagus, kidney and mouth.

Evidence on tissue expression from TISSUES for ERBB2 Gene

  • Nervous system(4.7)
  • Liver(4.6)
  • Intestine(4.4)
  • Lymph node(3.6)
  • Lung(3.3)
  • Skin(3.1)
  • Blood(2.9)
  • Kidney(2.9)
  • Muscle(2.9)
  • Stomach(2.9)
  • Heart(2.8)
  • Thyroid gland(2.4)
  • Gall bladder(2.3)
  • Pancreas(2.3)
  • Spleen(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for ERBB2 Gene

Germ Layers:
  • ectoderm
  • endoderm
Systems:
  • digestive
  • nervous
  • respiratory
Regions:
Head and neck:
  • brain
  • head
Thorax:
  • lung
Abdomen:
  • stomach
genes like me logo Genes that share expression patterns with ERBB2: view

No data available for mRNA differential expression in normal tissues for ERBB2 Gene

Orthologs for ERBB2 Gene

This gene was present in the common ancestor of animals.

Orthologs for ERBB2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ERBB2 34 33
  • 99.55 (n)
OneToOne
dog
(Canis familiaris)
Mammalia ERBB2 34