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 d... See more...

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
  • Receptor Tyrosine-Protein Kinase ErbB-2 3 4
  • Metastatic Lymph Node Gene 19 Protein 3 4
  • Proto-Oncogene C-ErbB-2 3 4
  • Proto-Oncogene Neu 3 4
  • EC 2.7.10.1 4 52
  • 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
  • C-Erb B2/Neu Protein 3
  • CD340 Antigen 4
  • HER-2/Neu 3
  • Herstatin 3
  • EC 2.7.10 52
  • 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 Gastric Cancer. 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 identical protein binding and protein kinase activity. An important paralog of this gene is EGFR.

UniProtKB/Swiss-Prot Summary 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 Rfam classification 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 2.6 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 507.3 +15.5 15460 8.8 FOXK2 ZNF217 TCF12 POLR2G NCOR1 PHF8 TEAD4 ZFX CTCF ZNF10 ERBB2 GRB7 PGAP3 MIEN1 NEUROD2 THRA ORMDL3 GSDMB MF281430-030
GH17J039686 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 500.7 +0.3 316 3 ZBTB40 ZNF217 SIN3A TCF12 NRF1 POLR2G SP1 NCOR1 PHF8 SIX5 PGAP3 ERBB2 lnc-PNMT-1 MIEN1 GRB7 STARD3 MED1 LN812234
GH17J039631 Promoter/Enhancer 2.4 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 11.1 -53.2 -53212 8.2 ZBTB40 ZNF217 EP300 CTCF ZSCAN5C NRF1 POLR2G NCOR1 GTF2E2 PHF8 STARD3 MED24 PGAP3 MED1 CDK12 MSL1 LOC105371762 TCAP PNMT NEUROD2
GH17J039766 Promoter/Enhancer 1.7 FANTOM5 Ensembl ENCODE dbSUPER 11.5 +87.0 86973 17.2 ZSCAN5C SIN3A RBAK ZNF639 ZNF10 EP300 ZBTB10 CLOCK ZNF623 TRIM28 GSDMB MED1 ORMDL3 SNORD124 GSDMA CDK12 ERBB2 MIEN1 GRB7 SNORA21
GH17J039799 Enhancer 1.4 FANTOM5 Ensembl ENCODE dbSUPER 10.1 +112.3 112287 6 SP1 ZNF10 EP300 ZIC2 ZNF423 KLF7 ATF2 ZNF341 OSR2 BCL11A GSDMA GSDMB RAPGEFL1 GRB7 MIEN1 PGAP3 ERBB2 IKZF3 ZPBP2 lnc-ZPBP2-6
- 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

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ERBB2

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

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). Interacts with SORL1; this interaction regulates ERBB2 subcellular distribution by promoting its recycling after internalization from endosomes back to the plasma membrane, hence stimulates ERBB2-mediated signaling (PubMed:31138794).
    Miscellaneous:
    • [Isoform 2]: Produced by alternative initiation at Met-611 of isoform 1.
    • [Isoform 3]: Produced by alternative initiation at Met-687 of isoform 1.
    • [Isoform 4]: Produced by alternative splicing of isoform 1.

    Three dimensional structures from OCA and Proteopedia for ERBB2 Gene

    Alternative splice isoforms for ERBB2 Gene

neXtProt entry for ERBB2 Gene

Selected DME Specific Peptides for ERBB2 Gene

P04626:
  • GGKVPIKW
  • KPYDGIP
  • SPLQRYSEDPT
  • RPRFRELV
  • LQVFETLEEITGYLYISAWP
  • QCAAGCTGP
  • FLRGQECV
  • RDLAARN
  • LDEAYVMA
  • CPYNYLST
  • AENPEYL
  • RLLGICLTS
  • MVKCWMID
  • TYNTDTFESM
  • RPAGATLERPKTLSP
  • LVDAEEYLVPQQGFF
  • MARDPQR
  • YALAVLDN
  • PLQRLRIVRGTQLFED
  • VKIPVAIK
  • GERLPQP
  • DSTFYRSLLEDDDMG
  • RLVHRDLAARNVLVKSPNHVKITDFGLARLL
  • SDVWSYGVT
  • CQPCPINCTHSC
  • YGVTVWE
  • KETELRK
  • RGRLGSQDLLNWC
  • GERLPQPPICTI
  • TQLMPYGCLLD
  • ETDGYVAPL
  • GLRELQLRSLTEILKGGVLI
  • GCPAEQRASP
  • ELVEPLTPSG
  • AARNVLV

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 Asn629, Asn68, Asn124, Asn187, Asn259, Asn530, and Asn571
  • Ubiquitination at Lys736, Lys747, and Lys753
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • ERBB2_HUMAN (1710)

Antibody Products

  • Abcam antibodies for ERBB2

Protein Products

  • Abcam proteins for ERBB2

Assay Products

  • Abcam assays for ERBB2

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

Protein Domains for ERBB2 Gene

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

Suggested Antigen Peptide Sequences for ERBB2 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ59426, highly similar to Receptor tyrosine-protein kinase erbB-2 (EC 2.7.10.1) (B4DTR1_HUMAN)
  • Receptor tyrosine-protein kinase erbB-2 variant (E2I6F8_HUMAN)
  • p185erbB2 (ERBB2_HUMAN)
  • ERBB2 (Q4H1F1_HUMAN)
  • ERBB2 (Q4H1F2_HUMAN)

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:
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={ECO:0000255 PROSITE-ProRule:PRU10028, ECO:0000269 PubMed:21454582};.
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:0004713 protein tyrosine kinase activity TAS,IGI --
GO:0004714 transmembrane receptor protein tyrosine kinase activity IDA 7514177
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

CRISPR 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. Early endosome. Cytoplasm, perinuclear region. Nucleus. Note=Translocation to the nucleus requires endocytosis, probably endosomal sorting and is mediated by importin beta-1/KPNB1. Also detected in VPS35-positive endosome-to-TGN retrograde vesicles (PubMed:31138794). {ECO:0000269 PubMed:31138794}.
[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
endosome 5
cytosol 5
extracellular 4
cytoskeleton 3
mitochondrion 3
lysosome 3
peroxisome 2
endoplasmic reticulum 2
golgi apparatus 2

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:0005634 nucleus IDA,IEA 16314522
GO:0005737 cytoplasm IEA --
GO:0005768 endosome IEA --
GO:0005769 early endosome IEA --
GO:0005829 cytosol IDA --
genes like me logo Genes that share ontologies with ERBB2: view

Pathways & Interactions for ERBB2 Gene

PathCards logo

SuperPathways for ERBB2 Gene

SuperPathway Contained pathways
1 RET signaling
2 GPCR Pathway
.73
.73
.62
.59
.58
.58
.55
.38
3 GAB1 signalosome
4 Signaling by ERBB2
5 Development ERBB-family signaling
.51
.51
.41
genes like me logo Genes that share pathways with ERBB2: view

Pathways by source for ERBB2 Gene

1 PharmGKB pathway for ERBB2 Gene
8 GeneGo (Thomson Reuters) pathways for ERBB2 Gene
  • Apoptosis and survival Role of CDK5 in neuronal death and survival
  • Development EGFR signaling pathway
  • Development EGFR signaling via PIP3
  • Development EGFR signaling via small GTPases
  • Development ERBB-family signaling
4 Tocris pathways for ERBB2 Gene
38 Qiagen pathways for ERBB2 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 ERBB2 Gene

SIGNOR curated interactions for ERBB2 Gene

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:0006357 regulation of transcription by RNA polymerase II TAS --
GO:0006468 protein phosphorylation TAS 10851066
GO:0007165 signal transduction IDA 10572067
genes like me logo Genes that share ontologies with ERBB2: view

Drugs & Compounds for ERBB2 Gene

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