Homo sapiens Protein: ERBB2
InnateDB Protein IDBP-46072.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol ERBB2
Protein Name v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian)
Synonyms CD340; HER-2; HER-2/neu; HER2; MLN 19; NEU; NGL; TKR1;
Species Homo sapiens
Ensembl Protein ENSP00000269571
InnateDB Gene IDBG-46068 (ERBB2)
Protein Structure
UniProt Annotation
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.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.
Subcellular Localization 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.
Disease Associations Hereditary diffuse gastric cancer (HDGC) [MIM:137215]: A cancer predisposition syndrome with increased susceptibility to diffuse gastric cancer. Diffuse gastric cancer is a malignant disease characterized by poorly differentiated infiltrating lesions resulting in thickening of the stomach. Malignant tumors start in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. Note=The gene represented in this entry is involved in disease pathogenesis.Glioma (GLM) [MIM:137800]: Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. Note=The gene represented in this entry is involved in disease pathogenesis.Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Lung cancer (LNCR) [MIM:211980]: A common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. Note=The gene represented in this entry is involved in disease pathogenesis.Gastric cancer (GASC) [MIM:613659]: A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. Note=The gene represented in this entry is involved in disease pathogenesis.Note=Chromosomal aberrations involving ERBB2 may be a cause gastric cancer. Deletions within 17q12 region producing fusion transcripts with CDK12, leading to CDK12-ERBB2 fusion leading to truncated CDK12 protein not in-frame with ERBB2.
Tissue Specificity Expressed in a variety of tumor tissues including primary breast tumors and tumors from small bowel, esophagus, kidney and mouth. {ECO:0000269PubMed:15380516}.
Number of Interactions This gene and/or its encoded proteins are associated with 209 experimentally validated interaction(s) in this database.
They are also associated with 11 interaction(s) predicted by orthology.
Experimentally validated
Total 209 [view]
Protein-Protein 199 [view]
Protein-DNA 7 [view]
Protein-RNA 2 [view]
DNA-DNA 1 [view]
Predicted by orthology
Total 11 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0001042 RNA polymerase I core binding
GO:0004672 protein kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004714 transmembrane receptor protein tyrosine kinase activity
GO:0004716 receptor signaling protein tyrosine kinase activity
GO:0004888 transmembrane signaling receptor activity
GO:0005006 epidermal growth factor-activated receptor activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008022 protein C-terminus binding
GO:0016772 transferase activity, transferring phosphorus-containing groups
GO:0019838 growth factor binding
GO:0019903 protein phosphatase binding
GO:0042802 identical protein binding
GO:0043125 ErbB-3 class receptor binding
GO:0046982 protein heterodimerization activity
GO:0046983 protein dimerization activity
Biological Process
GO:0001934 positive regulation of protein phosphorylation
GO:0006351 transcription, DNA-templated
GO:0006468 protein phosphorylation
GO:0007165 signal transduction
GO:0007166 cell surface receptor signaling pathway
GO:0007167 enzyme linked receptor protein signaling pathway
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway
GO:0007173 epidermal growth factor receptor signaling pathway
GO:0007399 nervous system development
GO:0007411 axon guidance
GO:0007422 peripheral nervous system development
GO:0007507 heart development
GO:0007528 neuromuscular junction development
GO:0008045 motor neuron axon guidance
GO:0008283 cell proliferation
GO:0008543 fibroblast growth factor receptor signaling pathway
GO:0014065 phosphatidylinositol 3-kinase signaling
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0023014 signal transduction by phosphorylation
GO:0030307 positive regulation of cell growth
GO:0030879 mammary gland development
GO:0032321 positive regulation of Rho GTPase activity
GO:0032886 regulation of microtubule-based process
GO:0033088 negative regulation of immature T cell proliferation in thymus
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0042060 wound healing
GO:0042552 myelination
GO:0043406 positive regulation of MAP kinase activity
GO:0045087 innate immune response
GO:0045727 positive regulation of translation
GO:0045765 regulation of angiogenesis
GO:0045785 positive regulation of cell adhesion
GO:0045943 positive regulation of transcription from RNA polymerase I promoter
GO:0045945 positive regulation of transcription from RNA polymerase III promoter
GO:0046777 protein autophosphorylation
GO:0048011 neurotrophin TRK receptor signaling pathway
GO:0048015 phosphatidylinositol-mediated signaling
GO:0048709 oligodendrocyte differentiation
GO:0050679 positive regulation of epithelial cell proliferation
GO:0070372 regulation of ERK1 and ERK2 cascade
Cellular Component
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005886 plasma membrane
GO:0010008 endosome membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0016323 basolateral plasma membrane
GO:0016324 apical plasma membrane
GO:0031410 cytoplasmic vesicle
GO:0043235 receptor complex
GO:0048471 perinuclear region of cytoplasm
Protein Structure and Domains
InterPro IPR000494 EGF receptor, L domain
IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR006211 Furin-like cysteine-rich domain
IPR006212 Furin-like repeat
IPR009030 Insulin-like growth factor binding protein, N-terminal
IPR011009 Protein kinase-like domain
IPR016245 Tyrosine protein kinase, EGF/ERB/XmrK receptor
IPR020635 Tyrosine-protein kinase, catalytic domain
PFAM PF01030
Post-translational Modifications
SwissProt P04626
PhosphoSite PhosphoSite-P04626
UniProt Splice Variant
Entrez Gene 2064
UniGene Hs.446352
RefSeq NP_004439
OMIM 164870
HPRD 01281
EMBL AC079199 AC087491 AH001455 AK295195 AY208911 BC167147 CH471152 KJ534831 L29395 M11730 M12036 M16789 M16790 M16791 M16792 M86910 M95667 X03363
GenPept AAA35808 AAA35809 AAA35978 AAA58637 AAA75493 AAC37531 AAF30295 AAI67147 AAO18082 AHW56471 BAG58195 CAA27060 EAW60597