InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ERBB2

Summary

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}.

Comments

Interactions

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]
RNA-RNA	0
DNA-RNA	0

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

PDB ID

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
PF00069
PF07714
PF00757

PRINTS

PR00109

PIRSF

PIRSF000619

SMART

SM00220
SM00261
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References