Tclin ERBB2 Receptor tyrosine-protein kinase erbB-2

Protein Summary

Description

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. 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]

Uniprot Accession IDs

• P04626
• B2RZG3
• B4DHN3
• Q14256
• Q6LDV1
• Q9UMK4
• X5D2V5

Gene Name

• ERBB2

Ensembl ID

• ENST00000269571
• ENSP00000269571
• ENSG00000141736
• ENST00000406381
• ENSP00000385185
• ENST00000541774
• ENSP00000446466
• ENST00000584601
• ENSP00000462438

Symbol

• HER2
• MLN19
• NEU
• NGL
• NEU
• NGL
• HER2
• TKR1
• CD340
• HER-2
• MLN 19
• HER-2/neu

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
biological term	1
hub protein	1
molecular function	1
protein domain	1

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tk Group / Egfr Family / Receptor Tyrosine-protein Kinase Erbb-2

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 36767.78   (req: < 5)

Gene RIFs: 3022   (req: <= 3)

Antibodies: 5131   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 36767.78   (req: >= 5)

Gene RIFs: 3022   (req: > 3)

Antibodies: 5131   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 54

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 452

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 16