Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

ERBB2 (P04626) - Overview - Molecular Target Synopsis

Protein


ERBB2, Receptor tyrosine-protein kinase erbB-2
Enzyme Classification 2.7.10.1
UniProt P04626

Also Known as ERBB2_HUMAN, ERBB2, HER2, MLN19, NEU, NGL

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. 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).

6BGT deposition date (2017-10-29)
STRUCTURE OF TRASTUZUMAB FAB MUTANT IN COMPLEX WITH HER2 EXTRACELLULAR DOMAIN
RCSB/PDB
Inspect Structure
See all 3D Structures for ERBB2

Isoforms / Transcripts (Protein Coding)


Drugs


ERBB2 is targeted by Approved Drugs Pertuzumab, Lapatinib, Trastuzumab. (see details)
Pertuzumab
Lapatinib
Trastuzumab

Sub-cellular localization


UniProt: ERBB2 is active in the following subcellular-locations: cell membrane, cytoplasm, nucleus, perinuclear region.
GO terms: ERBB2 is active in the following subcellular-locations: apical plasma membrane, basolateral plasma membrane, cytosol, endosome membrane, integral component of membrane, myelin sheath, nucleus, perinuclear region of cytoplasm, plasma membrane, receptor complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project ERBB2 has gain in 34 cell-lines, loss in 3 cell-lines and no signal in 968 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SK_OV_3, T47D, NCI_H522

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: UACC-893, HCC1419, ZR-75-30

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HMEC, IMR-90, HSMM

(see details)

RNA Interference


ERBB2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: CAOV3, MDAMB157. (see details)

3D Structures


For ERBB2 there are:
31 structures (47 chains) solved
14 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


ERBB2 has been screened with 4492 compounds (7682 bioactivities), 1394 compounds have bioactivities that show binding affinity of <= 500nM (2109 bioactivities). (see details)