ERBB2 - Receptor tyrosine-protein kinase erbB-2 - human protein (Function)
 
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ERBB2 »  Receptor tyrosine-protein kinase erbB-2   [ EC 2.7.10.1 ]
 
Protein also known as:  Tyrosine kinase-type cell surface receptor HER2; CD antigen CD340.
Gene name:  ERBB2
Entry whose protein(s) existence is based on evidence at protein level
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1 1786 6
GENE REF ISO

Function

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Overview 
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.  
1
  • UniProtKB
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.  
1
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
ErbB-3 class receptor bindingdefinition[GO:0043125]  
1
  • PINC
Contributes to growth factor bindingdefinition[GO:0019838]  
1
  • BHF-UCL
Identical protein bindingdefinition[GO:0042802]  
5
  • IntAct
Protein bindingdefinition[GO:0005515]  
47
  • IntAct
Protein C-terminus bindingdefinition[GO:0008022]  
1
  • UniProtKB
Protein dimerization activitydefinition[GO:0046983]  
1
  • UniProtKB
Protein heterodimerization activitydefinition[GO:0046982]  
2
  • UniProtKB
  • BHF-UCL
Protein phosphatase bindingdefinition[GO:0019903]  
1
  • UniProtKB
Protein tyrosine kinase activitydefinition[GO:0004713]  
2
  • MGI
  • BHF-UCL
Receptor signaling protein tyrosine kinase activitydefinition[GO:0004716] silver  
1
  • InterPro 2 GO
RNA polymerase I core bindingdefinition[GO:0001042]  
1
  • UniProtKB
Transmembrane receptor protein tyrosine kinase activitydefinition[GO:0004714]  
1
  • BHF-UCL
Transmembrane signaling receptor activitydefinition[GO:0004888]  
1
  • BHF-UCL
GO biological process 
Cell proliferationdefinition[GO:0008283]  
1
  • PINC
Cell surface receptor signaling pathwaydefinition[GO:0007166]  
1
  • MGI
Enzyme linked receptor protein signaling pathwaydefinition[GO:0007167]  
1
  • PINC
Heart developmentdefinition[GO:0007507] silver  
1
  • Ortholog Compara
Motor neuron axon guidancedefinition[GO:0008045] silver  
1
  • Ortholog Compara
Myelinationdefinition[GO:0042552] silver  
1
  • Ortholog Compara
Negative regulation of immature T cell proliferation in thymusdefinition[GO:0033088] silver  
1
  • Ortholog Compara
Neuromuscular junction developmentdefinition[GO:0007528] silver  
1
  • Ortholog Compara
Oligodendrocyte differentiationdefinition[GO:0048709] silver  
1
  • Ortholog Compara
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
6
  • GOC
  • InterPro 2 GO
  • EC 2 GO
  • UniProtKB KW
Peripheral nervous system developmentdefinition[GO:0007422] silver  
1
  • Ortholog Compara
Phosphatidylinositol 3-kinase signalingdefinition[GO:0014065]  
1
  • BHF-UCL
Positive regulation of cell adhesiondefinition[GO:0045785]  
1
  • BHF-UCL
Positive regulation of cell growthdefinition[GO:0030307]  
1
  • UniProtKB
Positive regulation of epithelial cell proliferationdefinition[GO:0050679]  
1
  • UniProtKB
Positive regulation of GTPase activitydefinition[GO:0043547]  
1
  • Ortholog Curator
Positive regulation of MAP kinase activitydefinition[GO:0043406]  
1
  • UniProtKB
Positive regulation of protein phosphorylationdefinition[GO:0001934]  
1
  • Ortholog Curator
Positive regulation of transcription from RNA polymerase I promoterdefinition[GO:0045943]  
1
  • UniProtKB
Positive regulation of transcription from RNA polymerase III promoterdefinition[GO:0045945]  
1
  • UniProtKB
Positive regulation of translationdefinition[GO:0045727]  
1
  • UniProtKB
Protein autophosphorylationdefinition[GO:0046777]  
1
  • BHF-UCL
Protein phosphorylationdefinition[GO:0006468]  
1
  • PINC
Regulation of angiogenesisdefinition[GO:0045765]  
1
  • UniProtKB
Regulation of ERK1 and ERK2 cascadedefinition[GO:0070372]  
1
  • UniProtKB
Regulation of microtubule-based processdefinition[GO:0032886]  
1
  • UniProtKB
Signal transductiondefinition[GO:0007165]  
1
  • UniProtKB
Signal transduction by protein phosphorylationdefinition[GO:0023014]  
2
  • GOC
  • InterPro 2 GO
Transcription, DNA-templateddefinition[GO:0006351]  
1
  • UniProtKB KW
Transmembrane receptor protein tyrosine kinase signaling pathwaydefinition[GO:0007169]  
2
  • BHF-UCL
Wound healingdefinition[GO:0042060]  
1
  • BHF-UCL
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.1: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
3
  • UniProtKB
  • PROSITE-ProRule
It is regulated in the following manner
Activated by dimerization. Not activated by EGF, TGF-alpha and amphiregulin. Interaction with PTK6 increases its intrinsic kinase activity.  
3
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Adherens junction  hsa04520+2064  
Bladder cancer  hsa05219+2064  
Calcium signaling pathway  hsa04020+2064  
Endometrial cancer  hsa05213+2064  
ErbB signaling pathway  hsa04012+2064  
Focal adhesion  hsa04510+2064  
Non-small cell lung cancer  hsa05223+2064  
Pancreatic cancer  hsa05212+2064  
Pathways in cancer  hsa05200+2064  
Prostate cancer  hsa05215+2064  
According to Reactome, this protein belongs to the following pathways:
Constitutive PI3K/AKT Signaling in Cancer  REACT_147727  
Downregulation of ERBB2:ERBB3 signaling  REACT_115662  
GRB2 events in ERBB2 signaling  REACT_115854  
GRB7 events in ERBB2 signaling  REACT_115896  
PI3K events in ERBB2 signaling  REACT_116008  
PIP3 activates AKT signaling  REACT_75829  
PLCG1 events in ERBB2 signaling  REACT_115720  
Sema4D induced cell migration and growth-cone collapse  REACT_19277  
SHC1 events in ERBB2 signaling  REACT_115993  
Signaling by ERBB2  REACT_115755  
 

Keywords

Biological process 
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Activator  definition   [KW-0010]
Kinase  definition   [KW-0418]
Receptor  definition   [KW-0675]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: HER2/neu
GenomeRNAi: 2064
PRO: PR:P04626
Chemistry
GuidetoPHARMACOLOGY: 2019