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Names & Taxonomy

Uniprot ID:: P04626
Entry Name:: ERBB2_HUMAN
Status:: reviewed
Protein Names:: Receptor tyrosine-protein kinase erbB-2 (EC 2.7.10.1) (Metastatic lymph node gene 19 protein) (MLN 19) (Proto-oncogene Neu) (Proto-oncogene c-ErbB-2) (Tyrosine kinase-type cell surface receptor HER2) (p185erbB2) (CD antigen CD340)
Gene Names:: ERBB2 HER2 MLN19 NEU NGL
Gene Names Primary:: ERBB2
Organism:: Homo sapiens (Human)

Structure

Length:: 1255
Sequence:: MELAALCRWGLLLALLPPGAASTQVCTGTDMKLRLPASPETHLDMLRHLYQGCQVVQGNLELTYLPTNASLSFLQDIQEVQGYVLIAHNQVRQVPLQRLRIVRGTQLFEDNYALAVLDNGDPLNNTTPVTGASPGGLRELQLRSLTEILKGGVLIQRNPQLCYQDTILWKDIFHKNNQLALTLIDTNRSRACHPCSPMCKGSRCWGESSEDCQSLTRTVCAGGCARCKGPLPTDCCHEQCAAGCTGPKHSDCLACLHFNHSGICELHCPALVTYNTDTFESMPNPEGRYTFGASCVTACPYNYLSTDVGSCTLVCPLHNQEVTAEDGTQRCEKCSKPCARVCYGLGMEHLREVRAVTSANIQEFAGCKKIFGSLAFLPESFDGDPASNTAPLQPEQLQVFETLEEITGYLYISAWPDSLPDLSVFQNLQVIRGRILHNGAYSLTLQGLGISWLGLRSLRELGSGLALIHHNTHLCFVHTVPWDQLFRNPHQALLHTANRPEDECVGEGLACHQLCARGHCWGPGPTQCVNCSQFLRGQECVEECRVLQGLPREYVNARHCLPCHPECQPQNGSVTCFGPEADQCVACAHYKDPPFCVARCPSGVKPDLSYMPIWKFPDEEGACQPCPINCTHSCVDLDDKGCPAEQRASPLTSIISAVVGILLVVVLGVVFGILIKRRQQKIRKYTMRRLLQETELVEPLTPSGAMPNQAQMRILKETELRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFVVIQNEDLGPASPLDSTFYRSLLEDDDMGDLVDAEEYLVPQQGFFCPDPAPGAGGMVHHRHRSSSTRSGGGDLTLGLEPSEEEAPRSPLAPSEGAGSDVFDGDLGMGAAKGLQSLPTHDPSPLQRYSEDPTVPLPSETDGYVAPLTCSPQPEYVNQPDVRPQPPSPREGPLPAARPAGATLERPKTLSPGKNGVVKDVFAFGGAVENPEYLTPQGGAAPQPHPPPAFSPAFDNLYYWDQDPPERGAPPSTFKGTPTAENPEYLGLDVPV
Proteomes:: UP000005640

Subcellular location

Subcellular Location:: 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.

Function

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.
Catalytic Activity:: ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
Enzyme Regulation:: ENZYME REGULATION: Activated by dimerization. Not activated by EGF, TGF-alpha and amphiregulin. Interaction with PTK6 increases its intrinsic kinase activity.
Active Site:: ACT_SITE 845 845 Proton acceptor.
Cross Reference Drug Bank:: DB05773 DB08916 DB01259 DB06366 DB00072
Gene Ontology Go:: apical plasma membrane
basolateral plasma membrane
cytoplasm
cytoplasmic vesicle
endosome membrane
integral component of membrane
myelin sheath
nucleus
perinuclear region of cytoplasm
plasma membrane
receptor complex
ATP binding
ErbB-3 class receptor binding
identical protein binding
protein C-terminus binding
protein dimerization activity
protein heterodimerization activity
protein phosphatase binding
protein tyrosine kinase activity
receptor signaling protein tyrosine kinase activity
RNA polymerase I core binding
transmembrane receptor protein tyrosine kinase activity
transmembrane signaling receptor activity
activation of MAPKK activity
axon guidance
cell proliferation
cell surface receptor signaling pathway
cellular response to growth factor stimulus
enzyme linked receptor protein signaling pathway
epidermal growth factor receptor signaling pathway
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
heart development
innate immune response
insulin receptor signaling pathway
MAPK cascade
motor neuron axon guidance
myelination
negative regulation of immature T cell proliferation in thymus
neuromuscular junction development
neurotrophin TRK receptor signaling pathway
oligodendrocyte differentiation
peptidyl-tyrosine phosphorylation
peripheral nervous system development
phosphatidylinositol 3-kinase signaling
phosphatidylinositol-mediated signaling
positive regulation of cell adhesion
positive regulation of cell growth
positive regulation of epithelial cell proliferation
positive regulation of GTPase activity
positive regulation of MAP kinase activity
positive regulation of protein phosphorylation
positive regulation of protein targeting to membrane
positive regulation of transcription from RNA polymerase I promoter
positive regulation of transcription from RNA polymerase III promoter
positive regulation of translation
protein autophosphorylation
protein phosphorylation
Ras protein signal transduction
regulation of angiogenesis
regulation of ERK1 and ERK2 cascade
regulation of microtubule-based process
signal transduction
small GTPase mediated signal transduction
transcription, DNA-templated
transmembrane receptor protein tyrosine kinase signaling pathway
vascular endothelial growth factor receptor signaling pathway
wound healing
Gene Ontology Biological Process:: activation of MAPKK activity
axon guidance
cell proliferation
cell surface receptor signaling pathway
cellular response to growth factor stimulus
enzyme linked receptor protein signaling pathway
epidermal growth factor receptor signaling pathway
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
heart development
innate immune response
insulin receptor signaling pathway
MAPK cascade
motor neuron axon guidance
myelination
negative regulation of immature T cell proliferation in thymus
neuromuscular junction development
neurotrophin TRK receptor signaling pathway
oligodendrocyte differentiation
peptidyl-tyrosine phosphorylation
peripheral nervous system development
phosphatidylinositol 3-kinase signaling
phosphatidylinositol-mediated signaling
positive regulation of cell adhesion
positive regulation of cell growth
positive regulation of epithelial cell proliferation
positive regulation of GTPase activity
positive regulation of MAP kinase activity
positive regulation of protein phosphorylation
positive regulation of protein targeting to membrane
positive regulation of transcription from RNA polymerase III promoter
positive regulation of transcription from RNA polymerase I promoter
positive regulation of translation
protein autophosphorylation
protein phosphorylation
Ras protein signal transduction
regulation of angiogenesis
regulation of ERK1 and ERK2 cascade
regulation of microtubule-based process
signal transduction
small GTPase mediated signal transduction
transcription, DNA-templated
transmembrane receptor protein tyrosine kinase signaling pathway
vascular endothelial growth factor receptor signaling pathway
wound healing
Gene Ontology Molecular Function:: ATP binding
ErbB-3 class receptor binding
identical protein binding
protein C-terminus binding
protein dimerization activity
protein heterodimerization activity
protein phosphatase binding
protein tyrosine kinase activity
receptor signaling protein tyrosine kinase activity
RNA polymerase I core binding
transmembrane receptor protein tyrosine kinase activity
transmembrane signaling receptor activity
Gene Ontology Cellular Component:: apical plasma membrane
basolateral plasma membrane
cytoplasm
cytoplasmic vesicle
endosome membrane
integral component of membrane
myelin sheath
nucleus
perinuclear region of cytoplasm
plasma membrane
receptor complex
Keywords:: 3D-structure
ATP-binding
Activator
Alternative initiation
Alternative splicing
Cell membrane
Chromosomal rearrangement
Complete proteome
Cytoplasm
Disulfide bond
Glycoprotein
Kinase
Membrane
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Receptor
Reference proteome
Signal
Transcription
Transcription regulation
Transferase
Transmembrane
Transmembrane helix
Tyrosine-protein kinase
Interacts With:: Itself; P00519; P42684; P60709; Q92625; O00213; O75815; Q16543; Q9NSE2; Q7Z7G1; P46109; Q99704; Q8TEW6; Q15075; P98172; P00533; P21860; Q15303; Q9UJM3; P09769; P06241; O75791; P62993; Q14451; O75367; O75367-3; P07900; P08238; P46940; P35568; Q08881; P23458; Q14974; Q9UQF2; Q13387; P42679; Q9Y316; O43639; Q02297-7; O00750; P27986; O00459; Q92569; P19174; P16885; O95602; Q05397; Q13882; Q06124; Q05209; P23467; P08575; Q12913; Q15262; Q16827; P49792; P20936; O95980; Q9NP31; P29353; P98077; Q92529; Q9H6Q3; O15524; P12931; P42224; P40763; Q7KZ85; P43405; Q9Y490; Q63HR2; Q68CZ2; Q96D37; P52735; O14980

Names & Taxonomy

Structure

Subcellular location

Function

Publication