UniProt functional annotation for P06494



	UniProt functional annotation for P06494

UniProt code: P06494.

Organism: Rattus norvegicus (Rat).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.

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 (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 (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P04626}.

Function: 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 (By similarity). {ECO:0000250}.

Catalytic activity: Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};

Subunit: Homodimer. Heterodimer with EGFR, ERBB3 and ERBB4. Part of a complex with EGFR and either PIK3C2A or PIK3C2B. May interact with PIK3C2B when phosphorylated on Tyr-1198. Interacts with PRKCABP and PLXNB1. Interacts (when phosphorylated on Tyr-1250) with MEMO1. Interacts with MUC1. Interacts (when phosphorylated on Tyr-1141) with GRB7 (via SH2 domain). Interacts (when phosphorylated on Tyr-1250) with ERBIN Interacts with SRC, KPNB1, RANBP2, EEA1, CRM1, CLTC, PTK6, RPA194, MYOC and ACTB. Interacts with HSP90AA1 and HSP90AB1; the interaction suppresses ERBB2 kinase activity (By similarity). Interacts with SORL1; this interaction regulates ERBB2 subcellular distribution by promoting its recycling after internalization from endosomes back to the plasma membrane, hence stimulates ERBB2-mediated signaling (By similarity). {ECO:0000250|UniProtKB:P04626, ECO:0000250|UniProtKB:P70424}.

Subcellular location: Cell membrane {ECO:0000250|UniProtKB:P04626}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P04626}. Early endosome {ECO:0000250|UniProtKB:P04626}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:P04626}. Nucleus {ECO:0000250|UniProtKB:P04626}. Note=Translocation to the nucleus requires endocytosis, probably endosomal sorting and is mediated by importin beta-1/KPNB1. Also detected in endosome-to-TGN retrograde vesicles. {ECO:0000250|UniProtKB:P04626}.

Ptm: Autophosphorylated. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Ligand-binding increases phosphorylation on tyrosine residues. Signaling via SEMA4C promotes phosphorylation at Tyr-1250. Dephosphorylated by PTPN12. {ECO:0000250|UniProtKB:P04626}.

Similarity: Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily. {ECO:0000255|PROSITE- ProRule:PRU00159}.

Sequence caution: Sequence=AAH61863.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAA27059.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Rattus norvegicus (Rat).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.



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 (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 (By similarity). {ECO:0000250, ECO:0000250\|UniProtKB:P04626}.



Function:		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 (By similarity). {ECO:0000250}.


Catalytic activity:		Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255\|PROSITE-ProRule:PRU10028};
Subunit:		Homodimer. Heterodimer with EGFR, ERBB3 and ERBB4. Part of a complex with EGFR and either PIK3C2A or PIK3C2B. May interact with PIK3C2B when phosphorylated on Tyr-1198. Interacts with PRKCABP and PLXNB1. Interacts (when phosphorylated on Tyr-1250) with MEMO1. Interacts with MUC1. Interacts (when phosphorylated on Tyr-1141) with GRB7 (via SH2 domain). Interacts (when phosphorylated on Tyr-1250) with ERBIN Interacts with SRC, KPNB1, RANBP2, EEA1, CRM1, CLTC, PTK6, RPA194, MYOC and ACTB. Interacts with HSP90AA1 and HSP90AB1; the interaction suppresses ERBB2 kinase activity (By similarity). Interacts with SORL1; this interaction regulates ERBB2 subcellular distribution by promoting its recycling after internalization from endosomes back to the plasma membrane, hence stimulates ERBB2-mediated signaling (By similarity). {ECO:0000250\|UniProtKB:P04626, ECO:0000250\|UniProtKB:P70424}.
Subcellular location:		Cell membrane {ECO:0000250\|UniProtKB:P04626}; Single-pass type I membrane protein {ECO:0000250\|UniProtKB:P04626}. Early endosome {ECO:0000250\|UniProtKB:P04626}. Cytoplasm, perinuclear region {ECO:0000250\|UniProtKB:P04626}. Nucleus {ECO:0000250\|UniProtKB:P04626}. Note=Translocation to the nucleus requires endocytosis, probably endosomal sorting and is mediated by importin beta-1/KPNB1. Also detected in endosome-to-TGN retrograde vesicles. {ECO:0000250\|UniProtKB:P04626}.
Ptm:		Autophosphorylated. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Ligand-binding increases phosphorylation on tyrosine residues. Signaling via SEMA4C promotes phosphorylation at Tyr-1250. Dephosphorylated by PTPN12. {ECO:0000250\|UniProtKB:P04626}.
Similarity:		Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily. {ECO:0000255\|PROSITE- ProRule:PRU00159}.
Sequence caution:		Sequence=AAH61863.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAA27059.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};