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P70424 (ERBB2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 151. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Receptor tyrosine-protein kinase erbB-2

EC=2.7.10.1
Alternative name(s):
Proto-oncogene Neu
Proto-oncogene c-ErbB-2
p185erbB2
CD_antigen=CD340
Gene names
Name:Erbb2
Synonyms:Kiaa3023, Neu
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1256 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.4

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. Ref.4

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Subunit structure

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-1197. Interacts with PRKCABP and PLXNB1. Interacts (when phosphorylated on Tyr-1249) with MEMO1. Interacts with MUC1. Interacts (when phosphorylated on Tyr-1140) with GRB7 (via SH2 domain). Interacts (when phosphorylated on Tyr-1249) with ERBB2IP. Interacts with KPNB1, RANBP2, EEA1, CRM1, CLTC, PTK6, RPA94 and ACTB By similarity. Interacts with SRC and MYOC. Ref.4 Ref.5 Ref.6

Subcellular location

Cell membrane; Single-pass type I membrane protein By similarity. Cytoplasmperinuclear region By similarity. Nucleus By similarity.

Tissue specificity

Expressed predominantly in uterine epithelial cells. In the muscle, expression localizes to the synaptic sites of muscle fibers.

Developmental stage

On days 1-4 of pregnancy, ERBB2 is detected primarily in epithelial cells, the day 1 uterus showing the highest accumulation. On day 5, the epithelium and the decidualizing stromal cells around the implanting blastocyst exhibit accumulation of this receptor. On days 6-8, the expression persists in the epithelium at both the implantation and interimplantation sites in addition to modest levels in the secondary decidual zone. On days 7 and 8, accumulation is also prominent in the trophoblastic giant cells.

Post-translational modification

Autophosphorylated. Ligand-binding increases phosphorylation on tyrosine residues. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Signaling via SEMA4C promotes phosphorylation at Tyr-1249 By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.

Contains 1 protein kinase domain.

Sequence caution

The sequence BAC98297.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCell membrane
Cytoplasm
Membrane
Nucleus
   DomainSignal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionActivator
Kinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processheart development

Inferred from mutant phenotype PubMed 12072561PubMed 9362461. Source: MGI

motor neuron axon guidance

Inferred from mutant phenotype PubMed 10655525. Source: MGI

myelination

Inferred from mutant phenotype PubMed 10704452. Source: MGI

negative regulation of immature T cell proliferation in thymus

Inferred from mutant phenotype PubMed 16230479. Source: MGI

nervous system development

Inferred from mutant phenotype PubMed 15496447. Source: MGI

neuromuscular junction development

Inferred from mutant phenotype PubMed 10655525. Source: MGI

peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: GOC

peripheral nervous system development

Inferred from mutant phenotype PubMed 9362461. Source: MGI

phosphatidylinositol 3-kinase signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of MAP kinase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of Rho GTPase activity

Inferred from mutant phenotype PubMed 22019888. Source: BHF-UCL

positive regulation of cell adhesion

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell growth

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein phosphorylation

Inferred from mutant phenotype PubMed 22019888. Source: BHF-UCL

positive regulation of transcription from RNA polymerase I promoter

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase III promoter

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of translation

Inferred from sequence or structural similarity. Source: UniProtKB

protein autophosphorylation

Inferred from electronic annotation. Source: Ensembl

regulation of ERK1 and ERK2 cascade

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of microtubule-based process

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transmembrane receptor protein tyrosine kinase signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

wound healing

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentapical plasma membrane

Inferred from direct assay PubMed 15306553. Source: MGI

basolateral plasma membrane

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay PubMed 15306553. Source: MGI

cytoplasmic vesicle

Inferred from direct assay PubMed 23553667. Source: MGI

endosome membrane

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Non-traceable author statement PubMed 15609325. Source: UniProtKB

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from direct assay PubMed 23553667. Source: MGI

receptor complex

Inferred from sequence orthology PubMed 23382219. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

RNA polymerase I core binding

Inferred from sequence or structural similarity. Source: UniProtKB

receptor signaling protein tyrosine kinase activity

Inferred from electronic annotation. Source: InterPro

transmembrane receptor protein tyrosine kinase activity

Inferred from sequence or structural similarity. Source: BHF-UCL

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 12561234Receptor tyrosine-protein kinase erbB-2
PRO_0000042181

Regions

Topological domain23 – 653631Extracellular Potential
Transmembrane654 – 67421Helical; Potential
Topological domain675 – 1256582Cytoplasmic Potential
Domain721 – 988268Protein kinase
Nucleotide binding727 – 7359ATP By similarity
Region677 – 69014Nuclear localization signal By similarity
Region677 – 69014Required for interaction with KPNB1 and EEA1 By similarity
Region1196 – 11983Interaction with PIK3C2B By similarity
Compositional bias193 – 26977Cys-rich
Compositional bias1117 – 116347Pro-rich

Sites

Active site8461Proton acceptor By similarity
Binding site7541ATP By similarity

Amino acid modifications

Modified residue10551Phosphoserine By similarity
Modified residue11081Phosphoserine By similarity
Modified residue11401Phosphotyrosine; by autocatalysis By similarity
Modified residue11971Phosphotyrosine Potential
Modified residue12491Phosphotyrosine; by autocatalysis By similarity
Glycosylation681N-linked (GlcNAc...) Potential
Glycosylation1251N-linked (GlcNAc...) Potential
Glycosylation1881N-linked (GlcNAc...) Potential
Glycosylation2601N-linked (GlcNAc...) Potential
Glycosylation5311N-linked (GlcNAc...) Potential
Glycosylation5721N-linked (GlcNAc...) Potential
Glycosylation6301N-linked (GlcNAc...) Potential
Disulfide bond26 ↔ 53 By similarity
Disulfide bond163 ↔ 193 By similarity
Disulfide bond196 ↔ 205 By similarity
Disulfide bond200 ↔ 213 By similarity
Disulfide bond221 ↔ 228 By similarity
Disulfide bond225 ↔ 236 By similarity
Disulfide bond237 ↔ 245 By similarity
Disulfide bond241 ↔ 253 By similarity
Disulfide bond256 ↔ 265 By similarity
Disulfide bond269 ↔ 296 By similarity
Disulfide bond300 ↔ 312 By similarity
Disulfide bond316 ↔ 332 By similarity
Disulfide bond335 ↔ 339 By similarity
Disulfide bond343 ↔ 368 By similarity
Disulfide bond476 ↔ 505 By similarity
Disulfide bond512 ↔ 521 By similarity
Disulfide bond516 ↔ 529 By similarity
Disulfide bond532 ↔ 541 By similarity
Disulfide bond545 ↔ 561 By similarity
Disulfide bond564 ↔ 577 By similarity
Disulfide bond568 ↔ 585 By similarity
Disulfide bond588 ↔ 597 By similarity
Disulfide bond601 ↔ 624 By similarity
Disulfide bond627 ↔ 635 By similarity
Disulfide bond631 ↔ 643 By similarity

Sequences

Sequence LengthMass (Da)Tools
P70424 [UniParc].

Last modified September 27, 2005. Version 3.
Checksum: 6040978428B93A28

FASTA1,256138,579
        10         20         30         40         50         60 
MELAAWCRWG FLLALLSPGA AGTQVCTGTD MKLRLPASPE THLDMLRHLY QGCQVVQGNL 

        70         80         90        100        110        120 
ELTYLPANAS LSFLQDIQEV QGYMLIAHNR VKHVPLQRLR IVRGTQLFED KYALAVLDNR 

       130        140        150        160        170        180 
DPLDNVTTAA PGRTPEGLRE LQLRSLTEIL KGGVLIRGNP QLCYQDMVLW KDVLRKNNQL 

       190        200        210        220        230        240 
APVDMDTNRS RACPPCAPTC KDNHCWGESP EDCQILTGTI CTSGCARCKG RLPTDCCHEQ 

       250        260        270        280        290        300 
CAAGCTGPKH SDCLACLHFN HSGICELHCP ALITYNTDTF ESMLNPEGRY TFGASCVTTC 

       310        320        330        340        350        360 
PYNYLSTEVG SCTLVCPPNN QEVTAEDGTQ RCEKCSKPCA GVCYGLGMEH LRGARAITSD 

       370        380        390        400        410        420 
NIQEFAGCKK IFGSLAFLPE SFDGNPSSGV APLKPEHLQV FETLEEITGY LYISAWPESF 

       430        440        450        460        470        480 
QDLSVFQNLR VIRGRILHDG AYSLTLQGLG IHSLGLRSLR ELGSGLALIH RNTHLCFVNT 

       490        500        510        520        530        540 
VPWDQLFRNP HQALLHSGNR PEEACGLEGL VCNSLCARGH CWGPGPTQCV NCSQFLRGQE 

       550        560        570        580        590        600 
CVEECRVWKG LPREYVRGKH CLPCHPECQP QNSSETCYGS EADQCEACAH YKDSSSCVAR 

       610        620        630        640        650        660 
CPSGVKPDLS YMPIWKYPDE EGICQPCPIN CTHSCVDLDE RGCPAEQRAS PVTFIIATVV 

       670        680        690        700        710        720 
GVLLFLIIVV VIGILIKRRR QKIRKYTMRR LLQETELVEP LTPSGAVPNQ AQMRILKETE 

       730        740        750        760        770        780 
LRKLKVLGSG AFGTVYKGIW IPDGENVKIP VAIKVLRENT SPKANKEILD EAYVMAGVGS 

       790        800        810        820        830        840 
PYVSRLLGIC LTSTVQLVTQ LMPYGCLLDH VREHRGRLGS QDLLNWCVQI AKGMSYLEEV 

       850        860        870        880        890        900 
RLVHRDLAAR NVLVKSPNHV KITDFGLARL LDIDETEYHA DGGKVPIKWM ALESILRRRF 

       910        920        930        940        950        960 
THQSDVWSYG VTVWELMTFG AKPYDGIPAR EIPDLLEKGE RLPQPPICTI DVYMIMVKCW 

       970        980        990       1000       1010       1020 
MIDSECRPRF RELVSEFSRM ARDPQRFVVI QNEDLGPSSP MDSTFYRSLL EDDDMGELVD 

      1030       1040       1050       1060       1070       1080 
AEEYLVPQQG FFSPDPALGT GSTAHRRHRS SSARSGGGEL TLGLEPSEEE PPRSPLAPSE 

      1090       1100       1110       1120       1130       1140 
GAGSDVFDGD LAVGVTKGLQ SLSPHDLSPL QRYSEDPTLP LPPETDGYVA PLACSPQPEY 

      1150       1160       1170       1180       1190       1200 
VNQPEVRPQS PLTPEGPPPP IRPAGATLER PKTLSPGKNG VVKDVFAFGG AVENPEYLAP 

      1210       1220       1230       1240       1250 
RAGTASQPHP SPAFSPAFDN LYYWDQNSSE QGPPPSTFEG TPTAENPEYL GLDVPV 

« Hide

References

« Hide 'large scale' references
[1]"Prediction of the coding sequences of mouse homologues of KIAA gene: III. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Nagase T., Ohara O., Koga H.
DNA Res. 10:167-180(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Embryonic tail.
[2]"Differential expression of the erbB2 gene in the periimplantation mouse uterus: potential mediator of signaling by epidermal growth factor-like growth factors."
Lim J., Dey S.K., Das S.K.
Endocrinology 138:1328-1337(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 786-934.
Strain: CD-1.
Tissue: Uterus.
[3]"Synapse-associated expression of an acetylcholine receptor-inducing protein, ARIA/heregulin, and its putative receptors, ErbB2 and ErbB3, in developing mammalian muscle."
Moscoso L.M., Chu G.C., Gautam M., Noakes P.G., Merlie J.P., Sanes J.R.
Dev. Biol. 172:158-169(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1012-1107.
[4]"Direct and specific interaction of c-Src with Neu is involved in signaling by the epidermal growth factor receptor."
Muthuswamy S.K., Muller W.J.
Oncogene 11:271-279(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SRC.
[5]"The ERBB2/HER2 receptor differentially interacts with ERBIN and PICK1 PSD-95/DLG/ZO-1 domain proteins."
Jaulin-Bastard F., Saito H., Le Bivic A., Ollendorff V., Marchetto S., Birnbaum D., Borg J.-P.
J. Biol. Chem. 276:15256-15263(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRKCABP.
[6]"Myocilin mediates myelination in the peripheral nervous system through ErbB2/3 signaling."
Kwon H.S., Johnson T.V., Joe M.K., Abu-Asab M., Zhang J., Chan C.C., Tomarev S.I.
J. Biol. Chem. 288:26357-26371(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MYOC.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK129487 mRNA. Translation: BAC98297.1. Different initiation.
U71126 mRNA. Translation: AAB17380.1.
L47239 mRNA. Translation: AAA93532.1.
RefSeqNP_001003817.1. NM_001003817.1.
UniGeneMm.290822.

3D structure databases

ProteinModelPortalP70424.
SMRP70424. Positions 23-630, 678-1026.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199496. 7 interactions.
IntActP70424. 4 interactions.
MINTMINT-138121.

Chemistry

ChEMBLCHEMBL2311234.

PTM databases

PhosphoSiteP70424.

Proteomic databases

PaxDbP70424.
PRIDEP70424.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000058295; ENSMUSP00000053897; ENSMUSG00000062312.
GeneID13866.
KEGGmmu:13866.
UCSCuc007lgi.1. mouse.

Organism-specific databases

CTD2064.
MGIMGI:95410. Erbb2.
RougeSearch...

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00600000084253.
HOGENOMHOG000230982.
HOVERGENHBG000490.
InParanoidP70424.
KOK05083.
OMAACYPLCA.
OrthoDBEOG7V49XM.
PhylomeDBP70424.
TreeFamTF106002.

Gene expression databases

ArrayExpressP70424.
BgeeP70424.
GenevestigatorP70424.

Family and domain databases

Gene3D3.80.20.20. 2 hits.
InterProIPR000494. EGF_rcpt_L.
IPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt_N_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016245. Tyr_kinase_EGF/ERB/XmrK_rcpt.
[Graphical view]
PfamPF00757. Furin-like. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]
PIRSFPIRSF000619. TyrPK_EGF-R. 1 hit.
PRINTSPR00109. TYRKINASE.
SMARTSM00261. FU. 4 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 2 hits.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio284764.
PROP70424.
SOURCESearch...

Entry information

Entry nameERBB2_MOUSE
AccessionPrimary (citable) accession number: P70424
Secondary accession number(s): Q61525, Q6ZPE0
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: September 27, 2005
Last modified: April 16, 2014
This is version 151 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot