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Reviewed, UniProtKB/Swiss-Prot P70424 (ERBB2_MOUSE)

Last modified November 3, 2009. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Receptor tyrosine-protein kinase erbB-2
    EC=2.7.10.1
Alternative name(s):
    p185erbB2
    C-erbB-2
    NEU proto-oncogene
    CD_antigen=CD340
Gene names
Name: Erbb2
Synonyms: Kiaa3023, Neu
OrganismMus musculus (Mouse)
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMus

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

Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Not activated by EGF, TGF-alpha and amphiregulin.

Catalytic activity

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

Subunit structure

Heterodimer with each of the other ERBB receptors Potential. Interacts with PRKCABP and PLXNB1. Part of a complex with EGFR and either PIK3C2A or PIK3C2B. May interact with PIK3C2B when phosphorylated on Tyr-1197 By similarity. Interacts with MEMO when phosphorylated on Tyr-1249 By similarity. Interacts with MUC1 By similarity.

Subcellular location

Membrane; Single-pass type I membrane protein.

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

Ligand-binding increases phosphorylation on tyrosine residues By similarity.

Sequence similarities

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

Contains 1 protein kinase domain.

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 – 67421 Potential
Topological domain675 – 1256582Cytoplasmic Potential
Domain721 – 988268Protein kinase
Nucleotide binding727 – 7359ATP 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 residue7361Phosphotyrosine By similarity
Modified residue10551Phosphoserine 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 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 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
P70424-1 [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: 14621295] [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: 9048643] [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: 7589796] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1012-1107.
[4]"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: 11278603] [Abstract]
Cited for: INTERACTION WITH PRKCABP.
[5]"Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks."
Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M.
Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007) [PubMed: 17389395] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1249, MASS SPECTROMETRY.
+Additional computationally mapped references.

Cross-references

Sequence databases

AK129487 mRNA. Translation: BAC98297.1. Different initiation.
U71126 mRNA. Translation: AAB17380.1.
L47239 mRNA. Translation: AAA93532.1.
IPIIPI00626433.
RefSeqNP_001003817.1.
UniGeneMm.290822
Mm.406337

3D structure databases

HSSPHSSP built from PDB template 1M14 based on UniProtKB Q9H2C9.
SMRP70424. Positions 23-630, 705-1027.
ModBaseSearch...

Protein-protein interaction databases

STRINGP70424.

PTM databases

PhosphoSiteP70424.

Proteomic databases

PRIDEP70424.

Genome annotation databases

EnsemblENSMUST00000058295; ENSMUSP00000053897; ENSMUSG00000062312; Mus musculus. [Genome view]
GeneID13866.
KEGGmmu:13866.
UCSCuc007lgi.1. mouse.

Organism-specific databases

CTD13866.
MGIMGI:95410. Erbb2.
RougeSearch...

Phylogenomic databases

HOGENOMP70424.
HOVERGENP70424.
OMAACYPLCA.

Enzyme and pathway databases

BRENDA2.7.10.1. 244.

Gene expression databases

ArrayExpressP70424.
BgeeP70424.
GenevestigatorP70424.
GermOnlineENSMUSG00000062312. Mus musculus.

Family and domain databases

InterProIPR000494. EGF_rcpt_L.
IPR006211. Furin-like.
IPR006212. Furin_repeat.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR016245. Tyr_kinase_rcpt_EGF/ERB/XmrK.
IPR001245. Tyr_pkinase.
IPR008266. Tyr_pkinase_AS.
IPR004019. YLP_motif.
[Graphical view]
PfamPF00757. Furin-like. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
PF02757. YLP. 2 hits.
[Graphical view]
PIRSFPIRSF000619. TyrPK_EGF-R. 1 hit.
PRINTSPR00109. TYRKINASE.
ProDomPD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00261. FU. 4 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio284764.
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: November 3, 2009
This is version 102 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

MGD cross-references

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

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents