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Q60553 (ERBB2_MESAU) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 105. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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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:NEU
OrganismMesocricetus auratus (Golden hamster)
Taxonomic identifier10036 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Cricetidae › Cricetinae › Mesocricetus

Protein attributes

Sequence length1254 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript 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.

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.

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-1196. Interacts with PRKCABP and PLXNB1. Interacts (when phosphorylated on Tyr-1247) with MEMO. Interacts with MUC1. Interacts (when phosphorylated on Tyr-1139) with GRB7 (via SH2 domain). Interacts (when phosphorylated on Tyr-1247) with ERBB2IP. Interacts with SRC, KPNB1, RANBP2, EEA1, CRM1, CLTC, PTK6, RPA94 and ACTB By similarity.

Subcellular location

Cell membrane; Single-pass type I membrane protein By similarity. Cytoplasm › perinuclear region By similarity. Nucleus By similarity.

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 By similarity.

Sequence similarities

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

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCell membrane
Cytoplasm
Membrane
Nucleus
   Coding sequence diversityPolymorphism
   DiseaseProto-oncogene
   DomainSignal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionActivator
Kinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Gene Ontology (GO)
   Biological processpositive regulation of cell growth

Inferred from sequence or structural similarity. Source: UniProtKB

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

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-dependent

Inferred from electronic annotation. Source: UniProtKB-KW

transmembrane receptor protein tyrosine kinase signaling pathway

Inferred from electronic annotation. Source: InterPro

   Cellular componentintegral to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   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 electronic annotation. Source: EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 12541232Receptor tyrosine-protein kinase erbB-2
PRO_0000016670

Regions

Topological domain23 – 652630Extracellular Potential
Transmembrane653 – 67523Helical; Potential
Topological domain676 – 1254579Cytoplasmic Potential
Domain720 – 987268Protein kinase
Nucleotide binding726 – 7349ATP By similarity
Region676 – 68914Nuclear localization signal By similarity
Region676 – 68914Required for interaction with KPNB1 and EEA1 By similarity
Region1195 – 11973Interaction with PIK3C2B By similarity
Compositional bias158 – 368211Cys-rich
Compositional bias472 – 644173Cys-rich

Sites

Active site8451Proton acceptor By similarity
Binding site7531ATP By similarity

Amino acid modifications

Modified residue7351Phosphotyrosine By similarity
Modified residue10541Phosphoserine By similarity
Modified residue11391Phosphotyrosine; by autocatalysis By similarity
Modified residue11961Phosphotyrosine Potential
Modified residue12471Phosphotyrosine; by autocatalysis By similarity
Glycosylation681N-linked (GlcNAc...) Potential
Glycosylation1251N-linked (GlcNAc...) Potential
Glycosylation1871N-linked (GlcNAc...) Potential
Glycosylation2591N-linked (GlcNAc...) Potential
Glycosylation5301N-linked (GlcNAc...) Potential
Glycosylation5711N-linked (GlcNAc...) Potential
Glycosylation6291N-linked (GlcNAc...) Potential
Disulfide bond26 ↔ 53 By similarity
Disulfide bond162 ↔ 192 By similarity
Disulfide bond195 ↔ 204 By similarity
Disulfide bond199 ↔ 212 By similarity
Disulfide bond236 ↔ 244 By similarity
Disulfide bond240 ↔ 252 By similarity
Disulfide bond255 ↔ 264 By similarity
Disulfide bond268 ↔ 295 By similarity
Disulfide bond299 ↔ 311 By similarity
Disulfide bond315 ↔ 331 By similarity
Disulfide bond334 ↔ 338 By similarity
Disulfide bond342 ↔ 367 By similarity
Disulfide bond475 ↔ 504 By similarity
Disulfide bond511 ↔ 520 By similarity
Disulfide bond515 ↔ 528 By similarity
Disulfide bond531 ↔ 540 By similarity
Disulfide bond544 ↔ 560 By similarity
Disulfide bond563 ↔ 576 By similarity
Disulfide bond567 ↔ 584 By similarity
Disulfide bond587 ↔ 596 By similarity
Disulfide bond600 ↔ 623 By similarity
Disulfide bond626 ↔ 634 By similarity
Disulfide bond630 ↔ 642 By similarity

Natural variations

Natural variant6581V → E in oncogenic NEU. Ref.1
Natural variant6591V → E in oncogenic NEU. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q60553 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 974C3791C21F2BE1

FASTA1,254138,253
        10         20         30         40         50         60 
MELAAWCGWG LLLALLSPGA SGTQVCTGTD MKLRLPASPE THLDIVRHLY QGCQVVQGNL 

        70         80         90        100        110        120 
ELTYLPANAT LSFLQDIQEV QGYMLIAHSQ VRHVPLQRLR IVRGTQLFED KYALAVLDNR 

       130        140        150        160        170        180 
DPLDNVTTAT GRTPEGLREL QLRSLTEILK GGVLIRGNPQ LCYQDTVLWK DVFRKNNQLA 

       190        200        210        220        230        240 
PVDIDTNRSR ACPPCAPACK DNHCWGASPE DCQTLTGTIA PRAVPAARAR LPTDCCHEQC 

       250        260        270        280        290        300 
AAGCTGPKHS DCLACLHFNH SGICELHCPA LVTYNTDTFE SMPNPEGRYT FGASCVTTCP 

       310        320        330        340        350        360 
YNYLSTEVGS CTLVCPLNNQ EVTAEDGTQR CEKCSKSCAR VCYGLGMEHL RGARAITSAN 

       370        380        390        400        410        420 
IQEFAGCKKI FGSLAFLPES FDGNPSSGIA PLTPEQLQVF ETLEEITGYL YISAWPDSLH 

       430        440        450        460        470        480 
DLSVFQNLRV IRGRVLHDGA YSLALQGLGI RWLGLRSLRE LGSGLVLIHR NTHLCFVHTV 

       490        500        510        520        530        540 
PWDQLFRNPH QALLHSGNPS EEECGLKDFA CYPLCAHGHC WGPGPTQCVN CSHFLRGQEC 

       550        560        570        580        590        600 
VKECRVWKGL PREYVNGKHC LPCHPECQPQ NSTETCTGSE ADQCTACPHY KDSPFCVARC 

       610        620        630        640        650        660 
PSGVKPDLSY MPIWKYPDEE GMCQPCPINC THSCVDLDER GCPAEQRASP ATSIIATVVG 

       670        680        690        700        710        720 
ILLFLVIGVV VGILIKRRRQ KIRKYTMRRL LQETELVEPL TPSGAMPNQA QMRILKETEL 

       730        740        750        760        770        780 
RKVKVLGSGA FGTVYKGIWI PDGENVKIPV AIKVLRENTS PKANKEILDE AYVMAGLGSP 

       790        800        810        820        830        840 
YVSRLLGICL TSTVQLVTQL MPYGCLLDHV REHRGRLGSQ DLLNWCVQIA KGMSYLEDVR 

       850        860        870        880        890        900 
LVHRDLAARN VLVKSPNHVK ITDFGLARLL DIDETEYHAD GGKVPIKWIA LESILRRRFT 

       910        920        930        940        950        960 
HQSDVWSYGV TVWELMTFGA KPYDGIPARE IPDLLEKGER LPQPPICTID VYMIMVKCWM 

       970        980        990       1000       1010       1020 
IDSECRPRFR ELVSEFSRMA RDPQRFVVIQ NEDLGPSSPL DSTFYRSLLE DDDMGDLVDA 

      1030       1040       1050       1060       1070       1080 
EEYLVPQQGF FFPDPAPGAG STAHRRHRSS STRSGGGELT LGMEPSGEEP PRSPLAPSEG 

      1090       1100       1110       1120       1130       1140 
AGSDVFEGEL GMGATKGPQS ISPRDLSPLQ RYSEDPTLPL PTETDGYVAP LACSPQPEYV 

      1150       1160       1170       1180       1190       1200 
NQPEVRPQPP LTPEGPLPPV RPAGATLERP KTLSPGKNGV VKDVFTFGGA VENPEYLVPR 

      1210       1220       1230       1240       1250 
GGSASQPHPP ALCPAFDNLY YWDQDPSERG SPPNTFEGTP TAENPEYLGL DVPV

« Hide

References

[1]"Cloning and activation of the Syrian hamster neu proto-oncogene."
Nakamura T., Ushijima T., Ishizaka Y., Nagao M., Arai M., Yamazaki Y., Ishikawa T.
Gene 140:251-255(1994) [PubMed: 7908275] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ONCOGENIC GLU-658 AND GLU-659.
Tissue: Nerve.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		D16295 mRNA. Translation: BAA03801.1.
PIRI48161.

3D structure databases

ProteinModelPortalQ60553.
SMRQ60553. Positions 23-629, 641-1025.
ModBaseSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Phylogenomic databases

HOVERGENHBG000490.

Enzyme and pathway databases

BRENDA2.7.10.1. 3239.

Family and domain databases

InterProIPR021157. Cyt_c1_TM_anchor_C.
IPR000494. EGF_rcpt_L.
IPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016245. Tyr_kinase_EGF/ERB/XmrK_rcpt.
[Graphical view]
Gene3DG3DSA:1.20.5.100. Cyt_c1_TM_anchor_C. 1 hit.
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]
SUPFAMSSF57184. Grow_fac_recept. 2 hits.
SSF56112. Kinase_like. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameERBB2_MESAU
AccessionPrimary (citable) accession number: Q60553
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: November 1, 1996
Last modified: January 25, 2012
This is version 105 of the entry and version 1 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

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents