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P06494 (ERBB2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 157. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·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):
Epidermal growth factor receptor-related protein
Proto-oncogene Neu
Proto-oncogene c-ErbB-2
p185erbB2
p185neu
CD_antigen=CD340
Gene names
Name:Erbb2
Synonyms:Neu
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1257 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.5

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.5

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-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 ERBB2IP Interacts with SRC, KPNB1, RANBP2, EEA1, CRM1, CLTC, PTK6, RPA94, MYOC and ACTB By similarity.

Subcellular location

Cell membrane; Single-pass type I membrane protein By similarity. Cytoplasmperinuclear region By similarity. Nucleus Ref.5.

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-1250 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 AAH61863.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence CAA27059.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCell membrane
Cytoplasm
Membrane
Nucleus
   Coding sequence diversityPolymorphism
   DiseaseProto-oncogene
   DomainSignal
Transmembrane
Transmembrane helix
   LigandATP-binding
DNA-binding
Nucleotide-binding
   Molecular functionActivator
Kinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcentral nervous system development

Traceable author statement PubMed 12853432. Source: RGD

estrus

Inferred from mutant phenotype PubMed 11956173. Source: RGD

glial cell differentiation

Inferred from genetic interaction PubMed 12853432. Source: RGD

liver development

Inferred from expression pattern PubMed 12454858. Source: RGD

mammary gland involution

Inferred from expression pattern PubMed 10653587. Source: RGD

negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 12673197. Source: RGD

peptidyl-tyrosine phosphorylation

Inferred from direct assay PubMed 1359541. Source: GOC

peripheral nervous system development

Inferred from mutant phenotype PubMed 15496447. Source: RGD

positive regulation of MAPK cascade

Inferred from mutant phenotype PubMed 16168116. Source: RGD

positive regulation of Ras protein signal transduction

Inferred from mutant phenotype PubMed 12673197. Source: RGD

positive regulation of cell growth

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 9271418. Source: RGD

positive regulation of phosphatidylinositol 3-kinase signaling

Inferred from mutant phenotype PubMed 16168116. Source: RGD

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 direct assay PubMed 1359541. Source: RGD

regulation of ERK1 and ERK2 cascade

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell differentiation

Traceable author statement Ref.7. Source: RGD

regulation of cell proliferation

Traceable author statement Ref.7. Source: RGD

regulation of microtubule-based process

Inferred from sequence or structural similarity. Source: UniProtKB

response to axon injury

Inferred from direct assay PubMed 15800203. Source: RGD

response to drug

Inferred from expression pattern PubMed 18184445. Source: RGD

response to progesterone

Inferred from expression pattern PubMed 17459743. Source: RGD

skeletal muscle tissue development

Inferred from expression pattern PubMed 8846777. Source: RGD

sympathetic nervous system development

Inferred from mutant phenotype PubMed 15496447. Source: RGD

tongue development

Inferred from expression pattern PubMed 10908606. Source: RGD

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transmembrane receptor protein tyrosine kinase signaling pathway

Inferred from electronic annotation. Source: InterPro

   Cellular_componentapical plasma membrane

Inferred from direct assay PubMed 15499570. Source: RGD

basal plasma membrane

Inferred from direct assay PubMed 15499570. Source: RGD

basolateral plasma membrane

Inferred from direct assay PubMed 15499570. Source: RGD

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

lateral loop

Inferred from direct assay PubMed 15800203. Source: RGD

membrane raft

Inferred from direct assay PubMed 18199961. Source: RGD

microvillus

Inferred from direct assay PubMed 15800203. Source: RGD

nucleus

Inferred from direct assay PubMed 17553674. Source: RGD

perinuclear region of cytoplasm

Inferred from direct assay PubMed 15800203. Source: RGD

plasma membrane

Traceable author statement. Source: Reactome

postsynaptic membrane

Inferred from direct assay PubMed 7589796. Source: RGD

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

DNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

Hsp90 protein binding

Inferred from physical interaction PubMed 15671027. Source: RGD

RNA polymerase I core binding

Inferred from sequence or structural similarity. Source: UniProtKB

glycoprotein binding

Inferred from physical interaction PubMed 15499570. Source: RGD

protein heterodimerization activity

Inferred from physical interaction PubMed 16168116PubMed 16769812. Source: RGD

protein tyrosine kinase activity

Inferred from direct assay PubMed 1359541. Source: RGD

receptor signaling protein tyrosine kinase activity

Inferred from electronic annotation. Source: InterPro

transmembrane receptor protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

ubiquitin protein ligase binding

Inferred from physical interaction PubMed 15671027. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 12571235Receptor tyrosine-protein kinase erbB-2
PRO_0000016671

Regions

Topological domain23 – 654632Extracellular Potential
Transmembrane655 – 67723Helical; Potential
Topological domain678 – 1257580Cytoplasmic Potential
Domain722 – 989268Protein kinase
Nucleotide binding728 – 7369ATP By similarity
Region678 – 69114Nuclear localization signal By similarity
Region678 – 69114Required for interaction with KPNB1 and EEA1 By similarity
Region1197 – 11993Interaction with PIK3C2B By similarity
Compositional bias159 – 369211Cys-rich
Compositional bias473 – 646174Cys-rich

Sites

Active site8471Proton acceptor By similarity
Binding site7551ATP By similarity

Amino acid modifications

Modified residue10561Phosphoserine By similarity
Modified residue11091Phosphoserine By similarity
Modified residue11411Phosphotyrosine; by autocatalysis By similarity
Modified residue11981Phosphotyrosine Potential
Modified residue12501Phosphotyrosine; by autocatalysis By similarity
Glycosylation681N-linked (GlcNAc...) Potential
Glycosylation1881N-linked (GlcNAc...) Potential
Glycosylation2601N-linked (GlcNAc...) Ref.7
Glycosylation5321N-linked (GlcNAc...) Potential
Glycosylation5731N-linked (GlcNAc...) Potential
Glycosylation6311N-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 ↔ 506 By similarity
Disulfide bond513 ↔ 522 By similarity
Disulfide bond517 ↔ 530 By similarity
Disulfide bond533 ↔ 542 By similarity
Disulfide bond546 ↔ 562 By similarity
Disulfide bond565 ↔ 578 By similarity
Disulfide bond569 ↔ 586 By similarity
Disulfide bond589 ↔ 598 By similarity
Disulfide bond602 ↔ 625 By similarity
Disulfide bond628 ↔ 636 By similarity
Disulfide bond632 ↔ 644 By similarity

Natural variations

Natural variant6611V → E in oncogenic NEU.

Experimental info

Sequence conflict1451S → G in AAH61863. Ref.2
Sequence conflict505 – 5095LCVSS → CGLE in AAH61863. Ref.2

Secondary structure

............................................................................................................... 1257
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P06494 [UniParc].

Last modified December 15, 1998. Version 3.
Checksum: 6129264583011402

FASTA1,257138,832
        10         20         30         40         50         60 
MELAAWCRWG FLLALLPPGI AGTQVCTGTD MKLRLPASPE THLDMLRHLY QGCQVVQGNL 

        70         80         90        100        110        120 
ELTYVPANAS LSFLQDIQEV QGYMLIAHNQ VKRVPLQRLR IVRGTQLFED KYALAVLDNR 

       130        140        150        160        170        180 
DPQDNVAAST PGRTPEGLRE LQLRSLTEIL KGGVLIRGNP QLCYQDMVLW KDVFRKNNQL 

       190        200        210        220        230        240 
APVDIDTNRS RACPPCAPAC KDNHCWGESP EDCQILTGTI CTSGCARCKG RLPTDCCHEQ 

       250        260        270        280        290        300 
CAAGCTGPKH SDCLACLHFN HSGICELHCP ALVTYNTDTF ESMHNPEGRY TFGASCVTTC 

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

       370        380        390        400        410        420 
NVQEFDGCKK IFGSLAFLPE SFDGDPSSGI APLRPEQLQV FETLEEITGY LYISAWPDSL 

       430        440        450        460        470        480 
RDLSVFQNLR IIRGRILHDG AYSLTLQGLG IHSLGLRSLR ELGSGLALIH RNAHLCFVHT 

       490        500        510        520        530        540 
VPWDQLFRNP HQALLHSGNR PEEDLCVSSG LVCNSLCAHG HCWGPGPTQC VNCSHFLRGQ 

       550        560        570        580        590        600 
ECVEECRVWK GLPREYVSDK RCLPCHPECQ PQNSSETCFG SEADQCAACA HYKDSSSCVA 

       610        620        630        640        650        660 
RCPSGVKPDL SYMPIWKYPD EEGICQPCPI NCTHSCVDLD ERGCPAEQRA SPVTFIIATV 

       670        680        690        700        710        720 
VGVLLFLILV VVVGILIKRR RQKIRKYTMR RLLQETELVE PLTPSGAMPN QAQMRILKET 

       730        740        750        760        770        780 
ELRKVKVLGS GAFGTVYKGI WIPDGENVKI PVAIKVLREN TSPKANKEIL DEAYVMAGVG 

       790        800        810        820        830        840 
SPYVSRLLGI CLTSTVQLVT QLMPYGCLLD HVREHRGRLG SQDLLNWCVQ IAKGMSYLED 

       850        860        870        880        890        900 
VRLVHRDLAA RNVLVKSPNH VKITDFGLAR LLDIDETEYH ADGGKVPIKW MALESILRRR 

       910        920        930        940        950        960 
FTHQSDVWSY GVTVWELMTF GAKPYDGIPA REIPDLLEKG ERLPQPPICT IDVYMIMVKC 

       970        980        990       1000       1010       1020 
WMIDSECRPR FRELVSEFSR MARDPQRFVV IQNEDLGPSS PMDSTFYRSL LEDDDMGDLV 

      1030       1040       1050       1060       1070       1080 
DAEEYLVPQQ GFFSPDPTPG TGSTAHRRHR SSSTRSGGGE LTLGLEPSEE GPPRSPLAPS 

      1090       1100       1110       1120       1130       1140 
EGAGSDVFDG DLAMGVTKGL QSLSPHDLSP LQRYSEDPTL PLPPETDGYV APLACSPQPE 

      1150       1160       1170       1180       1190       1200 
YVNQSEVQPQ PPLTPEGPLP PVRPAGATLE RPKTLSPGKN GVVKDVFAFG GAVENPEYLV 

      1210       1220       1230       1240       1250 
PREGTASPPH PSPAFSPAFD NLYYWDQNSS EQGPPPSNFE GTPTAENPEY LGLDVPV 

« Hide

References

« Hide 'large scale' references
[1]"The neu oncogene encodes an epidermal growth factor receptor-related protein."
Bargmann C.I., Hung M.-C., Weinberg R.A.
Nature 319:226-230(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Neuroblastoma.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Prostate.
[3]"Direct DNA sequencing of the rat neu oncogene transmembrane domain reveals no mutation in urinary bladder carcinomas induced by N-butyl-N-(4-hydroxybutyl)nitrosamine, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide or N-methyl-N-nitrosourea."
Masui T., Mann A.M., Macatee T.L., Garland E.M., Okamura T., Smith R.A., Cohen S.M.
Carcinogenesis 12:1975-1978(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 634-699.
[4]"An extended family of protein-tyrosine kinase genes differentially expressed in the vertebrate nervous system."
Lai C., Lemke G.
Neuron 6:691-704(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 852-905.
Tissue: Sciatic nerve.
[5]"Nuclear localization of p185neu tyrosine kinase and its association with transcriptional transactivation."
Xie Y., Hung M.C.
Biochem. Biophys. Res. Commun. 203:1589-1598(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[6]"Three dimensional structure of the transmembrane region of the proto-oncogenic and oncogenic forms of the neu protein."
Gullick W.J., Bottomley A.C., Lofts F.J., Doak D.G., Mulvey D., Newman R., Crumpton M.J., Sternberg M.J.E., Campbell I.D.
EMBO J. 11:43-48(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 650-668.
[7]"Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab."
Cho H.-S., Mason K., Ramyar K.X., Stanley A.M., Gabelli S.B., Denney D.W. Jr., Leahy D.J.
Nature 421:756-760(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 23-631 IN COMPLEX WITH THE ANTIBODY HERCEPTIN, DISULFIDE BONDS, GLYCOSYLATION AT ASN-260.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X03362 mRNA. Translation: CAA27059.1. Different initiation.
BC061863 mRNA. Translation: AAH61863.1. Different initiation.
PIRTVRTNU. A24562.
UniGeneRn.93966.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1IIJNMR-A647-681[»]
1N8YX-ray2.40C23-631[»]
2J1Hmodel-A/B649-681[»]
ProteinModelPortalP06494.
SMRP06494. Positions 23-631, 647-1027.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-132326.

Chemistry

BindingDBP06494.
ChEMBLCHEMBL3848.

PTM databases

PhosphoSiteP06494.

Proteomic databases

PaxDbP06494.
PRIDEP06494.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

UCSCRGD:2561. rat.

Organism-specific databases

RGD2561. Erbb2.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000230982.
HOVERGENHBG000490.
PhylomeDBP06494.

Enzyme and pathway databases

BRENDA2.7.10.1. 5301.

Gene expression databases

GenevestigatorP06494.

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

EvolutionaryTraceP06494.
PROP06494.

Entry information

Entry nameERBB2_RAT
AccessionPrimary (citable) accession number: P06494
Secondary accession number(s): Q6P732
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: December 15, 1998
Last modified: April 16, 2014
This is version 157 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references