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O18735 (ERBB2_CANFA) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 97. 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 c-ErbB-2
p185erbB2
CD_antigen=CD340
Gene names
Name:ERBB2
OrganismCanis familiaris (Dog) (Canis lupus familiaris)
Taxonomic identifier9615 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis

Protein attributes

Sequence length1259 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-1200. Interacts with PRKCABP and PLXNB1. Interacts (when phosphorylated on Tyr-1252) with MEMO1. Interacts with MUC1. Interacts (when phosphorylated on Tyr-1138) with GRB7 (via SH2 domain). Interacts (when phosphorylated on Tyr-1252) with ERBB2IP. Interacts with SRC, KPNB1, PTK6, RANBP2, EEA1, CRM1, CLTC, 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
   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 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

   Cellular componentintegral to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

perinuclear region of cytoplasm

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 – 12591237Receptor tyrosine-protein kinase erbB-2
PRO_0000016668

Regions

Topological domain23 – 653631Extracellular Potential
Transmembrane654 – 67421Helical; Potential
Topological domain675 – 1259585Cytoplasmic Potential
Domain719 – 986268Protein kinase
Nucleotide binding725 – 7339ATP By similarity
Region675 – 68814Nuclear localization signal By similarity
Region675 – 68814Required for interaction with KPNB1 and EEA1 By similarity
Region1199 – 12013Interaction with PIK3C2B By similarity
Compositional bias192 – 26877Cys-rich
Compositional bias1101 – 1219119Pro-rich

Sites

Active site8441Proton acceptor By similarity
Binding site7521ATP By similarity

Amino acid modifications

Modified residue7341Phosphotyrosine By similarity
Modified residue11381Phosphotyrosine; by autocatalysis By similarity
Modified residue12001Phosphotyrosine Potential
Modified residue12521Phosphotyrosine; by autocatalysis By similarity
Glycosylation681N-linked (GlcNAc...) Potential
Glycosylation2591N-linked (GlcNAc...) Potential
Glycosylation4211N-linked (GlcNAc...) Potential
Glycosylation5291N-linked (GlcNAc...) Potential
Glycosylation5701N-linked (GlcNAc...) Potential
Glycosylation6281N-linked (GlcNAc...) Potential
Disulfide bond26 ↔ 53 By similarity
Disulfide bond162 ↔ 192 By similarity
Disulfide bond195 ↔ 204 By similarity
Disulfide bond199 ↔ 212 By similarity
Disulfide bond220 ↔ 227 By similarity
Disulfide bond224 ↔ 235 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 ↔ 519 By similarity
Disulfide bond514 ↔ 527 By similarity
Disulfide bond530 ↔ 539 By similarity
Disulfide bond543 ↔ 559 By similarity
Disulfide bond562 ↔ 575 By similarity
Disulfide bond566 ↔ 583 By similarity
Disulfide bond586 ↔ 595 By similarity
Disulfide bond599 ↔ 622 By similarity
Disulfide bond625 ↔ 633 By similarity
Disulfide bond629 ↔ 641 By similarity

Sequences

Sequence LengthMass (Da)Tools
O18735 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: E37364D49C4ACD46

FASTA1,259137,991
        10         20         30         40         50         60 
MELAAWCRWG LLLALLPSGA AGTQVCTGTD MKLRLPASPE THLDMLRHLY QGCQVVQGNL 

        70         80         90        100        110        120 
ELTYLPANAS LSFLQDIQEV QGYVLIAHSQ VRQIPLQRLR IVRGTQLFED NYALAVLDNG 

       130        140        150        160        170        180 
DPLEGGIPAP GAAQGGLREL QLRSLTEILK GGVLIQRSPQ LCHQDTILWK DVFHKNNQLA 

       190        200        210        220        230        240 
LTLIDTNRFS ACPPCSPACK DAHCWGASSG DCQSLTRTVC AGGCARCKGP QPTDCCHEQC 

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

       310        320        330        340        350        360 
YNYLSTDVGS CTLVCPLNNQ EVTAEDGTQR CEKCSKPCAR VCYGLGMEHL REVRAVTSAN 

       370        380        390        400        410        420 
IQEFAGCKKI FGSLAFLPES FDGDPASNTA PLQPEQLRVF EALEEITGYL YISAWPDSLP 

       430        440        450        460        470        480 
NLSVFQNLRV IRGRVLHDGA YSLTLQGLGI SWLGLRSLRE LGSGLALIHR NARLCFVHTV 

       490        500        510        520        530        540 
PWDQLFRNPH QALLHSANRP EEECVGEGLA CYPCAHGHCW GPGPTQCVNC SQFLRGQECV 

       550        560        570        580        590        600 
EECRVLQGLP REYVKDRYCL PCHSECQPQN GSVTCFGSEA DQCVACAHYK DPPFCVARCP 

       610        620        630        640        650        660 
SGVKPDLSFM PIWKFADEEG TCQPCPINCT HSCADLDEKG CPAEQRASPV TSIIAAVVGI 

       670        680        690        700        710        720 
LLAVVVGLVL GILIKRRRQK IRKYTMRRLL QETELVEPLT PSGAMPNQAQ MRILKETELR 

       730        740        750        760        770        780 
KVKVLGSGAF GTVYKGIWIP DGENVKIPVA IKVLRENTSP KANKEILDEA YVMAGVGSPY 

       790        800        810        820        830        840 
VSRLLGICLT STVQLVTQLM PYGCLLDHVR EHRGRLGSQD LLNWCVQIAK GMSYLEDVRL 

       850        860        870        880        890        900 
VHRDLAARNV LVKSPNHVKI TDFGLARLLD IDETEYHADG GKVPIKWMAL ESIPPRRFTH 

       910        920        930        940        950        960 
QSDVWSYGVT VWELMTFGAK PYDGIPAREI PDLLEKGERL PQPPICTIDV YMIMVKCWMI 

       970        980        990       1000       1010       1020 
DSECRPRFRE LVAEFSRMAR DPQRFVVIQN EDLGPASPLD STFYRSLLED DDMGDLVDAE 

      1030       1040       1050       1060       1070       1080 
EYLVPQQGFF CPEPTPGAGG TAHRRHRSSS TRNGGGELTL GLEPSEEEPP KSPLAPSEGA 

      1090       1100       1110       1120       1130       1140 
GSDVFDGDLG MGAAKGLQSL PSQDPSPLQR YSEDPTVPLP PETDGKVAPL TCSPQPEYVN 

      1150       1160       1170       1180       1190       1200 
QPEVWPQPPL ALEGPLPPSR PAGATLERPK TLSPKTLSPG KNGVVKDVFA FGSAVENPEY 

      1210       1220       1230       1240       1250 
LAPRGRAAPQ PHPPPAFSPA FDNLYYWDQD PSERGSPPST FEGTPTAENP EYLGLDVPV

« Hide

References

[1]"cDNA cloning of erbB-2 from canine mammary gland."
Yokota H.
Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Mammary gland.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AB008451 mRNA. Translation: BAA23127.1.
RefSeqNP_001003217.1. NM_001003217.1.
UniGeneCfa.3747.

3D structure databases

ProteinModelPortalO18735.
SMRO18735. Positions 23-628, 640-1024.
ModBaseSearch...

Protein-protein interaction databases

STRINGO18735.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID403883.
KEGGcfa:403883.

Organism-specific databases

CTD2064.

Phylogenomic databases

eggNOGmaNOG16118.
GeneTreeENSGT00600000084253.
HOVERGENHBG000490.
InParanoidO18735.
OrthoDBEOG461434.

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.
KOK05083.
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. 3 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_CANFA
AccessionPrimary (citable) accession number: O18735
Entry history
Integrated into UniProtKB/Swiss-Prot: September 27, 2004
Last sequence update: January 1, 1998
Last modified: January 25, 2012
This is version 97 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

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