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UniProtKB/Swiss-Prot entry P21860


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name ERBB3_HUMAN
Primary accession number P21860
Secondary accession numbers None
Integrated into Swiss-Prot on May 1, 1991
Sequence was last modified on May 1, 1991 (Sequence version 1)
Annotations were last modified on    November 25, 2008 (Entry version 105)
Name and origin of the protein
Protein name Receptor tyrosine-protein kinase erbB-3 [Precursor]
Synonyms c-erbB3
EC 2.7.10.1
Tyrosine kinase-type cell surface receptor HER3
Gene name
Name: ERBB3
Synonyms: HER3
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
PubMed=2687875 [NCBI, ExPASy, EBI, Israel, Japan]
Kraus M.H., Issing W., Miki T., Popescu N.C., Aaronson S.A.;
"Isolation and characterization of ERBB3, a third member of the ERBB/epidermal growth factor receptor family: evidence for overexpression in a subset of human mammary tumors.";
Proc. Natl. Acad. Sci. U.S.A. 86:9193-9197(1989).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
PubMed=2164210 [NCBI, ExPASy, EBI, Israel, Japan]
Plowman G.D., Whitney G.S., Neubauer M.G., Green J.M., McDonald V.L., Todaro G.J., Shoyab M.;
"Molecular cloning and expression of an additional epidermal growth factor receptor-related gene.";
Proc. Natl. Acad. Sci. U.S.A. 87:4905-4909(1990).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
TISSUE=Placenta;
DOI=10.1006/bbrc.1993.1542; PubMed=7685162 [NCBI, ExPASy, EBI, Israel, Japan]
Katoh M., Yazaki Y., Sugimura T., Terada M.;
"c-erbB3 gene encodes secreted as well as transmembrane receptor tyrosine kinase.";
Biochem. Biophys. Res. Commun. 192:1189-1197(1993).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Skin;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
INTERACTION WITH PA2G4.
DOI=10.1016/S0303-7207(01)00387-2; PubMed=11325528 [NCBI, ExPASy, EBI, Israel, Japan]
Lessor T.J., Hamburger A.W.;
"Regulation of the ErbB3 binding protein Ebp1 by protein kinase C.";
Mol. Cell. Endocrinol. 175:185-191(2001).
[6]
INTERACTION WITH MUC1.
PubMed=12939402 [NCBI, ExPASy, EBI, Israel, Japan]
Li Y., Yu W.-H., Ren J., Chen W., Huang L., Kharbanda S., Loda M., Kufe D.;
"Heregulin targets gamma-catenin to the nucleolus by a mechanism dependent on the DF3/MUC1 oncoprotein.";
Mol. Cancer Res. 1:765-775(2003).
[7]
INTERACTION WITH CSPG5, AND FUNCTION.
DOI=10.1016/j.bbrc.2004.07.066; PubMed=15358134 [NCBI, ExPASy, EBI, Israel, Japan]
Kinugasa Y., Ishiguro H., Tokita Y., Oohira A., Ohmoto H., Higashiyama S.;
"Neuroglycan C, a novel member of the neuregulin family.";
Biochem. Biophys. Res. Commun. 321:1045-1049(2004).
[8]
INVOLVEMENT IN LCCS2.
DOI=10.1086/520770; PubMed=17701904 [NCBI, ExPASy, EBI, Israel, Japan]
Narkis G., Ofir R., Manor E., Landau D., Elbedour K., Birk O.S.;
"Lethal congenital contractural syndrome type 2 (LCCS2) is caused by a mutation in ERBB3 (Her3), a modulator of the phosphatidylinositol-3-kinase/Akt pathway.";
Am. J. Hum. Genet. 81:589-595(2007).
[9]
X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 20-640, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-250; ASN-353; ASN-408; ASN-414; ASN-437; ASN-469; ASN-522 AND ASN-566.
DOI=10.1126/science.1074611; PubMed=12154198 [NCBI, ExPASy, EBI, Israel, Japan]
Cho H.S., Leahy D.J.;
"Structure of the extracellular region of HER3 reveals an interdomain tether.";
Science 297:1330-1333(2002).
[10]
VARIANTS [LARGE SCALE ANALYSIS] TYR-20; LEU-30; MET-104; ILE-204; TRP-683; LEU-717; THR-744; ARG-998; CYS-1119; HIS-1127; ILE-1177 AND LYS-1254.
DOI=10.1038/nature05610; PubMed=17344846 [NCBI, ExPASy, EBI, Israel, Japan]
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
"Patterns of somatic mutation in human cancer genomes.";
Nature 446:153-158(2007).
Comments
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
M29366; AAA35790.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M34309; AAA35979.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
S61953; AAB26935.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC082992; AAH82992.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A36223; A36223.
JH0803; JH0803.
RefSeq NP_001005915.1; -.
NP_001973.2; -.
UniGene Hs.118681
3D structure databases
PDB
1M6B; X-ray; 2.60 A; A/B=20-640.[ExPASy / RCSB / EBI]
PDBsum 1M6B; -.
ModBase P21860.
Protein-protein interaction databases
DIP DIP:511N; -.
DIP:6093N; -.
DIP:94N; -.
IntAct P21860; -.
PTM databases
PhosphoSite P21860; -.
Organism-specific databases
H-InvDB HIX0010715; -.
HGNC HGNC:3431; ERBB3.
GenAtlas ERBB3.
HPA CAB000088; -.
MIM 190151; gene. [NCBI / EBI]
607598; phenotype. [NCBI / EBI]
Orphanet 137776; Lethal congenital contracture syndrome type 2.
PharmGKB PA27846; -.
GeneCards P21860.
Gene expression databases
ArrayExpress P21860; -.
CleanEx HS_ERBB3; -.
GermOnline ENSG00000065361; Homo sapiens.
Ontologies
GO
GO:0016323; Cellular component: basolateral plasma membrane (inferred from direct assay from UniProtKB).
GO:0005615; Cellular component: extracellular space (inferred from direct assay from UniProtKB).
GO:0005887; Cellular component: integral to plasma membrane (traceable author statement from ProtInc).
GO:0043235; Cellular component: receptor complex (inferred from sequence or structural similarity from UniProtKB).
GO:0005524; Molecular function: ATP binding (inferred from electronic annotation from InterPro).
GO:0019838; Molecular function: growth factor binding (inferred from physical interaction from UniProtKB).
GO:0046982; Molecular function: protein heterodimerization activity (inferred from direct assay from UniProtKB).
GO:0042803; Molecular function: protein homodimerization activity (non-traceable author statement from UniProtKB).
GO:0030296; Molecular function: protein tyrosine kinase activator activity (inferred from direct assay from UniProtKB).
GO:0004714; Molecular function: transmembrane receptor protein tyrosine kinase activity (inferred from electronic annotation from InterPro).
GO:0021545; Biological process: cranial nerve development (inferred from sequence or structural similarity from UniProtKB).
GO:0007507; Biological process: heart development (inferred from sequence or structural similarity from UniProtKB).
GO:0007162; Biological process: negative regulation of cell adhesion (inferred from direct assay from UniProtKB).
GO:0043524; Biological process: negative regulation of neuron apoptosis (inferred from sequence or structural similarity from UniProtKB).
GO:0051048; Biological process: negative regulation of secretion (inferred from direct assay from UniProtKB).
GO:0009968; Biological process: negative regulation of signal transduction (inferred from direct assay from UniProtKB).
GO:0014068; Biological process: positive regulation of phosphoinositide 3-kinase cascade (traceable author statement from UniProtKB).
GO:0006468; Biological process: protein amino acid phosphorylation (inferred from electronic annotation from InterPro).
GO:0042127; Biological process: regulation of cell proliferation (inferred from direct assay from UniProtKB).
GO:0014037; Biological process: Schwann cell differentiation (inferred from sequence or structural similarity from UniProtKB).
GO:0007169; Biological process: transmembrane receptor protein tyrosine kinase signaling pathway (inferred from electronic annotation from InterPro).
GO:0042060; Biological process: wound healing (non-traceable author statement from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR000494; EGF_rcpt_L.
IPR006211; Furin-like.
IPR006212; Furin_repeat.
IPR000719; Prot_kinase_core.
IPR017441; Protein_kinase_ATP_bd_CS.
IPR016245; Tyr_kinase_rcpt_EGF/ERB/XmrK.
IPR001245; Tyr_pkinase.
IPR008266; Tyr_pkinase_AS.
Graphical view of domain structure.
Pfam PF00757; Furin-like; 1.
PF07714; Pkinase_Tyr; 1.
PF01030; Recep_L_domain; 2.
Pfam graphical view of domain structure.
PIRSF PIRSF000619; TyrPK_EGF-R; 1.
PRINTS PR00109; TYRKINASE.
ProDom PD000001; Prot_kinase; 1.
[Domain structure / List of seq. sharing at least 1 domain]
SMART SM00261; FU; 5.
SM00219; TyrKc; 1.
SMART graphical view of domain structure.
PROSITE PS00107; PROTEIN_KINASE_ATP; FALSE_NEG.
PS50011; PROTEIN_KINASE_DOM; 1.
PS00109; PROTEIN_KINASE_TYR; FALSE_NEG.
PROSITE graphical view of domain structure (profiles).
ProtoNet P21860.
Genome annotation databases
Ensembl ENSG00000065361; Homo sapiens. [Contig view]
GeneID 2065; -.
KEGG hsa:2065; -.
Phylogenomic databases
HOGENOM P21860; -.
HOVERGEN P21860; -.
Other
NextBio 8391; -.
SOURCE ERBB3; Homo sapiens.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Alternative splicing; ATP-binding; Cell membrane; Glycoprotein; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Receptor; Secreted; Signal; Transferase; Transmembrane; Tyrosine-protein kinase.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom    To Length Description FTId
SIGNAL   1     19  19     Potential. 
CHAIN   20   1342  1323     Receptor tyrosine-protein kinase erbB-3. PRO_0000016672
TOPO_DOM   20    643  624     Extracellular (Potential). 
TRANSMEM   644    664  21     Potential. 
TOPO_DOM   665   1342  678     Cytoplasmic (Potential). 
DOMAIN   709    966  258     Protein kinase. 
NP_BIND   715    723  9     ATP (By similarity). 
ACT_SITE   834    834        Proton acceptor (By similarity). 
BINDING   742    742        ATP (By similarity). 
MOD_RES   1328   1328        Phosphotyrosine (By similarity). 
CARBOHYD   126    126        N-linked (GlcNAc...) (Potential). 
CARBOHYD   250    250        N-linked (GlcNAc...). 
CARBOHYD   353    353        N-linked (GlcNAc...). 
CARBOHYD   408    408        N-linked (GlcNAc...). 
CARBOHYD   414    414        N-linked (GlcNAc...). 
CARBOHYD   437    437        N-linked (GlcNAc...). 
CARBOHYD   469    469        N-linked (GlcNAc...). 
CARBOHYD   522    522        N-linked (GlcNAc...). 
CARBOHYD   566    566        N-linked (GlcNAc...). 
CARBOHYD   616    616        N-linked (GlcNAc...) (Potential). 
DISULFID   29     56         
DISULFID   156    183         
DISULFID   186    194         
DISULFID   190    202         
DISULFID   210    218         
DISULFID   214    226         
DISULFID   227    235         
DISULFID   231    243         
DISULFID   246    255         
DISULFID   259    286         
DISULFID   290    301         
DISULFID   305    320         
DISULFID   323    327         
DISULFID   500    509         
DISULFID   504    517         
DISULFID   520    529         
DISULFID   533    549         
DISULFID   552    565         
DISULFID   556    573         
DISULFID   576    585         
DISULFID   589    610        By similarity. 
DISULFID   613    621        By similarity. 
DISULFID   617    629        By similarity. 
VAR_SEQ   141    183        EILSGGVYIEKNDKLCHMDTIDWRDIVRDRDAEIVVKD NGRSC -> GQFPMVPSGLTPQPAQDWYLLDDDPRLLTLSASSKVPV TLAAV (in isoform 2). VSP_002893
VAR_SEQ   184   1342        Missing (in isoform 2). VSP_002894
VARIANT   20     20  1     S -> Y. VAR_042101 
VARIANT   30     30  1     P -> L. VAR_042102 
VARIANT   104    104  1     V -> M (in an ovarian mucinous carcinoma sample; somatic mutation). VAR_042103 
VARIANT   204    204  1     T -> I. VAR_042104 
VARIANT   683    683  1     R -> W. VAR_042105 
VARIANT   717    717  1     S -> L. VAR_042106 
VARIANT   744    744  1     I -> T. VAR_042107 
VARIANT   998    998  1     K -> R. VAR_042108 
VARIANT   1119   1119  1     S -> C. VAR_042109 
VARIANT   1127   1127  1     R -> H. VAR_042110 
VARIANT   1177   1177  1     L -> I. VAR_042111 
VARIANT   1254   1254  1     T -> K. VAR_042112 
CONFLICT   560    560        E -> G (in Ref. 2; AAA35979). 
CONFLICT   1064   1064        E -> G (in Ref. 2; AAA35979). 
STRAND   58     61  4      
STRAND   63     67  5      
HELIX   75     79  5      
STRAND   82     85  4      
STRAND   87     91  5      
STRAND   95     98  4      
TURN   112    114  3      
STRAND   115    120  6      
STRAND   133    135  3      
STRAND   146    150  5      
TURN   158    160  3      
HELIX   163    166  4      
STRAND   174    178  5      
STRAND   194    198  5      
STRAND   214    216  3      
STRAND   218    222  5      
STRAND   231    233  3      
STRAND   235    239  5      
HELIX   240    242  3      
STRAND   243    251  9      
STRAND   254    258  5      
STRAND   262    265  4      
TURN   267    269  3      
STRAND   270    274  5      
STRAND   280    282  3