ERBB3

V-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian)
PDB rendering based on 1m6b.
Available structures PDB 1M6B, 3KEX, 3LMG
Identifiers
Symbols	ERBB3; ErbB-3; HER3; LCCS2; MDA-BF-1; MGC88033; c-erbB-3; c-erbB3; erbB3-S; p180-ErbB3; p45-sErbB3; p85-sErbB3
External IDs	OMIM: 190151 MGI: 95411 HomoloGene: 20457 GeneCards: ERBB3 Gene
EC number	2.7.10.1
Gene Ontology Molecular function • nucleotide binding • protein tyrosine kinase activity • transmembrane receptor protein tyrosine kinase activity • receptor signaling protein tyrosine kinase activity • transmembrane receptor activity • protein binding • ATP binding • growth factor binding • growth factor binding • protein tyrosine kinase activator activity • protein homodimerization activity • protein heterodimerization activity • protein heterodimerization activity Cellular component • extracellular region • extracellular space • nucleus • plasma membrane • integral to plasma membrane • basolateral plasma membrane • apical plasma membrane • lateral plasma membrane • receptor complex • postsynaptic membrane Biological process • negative regulation of cell adhesion • signal transduction • transmembrane receptor protein tyrosine kinase signaling pathway • axonogenesis • peripheral nervous system development • heart development • skeletal muscle tissue development • circadian rhythm • negative regulation of signal transduction • Schwann cell differentiation • phosphatidylinositol 3-kinase cascade • positive regulation of phosphatidylinositol 3-kinase cascade • cranial nerve development • cellular response to insulin stimulus • wound healing • regulation of cell proliferation • odontogenesis • response to drug • negative regulation of neuron apoptosis • tongue development • positive regulation of glucose import • negative regulation of secretion • neuron apoptosis • mammary gland involution • positive regulation of protein tyrosine kinase activity Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2065	13867
Ensembl	ENSG00000065361	ENSMUSG00000018166
UniProt	P21860	O88458
RefSeq (mRNA)	NM_001005915.1	NM_010153.1
RefSeq (protein)	NP_001005915.1	NP_034283.1
Location (UCSC)	Chr 12: 56.47 – 56.5 Mb	Chr 10: 128 – 128.03 Mb
PubMed search	[1]	[2]

Receptor tyrosine-protein kinase erbB-3 is an enzyme that in humans is encoded by the ERBB3 gene.

This gene encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers, including prostate, bladder, and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. One isoform lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported, but they have not been thoroughly characterized.^[1]

It is thought that ERBB3, when activated, becomes a substrate for dimerization and subsequent phosphorylation by ERBB1, ERBB2 and ERBB4.

Like many of the receptor tyrosine-kinases, ERBB3 is activated by extracellular ligand. Ligands known to bind to ERBB3 include heregulin.

Interactions

ERBB3 has been shown to interact with Neuregulin 1,^[2][3][4] PA2G4,^[5][6] PIK3R1^[7][8] and RGS4.^[9]

See also

• Epidermal growth factor receptor family
• Epidermal growth factor receptor
• Receptor tyrosine-kinases

References

1. ^ "Entrez Gene: ERBB3 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2065. 
2. ^ Singer, E; Landgraf R, Horan T, Slamon D, Eisenberg D (Nov. 2001). "Identification of a heregulin binding site in HER3 extracellular domain". J. Biol. Chem. (United States) 276 (47): 44266–74. doi:10.1074/jbc.M105428200. ISSN 0021-9258. PMID 11555649. 
3. ^ Horan, T; Wen J, Arakawa T, Liu N, Brankow D, Hu S, Ratzkin B, Philo J S (Oct. 1995). "Binding of Neu differentiation factor with the extracellular domain of Her2 and Her3". J. Biol. Chem. (UNITED STATES) 270 (41): 24604–8. doi:10.1074/jbc.270.41.24604. ISSN 0021-9258. PMID 7592681. 
4. ^ Carraway, K L; Weber J L, Unger M J, Ledesma J, Yu N, Gassmann M, Lai C (May. 1997). "Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases". Nature (ENGLAND) 387 (6632): 512–6. doi:10.1038/387512a0. ISSN 0028-0836. PMID 9168115. 
5. ^ Lessor, T J; Hamburger A W (Apr. 2001). "Regulation of the ErbB3 binding protein Ebp1 by protein kinase C". Mol. Cell. Endocrinol. (Ireland) 175 (1–2): 185–91. doi:10.1016/S0303-7207(01)00387-2. ISSN 0303-7207. PMID 11325528. 
6. ^ Yoo, J Y; Wang X W, Rishi A K, Lessor T, Xia X M, Gustafson T A, Hamburger A W (Feb. 2000). "Interaction of the PA2G4 (EBP1) protein with ErbB-3 and regulation of this binding by heregulin". Br. J. Cancer (SCOTLAND) 82 (3): 683–90. doi:10.1054/bjoc.1999.0981. ISSN 0007-0920. PMC 2363329. PMID 10682683. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2363329. 
7. ^ Hellyer, N J; Kim M S, Koland J G (Nov. 2001). "Heregulin-dependent activation of phosphoinositide 3-kinase and Akt via the ErbB2/ErbB3 co-receptor". J. Biol. Chem. (United States) 276 (45): 42153–61. doi:10.1074/jbc.M102079200. ISSN 0021-9258. PMID 11546794. 
8. ^ Lin, J; Adam R M, Santiestevan E, Freeman M R (Jun. 1999). "The phosphatidylinositol 3'-kinase pathway is a dominant growth factor-activated cell survival pathway in LNCaP human prostate carcinoma cells". Cancer Res. (UNITED STATES) 59 (12): 2891–7. ISSN 0008-5472. PMID 10383151. 
9. ^ Thaminy, Safia; Auerbach Daniel, Arnoldo Anthony, Stagljar Igor (Jul. 2003). "Identification of novel ErbB3-interacting factors using the split-ubiquitin membrane yeast two-hybrid system". Genome Res. (United States) 13 (7): 1744–53. doi:10.1101/gr.1276503. ISSN 1088-9051. PMC 403748. PMID 12840049. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=403748. 

Further reading

• Corfas G, Roy K, Buxbaum JD (2004). "Neuregulin 1-erbB signaling and the molecular/cellular basis of schizophrenia". Nat. Neurosci. 7 (6): 575–80. doi:10.1038/nn1258. PMID 15162166. 
• Plowman GD, Whitney GS, Neubauer MG, et al. (1990). "Molecular cloning and expression of an additional epidermal growth factor receptor-related gene". Proc. Natl. Acad. Sci. U.S.A. 87 (13): 4905–9. doi:10.1073/pnas.87.13.4905. PMC 54229. PMID 2164210. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=54229. 
• Kraus MH, Issing W, Miki T, et al. (1990). "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 (23): 9193–7. doi:10.1073/pnas.86.23.9193. PMC 298460. PMID 2687875. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=298460. 
• Alimandi M, Romano A, Curia MC, et al. (1995). "Cooperative signaling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas". Oncogene 10 (9): 1813–21. PMID 7538656. 
• Wallasch C, Weiss FU, Niederfellner G, et al. (1995). "Heregulin-dependent regulation of HER2/neu oncogenic signaling by heterodimerization with HER3". EMBO J. 14 (17): 4267–75. PMC 394510. PMID 7556068. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=394510. 
• Horan T, Wen J, Arakawa T, et al. (1995). "Binding of Neu differentiation factor with the extracellular domain of Her2 and Her3". J. Biol. Chem. 270 (41): 24604–8. doi:10.1074/jbc.270.41.24604. PMID 7592681. 
• Shintani S, Funayama T, Yoshihama Y, et al. (1995). "Prognostic significance of ERBB3 overexpression in oral squamous cell carcinoma". Cancer Lett. 95 (1–2): 79–83. doi:10.1016/0304-3835(95)03866-U. PMID 7656248. 
• Katoh M, Yazaki Y, Sugimura T, Terada M (1993). "c-erbB3 gene encodes secreted as well as transmembrane receptor tyrosine kinase". Biochem. Biophys. Res. Commun. 192 (3): 1189–97. doi:10.1006/bbrc.1993.1542. PMID 7685162. 
• Culouscou JM, Plowman GD, Carlton GW, et al. (1993). "Characterization of a breast cancer cell differentiation factor that specifically activates the HER4/p180erbB4 receptor". J. Biol. Chem. 268 (25): 18407–10. PMID 7689552. 
• Zelada-Hedman M, Werer G, Collins P, et al. (1995). "High expression of the EGFR in fibroadenomas compared to breast carcinomas". Anticancer Res. 14 (5A): 1679–88. PMID 7847801. 
• Carraway KL, Sliwkowski MX, Akita R, et al. (1994). "The erbB3 gene product is a receptor for heregulin". J. Biol. Chem. 269 (19): 14303–6. PMID 8188716. 
• Shintani S, Funayama T, Yoshihama Y, et al. (1996). "Expression of c-erbB family gene products in adenoid cystic carcinoma of salivary glands: an immunohistochemical study". Anticancer Res. 15 (6B): 2623–6. PMID 8669836. 
• Chang H, Riese DJ, Gilbert W, et al. (1997). "Ligands for ErbB-family receptors encoded by a neuregulin-like gene". Nature 387 (6632): 509–12. doi:10.1038/387509a0. PMID 9168114. 
• Carraway KL, Weber JL, Unger MJ, et al. (1997). "Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases". Nature 387 (6632): 512–6. doi:10.1038/387512a0. PMID 9168115. 
• Fiddes RJ, Campbell DH, Janes PW, et al. (1998). "Analysis of Grb7 recruitment by heregulin-activated erbB receptors reveals a novel target selectivity for erbB3". J. Biol. Chem. 273 (13): 7717–24. doi:10.1074/jbc.273.13.7717. PMID 9516479. 
• Jones JT, Ballinger MD, Pisacane PI, et al. (1998). "Binding interaction of the heregulinbeta egf domain with ErbB3 and ErbB4 receptors assessed by alanine scanning mutagenesis". J. Biol. Chem. 273 (19): 11667–74. doi:10.1074/jbc.273.19.11667. PMID 9565587. 
• Lee H, Maihle NJ (1998). "Isolation and characterization of four alternate c-erbB3 transcripts expressed in ovarian carcinoma-derived cell lines and normal human tissues". Oncogene 16 (25): 3243–52. doi:10.1038/sj.onc.1201866. PMID 9681822. 
• Vijapurkar U, Cheng K, Koland JG (1998). "Mutation of a Shc binding site tyrosine residue in ErbB3/HER3 blocks heregulin-dependent activation of mitogen-activated protein kinase". J. Biol. Chem. 273 (33): 20996–1002. doi:10.1074/jbc.273.33.20996. PMID 9694850. 
• Yoo JY, Hamburger AW (1999). "Interaction of the p23/p198 protein with ErbB-3". Gene 229 (1–2): 215–21. doi:10.1016/S0378-1119(98)00604-0. PMID 10095121. 
• Lin J, Adam RM, Santiestevan E, Freeman MR (1999). "The phosphatidylinositol 3'-kinase pathway is a dominant growth factor-activated cell survival pathway in LNCaP human prostate carcinoma cells". Cancer Res. 59 (12): 2891–7. PMID 10383151.