The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

ERBB2IP  -  erbb2 interacting protein

Homo sapiens

Synonyms: Densin-180-like protein, ERBIN, Erbb2-interacting protein, Erbin, HEL-S-78, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of ERBB2IP


High impact information on ERBB2IP

  • ERBIN and ERBB2/HER2 colocalize to the lateral membrane of human intestinal epithelial cells [5].
  • Consequently, the biological function of ZO-1 is also broadened, as it interacts with both tight and adherens junction proteins, whereas Erbin is restricted to adherens junctions [6].
  • Site(-1) was found to be monospecific in the Erbin PDZ domain (accepts tryptophan only), bispecific in the first PDZ domain of ZO-1 (accepts tryptophan or tyrosine), and promiscuous in the Scribble PDZ domains [7].
  • Our data further indicate that the endocytosis deficiency of ErbB2 and of EGFR-ErbB2 heterodimers/oligomers cannot be explained by anchoring of ErbB2 to PDZ-containing proteins such as Erbin [8].
  • Although it interacts with the ErbB2 C terminus through the PDZ domain, Erbin has no effect on ErbB2 tyrosine phosphorylation or binding to the adaptor proteins Shc and Grb2 [9].

Chemical compound and disease context of ERBB2IP

  • Alanine and homolog scanning mutagenesis (in a combinatorial phage display format) identifies Erbin side chains that make energetically important contacts with the ligand [10].

Biological context of ERBB2IP

  • However, loss of function of one ERBB2IP copy or expression of a putative novel ERBB2IP fusion protein did not apparently modulate the DEB phenotype in both translocation patients [1].
  • ERBIN belongs to the newly described LAP (LRR and PDZ) protein family, whose function is crucial in non vertebrates for epithelial homeostasis [11].
  • BACKGROUND: ERBIN, an ErbB2 receptor-interacting protein, belongs to a recently described family of proteins termed the LAP [leucine-rich repeats and PSD-95/dLg-A/ZO-1 (PDZ) domains] family which has essential roles in establishment of cell polarity [12].
  • Origins of PDZ domain ligand specificity. Structure determination and mutagenesis of the Erbin PDZ domain [10].
  • Since phosphorylation of tyrosine -7 plays a critical role in ErbB2 function, the selective binding and sequestration of this residue in its unphosphorylated state by the Erbin PDZ provides a novel mechanism for regulation of the ErbB2-mediated signaling and oncogenicity [13].

Anatomical context of ERBB2IP


Associations of ERBB2IP with chemical compounds

  • Expression of Erbin increases the amount of ErbB2 labeled by biotin in transfected cells, suggesting that Erbin is able to increase ErbB2 surface expression [14].
  • Erbin contains a class I PDZ domain that binds to the C-terminal region of the receptor tyrosine kinase ErbB2, a class II ligand [13].
  • The isopropyl group of valine at position -2 of the ErbB2 peptide interacts with the Erbin Val(1351) and displaces the peptide backbone away from the alpha-helix, elucidating the molecular basis of class II ligand recognition by a class I PDZ domain [13].
  • Phosphorylation of tyrosine -7 abolishes this interaction but does not affect the binding of the four C-terminal peptidic residues to PDZ, as revealed by the crystal structure of the Erbin PDZ complexed with a phosphotyrosine-containing ErbB2 peptide [13].
  • The binding partners of Erbin, BP230 (BPAG1) and the integrin beta4 subunit, both involved in hemidesmosome (HD) function, and the presence of Erbin in HD suggested that it plays a role in establishment and maintenance of cell-basement membrane adhesions [1].

Physical interactions of ERBB2IP

  • We previously described Erbin as a mammalian LET-413 homologue interacting with ERBB2/HER2, an epidermal growth factor receptor family member [15].
  • Endogenous ERBIN was co-immunoprecipitated with p0071 [12].
  • Mutagenesis and peptide competition experiments showed that the association of Erbin with the cadherin-catenin complex was mediated by the interaction of its PDZ domain with the C-terminal PDZ domain-binding motifs (DSWV-COOH) of ARVCF and delta-catenin [2].
  • The Erbin PDZ domain binds with high affinity and specificity to the carboxyl termini of delta-catenin and ARVCF [2].
  • A second pool of Lano is complexed to Erbin [16].

Co-localisations of ERBB2IP

  • At these cell-cell contact regions, ERBIN co-localizes with p0071 [12].
  • Furthermore, ERBIN and ErbB2 were colocalized with PAPIN on the lateral membrane [17].

Other interactions of ERBB2IP


Analytical, diagnostic and therapeutic context of ERBB2IP


  1. Disruption of ERBB2IP is not associated with dystrophic epidermolysis bullosa in both father and son carrying a balanced 5;13 translocation. Stefanova, M., Zemke, K., Dimitrov, B., Has, C., Kern, J.S., Bruckner-Tuderman, L., Kutsche, K. J. Invest. Dermatol. (2005) [Pubmed]
  2. The Erbin PDZ domain binds with high affinity and specificity to the carboxyl termini of delta-catenin and ARVCF. Laura, R.P., Witt, A.S., Held, H.A., Gerstner, R., Deshayes, K., Koehler, M.F., Kosik, K.S., Sidhu, S.S., Lasky, L.A. J. Biol. Chem. (2002) [Pubmed]
  3. Role for erbin in bacterial activation of Nod2. Kufer, T.A., Kremmer, E., Banks, D.J., Philpott, D.J. Infect. Immun. (2006) [Pubmed]
  4. Comparative analysis of the expression of ERBIN and Erb-B2 in normal human skin and cutaneous carcinomas. Lebeau, S., Masouyé, I., Berti, M., Augsburger, E., Saurat, J.H., Borradori, L., Fontao, L. Br. J. Dermatol. (2005) [Pubmed]
  5. ERBIN: a basolateral PDZ protein that interacts with the mammalian ERBB2/HER2 receptor. Borg, J.P., Marchetto, S., Le Bivic, A., Ollendorff, V., Jaulin-Bastard, F., Saito, H., Fournier, E., Adélaïde, J., Margolis, B., Birnbaum, D. Nat. Cell Biol. (2000) [Pubmed]
  6. Comparative structural analysis of the Erbin PDZ domain and the first PDZ domain of ZO-1. Insights into determinants of PDZ domain specificity. Appleton, B.A., Zhang, Y., Wu, P., Yin, J.P., Hunziker, W., Skelton, N.J., Sidhu, S.S., Wiesmann, C. J. Biol. Chem. (2006) [Pubmed]
  7. Convergent and divergent ligand specificity among PDZ domains of the LAP and zonula occludens (ZO) families. Zhang, Y., Yeh, S., Appleton, B.A., Held, H.A., Kausalya, P.J., Phua, D.C., Wong, W.L., Lasky, L.A., Wiesmann, C., Hunziker, W., Sidhu, S.S. J. Biol. Chem. (2006) [Pubmed]
  8. The inhibitory effect of ErbB2 on epidermal growth factor-induced formation of clathrin-coated pits correlates with retention of epidermal growth factor receptor-ErbB2 oligomeric complexes at the plasma membrane. Haslekås, C., Breen, K., Pedersen, K.W., Johannessen, L.E., Stang, E., Madshus, I.H. Mol. Biol. Cell (2005) [Pubmed]
  9. Erbin suppresses the MAP kinase pathway. Huang, Y.Z., Zang, M., Xiong, W.C., Luo, Z., Mei, L. J. Biol. Chem. (2003) [Pubmed]
  10. Origins of PDZ domain ligand specificity. Structure determination and mutagenesis of the Erbin PDZ domain. Skelton, N.J., Koehler, M.F., Zobel, K., Wong, W.L., Yeh, S., Pisabarro, M.T., Yin, J.P., Lasky, L.A., Sidhu, S.S. J. Biol. Chem. (2003) [Pubmed]
  11. The ERBB2/HER2 receptor differentially interacts with ERBIN and PICK1 PSD-95/DLG/ZO-1 domain proteins. Jaulin-Bastard, F., Saito, H., Le Bivic, A., Ollendorff, V., Marchetto, S., Birnbaum, D., Borg, J.P. J. Biol. Chem. (2001) [Pubmed]
  12. ERBIN associates with p0071, an armadillo protein, at cell-cell junctions of epithelial cells. Izawa, I., Nishizawa, M., Tomono, Y., Ohtakara, K., Takahashi, T., Inagaki, M. Genes Cells (2002) [Pubmed]
  13. Novel mode of ligand recognition by the Erbin PDZ domain. Birrane, G., Chung, J., Ladias, J.A. J. Biol. Chem. (2003) [Pubmed]
  14. Erbin is a protein concentrated at postsynaptic membranes that interacts with PSD-95. Huang, Y.Z., Wang, Q., Xiong, W.C., Mei, L. J. Biol. Chem. (2001) [Pubmed]
  15. Interaction between Erbin and a Catenin-related protein in epithelial cells. Jaulin-Bastard, F., Arsanto, J.P., Le Bivic, A., Navarro, C., Vély, F., Saito, H., Marchetto, S., Hatzfeld, M., Santoni, M.J., Birnbaum, D., Borg, J.P. J. Biol. Chem. (2002) [Pubmed]
  16. Lano, a novel LAP protein directly connected to MAGUK proteins in epithelial cells. Saito, H., Santoni, M.J., Arsanto, J.P., Jaulin-Bastard, F., Le Bivic, A., Marchetto, S., Audebert, S., Isnardon, D., Adélaïde, J., Birnbaum, D., Borg, J.P. J. Biol. Chem. (2001) [Pubmed]
  17. Localization of p0071-interacting proteins, plakophilin-related armadillo-repeat protein-interacting protein (PAPIN) and ERBIN, in epithelial cells. Ohno, H., Hirabayashi, S., Iizuka, T., Ohnishi, H., Fujita, T., Hata, Y. Oncogene (2002) [Pubmed]
  18. Interaction partners of the PDZ domain of erbin. Ress, A., Moelling, K. Protein Pept. Lett. (2006) [Pubmed]
  19. Lap2alpha expression is controlled by E2F and deregulated in various human tumors. Parise, P., Finocchiaro, G., Masciadri, B., Quarto, M., Francois, S., Mancuso, F., Muller, H. Cell Cycle (2006) [Pubmed]
WikiGenes - Universities