Erbin (protein) explained

Erbb2 interacting protein (ERBB2IP), also known as erbin, is a protein which in humans is encoded by the ERBB2IP gene.^[1] Discovered in 1997, erbin is a 200kDa protein containing a PDZ domain.^[2]

Function

This gene is a member of the leucine-rich repeat and PDZ domain (LAP) family. The encoded protein contains 17 leucine-rich repeats and one PDZ domain. It binds to the unphosphorylated form of the ERBB2 protein and regulates ERBB2 function and localization. It has also been shown to affect the Ras signaling pathway by disrupting Ras-Raf interaction. Alternate transcriptional splice variants encoding different isoforms have been found for this gene, but only two of them have been characterized to date.

Clinical significance

Erbin's C-terminal PDZ domain is able to bind to ErbB2, a protein tyrosine kinase which is often associated with poor prognosis in epidermal oncogenesis.^[3] Erbin's N-terminal region has been shown to disrupt Ras to Raf binding and may be, through this action, a tumor suppressing protein.^[4]

Interactions

Erbin has been shown to interact with:

• Dystonin^[5]
• HER2/neu^{[6] [7] [8]}
• ITGB4^[5]
• Mothers against decapentaplegic homolog 3^[9]
• PKP4^{[10] [11] [12]} and
• KSR1^[13]

Further reading

• Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T . Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones . DNA Res. . 9 . 3 . 99–106 . 2003 . 12168954 . 10.1093/dnares/9.3.99 . free .
• Kolch W . Erbin: sorting out ErbB2 receptors or giving Ras a break? . Sci. STKE . 2003 . 199 . pe37 . 2003 . 12966186 . 10.1126/stke.2003.199.pe37 . 12590559 .
• Nagase T, Ishikawa K, Kikuno R, Hirosawa M, Nomura N, Ohara O . Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro . DNA Res. . 6 . 5 . 337–45 . 2000 . 10574462 . 10.1093/dnares/6.5.337 . free .
• Borg JP, Marchetto S, Le Bivic A, Ollendorff V, Jaulin-Bastard F, Saito H, Fournier E, Adélaïde J, Margolis B, Birnbaum D . ERBIN: a basolateral PDZ protein that interacts with the mammalian ERBB2/HER2 receptor . Nat. Cell Biol. . 2 . 7 . 407–14 . 2000 . 10878805 . 10.1038/35017038 . 9566913 .
• Jaulin-Bastard F, Saito H, Le Bivic A, Ollendorff V, Marchetto S, Birnbaum D, Borg JP . The ERBB2/HER2 receptor differentially interacts with ERBIN and PICK1 PSD-95/DLG/ZO-1 domain proteins . J. Biol. Chem. . 276 . 18 . 15256–63 . 2001 . 11278603 . 10.1074/jbc.M010032200 . free .
• Huang YZ, Wang Q, Xiong WC, Mei L . Erbin is a protein concentrated at postsynaptic membranes that interacts with PSD-95 . J. Biol. Chem. . 276 . 22 . 19318–26 . 2001 . 11279080 . 10.1074/jbc.M100494200 . free .
• Favre B, Fontao L, Koster J, Shafaatian R, Jaunin F, Saurat JH, Sonnenberg A, Borradori L . The hemidesmosomal protein bullous pemphigoid antigen 1 and the integrin beta 4 subunit bind to ERBIN. Molecular cloning of multiple alternative splice variants of ERBIN and analysis of their tissue expression . J. Biol. Chem. . 276 . 35 . 32427–36 . 2001 . 11375975 . 10.1074/jbc.M011005200 . free .
• Saito H, Santoni MJ, Arsanto JP, Jaulin-Bastard F, Le Bivic A, Marchetto S, Audebert S, Isnardon D, Adélaïde J, Birnbaum D, Borg JP . Lano, a novel LAP protein directly connected to MAGUK proteins in epithelial cells . J. Biol. Chem. . 276 . 34 . 32051–5 . 2001 . 11440998 . 10.1074/jbc.C100330200 . free .
• Jaulin-Bastard F, Arsanto JP, Le Bivic A, Navarro C, Vély F, Saito H, Marchetto S, Hatzfeld M, Santoni MJ, Birnbaum D, Borg JP . Interaction between Erbin and a Catenin-related protein in epithelial cells . J. Biol. Chem. . 277 . 4 . 2869–75 . 2002 . 11711544 . 10.1074/jbc.M109652200 . free .
• Laura RP, Witt AS, Held HA, Gerstner R, Deshayes K, Koehler MF, Kosik KS, Sidhu SS, Lasky LA . The Erbin PDZ domain binds with high affinity and specificity to the carboxyl termini of delta-catenin and ARVCF . J. Biol. Chem. . 277 . 15 . 12906–14 . 2002 . 11821434 . 10.1074/jbc.M200818200 . free .
• Izawa I, Nishizawa M, Tomono Y, Ohtakara K, Takahashi T, Inagaki M . ERBIN associates with p0071, an armadillo protein, at cell-cell junctions of epithelial cells . Genes Cells . 7 . 5 . 475–85 . 2002 . 12047349 . 10.1046/j.1365-2443.2002.00533.x . 12598418 . free .
• Ohno H, Hirabayashi S, Iizuka T, Ohnishi H, Fujita T, Hata Y . Localization of p0071-interacting proteins, plakophilin-related armadillo-repeat protein-interacting protein (PAPIN) and ERBIN, in epithelial cells . Oncogene . 21 . 46 . 7042–9 . 2002 . 12370826 . 10.1038/sj.onc.1205852 . free .
• Huang YZ, Zang M, Xiong WC, Luo Z, Mei L . Erbin suppresses the MAP kinase pathway . J. Biol. Chem. . 278 . 2 . 1108–14 . 2003 . 12379659 . 10.1074/jbc.M205413200 . free .
• Birrane G, Chung J, Ladias JA . Novel mode of ligand recognition by the Erbin PDZ domain . J. Biol. Chem. . 278 . 3 . 1399–402 . 2003 . 12444095 . 10.1074/jbc.C200571200 . free .
• Skelton NJ, Koehler MF, Zobel K, Wong WL, Yeh S, Pisabarro MT, Yin JP, Lasky LA, Sidhu SS . Origins of PDZ domain ligand specificity. Structure determination and mutagenesis of the Erbin PDZ domain . J. Biol. Chem. . 278 . 9 . 7645–54 . 2003 . 12446668 . 10.1074/jbc.M209751200 . free .
• Warner DR, Pisano MM, Roberts EA, Greene RM . Identification of three novel Smad binding proteins involved in cell polarity . FEBS Lett. . 539 . 1–3 . 167–73 . 2003 . 12650946 . 10.1016/S0014-5793(03)00155-8 . 7429554 . free .

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Notes and References

1. Web site: Entrez Gene: ERBB2IP erbb2 interacting protein.
2. Borg JP, Marchetto S, Le Bivic A, Ollendorff V, Jaulin-Bastard F, Saito H, Fournier E, Adélaïde J, Margolis B, Birnbaum D . ERBIN: a basolateral PDZ protein that interacts with the mammalian ERBB2/HER2 receptor . Nat. Cell Biol. . 2 . 7 . 407–414 . 2000 . 10878805 . 10.1038/35017038 . 9566913 .
3. Kolch W . Erbin: sorting out ErbB2 receptors or giving Ras a break? . Sci STKE . 2003 . 199 . pe37 . 2003 . 12966186 . 10.1126/stke.2003.199.pe37 . 12590559 .
4. Dai P, Xiong WC, Mei L . Erbin inhibits RAF activation by disrupting the sur-8-Ras-Raf complex . J. Biol. Chem. . 281 . 2 . 927–933 . 2006 . 16301319 . 10.1074/jbc.M507360200 . free .
5. Favre B, Fontao L, Koster J, Shafaatian R, Jaunin F, Saurat JH, Sonnenberg A, Borradori L . The hemidesmosomal protein bullous pemphigoid antigen 1 and the integrin beta 4 subunit bind to ERBIN. Molecular cloning of multiple alternative splice variants of ERBIN and analysis of their tissue expression . J. Biol. Chem. . 276 . 35 . 32427–36 . August 2001 . 11375975 . 10.1074/jbc.M011005200 . free .
6. Jaulin-Bastard F, Saito H, Le Bivic A, Ollendorff V, Marchetto S, Birnbaum D, Borg JP . The ERBB2/HER2 receptor differentially interacts with ERBIN and PICK1 PSD-95/DLG/ZO-1 domain proteins . J. Biol. Chem. . 276 . 18 . 15256–63 . May 2001 . 11278603 . 10.1074/jbc.M010032200 . free .
7. Borg JP, Marchetto S, Le Bivic A, Ollendorff V, Jaulin-Bastard F, Saito H, Fournier E, Adélaïde J, Margolis B, Birnbaum D . ERBIN: a basolateral PDZ protein that interacts with the mammalian ERBB2/HER2 receptor . Nat. Cell Biol. . 2 . 7 . 407–14 . July 2000 . 10878805 . 10.1038/35017038 . 9566913 .
8. Huang YZ, Zang M, Xiong WC, Luo Z, Mei L . Erbin suppresses the MAP kinase pathway . J. Biol. Chem. . 278 . 2 . 1108–14 . January 2003 . 12379659 . 10.1074/jbc.M205413200 . free .
9. Warner DR, Pisano MM, Roberts EA, Greene RM . Identification of three novel Smad binding proteins involved in cell polarity . FEBS Lett. . 539 . 1–3 . 167–73 . March 2003 . 12650946 . 10.1016/s0014-5793(03)00155-8. 7429554 . free .
10. Izawa I, Nishizawa M, Tomono Y, Ohtakara K, Takahashi T, Inagaki M . ERBIN associates with p0071, an armadillo protein, at cell-cell junctions of epithelial cells . Genes Cells . 7 . 5 . 475–85 . May 2002 . 12047349 . 10.1046/j.1365-2443.2002.00533.x. 12598418 . free .
11. Jaulin-Bastard F, Arsanto JP, Le Bivic A, Navarro C, Vély F, Saito H, Marchetto S, Hatzfeld M, Santoni MJ, Birnbaum D, Borg JP . Interaction between Erbin and a Catenin-related protein in epithelial cells . J. Biol. Chem. . 277 . 4 . 2869–75 . January 2002 . 11711544 . 10.1074/jbc.M109652200 . free .
12. Laura RP, Witt AS, Held HA, Gerstner R, Deshayes K, Koehler MF, Kosik KS, Sidhu SS, Lasky LA . The Erbin PDZ domain binds with high affinity and specificity to the carboxyl termini of delta-catenin and ARVCF . J. Biol. Chem. . 277 . 15 . 12906–14 . April 2002 . 11821434 . 10.1074/jbc.M200818200 . free .
13. Stevens. Payton D.. Wen. Yang-An. Xiong. Xiaopeng. Zaytseva. Yekaterina Y.. Li. Austin T.. Wang. Chi. Stevens. Ashley T.. Farmer. Trevor N.. Gan. Tong. Weiss. Heidi L.. Inagaki. Masaki. September 1, 2018. Erbin Suppresses KSR1-Mediated RAS/RAF Signaling and Tumorigenesis in Colorectal Cancer. Cancer Research. 78. 17. 4839–4852. 10.1158/0008-5472.CAN-17-3629. 1538-7445. 6510240. 29980571.