Erbin (protein)

Erbb2 interacting protein
PDB rendering based on 1mfg.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1MFG​, 1MFL​, 1N7T​, 2H3L​, 2QBW​, 3CH8​
Identifiers
Symbols	ERBB2IP ; ERBIN; HEL-S-78; LAP2
External IDs	OMIM: 606944 MGI: 1890169 HomoloGene: 41282 GeneCards: ERBB2IP Gene
Gene ontology Molecular function • receptor binding • ErbB-2 class receptor binding • integrin binding • structural constituent of cytoskeleton • protein binding Cellular component • basement membrane • nucleus • nucleoplasm • cytoplasm • plasma membrane • basal plasma membrane • basolateral plasma membrane • cell junction • hemidesmosome • nuclear membrane Biological process • protein targeting • cell cycle • cell adhesion • signal transduction • epidermal growth factor receptor signaling pathway • integrin-mediated signaling pathway • positive regulation of gene expression • cell growth • negative regulation of NF-kappaB transcription factor activity • response to muramyl dipeptide • response to lipopolysaccharide • intermediate filament cytoskeleton organization • basal protein localization • establishment or maintenance of epithelial cell apical/basal polarity • negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway • cellular response to tumor necrosis factor Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	55914	59079
Ensembl	ENSG00000112851	ENSMUSG00000021709
UniProt	Q96RT1	Q80TH2
RefSeq (mRNA)	NM_001006600	NM_001005868
RefSeq (protein)	NP_001006600	NP_001005868
Location (UCSC)	Chr 5: 65.93 – 66.08 Mb	Chr 13: 103.82 – 103.92 Mb
PubMed search

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.^[1]

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 (protein) has been shown to interact with:

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

References

1. "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 (2000). "ERBIN: a basolateral PDZ protein that interacts with the mammalian ERBB2/HER2 receptor". Nat. Cell Biol. 2 (7): 407–414. doi:10.1038/35017038. PMID 10878805.
3. Kolch W (2003). "Erbin: sorting out ErbB2 receptors or giving Ras a break?". Sci. STKE. 2003 (199): pe37. doi:10.1126/stke.2003.199.pe37. PMID 12966186.
4. Dai P, Xiong WC, Mei L (2006). "Erbin inhibits RAF activation by disrupting the sur-8-Ras-Raf complex". J. Biol. Chem. 281 (2): 927–933. doi:10.1074/jbc.M507360200. PMID 16301319.
5. Favre B, Fontao L, Koster J, Shafaatian R, Jaunin F, Saurat JH, Sonnenberg A, Borradori L (August 2001). "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. doi:10.1074/jbc.M011005200. PMID 11375975.
6. Jaulin-Bastard F, Saito H, Le Bivic A, Ollendorff V, Marchetto S, Birnbaum D, Borg JP (May 2001). "The ERBB2/HER2 receptor differentially interacts with ERBIN and PICK1 PSD-95/DLG/ZO-1 domain proteins". J. Biol. Chem. 276 (18): 15256–63. doi:10.1074/jbc.M010032200. PMID 11278603.
7. Borg JP, Marchetto S, Le Bivic A, Ollendorff V, Jaulin-Bastard F, Saito H, Fournier E, Adélaïde J, Margolis B, Birnbaum D (July 2000). "ERBIN: a basolateral PDZ protein that interacts with the mammalian ERBB2/HER2 receptor". Nat. Cell Biol. 2 (7): 407–14. doi:10.1038/35017038. PMID 10878805.
8. Huang YZ, Zang M, Xiong WC, Luo Z, Mei L (January 2003). "Erbin suppresses the MAP kinase pathway". J. Biol. Chem. 278 (2): 1108–14. doi:10.1074/jbc.M205413200. PMID 12379659.
9. Warner DR, Pisano MM, Roberts EA, Greene RM (March 2003). "Identification of three novel Smad binding proteins involved in cell polarity". FEBS Lett. 539 (1-3): 167–73. doi:10.1016/s0014-5793(03)00155-8. PMID 12650946.
10. Izawa I, Nishizawa M, Tomono Y, Ohtakara K, Takahashi T, Inagaki M (May 2002). "ERBIN associates with p0071, an armadillo protein, at cell-cell junctions of epithelial cells". Genes Cells 7 (5): 475–85. doi:10.1046/j.1365-2443.2002.00533.x. PMID 12047349.
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 (January 2002). "Interaction between Erbin and a Catenin-related protein in epithelial cells". J. Biol. Chem. 277 (4): 2869–75. doi:10.1074/jbc.M109652200. PMID 11711544.
12. Laura RP, Witt AS, Held HA, Gerstner R, Deshayes K, Koehler MF, Kosik KS, Sidhu SS, Lasky LA (April 2002). "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. doi:10.1074/jbc.M200818200. PMID 11821434.

Further reading

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

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