Erbin (protein)

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

ERBIN
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1MFG, 1MFL, 1N7T, 2H3L, 2QBW, 3CH8
Identifiers
Aliases	ERBIN, HEL-S-78, LAP2, ERBB2IP, erbb2 interacting protein
External IDs	OMIM: 606944; MGI: 1890169; HomoloGene: 41282; GeneCards: ERBIN; OMA:ERBIN - orthologs
Gene location (Human) Chr. Chromosome 5 (human) Band 5q12.3 Start 65,926,556 bp End 66,082,546 bp
Gene location (Mouse) Chr. Chromosome 13 (mouse) Band 13|13 D1 Start 103,955,295 bp End 104,057,022 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in corpus callosum external globus pallidus optic nerve subthalamic nucleus internal globus pallidus inferior ganglion of vagus nerve pars reticulata medulla oblongata mucosa of paranasal sinus superior vestibular nucleus Top expressed in parotid gland submandibular gland left lung lobe left colon conjunctival fornix epithelium of small intestine lacrimal gland seminal vesicula Gonadal ridge mesenteric lymph nodes More reference expression data BioGPS More reference expression data
Gene ontology Molecular function structural constituent of cytoskeleton ErbB-2 class receptor binding protein binding signaling receptor binding Cellular component cytoplasm nuclear membrane membrane plasma membrane hemidesmosome basement membrane cell junction basal plasma membrane basolateral plasma membrane nucleus nuclear speck neuromuscular junction postsynapse glutamatergic synapse postsynaptic specialization Biological process negative regulation of monocyte chemotactic protein-1 production protein targeting epidermal growth factor receptor signaling pathway negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway cellular response to tumor necrosis factor response to muramyl dipeptide basal protein localization cell growth response to lipopolysaccharide cell adhesion establishment or maintenance of epithelial cell apical/basal polarity intermediate filament cytoskeleton organization integrin-mediated signaling pathway negative regulation of NF-kappaB transcription factor activity signal transduction ERBB2 signaling pathway regulation of postsynaptic membrane neurotransmitter receptor levels Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 55914 59079 Ensembl ENSG00000112851 ENSMUSG00000021709 UniProt Q96RT1 Q80TH2 RefSeq (mRNA) NM_001006600 NM_001253697 NM_001253698 NM_001253699 NM_001253701 NM_018695 NM_001005868 NM_021563 NM_001289473 NM_001289474 NM_001289475 RefSeq (protein) NP_001006600 NP_001240626 NP_001240627 NP_001240628 NP_001240630 NP_061165 NP_001005868 NP_001276402 NP_001276403 NP_001276404 Location (UCSC) Chr 5: 65.93 – 66.08 Mb Chr 13: 103.96 – 104.06 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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. Erbin's N-terminal region has been shown to disrupt Ras to Raf binding and may be, through this action, a tumor suppressing protein.

Interactions

Erbin has been shown to interact with:

• Dystonin
• HER2/neu
• ITGB4
• Mothers against decapentaplegic homolog 3
• PKP4 and
• KSR1

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. S2CID 12590559.
• 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" (PDF). Nat. Cell Biol. 2 (7): 407–14. doi:10.1038/35017038. PMID 10878805. S2CID 9566913.
• 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. S2CID 12598418.
• 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. S2CID 7429554.

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