Erbin (protein)

Erbb2 interacting protein (ERBB2IP), also known as erbin, is a protein which in humans is encoded by the ERBB2IP gene.[5] Discovered in 1997, erbin is a 200kDa protein containing a PDZ domain.[6]

ERBIN
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesERBIN, HEL-S-78, LAP2, ERBB2IP, erbb2 interacting protein
External IDsOMIM: 606944 MGI: 1890169 HomoloGene: 41282 GeneCards: ERBIN
Orthologs
SpeciesHumanMouse
Entrez

55914

59079

Ensembl

ENSG00000112851

ENSMUSG00000021709

UniProt

Q96RT1

Q80TH2

RefSeq (mRNA)

NM_001005868
NM_021563
NM_001289473
NM_001289474
NM_001289475

RefSeq (protein)

NP_001005868
NP_001276402
NP_001276403
NP_001276404

Location (UCSC)Chr 5: 65.93 – 66.08 MbChr 13: 103.96 – 104.06 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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.[5]

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.[7] Erbin's N-terminal region has been shown to disrupt Ras to Raf binding and may be, through this action, a tumor suppressing protein.[8]

Interactions

Erbin has been shown to interact with:

References
  1. GRCh38: Ensembl release 89: ENSG00000112851 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000021709 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: ERBB2IP erbb2 interacting protein".
  6. 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): 407–414. doi:10.1038/35017038. PMID 10878805. S2CID 9566913.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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" (PDF). Nat. Cell Biol. 2 (7): 407–14. doi:10.1038/35017038. PMID 10878805. S2CID 9566913.
  12. 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.
  13. 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. S2CID 7429554.
  14. 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. S2CID 12598418.
  15. 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.
  16. 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.
  17. 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. doi:10.1158/0008-5472.CAN-17-3629. ISSN 1538-7445. PMC 6510240. PMID 29980571.

Further reading
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