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EZR
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases EZR, CVIL, CVL, HEL-S-105, VIL2, Ezrin
External IDs OMIM: 123900 MGI: 98931 HomoloGene: 55740 GeneCards: EZR
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001111077
NM_003379

NM_009510

RefSeq (protein)

NP_001104547
NP_003370

NP_033536

Location (UCSC) Chr 6: 158.77 – 158.82 Mb Chr 17: 7.01 – 7.05 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Ezrin also known as cytovillin or villin-2 is a protein that in humans is encoded by the EZR gene. [5]

Structure

The N-terminus of ezrin contains a FERM domain which is further subdivided into three subdomains. The C-terminus contains an ERM domain.

Function

The cytoplasmic peripheral protein encoded by this gene can be phosphorylated by protein- tyrosine kinase in microvilli and is a member of the ERM protein family. This protein serves as a linker between plasma membrane and actin cytoskeleton. It plays a key role in cell surface structure adhesion, migration, and organization. [6]

The N-terminal domain (also called FERM domain) binds sodium-hydrogen exchanger regulatory factor ( NHERF) protein (involving long-range allostery). [7] This binding can happen only when ezrin is in its active state. The activation of ezrin occurs in synergism of the two factors: 1) binding of the N-terminal domain to phosphatidylinositol(4,5)bis-phosphate ( PIP2) and 2) phosphorylation of threonine T567 in the C-terminal domain. [8] [9] Binding to actin filaments (via C-terminal) and to membrane proteins (via N-terminal) stabilizes the protein's conformation in its active mode. The membrane proteins like CD44 and ICAM-2 are indirect binding partners of ezrin, while EBP50 (ERM binding protein 50) can associate with ezrin directly. [10]

Interactions

VIL2 has been shown to interact with:

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000092820Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000052397Ensembl, 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. ^ Gould KL, Bretscher A, Esch FS, Hunter T (December 1989). "cDNA cloning and sequencing of the protein-tyrosine kinase substrate, ezrin, reveals homology to band 4.1". EMBO J. 8 (13): 4133–42. doi: 10.1002/j.1460-2075.1989.tb08598.x. PMC  401598. PMID  2591371.
  6. ^ "Entrez Gene: VIL2 villin 2 (ezrin)".
  7. ^ Farago B, Li J, Cornilescu G, Callaway DJ, Bu Z (2010). "Activation of nanoscale allosteric protein domain motion revealed by neutron spin echo spectroscopy". Biophysical Journal. 99 (10): 3473–82. Bibcode: 2010BpJ....99.3473F. doi: 10.1016/j.bpj.2010.09.058. PMC  2980739. PMID  21081097.
  8. ^ Jayasundar JJ, Ju JH, He L, Liu D, Meilleur F, Zhao J, Callaway DJ, Bu Z (2012). "Open conformation of ezrin bound to phosphatidylinositol 4,5-bisphosphate and to F-actin revealed by neutron scattering". J. Biol. Chem. 287 (44): 37119–33. doi: 10.1074/jbc.M112.380972. PMC  3481312. PMID  22927432.
  9. ^ Shabardina V, Kramer C, Gerdes B, Braunger J, Cordes A, Schaefer J, Mey I, Grill D, Gerke V, Steinem C (2016). "Mode of Ezrin-Membrane Interaction as a Function of PIP2 Binding and Pseudophosphorylation". Biophys. J. 110 (12): 2710–2719. Bibcode: 2016BpJ...110.2710S. doi: 10.1016/j.bpj.2016.05.009. PMC  4919509. PMID  27332129.
  10. ^ Ivetic A, Ridley AJ (2004). "Ezrin/radixin/moesin proteins and Rho GTPase signalling in leucocytes". Immunology. 112 (2): 165–176. doi: 10.1111/j.1365-2567.2004.01882.x. PMC  1782489. PMID  15147559.
  11. ^ Serrador JM, Nieto M, Alonso-Lebrero JL, del Pozo MA, Calvo J, Furthmayr H, Schwartz-Albiez R, Lozano F, González-Amaro R, Sánchez-Mateos P, Sánchez-Madrid F (June 1998). "CD43 interacts with moesin and ezrin and regulates its redistribution to the uropods of T lymphocytes at the cell-cell contacts". Blood. 91 (12): 4632–44. doi: 10.1182/blood.V91.12.4632. PMID  9616160.
  12. ^ a b Gajate C, Mollinedo F (March 2005). "Cytoskeleton-mediated death receptor and ligand concentration in lipid rafts forms apoptosis-promoting clusters in cancer chemotherapy". J. Biol. Chem. 280 (12): 11641–7. doi: 10.1074/jbc.M411781200. PMID  15659383.
  13. ^ Parlato S, Giammarioli AM, Logozzi M, Lozupone F, Matarrese P, Luciani F, Falchi M, Malorni W, Fais S (October 2000). "CD95 (APO-1/Fas) linkage to the actin cytoskeleton through ezrin in human T lymphocytes: a novel regulatory mechanism of the CD95 apoptotic pathway". EMBO J. 19 (19): 5123–34. doi: 10.1093/emboj/19.19.5123. PMC  302100. PMID  11013215.
  14. ^ a b c Heiska L, Alfthan K, Grönholm M, Vilja P, Vaheri A, Carpén O (August 1998). "Association of ezrin with intercellular adhesion molecule-1 and -2 (ICAM-1 and ICAM-2). Regulation by phosphatidylinositol 4, 5-bisphosphate". J. Biol. Chem. 273 (34): 21893–900. doi: 10.1074/jbc.273.34.21893. PMID  9705328.
  15. ^ Serrador JM, Vicente-Manzanares M, Calvo J, Barreiro O, Montoya MC, Schwartz-Albiez R, Furthmayr H, Lozano F, Sánchez-Madrid F (March 2002). "A novel serine-rich motif in the intercellular adhesion molecule 3 is critical for its ezrin/radixin/moesin-directed subcellular targeting". J. Biol. Chem. 277 (12): 10400–9. doi: 10.1074/jbc.M110694200. PMID  11784723.
  16. ^ Grönholm M, Sainio M, Zhao F, Heiska L, Vaheri A, Carpén O (March 1999). "Homotypic and heterotypic interaction of the neurofibromatosis 2 tumor suppressor protein merlin and the ERM protein ezrin". J. Cell Sci. 112 (6): 895–904. doi: 10.1242/jcs.112.6.895. PMID  10036239.
  17. ^ Gary R, Bretscher A (August 1995). "Ezrin self-association involves binding of an N-terminal domain to a normally masked C-terminal domain that includes the F-actin binding site". Mol. Biol. Cell. 6 (8): 1061–75. doi: 10.1091/mbc.6.8.1061. PMC  301263. PMID  7579708.
  18. ^ Gary R, Bretscher A (November 1993). "Heterotypic and homotypic associations between ezrin and moesin, two putative membrane-cytoskeletal linking proteins". Proc. Natl. Acad. Sci. U.S.A. 90 (22): 10846–50. Bibcode: 1993PNAS...9010846G. doi: 10.1073/pnas.90.22.10846. PMC  47875. PMID  8248180.
  19. ^ Gautreau A, Poullet P, Louvard D, Arpin M (June 1999). "Ezrin, a plasma membrane-microfilament linker, signals cell survival through the phosphatidylinositol 3-kinase/Akt pathway". Proc. Natl. Acad. Sci. U.S.A. 96 (13): 7300–5. Bibcode: 1999PNAS...96.7300G. doi: 10.1073/pnas.96.13.7300. PMC  22080. PMID  10377409.
  20. ^ Mykkänen OM, Grönholm M, Rönty M, Lalowski M, Salmikangas P, Suila H, Carpén O (October 2001). "Characterization of human palladin, a microfilament-associated protein". Mol. Biol. Cell. 12 (10): 3060–73. doi: 10.1091/mbc.12.10.3060. PMC  60155. PMID  11598191.
  21. ^ Koltzscher M, Neumann C, König S, Gerke V (June 2003). "Ca2+-dependent binding and activation of dormant ezrin by dimeric S100P". Mol. Biol. Cell. 14 (6): 2372–84. doi: 10.1091/mbc.E02-09-0553. PMC  194886. PMID  12808036.
  22. ^ Granés F, Urena JM, Rocamora N, Vilaró S (April 2000). "Ezrin links syndecan-2 to the cytoskeleton". J. Cell Sci. 113 (7): 1267–76. doi: 10.1242/jcs.113.7.1267. PMID  10704377.
  23. ^ Brdicková N, Brdicka T, Andera L, Spicka J, Angelisová P, Milgram SL, Horejsí V (October 2001). "Interaction between two adapter proteins, PAG and EBP50: a possible link between membrane rafts and actin cytoskeleton". FEBS Lett. 507 (2): 133–6. doi: 10.1016/s0014-5793(01)02955-6. PMID  11684085. S2CID  12676563.
  24. ^ Reczek D, Berryman M, Bretscher A (October 1997). "Identification of EBP50: A PDZ-containing phosphoprotein that associates with members of the ezrin-radixin-moesin family". J. Cell Biol. 139 (1): 169–79. doi: 10.1083/jcb.139.1.169. PMC  2139813. PMID  9314537.
  25. ^ Yun CH, Lamprecht G, Forster DV, Sidor A (October 1998). "NHE3 kinase A regulatory protein E3KARP binds the epithelial brush border Na+/H+ exchanger NHE3 and the cytoskeletal protein ezrin". J. Biol. Chem. 273 (40): 25856–63. doi: 10.1074/jbc.273.40.25856. PMID  9748260.
  26. ^ Sitaraman SV, Wang L, Wong M, Bruewer M, Hobert M, Yun CH, Merlin D, Madara JL (September 2002). "The adenosine 2b receptor is recruited to the plasma membrane and associates with E3KARP and Ezrin upon agonist stimulation". J. Biol. Chem. 277 (36): 33188–95. doi: 10.1074/jbc.M202522200. PMID  12080047.
  27. ^ Barreiro O, Yanez-Mo M, Serrador JM, Montoya MC, Vicente-Manzanares M, Tejedor R, Furthmayr H, Sanchez-Madrid F (June 2002). "Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes". J. Cell Biol. 157 (7): 1233–45. doi: 10.1083/jcb.200112126. PMC  2173557. PMID  12082081.

Further reading