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Ezrin

From Wikipedia, the free encyclopedia
EZR
Available structures
PDBOrtholog search:PDBeRCSB
Identifiers
AliasesEZR,CVIL, CVL, HEL-S-105, VIL2, Ezrin
External IDsOMIM:123900;MGI:98931;HomoloGene:55740;GeneCards:EZR;OMA:EZR - orthologs
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 MbChr 17: 7.01 – 7.05 Mb
PubMedsearch[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Ezrinalso known ascytovillinorvillin-2is aproteinthat in humans is encoded by theEZRgene.[5]

Structure[edit]

TheN-terminusof ezrin contains aFERM domainwhich is further subdivided into three subdomains. TheC-terminuscontains anERM domain.

Function[edit]

Thecytoplasmicperipheral proteinencoded by this gene can be phosphorylated by protein-tyrosine kinaseinmicrovilliand is a member of theERM protein family.This protein serves as a linker between plasma membrane andactincytoskeleton.It plays a key role in cell surface structure adhesion, migration, and organization.[6]

The N-terminal domain (also calledFERM domain) binds sodium-hydrogen exchanger regulatory factor (NHERF) protein (involving long-rangeallostery).[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 toactin filaments(via C-terminal) and to membrane proteins (via N-terminal) stabilizes the protein's conformation in its active mode. The membrane proteins likeCD44andICAM-2are indirect binding partners of ezrin, while EBP50 (ERM binding protein 50) can associate with ezrin directly.[10]

Interactions[edit]

VIL2 has been shown tointeractwith:

References[edit]

  1. ^abcGRCh38: Ensembl release 89: ENSG00000092820Ensembl,May 2017
  2. ^abcGRCm38: 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.PMC401598.PMID2591371.
  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.PMC2980739.PMID21081097.
  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.PMC3481312.PMID22927432.
  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.PMC4919509.PMID27332129.
  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.PMC1782489.PMID15147559.
  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.PMID9616160.
  12. ^abGajate 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.PMID15659383.
  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.PMC302100.PMID11013215.
  14. ^abcHeiska 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.PMID9705328.
  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.PMID11784723.
  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.PMID10036239.
  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.PMC301263.PMID7579708.
  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.PMC47875.PMID8248180.
  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.PMC22080.PMID10377409.
  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.PMC60155.PMID11598191.
  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.PMC194886.PMID12808036.
  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.PMID10704377.
  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.PMID11684085.S2CID12676563.
  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.PMC2139813.PMID9314537.
  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.PMID9748260.
  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.PMID12080047.
  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.PMC2173557.PMID12082081.

Further reading[edit]