Ezrin

Ezrin
PDB rendering based on 1ni2.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1NI2​
Identifiers
Symbols	EZR ; CVIL; CVL; HEL-S-105; VIL2
External IDs	OMIM: 123900 MGI: 98931 HomoloGene: 55740 GeneCards: EZR Gene
Gene ontology Molecular function • actin binding • protein binding • microtubule binding • protein domain specific binding • protein kinase A catalytic subunit binding • protein kinase A regulatory subunit binding • S100 protein binding • poly(A) RNA binding • cell adhesion molecule binding • actin filament binding • ATPase binding Cellular component • ruffle • immunological synapse • uropod • extracellular space • nucleolus • cytoplasm • endosome • cytosol • actin filament • plasma membrane • microvillus • brush border • focal adhesion • actin cytoskeleton • membrane • basolateral plasma membrane • apical plasma membrane • extrinsic component of membrane • filopodium • T-tubule • cortical cytoskeleton • microvillus membrane • vesicle • ruffle membrane • ciliary basal body • TCR signalosome • cell projection • myelin sheath • cell body • microspike • plasma membrane raft • apical part of cell • perinuclear region of cytoplasm • cell tip • extracellular exosome • cell periphery • astrocyte projection • Schwann cell microvillus • cytoplasmic side of apical plasma membrane Biological process • negative regulation of transcription from RNA polymerase II promoter • intestinal D-glucose absorption • sphingosine-1-phosphate signaling pathway • cytoskeletal anchoring at plasma membrane • leukocyte cell-cell adhesion • axon guidance • regulation of cell shape • regulation of cell size • positive regulation of gene expression • protein kinase A signaling • gland morphogenesis • membrane to membrane docking • microvillus assembly • astral microtubule organization • actin cytoskeleton reorganization • receptor internalization • regulation of microvillus length • regulation of actin cytoskeleton organization • cellular protein complex localization • positive regulation of multicellular organism growth • cortical microtubule organization • establishment of epithelial cell apical/basal polarity • filopodium assembly • phosphatidylinositol-mediated signaling • positive regulation of protein secretion • negative regulation of T cell receptor signaling pathway • actin filament bundle assembly • establishment of centrosome localization • establishment of endothelial barrier • negative regulation of ERK1 and ERK2 cascade • cellular response to cAMP • protein localization to cell cortex • establishment of protein localization to plasma membrane • positive regulation of establishment of protein localization to plasma membrane • negative regulation of interleukin-2 secretion • regulation of NIK/NF-kappaB signaling • regulation of organelle assembly • terminal web assembly • positive regulation of protein localization to early endosome • positive regulation of cellular protein catabolic process • negative regulation of p38MAPK cascade • positive regulation of early endosome to late endosome transport Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7430	22350
Ensembl	ENSG00000092820	ENSMUSG00000052397
UniProt	P15311	P26040
RefSeq (mRNA)	NM_001111077	NM_009510
RefSeq (protein)	NP_001104547	NP_033536
Location (UCSC)	Chr 6: 158.77 – 158.82 Mb	Chr 17: 6.74 – 6.78 Mb
PubMed search

Ezrin also known as cytovillin or villin-2 is a protein that in humans is encoded by the EZR gene.^[1]

Structure

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

Function

The cytoplasmic peripheral membrane protein encoded by this gene functions as a protein-tyrosine kinase substrate in microvilli. As a member of the ERM protein family, this protein serves as an intermediate between the plasma membrane and the actin cytoskeleton. It plays a key role in cell surface structure adhesion, migration, and organization.^[2]

The N-terminal FERM domain strongly binds sodium-hydrogen exchanger regulatory factor (NHERF) proteins (involving long-range allostery).^[3] The C-terminal binds to actin, phosphatidylinositol(4,5)bis-phosphate (PIP2)^[4] and membrane proteins like CD44 and ICAM-2.

Interactions

VIL2 has been shown to interact with:

• CD43,^[5]
• FASLG,^[6][7]
• ICAM-1,^[8]
• ICAM2,^[8]
• ICAM3,^[8][9]
• Merlin,^[10]
• MSN,^[6][11][12]
• PIK3R1,^[13]
• PALLD^[14]
• S100P,^[15]
• SDC2,^[16]
• SLC9A3R1,^[17][18]
• SLC9A3R2,^[19][20] and
• VCAM-1.^[21]

References

1. 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. PMC 401598. PMID 2591371.
2. "Entrez Gene: VIL2 villin 2 (ezrin)".
3. 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. doi:10.1016/j.bpj.2010.09.058. PMC 2980739. PMID 21081097.
4. 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.
5. 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. PMID 9616160.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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. PMID 10036239.
11. 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.
12. 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. doi:10.1073/pnas.90.22.10846. PMC 47875. PMID 8248180.
13. 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. doi:10.1073/pnas.96.13.7300. PMC 22080. PMID 10377409.
14. 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.
15. 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.
16. Granés F, Urena JM, Rocamora N, Vilaró S (April 2000). "Ezrin links syndecan-2 to the cytoskeleton". J. Cell. Sci. 113 (7): 1267–76. PMID 10704377.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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

• Martin TA, Harrison G, Mansel RE, Jiang WG (2004). "The role of the CD44/ezrin complex in cancer metastasis.". Crit. Rev. Oncol. Hematol. 46 (2): 165–86. doi:10.1016/S1040-8428(02)00172-5. PMID 12711360.