Ezrin

EZR
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4RM8, 4RMA, 4RM9, 1NI2
Identifiers
Aliases	EZR, CVIL, CVL, HEL-S-105, VIL2, Ezrin
External IDs	MGI: 98931 HomoloGene: 55740 GeneCards: EZR
Gene ontology Molecular function • protein domain specific binding • protein complex binding • cytoskeletal protein binding • protein kinase A regulatory subunit binding • protein kinase A catalytic subunit binding • S100 protein binding • actin filament binding • protein binding • cell adhesion molecule binding • microtubule binding • ATPase binding • actin binding • poly(A) RNA binding • cadherin binding involved in cell-cell adhesion Cellular component • cytoplasm • cytosol • endosome • membrane • focal adhesion • T-tubule • ruffle • Schwann cell microvillus • ruffle membrane • actin cytoskeleton • perinuclear region of cytoplasm • cytoskeleton • cell projection • cytoplasmic side of apical plasma membrane • myelin sheath • extracellular space • microvillus • microspike • nucleolus • apical plasma membrane • membrane raft • extracellular exosome • microvillus membrane • ciliary basal body • filopodium • cortical cytoskeleton • plasma membrane • apical part of cell • astrocyte projection • intracellular • cell cortex • brush border • actin filament • TCR signalosome • cell periphery • extrinsic component of membrane • cell body • vesicle • plasma membrane raft • uropod • basolateral plasma membrane • immunological synapse • cell tip • cell-cell adherens junction Biological process • leukocyte cell-cell adhesion • regulation of organelle assembly • sphingosine-1-phosphate signaling pathway • negative regulation of p38MAPK cascade • actin filament bundle assembly • establishment of epithelial cell apical/basal polarity • cytoskeletal anchoring at plasma membrane • positive regulation of multicellular organism growth • astral microtubule organization • cellular response to cAMP • establishment of endothelial barrier • microvillus assembly • positive regulation of cellular protein catabolic process • negative regulation of T cell receptor signaling pathway • positive regulation of establishment of protein localization to plasma membrane • gland morphogenesis • cortical microtubule organization • positive regulation of protein localization to early endosome • positive regulation of early endosome to late endosome transport • intestinal D-glucose absorption • establishment or maintenance of apical/basal cell polarity • regulation of NIK/NF-kappaB signaling • epithelial cell differentiation • regulation of actin cytoskeleton organization • negative regulation of interleukin-2 secretion • negative regulation of transcription from RNA polymerase II promoter • positive regulation of protein secretion • membrane to membrane docking • regulation of cell shape • protein kinase A signaling • establishment of centrosome localization • regulation of microvillus length • phosphatidylinositol-mediated signaling • regulation of cell size • actin cytoskeleton reorganization • filopodium assembly • receptor internalization • terminal web assembly • axon guidance • positive regulation of gene expression • cellular protein complex localization • negative regulation of ERK1 and ERK2 cascade • establishment of protein localization to plasma membrane • protein localization to cell cortex 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_003379	NM_009510
RefSeq (protein)	NP_001104547.1 NP_003370.2	NP_033536.2
Location (UCSC)	Chr 6: 158.77 – 158.82 Mb	Chr 17: 6.74 – 6.78 Mb
PubMed search	[1]	[2]
Wikidata

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Ezrin also known as cytovillin or villin-2 is a protein that in humans is encoded by the EZR gene.^[3]

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.^[4]

The N-terminal FERM domain strongly binds sodium-hydrogen exchanger regulatory factor (NHERF) proteins (involving long-range allostery).^[5] The C-terminal binds to actin, phosphatidylinositol(4,5)bis-phosphate (PIP2)^[6] and membrane proteins like CD44 and ICAM-2.

Interactions

VIL2 has been shown to interact with:

• CD43,^[7]
• FASLG,^[8][9]
• ICAM-1,^[10]
• ICAM2,^[10]
• ICAM3,^[10][11]
• Merlin,^[12]
• MSN,^[8][13][14]
• PIK3R1,^[15]
• PALLD^[16]
• S100P,^[17]
• SDC2,^[18]
• SLC9A3R1,^[19][20]
• SLC9A3R2,^[21][22] and
• VCAM-1.^[23]

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. 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.
4. "Entrez Gene: VIL2 villin 2 (ezrin)".
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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.