EZR |
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![](//upload.wikimedia.org/wikipedia/commons/thumb/0/04/Protein_VIL2_PDB_1ni2.png/250px-Protein_VIL2_PDB_1ni2.png) |
PDBに登録されている構造 |
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PDB | オルソログ検索: RCSB PDBe PDBj |
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PDBのIDコード一覧 |
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4RM8, 4RMA, 4RM9, 1NI2 |
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識別子 |
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記号 | EZR, CVIL, CVL, HEL-S-105, VIL2, Ezrin |
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外部ID | OMIM: 123900 MGI: 98931 HomoloGene: 55740 GeneCards: EZR |
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遺伝子の位置 (ヒト) |
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![6番染色体 (ヒト)](//upload.wikimedia.org/wikipedia/commons/thumb/0/03/Ideogram_human_chromosome_6.svg/300px-Ideogram_human_chromosome_6.svg.png) | 染色体 | 6番染色体 (ヒト)[1] |
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| バンド | データ無し | 開始点 | 158,765,741 bp[1] |
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終点 | 158,819,368 bp[1] |
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遺伝子の位置 (マウス) |
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![17番染色体 (マウス)](//upload.wikimedia.org/wikipedia/commons/thumb/1/13/Ideogram_house_mouse_chromosome_17.svg/260px-Ideogram_house_mouse_chromosome_17.svg.png) | 染色体 | 17番染色体 (マウス)[2] |
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| バンド | データ無し | 開始点 | 7,005,440 bp[2] |
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終点 | 7,050,183 bp[2] |
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遺伝子オントロジー |
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分子機能 | • protein domain specific binding • protein-containing complex binding • cytoskeletal protein binding • protein kinase A regulatory subunit binding • protein kinase A catalytic subunit binding • S100 protein binding • actin filament binding • 血漿タンパク結合 • cell adhesion molecule binding • microtubule binding • ATPase binding • actin binding • RNA結合 • cadherin binding • protein C-terminus binding • disordered domain specific binding • protein kinase A binding • identical protein binding
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細胞の構成要素 | • 細胞質 • 細胞質基質 • エンドソーム • 膜 • 焦点接着 • 横行小管 • ruffle • Schwann cell microvillus • ruffle membrane • actin cytoskeleton • perinuclear region of cytoplasm • 細胞骨格 • cell projection • cytoplasmic side of apical plasma membrane • ミエリン鞘 • 微絨毛 • microspike • apical plasma membrane • 脂質ラフト • エキソソーム • microvillus membrane • ciliary basal body • 糸状偽足 • cortical cytoskeleton • 細胞膜 • apical part of cell • astrocyte projection • 細胞内 • 細胞皮質 • 刷子縁 • マイクロフィラメント • TCR signalosome • 細胞周辺 • cell body • 小胞 • plasma membrane raft • uropod • basolateral plasma membrane • 免疫シナプス • cell tip • fibrillar center • 細胞外空間 • extrinsic component of membrane • 高分子複合体
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生物学的プロセス | • leukocyte cell-cell adhesion • regulation of organelle assembly • sphingosine-1-phosphate receptor signaling pathway • negative regulation of p38MAPK cascade • actin filament bundle assembly • establishment of epithelial cell apical/basal polarity • positive regulation of multicellular organism growth • astral microtubule organization • cellular response to cAMP • establishment of endothelial barrier • microvillus assembly • negative regulation of T cell receptor signaling pathway • 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 • 上皮細胞の分化 • regulation of actin cytoskeleton organization • negative regulation of transcription by RNA polymerase II • positive regulation of protein secretion • membrane to membrane docking • regulation of cell shape • protein kinase A signaling • establishment of centrosome localization • phosphatidylinositol-mediated signaling • regulation of cell size • actin cytoskeleton reorganization • filopodium assembly • receptor internalization • terminal web assembly • 軸索誘導 • positive regulation of gene expression • negative regulation of ERK1 and ERK2 cascade • protein localization to cell cortex • regulation of microvillus length • protein localization to plasma membrane • positive regulation of protein localization to plasma membrane
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出典:Amigo / QuickGO |
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オルソログ |
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種 | ヒト | マウス |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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RefSeq (mRNA) | | |
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RefSeq (タンパク質) | | |
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場所 (UCSC) | Chr 6: 158.77 – 158.82 Mb | Chr 6: 7.01 – 7.05 Mb |
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PubMed検索 | [3] | [4] |
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ウィキデータ |
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エズリン(Ezrin)は、ヒトではEZR遺伝子によりコードされるタンパク質である[5]。モエシン、ラディキシンとともにERMファミリーを構成する。シトビリン(cytovillin)やビリン2(Villin-2)とも呼ばれる。
構造
エズリンのN末端にはFERMドメインがあり、さらに3つのサブドメインへと分類される。C末端にはERMドメインがある。
機能
この遺伝子でコードされる細胞質表在性膜タンパク質は、微絨毛のチロシンキナーゼによってリン酸化される。アクチンからなる細胞骨格と細胞膜との間の架橋として機能しており、細胞表面の接着、移動、組織化等で重要な役割を果たしている[6]。
N末端のFERMドメインは、ナトリウム水素交換輸送体制御因子(NHERF)と結合する[7]。この結合は、エズリンが活性型でないと起こらない。エズリンの活性化は、(1)N末端ドメインがホスファチジルイノシトール4,5-ビスリン酸に結合する、(2)C末端のトレオニンT567がリン酸化するという2つの要因が協調することで起こる[8][9]。C末端のマイクロフィラメントへの結合、N末端の膜タンパク質への結合により、タンパク質の活性型立体配座が安定化される。CD44やICAM2のような膜タンパク質との結合は間接的なものであるが、EBP50は直接結合する[10]。
相互作用
エズリンは、以下のタンパク質とタンパク質間相互作用する。
- CD43[11]
- Fasリガンド[12][13]
- ICAM-1[14]
- ICAM2[14]
- ICAM3[14][15]
- マーリン[16]
- モエシン[12][17][18]
- PIK3R1[19]
- パラジン[20]
- S100P[21]
- シンデカン-2[22]
- SLC9A3R1[23][24]
- SLC9A3R2[25][26]
- VCAM-1[27]
出典
- ^ a b c GRCh38: Ensembl release 89: ENSG00000092820 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000052397 - Ensembl, May 2017
- ^ Human PubMed Reference:
- ^ Mouse PubMed Reference:
- ^ “cDNA cloning and sequencing of the protein-tyrosine kinase substrate, ezrin, reveals homology to band 4.1”. EMBO J. 8 (13): 4133-42. (December 1989). PMC 401598. PMID 2591371. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC401598/.
- ^ “Entrez Gene: VIL2 villin 2 (ezrin)”. 2020年3月31日閲覧。
- ^ “Activation of nanoscale allosteric protein domain motion revealed by neutron spin echo spectroscopy”. Biophysical Journal 99 (10): 3473-82. (2010). doi:10.1016/j.bpj.2010.09.058. PMC 2980739. PMID 21081097. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980739/.
- ^ “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. (2012). doi:10.1074/jbc.M112.380972. PMC 3481312. PMID 22927432. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481312/.
- ^ “Mode of Ezrin-Membrane Interaction as a Function of PIP2 Binding and Pseudophosphorylation”. Biophys. J. 110 (12): 2710-2719. (2016). doi:10.1016/j.bpj.2016.05.009. PMC 4919509. PMID 27332129. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919509/.
- ^ “Ezrin/radixin/moesin proteins and Rho GTPase signalling in leucocytes”. Immunology 112 (2): 165-176. (2004). doi:10.1111/j.1365-2567.2004.01882.x. PMC 1782489. PMID 15147559. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1782489/.
- ^ “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. (June 1998). PMID 9616160.
- ^ a b “Cytoskeleton-mediated death receptor and ligand concentration in lipid rafts forms apoptosis-promoting clusters in cancer chemotherapy”. J. Biol. Chem. 280 (12): 11641-7. (March 2005). doi:10.1074/jbc.M411781200. PMID 15659383.
- ^ “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. (October 2000). doi:10.1093/emboj/19.19.5123. PMC 302100. PMID 11013215. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC302100/.
- ^ a b c “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. (August 1998). doi:10.1074/jbc.273.34.21893. PMID 9705328.
- ^ “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. (March 2002). doi:10.1074/jbc.M110694200. PMID 11784723.
- ^ “Homotypic and heterotypic interaction of the neurofibromatosis 2 tumor suppressor protein merlin and the ERM protein ezrin”. J. Cell Sci. 112 (6): 895-904. (March 1999). PMID 10036239.
- ^ “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. (August 1995). doi:10.1091/mbc.6.8.1061. PMC 301263. PMID 7579708. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC301263/.
- ^ “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. (November 1993). doi:10.1073/pnas.90.22.10846. PMC 47875. PMID 8248180. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC47875/.
- ^ “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. (June 1999). doi:10.1073/pnas.96.13.7300. PMC 22080. PMID 10377409. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC22080/.
- ^ “Characterization of human palladin, a microfilament-associated protein”. Mol. Biol. Cell 12 (10): 3060-73. (October 2001). doi:10.1091/mbc.12.10.3060. PMC 60155. PMID 11598191. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC60155/.
- ^ “Ca2+-dependent binding and activation of dormant ezrin by dimeric S100P”. Mol. Biol. Cell 14 (6): 2372-84. (June 2003). doi:10.1091/mbc.E02-09-0553. PMC 194886. PMID 12808036. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC194886/.
- ^ “Ezrin links syndecan-2 to the cytoskeleton”. J. Cell Sci. 113 (7): 1267-76. (April 2000). PMID 10704377.
- ^ “Interaction between two adapter proteins, PAG and EBP50: a possible link between membrane rafts and actin cytoskeleton”. FEBS Lett. 507 (2): 133-6. (October 2001). doi:10.1016/s0014-5793(01)02955-6. PMID 11684085.
- ^ “Identification of EBP50: A PDZ-containing phosphoprotein that associates with members of the ezrin-radixin-moesin family”. J. Cell Biol. 139 (1): 169-79. (October 1997). doi:10.1083/jcb.139.1.169. PMC 2139813. PMID 9314537. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2139813/.
- ^ “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. (October 1998). doi:10.1074/jbc.273.40.25856. PMID 9748260.
- ^ “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. (September 2002). doi:10.1074/jbc.M202522200. PMID 12080047.
- ^ “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. (June 2002). doi:10.1083/jcb.200112126. PMC 2173557. PMID 12082081. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173557/.
関連文献
- “The role of the CD44/ezrin complex in cancer metastasis.”. Crit. Rev. Oncol. Hematol. 46 (2): 165-86. (2004). doi:10.1016/S1040-8428(02)00172-5. PMID 12711360.