Α-辅肌动蛋白2

位於1號人類染色體的基因

α-辅肌动蛋白2(英語:Alpha-actinin-2)是一种蛋白质,在人类中由ACTN2基因编码。[6]该基因编码一种在骨骼肌心肌中表达的α-辅肌动蛋白异构体,其功能是将肌原纤维肌动蛋白细丝和肌联蛋白锚定到Z盘上。

Α-辅肌动蛋白2
已知的結構
PDB直系同源搜索: PDBe RCSB
識別號
别名ACTN2;, CMD1AA, CMH23, actinin alpha 2, MYOCOZ, MPD6
外部IDOMIM102573 MGI109192 HomoloGene31016 GeneCardsACTN2
相關疾病
牙周炎、​dilated cardiomyopathy 1AA[1]
基因位置(人类
1號染色體
染色体1號染色體[2]
1號染色體
Α-辅肌动蛋白2的基因位置
Α-辅肌动蛋白2的基因位置
基因座1q43起始236,664,141 bp[2]
终止236,764,631 bp[2]
RNA表达模式




查阅更多表达数据
直系同源
物種人類小鼠
Entrez
Ensembl
UniProt
mRNA​序列

NM_001103
​NM_001278343
​NM_001278344

NM_033268

蛋白序列

NP_001094
​NP_001265272
​NP_001265273

NP_150371

基因位置​(UCSC)Chr 1: 236.66 – 236.76 MbChr 13: 12.28 – 12.36 Mb
PubMed​查找[4][5]
維基數據
檢視/編輯人類檢視/編輯小鼠

结构

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α-辅肌动蛋白2是一种103.8kDa的蛋白质,由894个氨基酸组成。[7][8]每个分子都是棒状的(长度为35nm),并且以反平行的方式同源二聚化。每个单体都有一个N端肌动蛋白结合区,由两个钙调理蛋白同源结构域、两个C端EF手结构域和四个串联血影蛋白样重复序列组成,形成分子中心区域的杆状结构域。[9] 人类α-辅肌动蛋白2在3.5Å处的高分辨率晶体结构最近得到解决。[10]α辅肌动蛋白属于血影蛋白基因超家族,它代表一组不同的肌动蛋白结合细胞骨架蛋白,包括血影蛋白抗肌萎缩蛋白肌营养相关蛋白丝束蛋白[9]骨骼肌、心脏和平滑肌亚型定位于Z盘和类似的致密体,它们有助于锚定肌原纤维肌动蛋白丝。α-肌动蛋白2已被证明与KCNA5[11][12]DLG1[11]DISC1[13]MYOZ1[14]GRIN2B[15]ADAM12[16]ACTN3[17]MYPN[18]PDLIM3[19]PKN[20]MYOT[21]TTN[22]NMDAR[23]SYNPO2[24]LDB3[25]MYOZ1[14]产生相互作用。

功能

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α-辅肌动蛋白2的主要功能是在Z盘上交联丝状肌动蛋白分子和来自相邻肌小节的肌联蛋白分子,该功能受磷脂调节。[26][27]从汉普顿等人的研究中可以清楚地看出,这种交联可以呈现多种构象,偏好60°和120°的角度。[28]α-辅肌动蛋白2还在Z盘上的对接信号分子中发挥作用,另外的研究还表明α-辅肌动蛋白2与心脏离子通道的结合有关,尤其是Kv1.5[11]

临床意义

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ACTN2的突变与肥厚型心肌病[29]扩张型心肌病心内膜弹力纤维增生症有关。[30]α-辅肌动蛋白2的不同功能反映在携带ACTN2突变的患者的不同临床表现中。[31]

参考资料

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  1. ^ 與Α-辅肌动蛋白2相關的疾病;在維基數據上查看/編輯參考. 
  2. ^ 2.0 2.1 2.2 GRCh38: Ensembl release 89: ENSG00000077522 - Ensembl, May 2017
  3. ^ 3.0 3.1 3.2 GRCm38: Ensembl release 89: ENSMUSG00000052374 - Ensembl, May 2017
  4. ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
  5. ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
  6. ^ Entrez Gene: ACTN2 actinin, alpha 2. [2023-03-10]. (原始内容存档于2010-03-05). 
  7. ^ Protein Information – Basic Information: Protein COPaKB ID: P35609. Cardiac Organellar Protein Atlas Knowledgebase. [2015-04-13]. (原始内容存档于2015-04-13). 
  8. ^ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P. Integration of cardiac proteome biology and medicine by a specialized knowledgebase. Circulation Research. October 2013, 113 (9): 1043–53. PMC 4076475 . PMID 23965338. doi:10.1161/CIRCRESAHA.113.301151. 
  9. ^ 9.0 9.1 Luther PK. The vertebrate muscle Z-disc: sarcomere anchor for structure and signalling. Journal of Muscle Research and Cell Motility. 2009, 30 (5–6): 171–85. PMC 2799012 . PMID 19830582. doi:10.1007/s10974-009-9189-6. 
  10. ^ Ribeiro Ede A, Pinotsis N, Ghisleni A, Salmazo A, Konarev PV, Kostan J, Sjöblom B, Schreiner C, Polyansky AA, Gkougkoulia EA, Holt MR, Aachmann FL, Zagrović B, Bordignon E, Pirker KF, Svergun DI, Gautel M, Djinović-Carugo K. The structure and regulation of human muscle α-actinin. Cell. December 2014, 159 (6): 1447–60. PMC 4259493 . PMID 25433700. doi:10.1016/j.cell.2014.10.056. 
  11. ^ 11.0 11.1 11.2 Eldstrom J, Choi WS, Steele DF, Fedida D. SAP97 increases Kv1.5 currents through an indirect N-terminal mechanism. FEBS Letters. July 2003, 547 (1–3): 205–11. PMID 12860415. doi:10.1016/S0014-5793(03)00668-9 . 
  12. ^ Maruoka ND, Steele DF, Au BP, Dan P, Zhang X, Moore ED, Fedida D. alpha-actinin-2 couples to cardiac Kv1.5 channels, regulating current density and channel localization in HEK cells. FEBS Letters. May 2000, 473 (2): 188–94. PMID 10812072. doi:10.1016/S0014-5793(00)01521-0 . 
  13. ^ Morris JA, Kandpal G, Ma L, Austin CP. DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation. Human Molecular Genetics. July 2003, 12 (13): 1591–608. PMID 12812986. doi:10.1093/hmg/ddg162 . 
  14. ^ 14.0 14.1 Faulkner G, Pallavicini A, Comelli A, Salamon M, Bortoletto G, Ievolella C, Trevisan S, Kojic' S, Dalla Vecchia F, Laveder P, Valle G, Lanfranchi G. FATZ, a filamin-, actinin-, and telethonin-binding protein of the Z-disc of skeletal muscle. The Journal of Biological Chemistry. December 2000, 275 (52): 41234–42. PMID 10984498. doi:10.1074/jbc.M007493200 . 
  15. ^ Wyszynski M, Lin J, Rao A, Nigh E, Beggs AH, Craig AM, Sheng M. Competitive binding of alpha-actinin and calmodulin to the NMDA receptor. Nature. January 1997, 385 (6615): 439–42. PMID 9009191. S2CID 4266742. doi:10.1038/385439a0. 
  16. ^ Galliano MF, Huet C, Frygelius J, Polgren A, Wewer UM, Engvall E. Binding of ADAM12, a marker of skeletal muscle regeneration, to the muscle-specific actin-binding protein, alpha -actinin-2, is required for myoblast fusion. The Journal of Biological Chemistry. May 2000, 275 (18): 13933–9. PMID 10788519. doi:10.1074/jbc.275.18.13933 . 
  17. ^ Chan Y, Tong HQ, Beggs AH, Kunkel LM. Human skeletal muscle-specific alpha-actinin-2 and -3 isoforms form homodimers and heterodimers in vitro and in vivo. Biochemical and Biophysical Research Communications. July 1998, 248 (1): 134–9. PMID 9675099. doi:10.1006/bbrc.1998.8920. 
  18. ^ Bang ML, Mudry RE, McElhinny AS, Trombitás K, Geach AJ, Yamasaki R, Sorimachi H, Granzier H, Gregorio CC, Labeit S. Myopalladin, a novel 145-kilodalton sarcomeric protein with multiple roles in Z-disc and I-band protein assemblies. The Journal of Cell Biology. April 2001, 153 (2): 413–27. PMC 2169455 . PMID 11309420. doi:10.1083/jcb.153.2.413. 
  19. ^ Pomiès P, Macalma T, Beckerle MC. Purification and characterization of an alpha-actinin-binding PDZ-LIM protein that is up-regulated during muscle differentiation. The Journal of Biological Chemistry. October 1999, 274 (41): 29242–50. PMID 10506181. doi:10.1074/jbc.274.41.29242 . 
  20. ^ Mukai H, Toshimori M, Shibata H, Takanaga H, Kitagawa M, Miyahara M, Shimakawa M, Ono Y. Interaction of PKN with alpha-actinin. The Journal of Biological Chemistry. February 1997, 272 (8): 4740–6. PMID 9030526. doi:10.1074/jbc.272.8.4740 . 
  21. ^ Salmikangas P, Mykkänen OM, Grönholm M, Heiska L, Kere J, Carpén O. Myotilin, a novel sarcomeric protein with two Ig-like domains, is encoded by a candidate gene for limb-girdle muscular dystrophy. Human Molecular Genetics. July 1999, 8 (7): 1329–36. PMID 10369880. doi:10.1093/hmg/8.7.1329. 
  22. ^ Young P, Ferguson C, Bañuelos S, Gautel M. Molecular structure of the sarcomeric Z-disk: two types of titin interactions lead to an asymmetrical sorting of alpha-actinin. The EMBO Journal. March 1998, 17 (6): 1614–24. PMC 1170509 . PMID 9501083. doi:10.1093/emboj/17.6.1614. 
  23. ^ Chunn CJ, Starr PR, Gilbert DN. Neutrophil toxicity of amphotericin B. Antimicrobial Agents and Chemotherapy. August 1977, 12 (2): 226–30. PMC 429889 . PMID 900919. doi:10.1128/aac.12.2.226. 
  24. ^ Linnemann A, van der Ven PF, Vakeel P, Albinus B, Simonis D, Bendas G, Schenk JA, Micheel B, Kley RA, Fürst DO. The sarcomeric Z-disc component myopodin is a multiadapter protein that interacts with filamin and alpha-actinin. European Journal of Cell Biology. September 2010, 89 (9): 681–92. PMID 20554076. doi:10.1016/j.ejcb.2010.04.004. 
  25. ^ Jani K, Schöck F. Zasp is required for the assembly of functional integrin adhesion sites. The Journal of Cell Biology. December 2007, 179 (7): 1583–97. PMC 2373490 . PMID 18166658. doi:10.1083/jcb.200707045. 
  26. ^ Young P, Gautel M. The interaction of titin and alpha-actinin is controlled by a phospholipid-regulated intramolecular pseudoligand mechanism. The EMBO Journal. December 2000, 19 (23): 6331–40. PMC 305858 . PMID 11101506. doi:10.1093/emboj/19.23.6331. 
  27. ^ Fukami K, Furuhashi K, Inagaki M, Endo T, Hatano S, Takenawa T. Requirement of phosphatidylinositol 4,5-bisphosphate for alpha-actinin function. Nature. September 1992, 359 (6391): 150–2. PMID 1326084. S2CID 4372960. doi:10.1038/359150a0. 
  28. ^ Hampton CM, Taylor DW, Taylor KA. Novel structures for alpha-actinin:F-actin interactions and their implications for actin-membrane attachment and tension sensing in the cytoskeleton. Journal of Molecular Biology. April 2007, 368 (1): 92–104. PMC 1919418 . PMID 17331538. doi:10.1016/j.jmb.2007.01.071. 
  29. ^ Chiu C, Bagnall RD, Ingles J, Yeates L, Kennerson M, Donald JA, Jormakka M, Lind JM, Semsarian C. Mutations in alpha-actinin-2 cause hypertrophic cardiomyopathy: a genome-wide analysis. Journal of the American College of Cardiology. March 2010, 55 (11): 1127–35. PMID 20022194. doi:10.1016/j.jacc.2009.11.016 . 
  30. ^ Mohapatra B, Jimenez S, Lin JH, Bowles KR, Coveler KJ, Marx JG, Chrisco MA, Murphy RT, Lurie PR, Schwartz RJ, Elliott PM, Vatta M, McKenna W, Towbin JA, Bowles NE. Mutations in the muscle LIM protein and alpha-actinin-2 genes in dilated cardiomyopathy and endocardial fibroelastosis. Molecular Genetics and Metabolism. 2003, 80 (1–2): 207–15. PMID 14567970. doi:10.1016/s1096-7192(03)00142-2. 
  31. ^ Bagnall RD, Molloy LK, Kalman JM, Semsarian C. Exome sequencing identifies a mutation in the ACTN2 gene in a family with idiopathic ventricular fibrillation, left ventricular noncompaction, and sudden death. BMC Medical Genetics. September 2014, 15 (1): 99. PMC 4355500 . PMID 25224718. doi:10.1186/s12881-014-0099-0. 

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