Α-辅肌动蛋白2

Α-辅肌动蛋白2
已知的結構
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	1H8B、1HCI、1QUU、4D1E、5A37、5A36、5A38、5A4B
識別號
别名	ACTN2；, CMD1AA, CMH23, actinin alpha 2, MYOCOZ, MPD6
外部ID	OMIM：102573 MGI：109192 HomoloGene：31016 GeneCards：ACTN2
相關疾病
	牙周炎、dilated cardiomyopathy 1AA[1]
基因位置（人类）
染色体	1號染色體[2]
终止	236,764,631 bp[2]
基因位置（小鼠）
染色体	小鼠13号染色体[3]
终止	12,355,641 bp[3]
RNA表达模式
	; ; ; ;
	查阅更多表达数据
基因本體
分子功能	• calcium ion binding; • protein dimerization activity; • protein homodimerization activity; • transmembrane transporter binding; • protein domain specific binding; • titin Z domain binding; • LIM domain binding; • titin binding; • 金屬離子結合; • cytoskeletal protein binding; • integrin binding; • actin filament binding; • 血浆蛋白结合; • nuclear receptor coactivator activity; • 相同蛋白质结合; • FATZ binding; • actin binding; • phosphatidylinositol-4,5-bisphosphate binding; • structural constituent of muscle;
細胞組分	• 細胞質; • 细胞质基质; • 偽足; • 粘着斑; • 絲狀偽足; • 细胞膜; • 肌节; • 树突棘; • 細胞外區域; • Z disc; • cortical actin cytoskeleton; • 微丝; • 外排體; • 细胞骨架; • platelet alpha granule lumen; • postsynaptic density membrane; • glutamatergic synapse; • postsynaptic density, intracellular component;
生物學過程	• positive regulation of cation channel activity; • regulation of apoptotic process; • 肌肉收缩; • positive regulation of potassium ion transport; • phospholipase C-activating angiotensin-activated signaling pathway; • cardiac muscle cell development; • regulation of membrane potential; • platelet degranulation; • actin filament uncapping; • MAPK cascade; • focal adhesion assembly; • negative regulation of protein localization to cell surface; • positive regulation of signaling receptor activity; • 細胞粘附; • negative regulation of potassium ion transmembrane transporter activity; • negative regulation of potassium ion transport; • regulation of nucleic acid-templated transcription; • microspike assembly; • positive regulation of endocytic recycling; • muscle filament sliding; • protein homotetramerization; • sarcomere organization; • positive regulation of potassium ion transmembrane transporter activity; • protein localization to plasma membrane; • positive regulation of nucleic acid-templated transcription; • regulation of NMDA receptor activity;
	Sources:Amigo / QuickGO
直系同源
	88
	11472
	ENSG00000077522
	ENSMUSG00000052374
	P35609
	Q9JI91
	NM_001103; NM_001278343; NM_001278344
	NM_033268
	NP_001094; NP_001265272; NP_001265273
	NP_150371
	維基數據

α-辅肌动蛋白2（英語：）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和心肌中表达的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。

结构

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、肌营养相关蛋白和丝束蛋白。[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]和MYOZ1[14]产生相互作用。

功能

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K_v1.5。[11]

临床意义

ACTN2的突变与肥厚型心肌病、[29]扩张型心肌病和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

.
GRCh38: Ensembl release 89: ENSG00000077522 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000052374 - Ensembl, May 2017
. National Center for Biotechnology Information, U.S. National Library of Medicine.
. National Center for Biotechnology Information, U.S. National Library of Medicine.
. [2023-03-10]. （原始内容存档于2010-03-05）.
. Cardiac Organellar Protein Atlas Knowledgebase. [2015-04-13]. （原始内容存档于2015-04-13）.
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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. . The Journal of Biological Chemistry. December 2000, 275 (52): 41234–42. PMID 10984498. doi:10.1074/jbc.M007493200 .
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Galliano MF, Huet C, Frygelius J, Polgren A, Wewer UM, Engvall E. . The Journal of Biological Chemistry. May 2000, 275 (18): 13933–9. PMID 10788519. doi:10.1074/jbc.275.18.13933 .
Chan Y, Tong HQ, Beggs AH, Kunkel LM. . Biochemical and Biophysical Research Communications. July 1998, 248 (1): 134–9. PMID 9675099. doi:10.1006/bbrc.1998.8920.
Bang ML, Mudry RE, McElhinny AS, Trombitás K, Geach AJ, Yamasaki R, Sorimachi H, Granzier H, Gregorio CC, Labeit S. . The Journal of Cell Biology. April 2001, 153 (2): 413–27. PMC 2169455 . PMID 11309420. doi:10.1083/jcb.153.2.413.
Pomiès P, Macalma T, Beckerle MC. . The Journal of Biological Chemistry. October 1999, 274 (41): 29242–50. PMID 10506181. doi:10.1074/jbc.274.41.29242 .
Mukai H, Toshimori M, Shibata H, Takanaga H, Kitagawa M, Miyahara M, Shimakawa M, Ono Y. . The Journal of Biological Chemistry. February 1997, 272 (8): 4740–6. PMID 9030526. doi:10.1074/jbc.272.8.4740 .
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Young P, Ferguson C, Bañuelos S, Gautel M. . The EMBO Journal. March 1998, 17 (6): 1614–24. PMC 1170509 . PMID 9501083. doi:10.1093/emboj/17.6.1614.
Chunn CJ, Starr PR, Gilbert DN. . Antimicrobial Agents and Chemotherapy. August 1977, 12 (2): 226–30. PMC 429889 . PMID 900919. doi:10.1128/aac.12.2.226.
Linnemann A, van der Ven PF, Vakeel P, Albinus B, Simonis D, Bendas G, Schenk JA, Micheel B, Kley RA, Fürst DO. . European Journal of Cell Biology. September 2010, 89 (9): 681–92. PMID 20554076. doi:10.1016/j.ejcb.2010.04.004.
Jani K, Schöck F. . The Journal of Cell Biology. December 2007, 179 (7): 1583–97. PMC 2373490 . PMID 18166658. doi:10.1083/jcb.200707045.
Young P, Gautel M. . The EMBO Journal. December 2000, 19 (23): 6331–40. PMC 305858 . PMID 11101506. doi:10.1093/emboj/19.23.6331.
Fukami K, Furuhashi K, Inagaki M, Endo T, Hatano S, Takenawa T. . Nature. September 1992, 359 (6391): 150–2. PMID 1326084. S2CID 4372960. doi:10.1038/359150a0.
Hampton CM, Taylor DW, Taylor KA. . Journal of Molecular Biology. April 2007, 368 (1): 92–104. PMC 1919418 . PMID 17331538. doi:10.1016/j.jmb.2007.01.071.
Chiu C, Bagnall RD, Ingles J, Yeates L, Kennerson M, Donald JA, Jormakka M, Lind JM, Semsarian C. . Journal of the American College of Cardiology. March 2010, 55 (11): 1127–35. PMID 20022194. doi:10.1016/j.jacc.2009.11.016 .
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. . Molecular Genetics and Metabolism. 2003, 80 (1–2): 207–15. PMID 14567970. doi:10.1016/s1096-7192(03)00142-2.
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延申阅读

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Young P, Ferguson C, Bañuelos S, Gautel M. . The EMBO Journal. March 1998, 17 (6): 1614–24. PMC 1170509 . PMID 9501083. doi:10.1093/emboj/17.6.1614.
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Maruoka ND, Steele DF, Au BP, Dan P, Zhang X, Moore ED, Fedida D. . FEBS Letters. May 2000, 473 (2): 188–94. PMID 10812072. doi:10.1016/S0014-5793(00)01521-0 .
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外部链接

Mass spectrometry characterization of human ACTN2 at COPaKB
GeneReviews/NIH/NCBI/UW entry on Familial Hypertrophic Cardiomyopathy Overview （页面存档备份，存于）
Human ACTN2 genome location and ACTN2 gene details page in the UCSC Genome Browser.

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[1] .

[refGRCh38Ensembl-2] GRCh38: Ensembl release 89: ENSG00000077522 - Ensembl, May 2017

[refGRCm38Ensembl-3] GRCm38: Ensembl release 89: ENSMUSG00000052374 - Ensembl, May 2017

[4] . National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] . National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-6] . [2023-03-10]. （原始内容存档于2010-03-05）.

[7] . Cardiac Organellar Protein Atlas Knowledgebase. [2015-04-13]. （原始内容存档于2015-04-13）.

[cite_PMID_|_23965338-8] 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. . Circulation Research. October 2013, 113 (9): 1043–53. PMC 4076475 . PMID 23965338. doi:10.1161/CIRCRESAHA.113.301151.

[cite_PMID_|_19830582-9] Luther PK. . 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. . Cell. December 2014, 159 (6): 1447–60. PMC 4259493 . PMID 25433700. doi:10.1016/j.cell.2014.10.056.

[pmid12860415-11] Eldstrom J, Choi WS, Steele DF, Fedida D. . FEBS Letters. July 2003, 547 (1–3): 205–11. PMID 12860415. doi:10.1016/S0014-5793(03)00668-9 .

[pmid10812072-12] Maruoka ND, Steele DF, Au BP, Dan P, Zhang X, Moore ED, Fedida D. . FEBS Letters. May 2000, 473 (2): 188–94. PMID 10812072. doi:10.1016/S0014-5793(00)01521-0 .

[pmid12812986-13] Morris JA, Kandpal G, Ma L, Austin CP. . Human Molecular Genetics. July 2003, 12 (13): 1591–608. PMID 12812986. doi:10.1093/hmg/ddg162 .

[pmid10984498-14] 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. . The Journal of Biological Chemistry. December 2000, 275 (52): 41234–42. PMID 10984498. doi:10.1074/jbc.M007493200 .

[pmid9009191-15] Wyszynski M, Lin J, Rao A, Nigh E, Beggs AH, Craig AM, Sheng M. . Nature. January 1997, 385 (6615): 439–42. PMID 9009191. S2CID 4266742. doi:10.1038/385439a0.

[pmid10788519-16] Galliano MF, Huet C, Frygelius J, Polgren A, Wewer UM, Engvall E. . The Journal of Biological Chemistry. May 2000, 275 (18): 13933–9. PMID 10788519. doi:10.1074/jbc.275.18.13933 .

[pmid9675099-17] Chan Y, Tong HQ, Beggs AH, Kunkel LM. . Biochemical and Biophysical Research Communications. July 1998, 248 (1): 134–9. PMID 9675099. doi:10.1006/bbrc.1998.8920.

[pmid11309420-18] Bang ML, Mudry RE, McElhinny AS, Trombitás K, Geach AJ, Yamasaki R, Sorimachi H, Granzier H, Gregorio CC, Labeit S. . 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. . 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. . 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. . 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. . 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. . 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. . 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. . 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 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. . Nature. September 1992, 359 (6391): 150–2. PMID 1326084. S2CID 4372960. doi:10.1038/359150a0.

[28] Hampton CM, Taylor DW, Taylor KA. . 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. . 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. . 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. . BMC Medical Genetics. September 2014, 15 (1): 99. PMC 4355500 . PMID 25224718. doi:10.1186/s12881-014-0099-0.