利用者:空色水色/Α-アクチニン2

ACTN2
PDBに登録されている構造
PDB	オルソログ検索: RCSB PDBe PDBj
PDBのIDコード一覧
	1H8B, 1HCI, 1QUU, 4D1E, 5A37, 5A36, 5A38, 5A4B
識別子
記号	ACTN2, CMD1AA, CMH23, actinin alpha 2, MYOCOZ, MPD6
外部ID	OMIM: 102573 MGI: 109192 HomoloGene: 31016 GeneCards: ACTN2
遺伝子の位置 (ヒト)
染色体	1番染色体 (ヒト)
終点	236,764,631 bp
遺伝子の位置 (マウス)
染色体	13番染色体 (マウス)
終点	12,355,641 bp
RNA発現パターン
	; ; ; ;
	さらなる参照発現データ
遺伝子オントロジー
分子機能	• 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; • 金属イオン結合; • cytoskeletal protein binding; • integrin binding; • actin filament binding; • 血漿タンパク結合; • nuclear receptor coactivator activity; • identical protein binding; • FATZ binding; • actin binding; • phosphatidylinositol-4,5-bisphosphate binding; • structural constituent of muscle;
細胞の構成要素	• 細胞質; • 細胞質基質; • 仮足; • 焦点接着; • 糸状偽足; • 細胞膜; • サルコメア; • 樹状突起スパイン; • 細胞外領域; • Z discdkac; • cortical actin cytoskeleton; • マイクロフィラメント; • エキソソーム; • 細胞骨格; • platelet alpha granule lumen; • postsynaptic density membrane; • glutamatergic synapse; • postsynaptic density, intracellular component;
生物学的プロセス	• positive regulation of cation channel activity; • regulation of apoptotic process; • 筋収縮; • positive regulation of potassium ion transport; • phospholipase C-activating angiotensin-activated signaling pathway; • cardiac muscle cell development; • 膜電位の制御; • platelet degranulation; • actin filament uncapping; • MAPK cascade; • focal adhesion assembly; • negative regulation of protein localization to cell surface; • positive regulation of signaling receptor activity; • 細胞接着; • 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;
	出典:Amigo / QuickGO
オルソログ
	88
	11472
	ENSG00000077522
	ENSMUSG00000052374
	P35609
	Q9JI91
	NM_001103; NM_001278343; NM_001278344
	NM_033268
	NP_001094; NP_001265272; NP_001265273
	NP_150371
	ウィキデータ
閲覧/編集ヒト	閲覧/編集マウス

α-アクチニン2（Alpha-actinin 2）は、ヒトのACTN2遺伝子にコードされたタンパク質である^[5]。この遺伝子は骨格筋および心筋の両方で発現される。α-アクチニン2はα-アクチニンアイソフォームの一つであり、筋原繊維アクチンの細フィラメントとチチンをZ板に固定する機能を持つ。

構造

α-アクチニン2は、894個のアミノ酸から成る103.8kDaのタンパク質である^[6]^[7]。3.5Åでのヒトα-アクチニン2の結晶構造が明らかにされている^[8]。長さ35nmの棒状であり、逆平行ホモ二量体化する。各単量体は、2つのカルポニン相同ドメイン、2つのC末端 EFハンドドメイン、および4つのタンデムスペクトリン様反復配列からなるN末端アクチン結合領域を有し、分子の中央領域に棒ドメインを形成する^[9]。

α-アクチニンは、スペクトリン、ジストロフィン、ユートロフィン、フィンブリンなどの細胞骨格アクチン結合タンパク質グループのスペクトリン遺伝子スーパーファミリーに属する^[9]。

骨格筋、心筋、および平滑筋に存在するアイソフォームは、Z板および類似の高密度体に局在し、筋原線維のアクチンフィラメントの固定を助ける。α-アクチニン2はKCNA5^[10]^[11]、DLG1^[10]、DISC1^[12]、MYOZ1^[13]、GRIN2B^[14]、ADAM12^[15]、ACTN3^[16]、MYPN^[17]、PDLIM3^[18]、PKN^[19]、MYOT^[20]、TTN^[21]、NMDAR^[22]、SYNPO2^[23]、LDB3^[24]、FATZ^[13]と相互作用する。

機能

α-アクチニン2の主な機能は、Z板でサルコメアの糸状アクチン分子およびチチン分子の架橋である。この機能はリン脂質によって調節される^[25]^[26]。架橋は、60°および120°の角度を好んだ立体配座を形成させる^[27]。

α-アクチニン2は心臓のイオンチャネル K_v1.5と結合する^[10]。

医療分野での重要性

ACTN2の突然変異は肥大型心筋症^[28]、拡張型心筋症および心内膜線維弾性症^[29]と関連する。ACTN2突然変異患者の多様な症例はα-アクチニン2の多様な機能を反映している^[30]。

脚注

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000077522 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000052374 - Ensembl, May 2017
^ Human PubMed Reference:
^ Mouse PubMed Reference:
^ “Entrez Gene: ACTN2 actinin, alpha 2”. 2018年9月21日閲覧。
^ “Protein Information – Basic Information: Protein COPaKB ID: P35609”. Cardiac Organellar Protein Atlas Knowledgebase. 2018年9月21日閲覧。
^ “Integration of cardiac proteome biology and medicine by a specialized knowledgebase”. Circulation Research 113 (9): 1043–53. (October 2013). doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
^ “The structure and regulation of human muscle α-actinin”. Cell 159 (6): 1447–60. (December 2014). doi:10.1016/j.cell.2014.10.056. PMC 4259493. PMID 25433700.
^ ^a ^b “The vertebrate muscle Z-disc: sarcomere anchor for structure and signalling”. Journal of Muscle Research and Cell Motility 30 (5–6): 171–85. (2009). doi:10.1007/s10974-009-9189-6. PMC 2799012. PMID 19830582.
^ ^a ^b ^c “SAP97 increases Kv1.5 currents through an indirect N-terminal mechanism”. FEBS Letters 547 (1–3): 205–11. (July 2003). doi:10.1016/S0014-5793(03)00668-9. PMID 12860415.
^ “alpha-actinin-2 couples to cardiac Kv1.5 channels, regulating current density and channel localization in HEK cells”. FEBS Letters 473 (2): 188–94. (May 2000). doi:10.1016/S0014-5793(00)01521-0. PMID 10812072.
^ “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 12 (13): 1591–608. (July 2003). doi:10.1093/hmg/ddg162. PMID 12812986.
^ ^a ^b “FATZ, a filamin-, actinin-, and telethonin-binding protein of the Z-disc of skeletal muscle”. The Journal of Biological Chemistry 275 (52): 41234–42. (December 2000). doi:10.1074/jbc.M007493200. PMID 10984498.
^ “Competitive binding of alpha-actinin and calmodulin to the NMDA receptor”. Nature 385 (6615): 439–42. (January 1997). doi:10.1038/385439a0. PMID 9009191.
^ “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 275 (18): 13933–9. (May 2000). doi:10.1074/jbc.275.18.13933. PMID 10788519.
^ “Human skeletal muscle-specific alpha-actinin-2 and -3 isoforms form homodimers and heterodimers in vitro and in vivo”. Biochemical and Biophysical Research Communications 248 (1): 134–9. (July 1998). doi:10.1006/bbrc.1998.8920. PMID 9675099.
^ “Myopalladin, a novel 145-kilodalton sarcomeric protein with multiple roles in Z-disc and I-band protein assemblies”. The Journal of Cell Biology 153 (2): 413–27. (April 2001). doi:10.1083/jcb.153.2.413. PMC 2169455. PMID 11309420.
^ “Purification and characterization of an alpha-actinin-binding PDZ-LIM protein that is up-regulated during muscle differentiation”. The Journal of Biological Chemistry 274 (41): 29242–50. (October 1999). doi:10.1074/jbc.274.41.29242. PMID 10506181.
^ “Interaction of PKN with alpha-actinin”. The Journal of Biological Chemistry 272 (8): 4740–6. (February 1997). doi:10.1074/jbc.272.8.4740. PMID 9030526.
^ “Myotilin, a novel sarcomeric protein with two Ig-like domains, is encoded by a candidate gene for limb-girdle muscular dystrophy”. Human Molecular Genetics 8 (7): 1329–36. (July 1999). doi:10.1093/hmg/8.7.1329. PMID 10369880.
^ “Molecular structure of the sarcomeric Z-disk: two types of titin interactions lead to an asymmetrical sorting of alpha-actinin”. The EMBO Journal 17 (6): 1614–24. (March 1998). doi:10.1093/emboj/17.6.1614. PMC 1170509. PMID 9501083.
^ “Neutrophil toxicity of amphotericin B”. Antimicrobial Agents and Chemotherapy 12 (2): 226–30. (August 1977). doi:10.1128/aac.12.2.226. PMC 429889. PMID 900919.
^ “The sarcomeric Z-disc component myopodin is a multiadapter protein that interacts with filamin and alpha-actinin”. European Journal of Cell Biology 89 (9): 681–92. (September 2010). doi:10.1016/j.ejcb.2010.04.004. PMID 20554076.
^ “Zasp is required for the assembly of functional integrin adhesion sites”. The Journal of Cell Biology 179 (7): 1583–97. (December 2007). doi:10.1083/jcb.200707045. PMC 2373490. PMID 18166658.
^ “The interaction of titin and alpha-actinin is controlled by a phospholipid-regulated intramolecular pseudoligand mechanism”. The EMBO Journal 19 (23): 6331–40. (December 2000). doi:10.1093/emboj/19.23.6331. PMC 305858. PMID 11101506.
^ “Requirement of phosphatidylinositol 4,5-bisphosphate for alpha-actinin function”. Nature 359 (6391): 150–2. (September 1992). doi:10.1038/359150a0. PMID 1326084.
^ “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 368 (1): 92–104. (April 2007). doi:10.1016/j.jmb.2007.01.071. PMC 1919418. PMID 17331538.
^ “Mutations in alpha-actinin-2 cause hypertrophic cardiomyopathy: a genome-wide analysis”. Journal of the American College of Cardiology 55 (11): 1127–35. (March 2010). doi:10.1016/j.jacc.2009.11.016. PMID 20022194.
^ “Mutations in the muscle LIM protein and alpha-actinin-2 genes in dilated cardiomyopathy and endocardial fibroelastosis”. Molecular Genetics and Metabolism 80 (1–2): 207–15. (2003). doi:10.1016/s1096-7192(03)00142-2. PMID 14567970.
^ “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 15 (1): 99. (September 2014). doi:10.1186/s12881-014-0099-0. PMC 4355500. PMID 25224718.

外部リンク

Mass spectrometry characterization of human ACTN2 at COPaKB
GeneReviews/NIH/NCBI/UW entry on Familial Hypertrophic Cardiomyopathy Overview
Human Human ACTN2 genome location and ACTN2 gene details page in the UCSC Genome Browser.UCSC Genome BrowserHuman ACTN2 genome location and ACTN2 gene details page in the UCSC Genome Browser.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000077522 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000052374 - Ensembl, May 2017

[3] Human PubMed Reference:

[4] Mouse PubMed Reference:

[entrez-5] “Entrez Gene: ACTN2 actinin, alpha 2”. 2018年9月21日閲覧。

[P35609-6] “Protein Information – Basic Information: Protein COPaKB ID: P35609”. Cardiac Organellar Protein Atlas Knowledgebase. 2018年9月21日閲覧。

[cite_PMID_|_23965338-7] “Integration of cardiac proteome biology and medicine by a specialized knowledgebase”. Circulation Research 113 (9): 1043–53. (October 2013). doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.

[8] “The structure and regulation of human muscle α-actinin”. Cell 159 (6): 1447–60. (December 2014). doi:10.1016/j.cell.2014.10.056. PMC 4259493. PMID 25433700.

[cite_PMID_|_19830582-9] “The vertebrate muscle Z-disc: sarcomere anchor for structure and signalling”. Journal of Muscle Research and Cell Motility 30 (5–6): 171–85. (2009). doi:10.1007/s10974-009-9189-6. PMC 2799012. PMID 19830582.

[pmid12860415-10] “SAP97 increases Kv1.5 currents through an indirect N-terminal mechanism”. FEBS Letters 547 (1–3): 205–11. (July 2003). doi:10.1016/S0014-5793(03)00668-9. PMID 12860415.

[pmid10812072-11] “alpha-actinin-2 couples to cardiac Kv1.5 channels, regulating current density and channel localization in HEK cells”. FEBS Letters 473 (2): 188–94. (May 2000). doi:10.1016/S0014-5793(00)01521-0. PMID 10812072.

[pmid12812986-12] “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 12 (13): 1591–608. (July 2003). doi:10.1093/hmg/ddg162. PMID 12812986.

[pmid10984498-13] “FATZ, a filamin-, actinin-, and telethonin-binding protein of the Z-disc of skeletal muscle”. The Journal of Biological Chemistry 275 (52): 41234–42. (December 2000). doi:10.1074/jbc.M007493200. PMID 10984498.

[pmid9009191-14] “Competitive binding of alpha-actinin and calmodulin to the NMDA receptor”. Nature 385 (6615): 439–42. (January 1997). doi:10.1038/385439a0. PMID 9009191.

[pmid10788519-15] “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 275 (18): 13933–9. (May 2000). doi:10.1074/jbc.275.18.13933. PMID 10788519.

[pmid9675099-16] “Human skeletal muscle-specific alpha-actinin-2 and -3 isoforms form homodimers and heterodimers in vitro and in vivo”. Biochemical and Biophysical Research Communications 248 (1): 134–9. (July 1998). doi:10.1006/bbrc.1998.8920. PMID 9675099.

[pmid11309420-17] “Myopalladin, a novel 145-kilodalton sarcomeric protein with multiple roles in Z-disc and I-band protein assemblies”. The Journal of Cell Biology 153 (2): 413–27. (April 2001). doi:10.1083/jcb.153.2.413. PMC 2169455. PMID 11309420.

[18] “Purification and characterization of an alpha-actinin-binding PDZ-LIM protein that is up-regulated during muscle differentiation”. The Journal of Biological Chemistry 274 (41): 29242–50. (October 1999). doi:10.1074/jbc.274.41.29242. PMID 10506181.

[19] “Interaction of PKN with alpha-actinin”. The Journal of Biological Chemistry 272 (8): 4740–6. (February 1997). doi:10.1074/jbc.272.8.4740. PMID 9030526.

[20] “Myotilin, a novel sarcomeric protein with two Ig-like domains, is encoded by a candidate gene for limb-girdle muscular dystrophy”. Human Molecular Genetics 8 (7): 1329–36. (July 1999). doi:10.1093/hmg/8.7.1329. PMID 10369880.

[21] “Molecular structure of the sarcomeric Z-disk: two types of titin interactions lead to an asymmetrical sorting of alpha-actinin”. The EMBO Journal 17 (6): 1614–24. (March 1998). doi:10.1093/emboj/17.6.1614. PMC 1170509. PMID 9501083.

[22] “Neutrophil toxicity of amphotericin B”. Antimicrobial Agents and Chemotherapy 12 (2): 226–30. (August 1977). doi:10.1128/aac.12.2.226. PMC 429889. PMID 900919.

[23] “The sarcomeric Z-disc component myopodin is a multiadapter protein that interacts with filamin and alpha-actinin”. European Journal of Cell Biology 89 (9): 681–92. (September 2010). doi:10.1016/j.ejcb.2010.04.004. PMID 20554076.

[24] “Zasp is required for the assembly of functional integrin adhesion sites”. The Journal of Cell Biology 179 (7): 1583–97. (December 2007). doi:10.1083/jcb.200707045. PMC 2373490. PMID 18166658.

[25] “The interaction of titin and alpha-actinin is controlled by a phospholipid-regulated intramolecular pseudoligand mechanism”. The EMBO Journal 19 (23): 6331–40. (December 2000). doi:10.1093/emboj/19.23.6331. PMC 305858. PMID 11101506.

[26] “Requirement of phosphatidylinositol 4,5-bisphosphate for alpha-actinin function”. Nature 359 (6391): 150–2. (September 1992). doi:10.1038/359150a0. PMID 1326084.

[27] “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 368 (1): 92–104. (April 2007). doi:10.1016/j.jmb.2007.01.071. PMC 1919418. PMID 17331538.

[28] “Mutations in alpha-actinin-2 cause hypertrophic cardiomyopathy: a genome-wide analysis”. Journal of the American College of Cardiology 55 (11): 1127–35. (March 2010). doi:10.1016/j.jacc.2009.11.016. PMID 20022194.

[29] “Mutations in the muscle LIM protein and alpha-actinin-2 genes in dilated cardiomyopathy and endocardial fibroelastosis”. Molecular Genetics and Metabolism 80 (1–2): 207–15. (2003). doi:10.1016/s1096-7192(03)00142-2. PMID 14567970.

[30] “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 15 (1): 99. (September 2014). doi:10.1186/s12881-014-0099-0. PMC 4355500. PMID 25224718.

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