ACTA2 explained

ACTA2 (actin alpha 2) is an actin protein with several aliases including alpha-actin, alpha-actin-2, aortic smooth muscle or alpha smooth muscle actin (α-SMA, SMactin, alpha-SM-actin, ASMA). Actins are a family of globular multi-functional proteins that form microfilaments. ACTA2 is one of 6 different actin isoforms and is involved in the contractile apparatus of smooth muscle. ACTA2 (as with all the actins) is extremely highly conserved and found in nearly all mammals.

In humans, ACTA2 is encoded by the ACTA2 gene located on 10q22-q24.^[1] Mutations in this gene cause a variety of vascular diseases, such as thoracic aortic disease, coronary artery disease, stroke, Moyamoya disease, and multisystemic smooth muscle dysfunction syndrome.^[2]

ACTA2 (commonly referred to as alpha-smooth muscle actin or α-SMA) is often used as a marker of myofibroblast formation.^[3] Studies have shown that ACTA2 is associated with TGF-β pathway that enhances contractile properties of hepatic stellate cells leading to liver fibrosis and cirrhosis.^[4]

Further reading

• Snásel J, Pichová I . The cleavage of host cell proteins by HIV-1 protease . Folia Biologica . 42 . 5 . 227–30 . 1997 . 8997639 . 10.1007/BF02818986 . 7617882 .
• Adams LD, Tomasselli AG, Robbins P, Moss B, Heinrikson RL . HIV-1 protease cleaves actin during acute infection of human T-lymphocytes . AIDS Research and Human Retroviruses . 8 . 2 . 291–5 . February 1992 . 1540415 . 10.1089/aid.1992.8.291 .
• Harris DE, Warshaw DM, Periasamy M . Nucleotide sequences of the rabbit alpha-smooth-muscle and beta-non-muscle actin mRNAs . Gene . 112 . 2 . 265–6 . March 1992 . 1555776 . 10.1016/0378-1119(92)90388-6 .
• Tomasselli AG, Hui JO, Adams L, Chosay J, Lowery D, Greenberg B, Yem A, Deibel MR, Zürcher-Neely H, Heinrikson RL . Actin, troponin C, Alzheimer amyloid precursor protein and pro-interleukin 1 beta as substrates of the protease from human immunodeficiency virus . The Journal of Biological Chemistry . 266 . 22 . 14548–53 . August 1991 . 10.1016/S0021-9258(18)98721-1 . 1907279 . free .
• Jahoda CA, Reynolds AJ, Chaponnier C, Forester JC, Gabbiani G . Smooth muscle alpha-actin is a marker for hair follicle dermis in vivo and in vitro . Journal of Cell Science . 99 (Pt 3) . 3 . 627–36 . July 1991 . 10.1242/jcs.99.3.627 . 1939373 .
• Ueyama H, Ohsugi R . TaqI polymorphism in the 3' flanking region of the human aortic smooth muscle actin gene . Nucleic Acids Research . 18 . 5 . 1318 . March 1990 . 1969628 . 330483 . 10.1093/nar/18.5.1318 .
• Shoeman RL, Kesselmier C, Mothes E, Höner B, Traub P . Non-viral cellular substrates for human immunodeficiency virus type 1 protease . FEBS Letters . 278 . 2 . 199–203 . January 1991 . 1991513 . 10.1016/0014-5793(91)80116-K . 37002682 . free . 1991FEBSL.278..199S .
• Nakano Y, Nishihara T, Sasayama S, Miwa T, Kamada S, Kakunaga T . Transcriptional regulatory elements in the 5' upstream and first intron regions of the human smooth muscle (aortic type) alpha-actin-encoding gene . Gene . 99 . 2 . 285–9 . March 1991 . 2022339 . 10.1016/0378-1119(91)90140-7 .
• Reddy S, Ozgur K, Lu M, Chang W, Mohan SR, Kumar CC, Ruley HE . Structure of the human smooth muscle alpha-actin gene. Analysis of a cDNA and 5' upstream region . The Journal of Biological Chemistry . 265 . 3 . 1683–7 . January 1990 . 10.1016/S0021-9258(19)40070-7 . 2295650 . free .
• Kamada S, Nakano Y, Kakunaga T . Structure of 3'-downstream segment of the human smooth muscle (aortic-type) alpha-actin-encoding gene and isolation of the specific DNA probe . Gene . 84 . 2 . 455–62 . December 1989 . 2612915 . 10.1016/0378-1119(89)90520-9 .
• Kamada S, Kakunaga T . The nucleotide sequence of a human smooth muscle alpha-actin (aortic type) cDNA . Nucleic Acids Research . 17 . 4 . 1767 . February 1989 . 2701935 . 331843 . 10.1093/nar/17.4.1767 .
• Kedes L, Ng SY, Lin CS, Gunning P, Eddy R, Shows T, Leavitt J . The human beta-actin multigene family . Transactions of the Association of American Physicians . 98 . 42–6 . 1986 . 3842206 .
• Ueyama H, Hamada H, Battula N, Kakunaga T . Structure of a human smooth muscle actin gene (aortic type) with a unique intron site . Molecular and Cellular Biology . 4 . 6 . 1073–8 . June 1984 . 6330528 . 368875 . 10.1128/MCB.4.6.1073.
• Strauch AR, Rubenstein PA . A vascular smooth muscle alpha-isoactin biosynthetic intermediate in BC3H1 cells. Identification of acetylcysteine at the NH2 terminus . The Journal of Biological Chemistry . 259 . 11 . 7224–9 . June 1984 . 10.1016/S0021-9258(17)39861-7 . 6725286 . free .
• Ueyama H, Inazawa J, Ariyama T, Nishino H, Ochiai Y, Ohkubo I, Miwa T . Reexamination of chromosomal loci of human muscle actin genes by fluorescence in situ hybridization . The Japanese Journal of Human Genetics . 40 . 1 . 145–8 . March 1995 . 7780165 . 10.1007/BF01874078 . free .
• Arora PD, McCulloch CA . Dependence of collagen remodelling on alpha-smooth muscle actin expression by fibroblasts . Journal of Cellular Physiology . 159 . 1 . 161–75 . April 1994 . 8138584 . 10.1002/jcp.1041590120 . 84214215 .
• Iwata Y, Pan Y, Yoshida T, Hanada H, Shigekawa M . Alpha1-syntrophin has distinct binding sites for actin and calmodulin . FEBS Letters . 423 . 2 . 173–7 . February 1998 . 9512352 . 10.1016/S0014-5793(98)00085-4 . 26209999 . 1998FEBSL.423..173I .
• Comer KA, Dennis PA, Armstrong L, Catino JJ, Kastan MB, Kumar CC . Human smooth muscle alpha-actin gene is a transcriptional target of the p53 tumor suppressor protein . Oncogene . 16 . 10 . 1299–308 . March 1998 . 9546431 . 10.1038/sj.onc.1201645 . 11098751 .

External links

• GeneReviews/NIH/NCBI/UW entry on Thoracic Aortic Aneurysms and Aortic Dissections

Notes and References

1. Ueyama H, Bruns G, Kanda N . Assignment of the vascular smooth muscle actin gene ACTSA to human chromosome 10 . Jinrui Idengaku Zasshi. The Japanese Journal of Human Genetics . 35 . 2 . 145–50 . June 1990 . 2398629 . 10.1007/BF01876459 . free .
2. Web site: Entrez Gene: ACTA2 actin, alpha 2, smooth muscle, aorta.
3. Nagamoto T, Eguchi G, Beebe DC . Alpha-smooth muscle actin expression in cultured lens epithelial cells . Investigative Ophthalmology & Visual Science . 41 . 5 . 1122–9 . April 2000 . 10752950 .
4. Hassan . Sobia . Shah . Hussain . Shawana . Summayya . Dysregulated epidermal growth factor and tumor growth factor-beta receptor signaling through GFAP-ACTA2 protein interaction in liver fibrosis . Pakistan Journal of Medical Sciences . 2020 . 36 . 4 . 782–787 . 10.12669/pjms.36.4.1845 . 32494274 . 7260937 .