ACTC1 encodes cardiac muscle alpha actin. This isoform differs from the alpha actin that is expressed in skeletal muscle, ACTA1. Alpha cardiac actin is the major protein of the thin filament in cardiac sarcomeres, which are responsible for muscle contraction and generation of force to support the pump function of the heart.
Cardiac alpha actin is a 42.0 kDa protein composed of 377 amino acids. Cardiac alpha actin is a filamentous protein extending from a complex mesh with cardiac alpha-actinin (ACTN2) at Z-lines towards the center of the sarcomere. Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to four others. The atomic structure of monomeric actin was solved by Kabsch et al., and closely thereafter this same group published the structure of the actin filament.Actins are highly conserved proteins; the alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. Cardiac (ACTC1) and skeletal (ACTA1) alpha actins differ by only four amino acids (Asp4Glu, Glu5Asp, Leu301Met, Ser360Thr; cardiac/skeletal). The actin monomer has two asymmetric domains; the larger inner domain comprised by sub-domains 3 and 4, and the smaller outer domain by sub-domains 1 and 2. Both the amino and carboxy-termini lie in sub-domain 1 of the outer domain.
Actin is a dynamic structure that can adapt two states of flexibility, with the greatest difference between the states occurring as a result of movement within sub-domain 2. Myosin binding increases the flexibility of actin, and cross-linking studies have shown that myosin subfragment-1 binds to actin amino acid residues 48-67 within actin sub-domain 2, which may account for this effect.
It has been suggested that the ACTC1 gene has a role during development. Experiments in chick embryos found an association between ACTC1knockdown and a reduction in the artrial septa.
^Orlova A, Egelman EH (Jul 1993). "A conformational change in the actin subunit can change the flexibility of the actin filament". Journal of Molecular Biology. 232 (2): 334–41. doi:10.1006/jmbi.1993.1393. PMID8345515.
^Bertrand R, Derancourt J, Kassab R (May 1994). "The covalent maleimidobenzoyl-actin-myosin head complex. Cross-linking of the 50 kDa heavy chain region to actin subdomain-2". FEBS Letters. 345 (2-3): 113–9. doi:10.1016/0014-5793(94)00398-x. PMID8200441.
^ abMatsson H, Eason J, Bookwalter CS, Klar J, Gustavsson P, Sunnegårdh J, Enell H, Jonzon A, Vikkula M, Gutierrez I, Granados-Riveron J, Pope M, Bu'Lock F, Cox J, Robinson TE, Song F, Brook DJ, Marston S, Trybus KM, Dahl N (Jan 2008). "Alpha-cardiac actin mutations produce atrial septal defects". Human Molecular Genetics. 17 (2): 256–65. doi:10.1093/hmg/ddm302. PMID17947298.
^Takai E; et al. (Oct 1999). "Mutational analysis of the cardiac actin gene in familial and sporadic dilated cardiomyopathy.". Am J Med Genet. 86 (4): 325–7. doi:10.1002/(SICI)1096-8628.
^Mayosi BM; et al. (Oct 1999). "Cardiac and skeletal actin gene mutations are not a common cause of dilated cardiomyopathy.". J Med Genet. 36 (10): 796–7. doi:10.1136/jmg.36.10.796.
^Olson TM, Doan TP, Kishimoto NY, Whitby FG, Ackerman MJ, Fananapazir L (Sep 2000). "Inherited and de novo mutations in the cardiac actin gene cause hypertrophic cardiomyopathy". Journal of Molecular and Cellular Cardiology. 32 (9): 1687–94. doi:10.1006/jmcc.2000.1204. PMID10966831.
^Arad M, Penas-Lado M, Monserrat L, Maron BJ, Sherrid M, Ho CY, Barr S, Karim A, Olson TM, Kamisago M, Seidman JG, Seidman CE (Nov 2005). "Gene mutations in apical hypertrophic cardiomyopathy". Circulation. 112 (18): 2805–11. doi:10.1161/CIRCULATIONAHA.105.547448. PMID16267253.
^Monserrat L, Hermida-Prieto M, Fernandez X, Rodríguez I, Dumont C, Cazón L, Cuesta MG, Gonzalez-Juanatey C, Peteiro J, Alvarez N, Penas-Lado M, Castro-Beiras A (Aug 2007). "Mutation in the alpha-cardiac actin gene associated with apical hypertrophic cardiomyopathy, left ventricular non-compaction, and septal defects". European Heart Journal. 28 (16): 1953–61. doi:10.1093/eurheartj/ehm239. PMID17611253.
^Klaassen S, Probst S, Oechslin E, Gerull B, Krings G, Schuler P, Greutmann M, Hürlimann D, Yegitbasi M, Pons L, Gramlich M, Drenckhahn JD, Heuser A, Berger F, Jenni R, Thierfelder L (Jun 2008). "Mutations in sarcomere protein genes in left ventricular noncompaction". Circulation. 117 (22): 2893–901. doi:10.1161/CIRCULATIONAHA.107.746164. PMID18506004.
Adams LD, Tomasselli AG, Robbins P, Moss B, Heinrikson RL (Feb 1992). "HIV-1 protease cleaves actin during acute infection of human T-lymphocytes". AIDS Research and Human Retroviruses. 8 (2): 291–5. doi:10.1089/aid.1992.8.291. PMID1540415.
Tomasselli AG, Hui JO, Adams L, Chosay J, Lowery D, Greenberg B, Yem A, Deibel MR, Zürcher-Neely H, Heinrikson RL (Aug 1991). "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. PMID1907279.
Shoeman RL, Kesselmier C, Mothes E, Höner B, Traub P (Jan 1991). "Non-viral cellular substrates for human immunodeficiency virus type 1 protease". FEBS Letters. 278 (2): 199–203. doi:10.1016/0014-5793(91)80116-K. PMID1991513.
Buckingham M, Alonso S, Barton P, Cohen A, Daubas P, Garner I, Robert B, Weydert A (Dec 1986). "Actin and myosin multigene families: their expression during the formation and maturation of striated muscle". American Journal of Medical Genetics. 25 (4): 623–34. doi:10.1002/ajmg.1320250405. PMID3789022.
Ueyama H, Inazawa J, Ariyama T, Nishino H, Ochiai Y, Ohkubo I, Miwa T (Mar 1995). "Reexamination of chromosomal loci of human muscle actin genes by fluorescence in situ hybridization". The Japanese Journal of Human Genetics. 40 (1): 145–8. doi:10.1007/BF01874078. PMID7780165.
Dunwoodie SL, Joya JE, Arkell RM, Hardeman EC (Apr 1994). "Multiple regions of the human cardiac actin gene are necessary for maturation-based expression in striated muscle". The Journal of Biological Chemistry. 269 (16): 12212–9. PMID8163527.