Biology:ACTC1

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

ACTC1 encodes cardiac muscle alpha actin.[1][2] 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.

Structure

Cardiac alpha actin is a 42.0 kDa protein composed of 377 amino acids.[3][4] 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.,[5] and closely thereafter this same group published the structure of the actin filament.[6] 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.

Function

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.[7] Myosin binding increases the flexibility of actin,[8] 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.[9]

It has been suggested that the ACTC1 gene has a role during development. Experiments in chick embryos found an association between ACTC1 knockdown and a reduction in the atrial septa.[10]

Clinical significance

Polymorphisms in ACTC1 have been linked to dilated cardiomyopathy in a small number of Japanese patients.[11] Further studies in patients from South Africa found no association.[12] The E101K missense mutation has been associated with hypertrophic cardiomyopathy[13][14][15][16] and left ventricular noncompaction.[17] Another mutation has in the ACTC1 gene has been associated with atrial septal defects.[10]

References

  1. ↑ "Regional localization of the gene for cardiac muscle actin (ACTC) on chromosome 15q". Genomics 13 (3): 904–5. Jul 1992. doi:10.1016/0888-7543(92)90185-U. PMID 1639426. 
  2. ↑ "Entrez Gene: ACTC1 actin, alpha, cardiac muscle 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=70. 
  3. ↑ "Protein Information – Basic Information: Protein COPaKB ID: P68032". http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P68032. 
  4. ↑ "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–53. Oct 2013. doi:10.1161/CIRCRESAHA.113.301151. PMID 23965338. 
  5. ↑ "Atomic structure of the actin:DNase I complex". Nature 347 (6288): 37–44. Sep 1990. doi:10.1038/347037a0. PMID 2395459. Bibcode: 1990Natur.347...37K. 
  6. ↑ "Atomic model of the actin filament". Nature 347 (6288): 44–9. Sep 1990. doi:10.1038/347044a0. PMID 2395461. Bibcode: 1990Natur.347...44H. 
  7. ↑ "New insights into actin filament dynamics". Current Opinion in Structural Biology 5 (2): 172–80. Apr 1995. doi:10.1016/0959-440x(95)80072-7. PMID 7648318. 
  8. ↑ "A conformational change in the actin subunit can change the flexibility of the actin filament". Journal of Molecular Biology 232 (2): 334–41. Jul 1993. doi:10.1006/jmbi.1993.1393. PMID 8345515. 
  9. ↑ "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. May 1994. doi:10.1016/0014-5793(94)00398-x. PMID 8200441. 
  10. ↑ 10.0 10.1 "Alpha-cardiac actin mutations produce atrial septal defects". Human Molecular Genetics 17 (2): 256–65. Jan 2008. doi:10.1093/hmg/ddm302. PMID 17947298. 
  11. ↑ Takai E (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(19991008)86:4<325::aid-ajmg5>3.0.co;2-u. PMID 10494087. 
  12. ↑ Mayosi BM (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. PMID 10528865. 
  13. ↑ "Inherited and de novo mutations in the cardiac actin gene cause hypertrophic cardiomyopathy". Journal of Molecular and Cellular Cardiology 32 (9): 1687–94. Sep 2000. doi:10.1006/jmcc.2000.1204. PMID 10966831. 
  14. ↑ "Gene mutations in apical hypertrophic cardiomyopathy". Circulation 112 (18): 2805–11. Nov 2005. doi:10.1161/CIRCULATIONAHA.105.547448. PMID 16267253. 
  15. ↑ "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. Aug 2007. doi:10.1093/eurheartj/ehm239. PMID 17611253. 
  16. ↑ "Shared genetic causes of cardiac hypertrophy in children and adults". The New England Journal of Medicine 358 (18): 1899–908. May 2008. doi:10.1056/NEJMoa075463. PMID 18403758. 
  17. ↑ "Mutations in sarcomere protein genes in left ventricular noncompaction". Circulation 117 (22): 2893–901. Jun 2008. doi:10.1161/CIRCULATIONAHA.107.746164. PMID 18506004. 

Further reading

External links



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