ACTC1

ACTC1 encodes cardiac muscle alpha actin.[5][6] 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.

ACTC1
Identifiers
AliasesACTC1, ACTC, ASD5, CMD1R, CMH11, LVNC4, actin, alpha, cardiac muscle 1, actin alpha cardiac muscle 1
External IDsOMIM: 102540 MGI: 87905 HomoloGene: 68446 GeneCards: ACTC1
Gene location (Human)
Chr.Chromosome 15 (human)[1]
Band15q14Start34,790,230 bp[1]
End34,795,549 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

70

11464

Ensembl

ENSG00000159251

ENSMUSG00000068614

UniProt

P68032

P68033

RefSeq (mRNA)

NM_005159

NM_009608

RefSeq (protein)

NP_005150

NP_033738

Location (UCSC)Chr 15: 34.79 – 34.8 MbChr 2: 114.05 – 114.05 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Structure

Cardiac alpha actin is a 42.0 kDa protein composed of 377 amino acids.[7][8] 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.,[9] and closely thereafter this same group published the structure of the actin filament.[10] 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.[11] Myosin binding increases the flexibility of actin,[12] 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.[13]

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.[14]

Clinical significance

Polymorphisms in ACTC1 have been linked to Dilated Cardiomyopathy in a small number of Japanese patients.[15] Further studies in patients from South Africa found no association.[16] The E101K missense mutation has been associated with Hypertrophic Cardiomyopathy[17][18][19][20] and Left Ventricular Noncompaction.[21] Another mutation has in the ACTC1 gene has been associated with atrial septal defects.[14]

References
  1. GRCh38: Ensembl release 89: ENSG00000159251 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000068614 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Kramer PL, Luty JA, Litt M (Jul 1992). "Regional localization of the gene for cardiac muscle actin (ACTC) on chromosome 15q". Genomics. 13 (3): 904–5. doi:10.1016/0888-7543(92)90185-U. PMID 1639426.
  6. "Entrez Gene: ACTC1 actin, alpha, cardiac muscle 1".
  7. "Protein Information – Basic Information: Protein COPaKB ID: P68032". Cardiac Organellar Protein Atlas Knowledgebase. Archived from the original on 2015-09-24. Retrieved 2015-03-15.
  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 (Oct 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
  9. Kabsch W, Mannherz HG, Suck D, Pai EF, Holmes KC (Sep 1990). "Atomic structure of the actin:DNase I complex". Nature. 347 (6288): 37–44. Bibcode:1990Natur.347...37K. doi:10.1038/347037a0. PMID 2395459.
  10. Holmes KC, Popp D, Gebhard W, Kabsch W (Sep 1990). "Atomic model of the actin filament". Nature. 347 (6288): 44–9. Bibcode:1990Natur.347...44H. doi:10.1038/347044a0. PMID 2395461.
  11. Egelman EH, Orlova A (Apr 1995). "New insights into actin filament dynamics". Current Opinion in Structural Biology. 5 (2): 172–80. doi:10.1016/0959-440x(95)80072-7. PMID 7648318.
  12. 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. PMID 8345515.
  13. 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. PMID 8200441.
  14. Matsson 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. PMID 17947298.
  15. 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(19991008)86:4<325::aid-ajmg5>3.0.co;2-u. PMID 10494087.
  16. 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. PMC 1734242. PMID 10528865.
  17. 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. PMID 10966831.
  18. 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. PMID 16267253.
  19. 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. PMID 17611253.
  20. Morita H, Rehm HL, Menesses A, McDonough B, Roberts AE, Kucherlapati R, Towbin JA, Seidman JG, Seidman CE (May 2008). "Shared genetic causes of cardiac hypertrophy in children and adults". The New England Journal of Medicine. 358 (18): 1899–908. doi:10.1056/NEJMoa075463. PMC 2752150. PMID 18403758.
  21. 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. PMID 18506004.

Further reading
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