ACTC1

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Actin, alpha, cardiac muscle 1
Protein ACTC1 PDB 1atn.png
PDB rendering based on 1atn.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols ACTC1 ; ACTC; ASD5; CMD1R; CMH11; LVNC4
External IDs OMIM102540 MGI87905 HomoloGene68446 GeneCards: ACTC1 Gene
RNA expression pattern
PBB GE ACTC1 205132 at tn.png
More reference expression data
Orthologs
Species Human Mouse
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:
35.08 – 35.09 Mb
Chr 2:
114.05 – 114.05 Mb
PubMed search [1] [2]

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[edit]

Cardiac alpha actin is a 42.0 kDa protein composed of 377 amino acids (See human ACTC1 sequence features here). 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. (PMID 2395459), and closely thereafter this same group published the structure of the actin filament (PMID 2395461). 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[edit]

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 (PMID 7648318). Myosin binding increases the flexibility of actin (PMID 8345515), 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 (PMID 8200441).

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 artrial septa.[3]

Clinical Significance[edit]

Polymorphisms in ACTC1 have been linked to Dilated Cardiomyopathy in a small number of Japanese patients.[4] Further studies in patients from South Africa found no association.[5] The E101K missense mutation has been associated with Hypertrophic Cardiomyopathy[6][7][8][9] and Left Ventricular Noncompaction.[10] Another mutation has in the ACTC1 gene has been associated with atrial septal defects.[3]

References[edit]

  1. ^ Kramer PL, Luty JA, Litt M (Aug 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. 
  2. ^ "Entrez Gene: ACTC1 actin, alpha, cardiac muscle 1". 
  3. ^ a b Matsson H et al. (Jan 2008). "Alpha-cardiac actin mutations produce atrial septal defects.". Hum Mol Genet. 17 (2): 256–65. doi:10.1093/hmg/ddm302. PMID 17947298. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ Olson TM et al. (Sep 2000). "Inherited and de novo mutations in the cardiac actin gene cause hypertrophic cardiomyopathy.". J Mol Cell Cardiol. 32 (9): 1687–94. doi:10.1006/jmcc.2000.1204. PMID 10966831. 
  7. ^ Arad M et al. (Nov 2005). "Gene mutations in apical hypertrophic cardiomyopathy.". Circulation. 112 (18): 2805–11. doi:10.1161/CIRCULATIONAHA.105.547448. 
  8. ^ Monserrat L et al. (Aug 2007). "Mutation in the alpha-cardiac actin gene associated with apical hypertrophic cardiomyopathy, left ventricular non-compaction, and septal defects.". Eur Heart J. 28 (16): 1953–61. doi:10.1093/eurheartj/ehm239. 
  9. ^ Morita H et al. (May 2008). "Shared genetic causes of cardiac hypertrophy in children and adults.". N Engl J Med. 358 (18): 1899–908. doi:10.1056/NEJMoa075463. 
  10. ^ Klaassen S et al. (June 2008). "Mutations in sarcomere protein genes in left ventricular noncompaction.". Circulation. 117 (22): 2893–901. doi:10.1161/CIRCULATIONAHA.107.746164. PMID 1850600. 

Further reading[edit]

External links[edit]