ACTC1

ACTC1
Identifiers
Aliases	ACTC1, ACTC, ASD5, CMD1R, CMH11, LVNC4, actin, alpha, cardiac muscle 1, actin alpha cardiac muscle 1
External IDs	OMIM: 102540; MGI: 87905; HomoloGene: 68446; GeneCards: ACTC1; OMA:ACTC1 - orthologs
Gene location (Human) Chr. Chromosome 15 (human)[1] Band 15q14 Start 34,790,230 bp[1] End 34,795,549 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 E4|2 57.55 cM Start 113,877,763 bp[2] End 113,884,029 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in myocardium of left ventricle right ventricle cardiac muscle tissue of right atrium right auricle apex of heart vena cava glutes seminal vesicula tibialis anterior muscle popliteal artery Top expressed in atrioventricular valve endocardial cushion cardiac muscle tissue of left ventricle atrium interventricular septum vastus lateralis muscle triceps brachii muscle human fetus extraocular muscle digastric muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding myosin binding ATPase activity ATP binding Cellular component cytoplasm cell body cytosol blood microparticle membrane I band focal adhesion filopodium sarcomere actin filament extracellular exosome cytoskeleton lamellipodium extracellular space synapse glutamatergic synapse Biological process actin-myosin filament sliding cardiac muscle contraction actomyosin structure organization negative regulation of apoptotic process cardiac muscle tissue morphogenesis actin filament-based movement skeletal muscle thin filament assembly cardiac myofibril assembly actin-mediated cell contraction positive regulation of gene expression muscle filament sliding mesenchyme migration response to ethanol heart contraction apoptotic process actin filament organization Sources:Amigo / QuickGO
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: 34.79 – 34.8 Mb Chr 2: 113.88 – 113.88 Mb PubMed search [3] [4]
Wikidata
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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.

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

Further reading

External links

• Mass spectrometry characterization of human ACTC1 at COPaKB
• GeneReviews/NIH/NCBI/UW entry on Familial Hypertrophic Cardiomyopathy Overview
• Human ACTC1 genome location and ACTC1 gene details page in the UCSC Genome Browser.