ACTC1

{{short description|Protein-coding gene in the species Homo sapiens}}

ACTC1 encodes cardiac muscle alpha actin.{{cite journal | vauthors = Kramer PL, Luty JA, Litt M | title = Regional localization of the gene for cardiac muscle actin (ACTC) on chromosome 15q | journal = Genomics | volume = 13 | issue = 3 | pages = 904–5 | date = Jul 1992 | pmid = 1639426 | doi = 10.1016/0888-7543(92)90185-U }}{{cite web | title = Entrez Gene: ACTC1 actin, alpha, cardiac muscle 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=70}} 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.{{cite web|title=Protein Information {{ndash}} Basic Information: Protein COPaKB ID: P68032|website=Cardiac Organellar Protein Atlas Knowledgebase|url=http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P68032|access-date=2015-03-15|archive-url=https://web.archive.org/web/20150924025541/http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P68032|archive-date=2015-09-24|url-status=dead}}{{cite journal | vauthors = 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 | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date = Oct 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }} 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.,{{cite journal | vauthors = Kabsch W, Mannherz HG, Suck D, Pai EF, Holmes KC | title = Atomic structure of the actin:DNase I complex | journal = Nature | volume = 347 | issue = 6288 | pages = 37–44 | date = Sep 1990 | pmid = 2395459 | doi = 10.1038/347037a0 | bibcode = 1990Natur.347...37K | s2cid = 925337 }} and closely thereafter this same group published the structure of the actin filament.{{cite journal | vauthors = Holmes KC, Popp D, Gebhard W, Kabsch W | title = Atomic model of the actin filament | journal = Nature | volume = 347 | issue = 6288 | pages = 44–9 | date = Sep 1990 | pmid = 2395461 | doi = 10.1038/347044a0 | bibcode = 1990Natur.347...44H | s2cid = 4317981 }} 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.{{cite journal | vauthors = Egelman EH, Orlova A | title = New insights into actin filament dynamics | journal = Current Opinion in Structural Biology | volume = 5 | issue = 2 | pages = 172–80 | date = Apr 1995 | pmid = 7648318 | doi = 10.1016/0959-440x(95)80072-7 }} Myosin binding increases the flexibility of actin,{{cite journal | vauthors = Orlova A, Egelman EH | title = A conformational change in the actin subunit can change the flexibility of the actin filament | journal = Journal of Molecular Biology | volume = 232 | issue = 2 | pages = 334–41 | date = Jul 1993 | pmid = 8345515 | doi = 10.1006/jmbi.1993.1393 }} 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.{{cite journal | vauthors = Bertrand R, Derancourt J, Kassab R | title = The covalent maleimidobenzoyl-actin-myosin head complex. Cross-linking of the 50 kDa heavy chain region to actin subdomain-2 | journal = FEBS Letters | volume = 345 | issue = 2–3 | pages = 113–9 | date = May 1994 | pmid = 8200441 | doi = 10.1016/0014-5793(94)00398-x | doi-access = free | bibcode = 1994FEBSL.345..113B }}

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.{{cite journal | vauthors = 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 | title = Alpha-cardiac actin mutations produce atrial septal defects | journal = Human Molecular Genetics | volume = 17 | issue = 2 | pages = 256–65 | date = Jan 2008 | pmid = 17947298 | doi = 10.1093/hmg/ddm302 | doi-access = free }}

Clinical significance

Polymorphisms in ACTC1 have been linked to dilated cardiomyopathy in a small number of Japanese patients.{{cite journal | title=Mutational analysis of the cardiac actin gene in familial and sporadic dilated cardiomyopathy. | author=Takai E | journal=Am J Med Genet |date=Oct 1999 | volume=86 | issue=4 | pages=325–7 | doi=10.1002/(sici)1096-8628(19991008)86:4<325::aid-ajmg5>3.0.co;2-u| pmid=10494087 |display-authors=etal}} Further studies in patients from South Africa found no association.{{cite journal | title=Cardiac and skeletal actin gene mutations are not a common cause of dilated cardiomyopathy. | author=Mayosi BM | journal=J Med Genet |date=Oct 1999 | volume=36 | issue=10 | pages=796–7 | doi=10.1136/jmg.36.10.796|display-authors=etal| pmc=1734242 | pmid=10528865}} The E101K missense mutation has been associated with hypertrophic cardiomyopathy{{cite journal | vauthors = Olson TM, Doan TP, Kishimoto NY, Whitby FG, Ackerman MJ, Fananapazir L | title = Inherited and de novo mutations in the cardiac actin gene cause hypertrophic cardiomyopathy | journal = Journal of Molecular and Cellular Cardiology | volume = 32 | issue = 9 | pages = 1687–94 | date = Sep 2000 | pmid = 10966831 | doi = 10.1006/jmcc.2000.1204 }}{{cite journal | vauthors = 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 | title = Gene mutations in apical hypertrophic cardiomyopathy | journal = Circulation | volume = 112 | issue = 18 | pages = 2805–11 | date = Nov 2005 | pmid = 16267253 | doi = 10.1161/CIRCULATIONAHA.105.547448 | doi-access = free }}{{cite journal | vauthors = 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 | title = Mutation in the alpha-cardiac actin gene associated with apical hypertrophic cardiomyopathy, left ventricular non-compaction, and septal defects | journal = European Heart Journal | volume = 28 | issue = 16 | pages = 1953–61 | date = Aug 2007 | pmid = 17611253 | doi = 10.1093/eurheartj/ehm239 | doi-access = free }}{{cite journal | vauthors = Morita H, Rehm HL, Menesses A, McDonough B, Roberts AE, Kucherlapati R, Towbin JA, Seidman JG, Seidman CE | title = Shared genetic causes of cardiac hypertrophy in children and adults | journal = The New England Journal of Medicine | volume = 358 | issue = 18 | pages = 1899–908 | date = May 2008 | pmid = 18403758 | pmc = 2752150 | doi = 10.1056/NEJMoa075463 }} and left ventricular noncompaction.{{cite journal | vauthors = 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 | title = Mutations in sarcomere protein genes in left ventricular noncompaction | journal = Circulation | volume = 117 | issue = 22 | pages = 2893–901 | date = Jun 2008 | pmid = 18506004 | doi = 10.1161/CIRCULATIONAHA.107.746164 | doi-access = free }} Another mutation has in the ACTC1 gene has been associated with atrial septal defects.

References

External links

[https://web.archive.org/web/20150924025541/http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P68032 Mass spectrometry characterization of human ACTC1 at COPaKB]
[https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=hyper-card GeneReviews/NIH/NCBI/UW entry on Familial Hypertrophic Cardiomyopathy Overview]
{{UCSC gene info|ACTC1}}

Category:Human proteins