User:ILoveBugs9/Myocardin
Myocardin is a protein that in humans is encoded by the MYOCD gene[1][2][3][4].
Myocardin is a smooth muscle cell and cardiac muscle cell-specific transcriptional coactivator of serum response factor (SRF)[3][4]. When expressed in smooth muscle precursor cells and abnormally in nonmuscle cells, myocardin can induce smooth muscle cell differentiation[5]. Myocardin can also function in the differentiation of myocardial cells[4].
![](http://upload.wikimedia.org/wikipedia/commons/thumb/3/3b/Annotated_AlphaFold_Myocardin_Structure.png/220px-Annotated_AlphaFold_Myocardin_Structure.png)
Structure
[edit]Myocardin consists of four distinct regions, one of which is the SAF-A/B, Acinus, and PIAS (SAP) domain[1]. SAP domains are highly conserved motifs containing alpha helices that generally contain hydrophobic, polar, and bulky amino acids[6][7].
Myocardin also contains a basic region and a glutamine-rich region believed to be involved in binding SRF[1].
Through a series of deletion mutations, researchers have also identified a dimerization motif spanning amino acid residues 513–713, containing an alpha helical leucine zipper analog between residues 513-556[3].
Function
[edit]Myocardin is a transcriptional coactivator, enhancing the activity of specific genes involved in smooth muscle development and function by interacting with transcription factor, SRF[3][4][8]. Myocardin can induce smooth muscle cell differentiation when it is expressed in appropriate cells[5]. Researchers have also found that myocardin plays a role in myocardial cell differentiation by inhibiting myocardin in Xenopus embryos[4].
Amino acid residues 541–807 of myocardin are believed to play a key role in mediating its ability to activate transcription[4]. Upon its initial discovery, researchers fused myocardin with the well studied GAL 4 transcription factor and examined how the regulation of GAL4-associated genes was affected[4]. Myocardin is believed to activate transcription by binding to CArG box regions of DNA, characterized by the sequence CC(A/T)6GG, of muscle function genes, because mutations to these regions have led to an observed reduction in their sensitivity to myocardin[4].
Myocardin contributes to the expression of cardiac muscle cell differentiation by interacting with myocyte enhancer factor 2 (MEF2) or SRF, enhancing their transcriptional activity[9]. Conversely, in smooth muscle cells, myocardin associates with the transcriptional coactivator, p300, stimulting acetylation and consequent expression of smooth muscle cell genes, as well as acetylation of myocardin itself[10][11]. Class II HDAC proteins are responsible for histone deacetylation, and have been found to inhibit the activity of myocardin[10].
MYOCD Gene
[edit]There are four known transcript variants (isoforms) of the MYOCD gene[9][12]. While the exact function of each isoform is not well understood, it is suggested that each variant may have tissue-specific functions[13]. Real-time polymerase chain reaction (RT-PCR) have realved two tissue-specific isoforms, myocardin-856, expressed in smooth muscle and found to interact with SRF, and myocardin-935, expressed in cardiac muscle and found to interact with either MEF2 or SRF[9].
Expression of MYOCD is specifically observed in the cardaic and smooth muscle tissues, such as the arteries, female reproductive organs and colon[4][5][14]. Expression is also observed in the heart, aorta, and bladder, tissues in which smooth muscle can be found[5][15].
References
[edit]- ^ a b c Wang, Da-Zhi; Li, Shijie; Hockemeyer, Dirk; Sutherland, Lillian; Wang, Zhigao; Schratt, Gerhard; Richardson, James A.; Nordheim, Alfred; Olson, Eric N. (2002-11-12). "Potentiation of serum response factor activity by a family of myocardin-related transcription factors". Proceedings of the National Academy of Sciences of the United States of America. 99 (23): 14855–14860. doi:10.1073/pnas.222561499. ISSN 0027-8424. PMC 137508. PMID 12397177.
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: CS1 maint: PMC format (link) - ^ "MYOCD myocardin [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-04-07.
- ^ a b c d Wang, Zhigao; Wang, Da-Zhi; Pipes, G. C. Teg; Olson, Eric N. (2003-06-10). "Myocardin is a master regulator of smooth muscle gene expression". Proceedings of the National Academy of Sciences. 100 (12): 7129–7134. doi:10.1073/pnas.1232341100. ISSN 0027-8424. PMC 165841. PMID 12756293.
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: CS1 maint: PMC format (link) - ^ a b c d e f g h i Wang, Da-Zhi; Chang, Priscilla S.; Wang, Zhigao; Sutherland, Lillian; Richardson, James A.; Small, Eric; Krieg, Paul A.; Olson, Eric N. (29 June 2001). "Activation of Cardiac Gene Expression by Myocardin, a Transcriptional Cofactor for Serum Response Factor". Cell. 105 (7): 851–862. doi:10.1016/s0092-8674(01)00404-4. ISSN 0092-8674.
- ^ a b c d Du, Kevin L.; Ip, Hon S.; Li, Jian; Chen, Mary; Dandre, Frederic; Yu, William; Lu, Min Min; Owens, Gary K.; Parmacek, Michael S. (2003-04-01). "Myocardin Is a Critical Serum Response Factor Cofactor in the Transcriptional Program Regulating Smooth Muscle Cell Differentiation". Molecular and Cellular Biology. 23 (7): 2425–2437. doi:10.1128/MCB.23.7.2425-2437.2003. ISSN 1098-5549. PMC 150745. PMID 12640126.
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: CS1 maint: PMC format (link) - ^ Aravind, L.; Koonin, Eugene V. (1 March 2000). "SAP – a putative DNA-binding motif involved in chromosomal organization". Trends in Biochemical Sciences. 25 (3): 112–114. doi:10.1016/s0968-0004(99)01537-6. ISSN 0968-0004.
- ^ Hnízda, Aleš; Tesina, Petr; Nguyen, Thanh‐Binh; Kukačka, Zdeněk; Kater, Lukas; Chaplin, Amanda K.; Beckmann, Roland; Ascher, David B.; Novák, Petr; Blundell, Tom L. (29 January 2021). "SAP domain forms a flexible part of DNA aperture in Ku70/80". The Federation of European Biochemical Societies Journal. 288 (14): 4382–4393. doi:10.1111/febs.15732. ISSN 1742-464X. PMC 8653891. PMID 33511782.
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: CS1 maint: PMC format (link) - ^ Long, Xiaochun; Tharp, Darla L.; Georger, Mary A.; Slivano, Orazio J.; Lee, Monica Y.; Wamhoff, Brian R.; Bowles, Douglas K.; Miano, Joseph M. (27 November 2009). "The Smooth Muscle Cell-restricted KCNMB1 Ion Channel Subunit Is a Direct Transcriptional Target of Serum Response Factor and Myocardin". Journal of Biological Chemistry. 284 (48): 33671–33682. doi:10.1074/jbc.m109.050419. ISSN 0021-9258. PMC 2785209. PMID 19801679.
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: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ a b c Creemers, Esther E.; Sutherland, Lillian B.; Oh, Jiyeon; Barbosa, Ana C.; Olson, Eric N. (7 July 2006). "Coactivation of MEF2 by the SAP Domain Proteins Myocardin and MASTR". Molecular Cell. 23 (1): 83–96. doi:10.1016/j.molcel.2006.05.026. ISSN 1097-2765.
- ^ a b Cao, Dongsun; Wang, Zhigao; Zhang, Chun-Li; Oh, Jiyeon; Xing, Weibing; Li, Shijie; Richardson, James A.; Wang, Da-Zhi; Olson, Eric N. (2005-01-01). "Modulation of Smooth Muscle Gene Expression by Association of Histone Acetyltransferases and Deacetylases with Myocardin". Molecular and Cellular Biology. 25 (1): 364–376. doi:10.1128/MCB.25.1.364-376.2005. ISSN 1098-5549. PMC 538763. PMID 15601857.
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: CS1 maint: PMC format (link) - ^ Cao, Dongsun; Wang, Chunbo; Tang, Ruhang; Chen, Huaqun; Zhang, Zheng; Tatsuguchi, Mariko; Wang, Da-Zhi (9 November 2012). "Acetylation of Myocardin Is Required for the Activation of Cardiac and Smooth Muscle Genes". Journal of Biological Chemistry. 287 (46): 38495–38504. doi:10.1074/jbc.m112.353649. ISSN 0021-9258. PMC 3493894. PMID 23007391.
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: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ "Human hg19 chr17:12,543,845-12,696,012 UCSC Genome Browser v462". genome.ucsc.edu. Retrieved 2024-04-07.
- ^ Imamura, Masaaki; Long, Xiaochun; Nanda, Vivek; Miano, Joseph M. (15 September 2010). "Expression and functional activity of four myocardin isoforms". Gene. 464 (1–2): 1–10. doi:10.1016/j.gene.2010.03.012. ISSN 0378-1119.
- ^ "GTEx Portal". www.gtexportal.org. Retrieved 2024-04-07.
- ^ Imamura, Masaaki; Long, Xiaochun; Nanda, Vivek; Miano, Joseph M. (2010-09-15). "Expression and functional activity of four myocardin isoforms". Gene. 464 (1): 1–10. doi:10.1016/j.gene.2010.03.012. ISSN 0378-1119.