MYOZ2 explained

Myozenin-2, also referred to as Calsarcin-1, is a protein that in humans is encoded by the MYOZ2 gene.^{[1] [2] [3]} The Calsarcin-1 isoform is a muscle protein expressed in cardiac muscle and slow-twitch skeletal muscle, which functions to tether calcineurin to alpha-actinin at Z-discs, and inhibit the pathological cardiac hypertrophic response. This differs from the fast-skeletal muscle isoform, calsarcin-2.

Structure

Calsarcin-1 is a 29.9 kDa protein composed of 264 amino acids.^{[4] [5]} Calsarcin-1 and calsarcin-2 are only 31% homologous (94 identical amino acids), exhibiting the highest homology at N- and C-termini. Calsarcin-1 binds to alpha-actinin,^[6] gamma-filamin,^[7] telethonin,^[8] Overexpression of calsarcin-1 in mice (CS1Tg) was protective against Angiotensin II-induced pathologic cardiac hypertrophy, evidenced by preserved fractional shortening and contractility, as well as a blunted induction of the fetal hypertrophic gene program and significantly reduced expression of calcineurin-stimulated MCIP1.4 gene expression. Taken together, these studies strongly support a role for calsarcin-1 in suppressing pathologic cardiac hypertrophy.

Clinical Significance

Two missense mutations in MYOZ2, Ser48Pro and Ile246Met, have been shown to be causal for rare forms of familial hypertrophic cardiomyopathy.^[9]

Further reading

• Faulkner G, Pallavicini A, Formentin E, Comelli A, Ievolella C, Trevisan S, Bortoletto G, Scannapieco P, Salamon M, Mouly V, Valle G, Lanfranchi G . ZASP: a new Z-band alternatively spliced PDZ-motif protein . The Journal of Cell Biology . 146 . 2 . 465–75 . July 1999 . 10427098 . 3206570 . 10.1083/jcb.146.2.465 .
• Frey N, Richardson JA, Olson EN . Calsarcins, a novel family of sarcomeric calcineurin-binding proteins . Proceedings of the National Academy of Sciences of the United States of America . 97 . 26 . 14632–7 . December 2000 . 11114196 . 18970 . 10.1073/pnas.260501097 . 2000PNAS...9714632F . free .
• Ahmad F, Gonzalez O, Ramagli L, Xu J, Siciliano MJ, Bachinski LL, Roberts R . Identification and characterization of a novel gene (C4orf5) located on human chromosome 4q with specific expression in cardiac and skeletal muscle . Genomics . 70 . 3 . 347–53 . December 2000 . 11161785 . 10.1006/geno.2000.6399 .
• Takada F, Vander Woude DL, Tong HQ, Thompson TG, Watkins SC, Kunkel LM, Beggs AH . Myozenin: an alpha-actinin- and gamma-filamin-binding protein of skeletal muscle Z lines . Proceedings of the National Academy of Sciences of the United States of America . 98 . 4 . 1595–600 . February 2001 . 11171996 . 29302 . 10.1073/pnas.041609698 . free .
• Frey N, Olson EN . Calsarcin-3, a novel skeletal muscle-specific member of the calsarcin family, interacts with multiple Z-disc proteins . The Journal of Biological Chemistry . 277 . 16 . 13998–4004 . April 2002 . 11842093 . 10.1074/jbc.M200712200 . free .
• Gontier Y, Taivainen A, Fontao L, Sonnenberg A, van der Flier A, Carpen O, Faulkner G, Borradori L . The Z-disc proteins myotilin and FATZ-1 interact with each other and are connected to the sarcolemma via muscle-specific filamins . Journal of Cell Science . 118 . Pt 16 . 3739–49 . August 2005 . 16076904 . 10.1242/jcs.02484 . free .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Posch MG, Perrot A, Dietz R, Ozcelik C, Pankuweit S, Ruppert V, Richter A, Maisch B . Mutations in MYOZ1 as well as MYOZ2 encoding the calsarcins are not associated with idiopathic and familial dilated cardiomyopathy . Molecular Genetics and Metabolism . 91 . 2 . 207–8 . June 2007 . 17434779 . 10.1016/j.ymgme.2007.02.014 .

External links

• Mass spectrometry characterization of human MYOZ2 at COPaKB

Notes and References

1. Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction . Analytical Biochemistry . 236 . 1 . 107–13 . April 1996 . 8619474 . 10.1006/abio.1996.0138 .
2. Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . Large-scale concatenation cDNA sequencing . Genome Research . 7 . 4 . 353–8 . April 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
3. Web site: Entrez Gene: MYOZ2 myozenin 2.
4. http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=Q9NPC6
5. 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 . Integration of cardiac proteome biology and medicine by a specialized knowledgebase . Circulation Research . 113 . 9 . 1043–53 . October 2013 . 23965338 . 4076475 . 10.1161/CIRCRESAHA.113.301151 .
6. Frey N, Richardson JA, Olson EN . Calsarcins, a novel family of sarcomeric calcineurin-binding proteins . Proceedings of the National Academy of Sciences of the United States of America . 97 . 26 . 14632–7 . December 2000 . 11114196 . 18970 . 10.1073/pnas.260501097 . 2000PNAS...9714632F . free .
7. Frey N, Barrientos T, Shelton JM, Frank D, Rütten H, Gehring D, Kuhn C, Lutz M, Rothermel B, Bassel-Duby R, Richardson JA, Katus HA, Hill JA, Olson EN . Mice lacking calsarcin-1 are sensitized to calcineurin signaling and show accelerated cardiomyopathy in response to pathological biomechanical stress . Nature Medicine . 10 . 12 . 1336–43 . December 2004 . 15543153 . 10.1038/nm1132 . 33712044 .
8. [LDB3|ZASP/Cypher]
9. Osio A, Tan L, Chen SN, Lombardi R, Nagueh SF, Shete S, Roberts R, Willerson JT, Marian AJ . Myozenin 2 is a novel gene for human hypertrophic cardiomyopathy . Circulation Research . 100 . 6 . 766–8 . March 2007 . 17347475 . 2775141 . 10.1161/01.RES.0000263008.66799.aa .