Myomesin-1 is a
protein that in humans is encoded by the MYOM1gene.[5][6] Myomesin-1 is expressed in muscle cells and functions to stabilize the three-dimensional conformation of the
thick filament. Embryonic forms of Myomesin-1 have been detected in
dilated cardiomyopathy.
Structure
Alternatively spliced variants of MYOM1, including EH-myomesin,[7] Skelemin[8] and Myomesin-1[8][9][10] have been identified; with Skelemin having an additional 96 amino acids rich in
serine and
proline residues.[8] Myomesin-1, like
myomesin 2 and
titin, is a member of a family of
myosin-associated proteins containing structural modules with strong homology to either
fibronectin type III (motif I) or
immunoglobulin C2 (motif II) domains. Myomesin-1 bears uniqueness within this family in that it has
intermediate filament core-like motifs, one near each terminus.[11] Myomesin-1 and
Myomesin-2 each have a unique
N-terminal region followed by 12 modules of motif I or motif II, in the arrangement II-II-I-I-I-I-I-II-II-II-II-II. The two proteins share 50% sequence identity in this repeat-containing region. The head structure formed by these 2 proteins on one end of the
titin string extends into the center of the
M band. Alternatively spliced, tissue-specific transcript variants encoding different
isoforms have been identified.[12] Myomesin-1 can dimerize in an anti-parallel fashion via its
C-terminal region.[13]
Function
Titin, together with its associated proteins, interconnects the major structure of
sarcomeres, the
M bands and
Z discs. The
C-terminal end of the titin string extends into the
M line, where it binds tightly to Myomesin-1 and
myomesin 2. Skelemin/Myomesin-1 is concentrated at peripheral regions of M-bands, and is postulated to link
myofibrils with the
intermediate filamentcytoskeleton.[11] Skelemin/Myomesin-1 has been detected in the nucleus as well as the cytoskeletal, suggesting that it may play a role in gene expression.[14] Myomesin-1 functions to mediate stretch-induced signaling,[15] and the EH-myomesin splice variant, expressed in embryonic hearts and in
dilated cardiomyopathy, can modulate its elasticity.[16]
Clinical Significance
The fetal EH-myomesin alternatively spliced form of MYOM1 has been shown to be reexpressed at an early timepoint in the progression of
dilated cardiomyopathy, coincident with isoform switches in
titin.[17]
MYOM1 has also been shown to be abnormally spliced in patients with
myotonic dystrophy type I; specifically, exon 17a.[18]
Interactions
Skelemin/Myomesin-1 has been shown to
interact with:
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Speel EJ, van der Ven PF, Albrechts JC, Ramaekers FC, Fürst DO, Hopman AH (Nov 1998). "Assignment of the human gene for the sarcomeric M-band protein myomesin (MYOM1) to 18p11.31-p11.32". Genomics. 54 (1): 184–6.
doi:
10.1006/geno.1998.5503.
PMID9806852.
^
abcSteiner F, Weber K, Fürst DO (Feb 1999). "M band proteins myomesin and skelemin are encoded by the same gene: analysis of its organization and expression". Genomics. 56 (1): 78–89.
doi:
10.1006/geno.1998.5682.
PMID10036188.
^Lange S, Himmel M, Auerbach D, Agarkova I, Hayess K, Fürst DO, Perriard JC, Ehler E (Jan 2005). "Dimerisation of myomesin: implications for the structure of the sarcomeric M-band". Journal of Molecular Biology. 345 (2): 289–98.
doi:
10.1016/j.jmb.2004.10.040.
PMID15571722.
^Reddy KB, Fox JE, Price MG, Kulkarni S, Gupta S, Das B, Smith DM (2008). "Nuclear localization of Myomesin-1: possible functions". Journal of Muscle Research and Cell Motility. 29 (1): 1–8.
doi:
10.1007/s10974-008-9137-x.
PMID18521710.
S2CID12298270.
^Schoenauer R, Bertoncini P, Machaidze G, Aebi U, Perriard JC, Hegner M, Agarkova I (Jun 2005). "Myomesin is a molecular spring with adaptable elasticity". Journal of Molecular Biology. 349 (2): 367–79.
doi:
10.1016/j.jmb.2005.03.055.
PMID15890201.
^Koebis M, Ohsawa N, Kino Y, Sasagawa N, Nishino I, Ishiura S (Sep 2011). "Alternative splicing of myomesin 1 gene is aberrantly regulated in myotonic dystrophy type 1". Genes to Cells. 16 (9): 961–72.
doi:
10.1111/j.1365-2443.2011.01542.x.
PMID21794030.
S2CID3272510.
Vinkemeier U, Obermann W, Weber K, Fürst DO (Sep 1993). "The globular head domain of titin extends into the center of the sarcomeric M band. cDNA cloning, epitope mapping and immunoelectron microscopy of two titin-associated proteins". Journal of Cell Science. 106 (1): 319–30.
doi:
10.1242/jcs.106.1.319.
PMID7505783.
Obermann WM, Plessmann U, Weber K, Fürst DO (Oct 1995). "Purification and biochemical characterization of myomesin, a myosin-binding and titin-binding protein, from bovine skeletal muscle". European Journal of Biochemistry. 233 (1): 110–5.
doi:
10.1111/j.1432-1033.1995.110_1.x.
PMID7588733.
Steiner F, Weber K, Fürst DO (Feb 1999). "M band proteins myomesin and skelemin are encoded by the same gene: analysis of its organization and expression". Genomics. 56 (1): 78–89.
doi:
10.1006/geno.1998.5682.
PMID10036188.
Porter JD, Merriam AP, Gong B, Kasturi S, Zhou X, Hauser KF, Andrade FH, Cheng G (Sep 2003). "Postnatal suppression of myomesin, muscle creatine kinase and the M-line in rat extraocular muscle". The Journal of Experimental Biology. 206 (Pt 17): 3101–12.
doi:
10.1242/jeb.00511.
PMID12878677.
S2CID21867785.
Hornemann T, Kempa S, Himmel M, Hayess K, Fürst DO, Wallimann T (Sep 2003). "Muscle-type creatine kinase interacts with central domains of the M-band proteins myomesin and M-protein". Journal of Molecular Biology. 332 (4): 877–87.
doi:
10.1016/S0022-2836(03)00921-5.
PMID12972258.
Lange S, Himmel M, Auerbach D, Agarkova I, Hayess K, Fürst DO, Perriard JC, Ehler E (Jan 2005). "Dimerisation of myomesin: implications for the structure of the sarcomeric M-band". Journal of Molecular Biology. 345 (2): 289–98.
doi:
10.1016/j.jmb.2004.10.040.
PMID15571722.
Schoenauer R, Bertoncini P, Machaidze G, Aebi U, Perriard JC, Hegner M, Agarkova I (Jun 2005). "Myomesin is a molecular spring with adaptable elasticity". Journal of Molecular Biology. 349 (2): 367–79.
doi:
10.1016/j.jmb.2005.03.055.
PMID15890201.
Myomesin-1 is a
protein that in humans is encoded by the MYOM1gene.[5][6] Myomesin-1 is expressed in muscle cells and functions to stabilize the three-dimensional conformation of the
thick filament. Embryonic forms of Myomesin-1 have been detected in
dilated cardiomyopathy.
Structure
Alternatively spliced variants of MYOM1, including EH-myomesin,[7] Skelemin[8] and Myomesin-1[8][9][10] have been identified; with Skelemin having an additional 96 amino acids rich in
serine and
proline residues.[8] Myomesin-1, like
myomesin 2 and
titin, is a member of a family of
myosin-associated proteins containing structural modules with strong homology to either
fibronectin type III (motif I) or
immunoglobulin C2 (motif II) domains. Myomesin-1 bears uniqueness within this family in that it has
intermediate filament core-like motifs, one near each terminus.[11] Myomesin-1 and
Myomesin-2 each have a unique
N-terminal region followed by 12 modules of motif I or motif II, in the arrangement II-II-I-I-I-I-I-II-II-II-II-II. The two proteins share 50% sequence identity in this repeat-containing region. The head structure formed by these 2 proteins on one end of the
titin string extends into the center of the
M band. Alternatively spliced, tissue-specific transcript variants encoding different
isoforms have been identified.[12] Myomesin-1 can dimerize in an anti-parallel fashion via its
C-terminal region.[13]
Function
Titin, together with its associated proteins, interconnects the major structure of
sarcomeres, the
M bands and
Z discs. The
C-terminal end of the titin string extends into the
M line, where it binds tightly to Myomesin-1 and
myomesin 2. Skelemin/Myomesin-1 is concentrated at peripheral regions of M-bands, and is postulated to link
myofibrils with the
intermediate filamentcytoskeleton.[11] Skelemin/Myomesin-1 has been detected in the nucleus as well as the cytoskeletal, suggesting that it may play a role in gene expression.[14] Myomesin-1 functions to mediate stretch-induced signaling,[15] and the EH-myomesin splice variant, expressed in embryonic hearts and in
dilated cardiomyopathy, can modulate its elasticity.[16]
Clinical Significance
The fetal EH-myomesin alternatively spliced form of MYOM1 has been shown to be reexpressed at an early timepoint in the progression of
dilated cardiomyopathy, coincident with isoform switches in
titin.[17]
MYOM1 has also been shown to be abnormally spliced in patients with
myotonic dystrophy type I; specifically, exon 17a.[18]
Interactions
Skelemin/Myomesin-1 has been shown to
interact with:
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Speel EJ, van der Ven PF, Albrechts JC, Ramaekers FC, Fürst DO, Hopman AH (Nov 1998). "Assignment of the human gene for the sarcomeric M-band protein myomesin (MYOM1) to 18p11.31-p11.32". Genomics. 54 (1): 184–6.
doi:
10.1006/geno.1998.5503.
PMID9806852.
^
abcSteiner F, Weber K, Fürst DO (Feb 1999). "M band proteins myomesin and skelemin are encoded by the same gene: analysis of its organization and expression". Genomics. 56 (1): 78–89.
doi:
10.1006/geno.1998.5682.
PMID10036188.
^Lange S, Himmel M, Auerbach D, Agarkova I, Hayess K, Fürst DO, Perriard JC, Ehler E (Jan 2005). "Dimerisation of myomesin: implications for the structure of the sarcomeric M-band". Journal of Molecular Biology. 345 (2): 289–98.
doi:
10.1016/j.jmb.2004.10.040.
PMID15571722.
^Reddy KB, Fox JE, Price MG, Kulkarni S, Gupta S, Das B, Smith DM (2008). "Nuclear localization of Myomesin-1: possible functions". Journal of Muscle Research and Cell Motility. 29 (1): 1–8.
doi:
10.1007/s10974-008-9137-x.
PMID18521710.
S2CID12298270.
^Schoenauer R, Bertoncini P, Machaidze G, Aebi U, Perriard JC, Hegner M, Agarkova I (Jun 2005). "Myomesin is a molecular spring with adaptable elasticity". Journal of Molecular Biology. 349 (2): 367–79.
doi:
10.1016/j.jmb.2005.03.055.
PMID15890201.
^Koebis M, Ohsawa N, Kino Y, Sasagawa N, Nishino I, Ishiura S (Sep 2011). "Alternative splicing of myomesin 1 gene is aberrantly regulated in myotonic dystrophy type 1". Genes to Cells. 16 (9): 961–72.
doi:
10.1111/j.1365-2443.2011.01542.x.
PMID21794030.
S2CID3272510.
Vinkemeier U, Obermann W, Weber K, Fürst DO (Sep 1993). "The globular head domain of titin extends into the center of the sarcomeric M band. cDNA cloning, epitope mapping and immunoelectron microscopy of two titin-associated proteins". Journal of Cell Science. 106 (1): 319–30.
doi:
10.1242/jcs.106.1.319.
PMID7505783.
Obermann WM, Plessmann U, Weber K, Fürst DO (Oct 1995). "Purification and biochemical characterization of myomesin, a myosin-binding and titin-binding protein, from bovine skeletal muscle". European Journal of Biochemistry. 233 (1): 110–5.
doi:
10.1111/j.1432-1033.1995.110_1.x.
PMID7588733.
Steiner F, Weber K, Fürst DO (Feb 1999). "M band proteins myomesin and skelemin are encoded by the same gene: analysis of its organization and expression". Genomics. 56 (1): 78–89.
doi:
10.1006/geno.1998.5682.
PMID10036188.
Porter JD, Merriam AP, Gong B, Kasturi S, Zhou X, Hauser KF, Andrade FH, Cheng G (Sep 2003). "Postnatal suppression of myomesin, muscle creatine kinase and the M-line in rat extraocular muscle". The Journal of Experimental Biology. 206 (Pt 17): 3101–12.
doi:
10.1242/jeb.00511.
PMID12878677.
S2CID21867785.
Hornemann T, Kempa S, Himmel M, Hayess K, Fürst DO, Wallimann T (Sep 2003). "Muscle-type creatine kinase interacts with central domains of the M-band proteins myomesin and M-protein". Journal of Molecular Biology. 332 (4): 877–87.
doi:
10.1016/S0022-2836(03)00921-5.
PMID12972258.
Lange S, Himmel M, Auerbach D, Agarkova I, Hayess K, Fürst DO, Perriard JC, Ehler E (Jan 2005). "Dimerisation of myomesin: implications for the structure of the sarcomeric M-band". Journal of Molecular Biology. 345 (2): 289–98.
doi:
10.1016/j.jmb.2004.10.040.
PMID15571722.
Schoenauer R, Bertoncini P, Machaidze G, Aebi U, Perriard JC, Hegner M, Agarkova I (Jun 2005). "Myomesin is a molecular spring with adaptable elasticity". Journal of Molecular Biology. 349 (2): 367–79.
doi:
10.1016/j.jmb.2005.03.055.
PMID15890201.