Group:MUZIC:MLP: Difference between revisions

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== Introduction ==

The '''Cystein and glycine-rich protein 3 (CSRP3)''', or as also known as '''Muscle LIM Protein''' (MLP), is one of the three CSRP family members identified in vertebrates. CSRP3 has been identified muscle and cardiac cells<ref>PMID: 7490106</ref>. The three family members contain 192-194 residues and two [[LIM]] domains adjacent to a flexible glycine-rich linker. Each LIM domain comprises two Zn-binding motifs CCHC and CCCC representing a structural and presumably functional independent unit.

The '''Cystein and glycine-rich protein 3 (CSRP3)''', or as also known as '''Muscle LIM Protein''' (MLP), is one of the three CSRP family members identified in vertebrates. CSRP3 has been identified muscle and cardiac cells<ref name="r1">PMID: 7490106</ref>. The three family members contain 192-194 residues and two [[LIM]] domains adjacent to a flexible glycine-rich linker. Each LIM domain comprises two Zn-binding motifs CCHC and CCCC representing a structural and presumably functional independent unit.

== Sequence Annotation ==

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== Function and Interactions ==

All three CSRPs are associated with the actin cytoskeleton and have similar functions in different muscle varieties. They up-regulate the myogenesis and have specific roles in the organisation of cytosolic structures in cardiomyocytes. It was also suggested that CSRPs may have a role in stretch sensing<ref>PMID: 12507422</ref>. MLP (CSRP3) is localized mainly in Z and M-lines in striated muscles. Within the Z-disc, the interaction of CSRP3 with [http://www.proteopedia.org/wiki/index.php/Group:MUZIC:Telethonin telethonin] has been reported previously<ref>PMID: 12507422</ref>, <ref>PMID: 16407954</ref>, however recent reports demonstrate that this interaction is not existing <ref>PMID:18505755</ref>. CSRP3 is mainly interacting with [[α-actinin 2]] as well as has been suggested to interact with βI-spectrin, N-RAP (Nebulin-related-anchoring protein) and cofilin2 (CFL2), underlying the essential role of CSRP3 as a scaffold protein in the sarcomere. During myofibrilogenesis CSRP3 has been suggested to form complexes with the muscle helix-loop-helix transcription factors MyoD, MRF4 and myogenin <ref>PMID:18505755</ref>. Finally, it is essential for the anchorage of calcineurin to the Z line<ref>PMID: 15665106</ref>.

All three CSRPs are associated with the actin cytoskeleton and have similar functions in different muscle varieties. They up-regulate the myogenesis and have specific roles in the organisation of cytosolic structures in cardiomyocytes. It was also suggested that CSRPs may have a role in stretch sensing<ref name="r2">PMID: 12507422</ref>. MLP (CSRP3) is localized mainly in Z and M-lines in striated muscles. Within the Z-disc, the interaction of CSRP3 with [http://www.proteopedia.org/wiki/index.php/Group:MUZIC:Telethonin telethonin] has been reported previously<ref name="r2">PMID: 12507422</ref>, <ref>PMID: 16407954</ref>, however recent reports demonstrate that this interaction is not existing <ref>PMID:18505755</ref>. CSRP3 is mainly interacting with [[α-actinin 2]] as well as has been suggested to interact with βI-spectrin, N-RAP (Nebulin-related-anchoring protein) and cofilin2 (CFL2), underlying the essential role of CSRP3 as a scaffold protein in the sarcomere. During myofibrilogenesis CSRP3 has been suggested to form complexes with the muscle helix-loop-helix transcription factors MyoD, MRF4 and myogenin <ref>PMID:18505755</ref>. Finally, it is essential for the anchorage of calcineurin to the Z line<ref>PMID: 15665106</ref>.

== Pathology ==

Mutations on the first LIM domain have been linked to familial hypertrophic cardiomyopathy (HCM). All of them ('''L44P, S54R, E55G, C58G''') are related to the proper binding of Zinc to the protein, thus causing conformational alterations. Familial hypertrophic cardiomyopathy is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death <ref>PMID:12642359</ref>.

The mutation '''W4R''' in CSRP3 has been reported to cause dilated cardiomyopathy (DCM) of type 1Mv. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia and patients have the risk of premature death <ref>PMID:12507422</ref>. However a more recent report demonstrates that the W4R mutation is not sufficient to cause DCM <ref>PMID:18505755</ref>.

The mutation '''W4R''' in CSRP3 has been reported to cause dilated cardiomyopathy (DCM) of type 1Mv. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia and patients have the risk of premature death <ref name="r2">PMID:12507422</ref>. However a more recent report demonstrates that the W4R mutation is not sufficient to cause DCM <ref>PMID:18505755</ref>.

== References ==

Group:MUZIC:MLP: Difference between revisions

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@@ Line 2: / Line 2: @@
 == Introduction ==
-The '''Cystein and glycine-rich protein 3 (CSRP3)''', or as also known as '''Muscle LIM Protein''' (MLP), is one of the three CSRP family members identified in vertebrates. CSRP3 has been identified muscle and cardiac cells<ref>PMID: 7490106</ref>. The three family members contain 192-194 residues and two [[LIM]] domains adjacent to a flexible glycine-rich linker. Each LIM domain comprises two Zn-binding motifs CCHC and CCCC representing a structural and presumably functional independent unit.
+The '''Cystein and glycine-rich protein 3 (CSRP3)''', or as also known as '''Muscle LIM Protein''' (MLP), is one of the three CSRP family members identified in vertebrates. CSRP3 has been identified muscle and cardiac cells<ref name="r1">PMID: 7490106</ref>. The three family members contain 192-194 residues and two [[LIM]] domains adjacent to a flexible glycine-rich linker. Each LIM domain comprises two Zn-binding motifs CCHC and CCCC representing a structural and presumably functional independent unit.
 == Sequence Annotation ==
@@ Line 15: / Line 15: @@
 == Function and Interactions ==
-All three CSRPs are associated with the actin cytoskeleton and have similar functions in different muscle varieties. They up-regulate the myogenesis and have specific roles in the organisation of cytosolic structures in cardiomyocytes. It was also suggested that CSRPs may have a role in stretch sensing<ref>PMID: 12507422</ref>. MLP (CSRP3) is localized mainly in Z and M-lines in striated muscles. Within the Z-disc, the interaction of CSRP3 with [http://www.proteopedia.org/wiki/index.php/Group:MUZIC:Telethonin telethonin] has been reported previously<ref>PMID: 12507422</ref>, <ref>PMID: 16407954</ref>, however recent reports demonstrate that this interaction is not existing <ref>PMID:18505755</ref>. CSRP3 is mainly interacting with [[α-actinin 2]] as well as has been suggested to interact with βI-spectrin, N-RAP (Nebulin-related-anchoring protein) and cofilin2 (CFL2), underlying the essential role of CSRP3 as a scaffold protein in the sarcomere. During myofibrilogenesis CSRP3 has been suggested to form complexes with the muscle helix-loop-helix transcription factors MyoD, MRF4 and myogenin <ref>PMID:18505755</ref>. Finally, it is essential for the anchorage of calcineurin to the Z line<ref>PMID: 15665106</ref>.
+All three CSRPs are associated with the actin cytoskeleton and have similar functions in different muscle varieties. They up-regulate the myogenesis and have specific roles in the organisation of cytosolic structures in cardiomyocytes. It was also suggested that CSRPs may have a role in stretch sensing<ref name="r2">PMID: 12507422</ref>. MLP (CSRP3) is localized mainly in Z and M-lines in striated muscles. Within the Z-disc, the interaction of CSRP3 with [http://www.proteopedia.org/wiki/index.php/Group:MUZIC:Telethonin telethonin] has been reported previously<ref name="r2">PMID: 12507422</ref>, <ref>PMID: 16407954</ref>, however recent reports demonstrate that this interaction is not existing <ref>PMID:18505755</ref>. CSRP3 is mainly interacting with [[α-actinin 2]] as well as has been suggested to interact with βI-spectrin, N-RAP (Nebulin-related-anchoring protein) and cofilin2 (CFL2), underlying the essential role of CSRP3 as a scaffold protein in the sarcomere. During myofibrilogenesis CSRP3 has been suggested to form complexes with the muscle helix-loop-helix transcription factors MyoD, MRF4 and myogenin <ref>PMID:18505755</ref>. Finally, it is essential for the anchorage of calcineurin to the Z line<ref>PMID: 15665106</ref>.
 == Pathology ==
 Mutations on the first LIM domain have been linked to familial hypertrophic cardiomyopathy (HCM). All of them ('''L44P, S54R, E55G, C58G''') are related to the proper binding of Zinc to the protein, thus causing conformational alterations. Familial hypertrophic cardiomyopathy is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death <ref>PMID:12642359</ref>.
-The mutation '''W4R''' in CSRP3 has been reported to cause dilated cardiomyopathy (DCM) of type 1Mv. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia and patients have the risk of premature death <ref>PMID:12507422</ref>. However a more recent report demonstrates that the W4R mutation is not sufficient to cause DCM <ref>PMID:18505755</ref>.
+The mutation '''W4R''' in CSRP3 has been reported to cause dilated cardiomyopathy (DCM) of type 1Mv. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia and patients have the risk of premature death <ref name="r2">PMID:12507422</ref>. However a more recent report demonstrates that the W4R mutation is not sufficient to cause DCM <ref>PMID:18505755</ref>.
 == References ==
 <references />