Proteopedia - User contributions [en]

Group:MUZIC:Plectin

2013-02-28T11:55:20Z

Jae-Geun Song: /* Sequence annotation */

== Introduction ==
Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms.
Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain (isoform 1c),skeletal muscle (isoform 1d) and skin(isoform 1a). <ref>PMID:10556294</ref>.

[[Image:isoforms.gif]]

<Structure load='3PE0' size='300' frame='true' align='right' caption='Crystal structure of SR4-SR5-SH3 regions in the plakin domain (PDB:3PE0)' scene='User:Jae-Geun_Song/Workbench/plectin/Plakin/1'/>

== Sequence annotation ==
Human plectin contains 4,684 amino acids <ref>PMID:8633055</ref>. Plectin can be divided in three main sections; a central coiled-coil rod domain(exon 31), N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region (exon 32) is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin <ref>PMID:3430617</ref>. N-terminal globular region contains actin binding domain comprising two calponin homology (exon 2-8) and plakin domain (exon 9-30).

[[Image:plectin.jpg]]

Schematic domain map of plectin (Winter, 2013)

== Structures ==

'''1. Actin Binding Domain (ABD)'''

<Structure load='1sh6' size='300' frame='true' align='right' caption='The actin binding domain of plectin (PDB:1SH6)' scene='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/1'/>

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain(<scene name='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/3'>CH1 and CH2</scene>)<ref>PMID:9164454</ref>. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported <ref>PMID: 15128297</ref>.

'''2. Plakin domain'''

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.<ref>PMID: 21288893 </ref>

'''3. Integrin β4-Plectin complex'''
The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.<ref>PMID: 19242489 </ref>

== Function and Interactions ==
Proteins coordinate various cytoskeletal networks are termed as cytolinkers, which are able to interlink different types of cytoskeletons. Plectin is one of the well-characterized cytolinker and expressed in diverse cell types and tissues, a number of different binding partners of plectin have been identified.

Intermediate filament(IF) binding sites of plectin is located between plakin repeats 5 and 6 in C-terminal globular domain. Several IF proteins were identified to interact with plectin such as vimentin, desmin, GFAP(glial fibrillary acidic protein) and cytokeratins <ref>PMID: 8830774 </ref> .

The actin binding domain(ABD)in N-terminal globular domain has a role to interact with integrin subunit beta 4 to establish mechanical stability in hemedesmosomes along with its function for binding to actin filament(F-actin). Calmodulin(CaM) is also known to bind the ABD of plectin to modulate the hemidesmosome disassembly <ref> PMID: 19419971 </ref>.

<Structure load='3F7P' size='300' frame='true' align='right' caption='Crystal structure of plectin ABD(magenta) and integrin beta 4 (green) complex (PDB:3F7P)' scene='Group:MUZIC:Plectin/Plecint/1' />

== Pathology ==
It has been reported that patients with EBS-MD (Epidermolysis bullosa simplex with muscular dystrophy),a genetic disorder characterized severe skin blistering disease combined with muscular dystrophy, have a muation on plectin gene(PLEC1). This mutation leads to premature termination of translation.<ref>PMID: 8941634 </ref>
In addition, site-specific missense mutation(R2110W) on plectin rod domain causes an autosomal dominant form of disease termed EBS-Ogna without muscular dystrophy.<ref>PMID: 9067706 </ref>
Plectin deficient(-/-) mice also exhibit similar skin and muscle phenotypes of human patients suffering from EBS-MD and died 2-3 days after birth. <ref>PMID: 9389647</ref>

== References ==

<references/>

Group:MUZIC:Myostatin

2013-02-11T11:27:12Z

Jae-Geun Song: /* Structure */

<Structure load='3hh2' size='400' frame='true' align='right' caption='The structure of myostatin:follistatin 288 (PDB 3HH2)' scene='Group:MUZIC:Myostatin/Myostatin/1'/>

== Introduction ==

Myostatin which is also known as growth and developmental factor-8(GDF-8) was originally identified in a screen for novel mammalian members of the transforming growth factor-ß (TGF-ß) superfamily of growth and differentiation factors.The phenotype of myostatin knock-out mice suggested that myostatin functions as a negative regulator of muscle growth, and it was on this basis that myostatin was given its name <ref>PMID:9139826</ref>. For these reasons, inhibitors targeting myostatin have been regarded as potential drugs in the treatment of muscle-wasting disorders such as muscular dystrophy <ref>PMID: 18425412 </ref>.

== Sequence annotation ==
Myostatin consists of three functional fragments: signal peptide, N-terminal and C-terminal fragments. Amino acid sequences among vertebrate species are highly conserved, which also suggests the conserved function of myostatin among vertebrates <ref>PMID: 9356471 </ref>.

[[Image:myostatin.jpg]]

== Structure ==
The complex of two follistatin 288 molecules bound to one myostatin dimer was resolved to 2.15 Å using X-ray crystallography and deposited in PDB. Myostatin shows a typical hand-shaped structure of TGF-beta family. When myostatin binds to Fst288, which increase the affinity to heparin due to the continuous basic surface of the complex <ref>PMID: 19644449</ref>.
(Green:myostatin C-terminal dimer, yellow: follinstatin 288)

[[Image:Myo2.png]]

== Function and Interactions ==
Myostatin is initially formed as a precursor protein which undergoes two proteolytic processing events in order to generate the biologically active molecule. First the N-terminal signal sequence is removed, a second cleavage generates the C-terminal fragment, which possesses receptor-binding activity and modulates a signal transduction cascade in the target cell <ref>PMID: 15473835</ref>.
The N-terminal fragment after proteolytic processing has been referred to as the propeptide (shown blue). One mechanism for activating myostatin latency appears to be proteolytic cleavage of the propeptide <ref>PMID: 14671324 </ref>. In addition to the regulation of intracellular myostation processing,follistatin has been known to be capable of binding and inhibiting the activity of the myostatin C-terminal dimer (shown yellow). <ref>PMID: 2106159 </ref>.

The interaction of myostatin with titin-cap(T-cap),a Z-disk protein which binds to N-terminal domain of titin,was identified by a yeast two-hybrid system. <ref>PMID: 12209887 </ref> It is presumed that myostatin has a putative role in the muscle Z-disk regulation.

[[Image:Myo1.gif]]
(Processing of myostatin protein. Lee,2004)

== Pathology ==
Mice lacking C-terminal domain of myostatin shows dramatic increases in skeletal muscle mass, which are observed for the entire life of mice. In addition, myostatin mutant mice fail to accumulate fat as a function of age and suppress the development of insulin resistance <ref>PMID: 11877467</ref>. Thus, the targeting myostatin pathway might be an effective way to promote muscle growth for the patients with muscle degenerative diseases, such as muscular dystrophy and to prevent obesity <ref>PMID: 15473835 </ref>.

== References ==
<references/>

Group:MUZIC:Myostatin

2013-02-11T11:26:29Z

Jae-Geun Song: /* Structure */

<Structure load='3hh2' size='400' frame='true' align='right' caption='The structure of myostatin:follistatin 288 (PDB 3HH2)' scene='Group:MUZIC:Myostatin/Myostatin/1'/>

== Introduction ==

Myostatin which is also known as growth and developmental factor-8(GDF-8) was originally identified in a screen for novel mammalian members of the transforming growth factor-ß (TGF-ß) superfamily of growth and differentiation factors.The phenotype of myostatin knock-out mice suggested that myostatin functions as a negative regulator of muscle growth, and it was on this basis that myostatin was given its name <ref>PMID:9139826</ref>. For these reasons, inhibitors targeting myostatin have been regarded as potential drugs in the treatment of muscle-wasting disorders such as muscular dystrophy <ref>PMID: 18425412 </ref>.

== Sequence annotation ==
Myostatin consists of three functional fragments: signal peptide, N-terminal and C-terminal fragments. Amino acid sequences among vertebrate species are highly conserved, which also suggests the conserved function of myostatin among vertebrates <ref>PMID: 9356471 </ref>.

[[Image:myostatin.jpg]]

== Structure ==
The complex of two follistatin 288 molecules bound to one myostatin dimer was resolved to 2.15 Å using X-ray crystallography and deposited in PDB. Myostatin shows a typical hand-shaped structure of TGF-beta family. When myostatin binds to Fst288, which increase the affinity to heparin due to the basic surfece of the complex <ref>PMID: 19644449</ref>.
(Green:myostatin C-terminal dimer, yellow: follinstatin 288)

[[Image:Myo2.png]]

== Function and Interactions ==
Myostatin is initially formed as a precursor protein which undergoes two proteolytic processing events in order to generate the biologically active molecule. First the N-terminal signal sequence is removed, a second cleavage generates the C-terminal fragment, which possesses receptor-binding activity and modulates a signal transduction cascade in the target cell <ref>PMID: 15473835</ref>.
The N-terminal fragment after proteolytic processing has been referred to as the propeptide (shown blue). One mechanism for activating myostatin latency appears to be proteolytic cleavage of the propeptide <ref>PMID: 14671324 </ref>. In addition to the regulation of intracellular myostation processing,follistatin has been known to be capable of binding and inhibiting the activity of the myostatin C-terminal dimer (shown yellow). <ref>PMID: 2106159 </ref>.

The interaction of myostatin with titin-cap(T-cap),a Z-disk protein which binds to N-terminal domain of titin,was identified by a yeast two-hybrid system. <ref>PMID: 12209887 </ref> It is presumed that myostatin has a putative role in the muscle Z-disk regulation.

[[Image:Myo1.gif]]
(Processing of myostatin protein. Lee,2004)

== Pathology ==
Mice lacking C-terminal domain of myostatin shows dramatic increases in skeletal muscle mass, which are observed for the entire life of mice. In addition, myostatin mutant mice fail to accumulate fat as a function of age and suppress the development of insulin resistance <ref>PMID: 11877467</ref>. Thus, the targeting myostatin pathway might be an effective way to promote muscle growth for the patients with muscle degenerative diseases, such as muscular dystrophy and to prevent obesity <ref>PMID: 15473835 </ref>.

== References ==
<references/>

Group:MUZIC:Myostatin

2013-02-11T11:14:57Z

Jae-Geun Song: /* Sequence annotation */

<Structure load='3hh2' size='400' frame='true' align='right' caption='The structure of myostatin:follistatin 288 (PDB 3HH2)' scene='Group:MUZIC:Myostatin/Myostatin/1'/>

== Introduction ==

Myostatin which is also known as growth and developmental factor-8(GDF-8) was originally identified in a screen for novel mammalian members of the transforming growth factor-ß (TGF-ß) superfamily of growth and differentiation factors.The phenotype of myostatin knock-out mice suggested that myostatin functions as a negative regulator of muscle growth, and it was on this basis that myostatin was given its name <ref>PMID:9139826</ref>. For these reasons, inhibitors targeting myostatin have been regarded as potential drugs in the treatment of muscle-wasting disorders such as muscular dystrophy <ref>PMID: 18425412 </ref>.

== Sequence annotation ==
Myostatin consists of three functional fragments: signal peptide, N-terminal and C-terminal fragments. Amino acid sequences among vertebrate species are highly conserved, which also suggests the conserved function of myostatin among vertebrates <ref>PMID: 9356471 </ref>.

[[Image:myostatin.jpg]]

== Structure ==
One structure of myostatin is currently available in Protein Data Bank.
The complex of two follistatin 288 molecules bound to one myostatin dimer was resolved to 2.15 Å using X-ray crystallography and deposited in PDB.
(Green:myostatin C-terminal dimer, yellow: follinstatin 288)

[[Image:Myo2.png]]

== Function and Interactions ==
Myostatin is initially formed as a precursor protein which undergoes two proteolytic processing events in order to generate the biologically active molecule. First the N-terminal signal sequence is removed, a second cleavage generates the C-terminal fragment, which possesses receptor-binding activity and modulates a signal transduction cascade in the target cell <ref>PMID: 15473835</ref>.
The N-terminal fragment after proteolytic processing has been referred to as the propeptide (shown blue). One mechanism for activating myostatin latency appears to be proteolytic cleavage of the propeptide <ref>PMID: 14671324 </ref>. In addition to the regulation of intracellular myostation processing,follistatin has been known to be capable of binding and inhibiting the activity of the myostatin C-terminal dimer (shown yellow). <ref>PMID: 2106159 </ref>.

The interaction of myostatin with titin-cap(T-cap),a Z-disk protein which binds to N-terminal domain of titin,was identified by a yeast two-hybrid system. <ref>PMID: 12209887 </ref> It is presumed that myostatin has a putative role in the muscle Z-disk regulation.

[[Image:Myo1.gif]]
(Processing of myostatin protein. Lee,2004)

== Pathology ==
Mice lacking C-terminal domain of myostatin shows dramatic increases in skeletal muscle mass, which are observed for the entire life of mice. In addition, myostatin mutant mice fail to accumulate fat as a function of age and suppress the development of insulin resistance <ref>PMID: 11877467</ref>. Thus, the targeting myostatin pathway might be an effective way to promote muscle growth for the patients with muscle degenerative diseases, such as muscular dystrophy and to prevent obesity <ref>PMID: 15473835 </ref>.

== References ==
<references/>

Group:MUZIC:Myostatin

2013-02-11T11:14:45Z

Jae-Geun Song: /* Sequence annotation */

<Structure load='3hh2' size='400' frame='true' align='right' caption='The structure of myostatin:follistatin 288 (PDB 3HH2)' scene='Group:MUZIC:Myostatin/Myostatin/1'/>

== Introduction ==

Myostatin which is also known as growth and developmental factor-8(GDF-8) was originally identified in a screen for novel mammalian members of the transforming growth factor-ß (TGF-ß) superfamily of growth and differentiation factors.The phenotype of myostatin knock-out mice suggested that myostatin functions as a negative regulator of muscle growth, and it was on this basis that myostatin was given its name <ref>PMID:9139826</ref>. For these reasons, inhibitors targeting myostatin have been regarded as potential drugs in the treatment of muscle-wasting disorders such as muscular dystrophy <ref>PMID: 18425412 </ref>.

== Sequence annotation ==
Myostatin consists of three functional fragments: signal peptide, N-terminal and C-terminal fragments. Amino acid sequences among vertebrate species are highly conserved, which also suggests the conserved function of myostatin among vertebrates <ref>PMID: 9356471 </ref>.
[[Image:myostatin.jpg]]

== Structure ==
One structure of myostatin is currently available in Protein Data Bank.
The complex of two follistatin 288 molecules bound to one myostatin dimer was resolved to 2.15 Å using X-ray crystallography and deposited in PDB.
(Green:myostatin C-terminal dimer, yellow: follinstatin 288)

[[Image:Myo2.png]]

== Function and Interactions ==
Myostatin is initially formed as a precursor protein which undergoes two proteolytic processing events in order to generate the biologically active molecule. First the N-terminal signal sequence is removed, a second cleavage generates the C-terminal fragment, which possesses receptor-binding activity and modulates a signal transduction cascade in the target cell <ref>PMID: 15473835</ref>.
The N-terminal fragment after proteolytic processing has been referred to as the propeptide (shown blue). One mechanism for activating myostatin latency appears to be proteolytic cleavage of the propeptide <ref>PMID: 14671324 </ref>. In addition to the regulation of intracellular myostation processing,follistatin has been known to be capable of binding and inhibiting the activity of the myostatin C-terminal dimer (shown yellow). <ref>PMID: 2106159 </ref>.

The interaction of myostatin with titin-cap(T-cap),a Z-disk protein which binds to N-terminal domain of titin,was identified by a yeast two-hybrid system. <ref>PMID: 12209887 </ref> It is presumed that myostatin has a putative role in the muscle Z-disk regulation.

[[Image:Myo1.gif]]
(Processing of myostatin protein. Lee,2004)

== Pathology ==
Mice lacking C-terminal domain of myostatin shows dramatic increases in skeletal muscle mass, which are observed for the entire life of mice. In addition, myostatin mutant mice fail to accumulate fat as a function of age and suppress the development of insulin resistance <ref>PMID: 11877467</ref>. Thus, the targeting myostatin pathway might be an effective way to promote muscle growth for the patients with muscle degenerative diseases, such as muscular dystrophy and to prevent obesity <ref>PMID: 15473835 </ref>.

== References ==
<references/>

Group:MUZIC:Myostatin

2013-02-11T11:14:17Z

Jae-Geun Song:

<Structure load='3hh2' size='400' frame='true' align='right' caption='The structure of myostatin:follistatin 288 (PDB 3HH2)' scene='Group:MUZIC:Myostatin/Myostatin/1'/>

== Introduction ==

Myostatin which is also known as growth and developmental factor-8(GDF-8) was originally identified in a screen for novel mammalian members of the transforming growth factor-ß (TGF-ß) superfamily of growth and differentiation factors.The phenotype of myostatin knock-out mice suggested that myostatin functions as a negative regulator of muscle growth, and it was on this basis that myostatin was given its name <ref>PMID:9139826</ref>. For these reasons, inhibitors targeting myostatin have been regarded as potential drugs in the treatment of muscle-wasting disorders such as muscular dystrophy <ref>PMID: 18425412 </ref>.

== Sequence annotation ==
Myostatin consists of three functional fragments: signal peptide, N-terminal and C-terminal fragments. Amino acid sequences among vertebrate species are highly conserved, which also suggests the conserved function of myostatin among vertebrates <ref>PMID: 9356471 </ref>.
[[Image:myostatin.jpg]]

== Structure ==
One structure of myostatin is currently available in Protein Data Bank.
The complex of two follistatin 288 molecules bound to one myostatin dimer was resolved to 2.15 Å using X-ray crystallography and deposited in PDB.
(Green:myostatin C-terminal dimer, yellow: follinstatin 288)

[[Image:Myo2.png]]

== Function and Interactions ==
Myostatin is initially formed as a precursor protein which undergoes two proteolytic processing events in order to generate the biologically active molecule. First the N-terminal signal sequence is removed, a second cleavage generates the C-terminal fragment, which possesses receptor-binding activity and modulates a signal transduction cascade in the target cell <ref>PMID: 15473835</ref>.
The N-terminal fragment after proteolytic processing has been referred to as the propeptide (shown blue). One mechanism for activating myostatin latency appears to be proteolytic cleavage of the propeptide <ref>PMID: 14671324 </ref>. In addition to the regulation of intracellular myostation processing,follistatin has been known to be capable of binding and inhibiting the activity of the myostatin C-terminal dimer (shown yellow). <ref>PMID: 2106159 </ref>.

The interaction of myostatin with titin-cap(T-cap),a Z-disk protein which binds to N-terminal domain of titin,was identified by a yeast two-hybrid system. <ref>PMID: 12209887 </ref> It is presumed that myostatin has a putative role in the muscle Z-disk regulation.

[[Image:Myo1.gif]]
(Processing of myostatin protein. Lee,2004)

== Pathology ==
Mice lacking C-terminal domain of myostatin shows dramatic increases in skeletal muscle mass, which are observed for the entire life of mice. In addition, myostatin mutant mice fail to accumulate fat as a function of age and suppress the development of insulin resistance <ref>PMID: 11877467</ref>. Thus, the targeting myostatin pathway might be an effective way to promote muscle growth for the patients with muscle degenerative diseases, such as muscular dystrophy and to prevent obesity <ref>PMID: 15473835 </ref>.

== References ==
<references/>

Group:MUZIC:Myostatin

2013-02-11T11:13:58Z

Jae-Geun Song: /* Sequence annotation */

<Structure load='3hh2' size='400' frame='true' align='right' caption='The structure of myostatin:follistatin 288 (PDB 3HH2)' scene='Group:MUZIC:Myostatin/Myostatin/1'/>

== Introduction ==

Myostatin which is also known as growth and developmental factor-8(GDF-8) was originally identified in a screen for novel mammalian members of the transforming growth factor-ß (TGF-ß) superfamily of growth and differentiation factors.The phenotype of myostatin knock-out mice suggested that myostatin functions as a negative regulator of muscle growth, and it was on this basis that myostatin was given its name <ref>PMID:9139826</ref>. For these reasons, inhibitors targeting myostatin have been regarded as potential drugs in the treatment of muscle-wasting disorders such as muscular dystrophy <ref>PMID: 18425412 </ref>.

== Sequence annotation ==
Myostatin consists of three functional fragments: signal peptide, N-terminal and C-terminal fragments. Amino acid sequences among vertebrate species are highly conserved, which also suggests the conserved function of myostatin among vertebrates <ref>PMID: 9356471 </ref>.

[[Image:myostatin.jpg]]

== Structure ==
One structure of myostatin is currently available in Protein Data Bank.
The complex of two follistatin 288 molecules bound to one myostatin dimer was resolved to 2.15 Å using X-ray crystallography and deposited in PDB.
(Green:myostatin C-terminal dimer, yellow: follinstatin 288)

[[Image:Myo2.png]]

== Function and Interactions ==
Myostatin is initially formed as a precursor protein which undergoes two proteolytic processing events in order to generate the biologically active molecule. First the N-terminal signal sequence is removed, a second cleavage generates the C-terminal fragment, which possesses receptor-binding activity and modulates a signal transduction cascade in the target cell <ref>PMID: 15473835</ref>.
The N-terminal fragment after proteolytic processing has been referred to as the propeptide (shown blue). One mechanism for activating myostatin latency appears to be proteolytic cleavage of the propeptide <ref>PMID: 14671324 </ref>. In addition to the regulation of intracellular myostation processing,follistatin has been known to be capable of binding and inhibiting the activity of the myostatin C-terminal dimer (shown yellow). <ref>PMID: 2106159 </ref>.

The interaction of myostatin with titin-cap(T-cap),a Z-disk protein which binds to N-terminal domain of titin,was identified by a yeast two-hybrid system. <ref>PMID: 12209887 </ref> It is presumed that myostatin has a putative role in the muscle Z-disk regulation.

[[Image:Myo1.gif]]
(Processing of myostatin protein. Lee,2004)

== Pathology ==
Mice lacking C-terminal domain of myostatin shows dramatic increases in skeletal muscle mass, which are observed for the entire life of mice. In addition, myostatin mutant mice fail to accumulate fat as a function of age and suppress the development of insulin resistance <ref>PMID: 11877467</ref>. Thus, the targeting myostatin pathway might be an effective way to promote muscle growth for the patients with muscle degenerative diseases, such as muscular dystrophy and to prevent obesity <ref>PMID: 15473835 </ref>.

== References ==
<references/>

Group:MUZIC:Myostatin

2013-02-11T11:12:02Z

Jae-Geun Song: /* Sequence annotation */

<Structure load='3hh2' size='400' frame='true' align='right' caption='The structure of myostatin:follistatin 288 (PDB 3HH2)' scene='Group:MUZIC:Myostatin/Myostatin/1'/>

== Introduction ==

Myostatin which is also known as growth and developmental factor-8(GDF-8) was originally identified in a screen for novel mammalian members of the transforming growth factor-ß (TGF-ß) superfamily of growth and differentiation factors.The phenotype of myostatin knock-out mice suggested that myostatin functions as a negative regulator of muscle growth, and it was on this basis that myostatin was given its name <ref>PMID:9139826</ref>. For these reasons, inhibitors targeting myostatin have been regarded as potential drugs in the treatment of muscle-wasting disorders such as muscular dystrophy <ref>PMID: 18425412 </ref>.

== Sequence annotation ==
Myostatin consists of three functional fragments: signal peptide, N-terminal and C-terminal fragments. Amino acid sequences among vertebrate species are highly conserved, which also suggests the conserved function of myostatin among vertebrates. [[Image:myostatin.jpg]]

== Structure ==
One structure of myostatin is currently available in Protein Data Bank.
The complex of two follistatin 288 molecules bound to one myostatin dimer was resolved to 2.15 Å using X-ray crystallography and deposited in PDB.
(Green:myostatin C-terminal dimer, yellow: follinstatin 288)

[[Image:Myo2.png]]

== Function and Interactions ==
Myostatin is initially formed as a precursor protein which undergoes two proteolytic processing events in order to generate the biologically active molecule. First the N-terminal signal sequence is removed, a second cleavage generates the C-terminal fragment, which possesses receptor-binding activity and modulates a signal transduction cascade in the target cell <ref>PMID: 15473835</ref>.
The N-terminal fragment after proteolytic processing has been referred to as the propeptide (shown blue). One mechanism for activating myostatin latency appears to be proteolytic cleavage of the propeptide <ref>PMID: 14671324 </ref>. In addition to the regulation of intracellular myostation processing,follistatin has been known to be capable of binding and inhibiting the activity of the myostatin C-terminal dimer (shown yellow). <ref>PMID: 2106159 </ref>.

The interaction of myostatin with titin-cap(T-cap),a Z-disk protein which binds to N-terminal domain of titin,was identified by a yeast two-hybrid system. <ref>PMID: 12209887 </ref> It is presumed that myostatin has a putative role in the muscle Z-disk regulation.

[[Image:Myo1.gif]]
(Processing of myostatin protein. Lee,2004)

== Pathology ==
Mice lacking C-terminal domain of myostatin shows dramatic increases in skeletal muscle mass, which are observed for the entire life of mice. In addition, myostatin mutant mice fail to accumulate fat as a function of age and suppress the development of insulin resistance <ref>PMID: 11877467</ref>. Thus, the targeting myostatin pathway might be an effective way to promote muscle growth for the patients with muscle degenerative diseases, such as muscular dystrophy and to prevent obesity <ref>PMID: 15473835 </ref>.

== References ==
<references/>

Group:MUZIC:Myostatin

2013-02-11T11:00:21Z

Jae-Geun Song: /* Function and Interactions */

<Structure load='3hh2' size='400' frame='true' align='right' caption='The structure of myostatin:follistatin 288 (PDB 3HH2)' scene='Group:MUZIC:Myostatin/Myostatin/1'/>

== Introduction ==

Myostatin which is also known as growth and developmental factor-8(GDF-8) was originally identified in a screen for novel mammalian members of the transforming growth factor-ß (TGF-ß) superfamily of growth and differentiation factors.The phenotype of myostatin knock-out mice suggested that myostatin functions as a negative regulator of muscle growth, and it was on this basis that myostatin was given its name <ref>PMID:9139826</ref>. For these reasons, inhibitors targeting myostatin have been regarded as potential drugs in the treatment of muscle-wasting disorders such as muscular dystrophy <ref>PMID: 18425412 </ref>.

== Sequence annotation ==
Myostatin consists of three functional fragments: signal peptide, N-terminal and C-terminal fragments. Myostatin is synthesized as a precursor protein, N-terminal and C-terminal fragments are proteolytically cleaved.
[[Image:myostatin.jpg]]

== Structure ==
One structure of myostatin is currently available in Protein Data Bank.
The complex of two follistatin 288 molecules bound to one myostatin dimer was resolved to 2.15 Å using X-ray crystallography and deposited in PDB.
(Green:myostatin C-terminal dimer, yellow: follinstatin 288)

[[Image:Myo2.png]]

== Function and Interactions ==
Myostatin is initially formed as a precursor protein which undergoes two proteolytic processing events in order to generate the biologically active molecule. First the N-terminal signal sequence is removed, a second cleavage generates the C-terminal fragment, which possesses receptor-binding activity and modulates a signal transduction cascade in the target cell <ref>PMID: 15473835</ref>.
The N-terminal fragment after proteolytic processing has been referred to as the propeptide (shown blue). One mechanism for activating myostatin latency appears to be proteolytic cleavage of the propeptide <ref>PMID: 14671324 </ref>. In addition to the regulation of intracellular myostation processing,follistatin has been known to be capable of binding and inhibiting the activity of the myostatin C-terminal dimer (shown yellow). <ref>PMID: 2106159 </ref>.

The interaction of myostatin with titin-cap(T-cap),a Z-disk protein which binds to N-terminal domain of titin,was identified by a yeast two-hybrid system. <ref>PMID: 12209887 </ref> It is presumed that myostatin has a putative role in the muscle Z-disk regulation.

[[Image:Myo1.gif]]
(Processing of myostatin protein. Lee,2004)

== Pathology ==
Mice lacking C-terminal domain of myostatin shows dramatic increases in skeletal muscle mass, which are observed for the entire life of mice. In addition, myostatin mutant mice fail to accumulate fat as a function of age and suppress the development of insulin resistance <ref>PMID: 11877467</ref>. Thus, the targeting myostatin pathway might be an effective way to promote muscle growth for the patients with muscle degenerative diseases, such as muscular dystrophy and to prevent obesity <ref>PMID: 15473835 </ref>.

== References ==
<references/>

Group:MUZIC:Myostatin

2013-02-11T10:59:15Z

Jae-Geun Song: /* Sequence annotation */

<Structure load='3hh2' size='400' frame='true' align='right' caption='The structure of myostatin:follistatin 288 (PDB 3HH2)' scene='Group:MUZIC:Myostatin/Myostatin/1'/>

== Introduction ==

Myostatin which is also known as growth and developmental factor-8(GDF-8) was originally identified in a screen for novel mammalian members of the transforming growth factor-ß (TGF-ß) superfamily of growth and differentiation factors.The phenotype of myostatin knock-out mice suggested that myostatin functions as a negative regulator of muscle growth, and it was on this basis that myostatin was given its name <ref>PMID:9139826</ref>. For these reasons, inhibitors targeting myostatin have been regarded as potential drugs in the treatment of muscle-wasting disorders such as muscular dystrophy <ref>PMID: 18425412 </ref>.

== Sequence annotation ==
Myostatin consists of three functional fragments: signal peptide, N-terminal and C-terminal fragments. Myostatin is synthesized as a precursor protein, N-terminal and C-terminal fragments are proteolytically cleaved.
[[Image:myostatin.jpg]]

== Structure ==
One structure of myostatin is currently available in Protein Data Bank.
The complex of two follistatin 288 molecules bound to one myostatin dimer was resolved to 2.15 Å using X-ray crystallography and deposited in PDB.
(Green:myostatin C-terminal dimer, yellow: follinstatin 288)

[[Image:Myo2.png]]

== Function and Interactions ==
Myostatin is initially formed as a precursor protein which undergoes two proteolytic processing events in order to generate the biologically active molecule. First the N-terminal signal sequence is removed, a second cleavage generates the C-terminal fragment, which possesses receptor-binding activity and modulates a signal transduction cascade in the target cell <ref>PMID:9139826</ref>.
The N-terminal fragment after proteolytic processing has been referred to as the propeptide (shown blue). One mechanism for activating myostatin latency appears to be proteolytic cleavage of the propeptide <ref>PMID: 14671324 </ref>. In addition to the regulation of intracellular myostation processing,follistatin has been known to be capable of binding and inhibiting the activity of the myostatin C-terminal dimer (shown yellow). <ref>PMID: 2106159 </ref>.

The interaction of myostatin with titin-cap(T-cap),a Z-disk protein which binds to N-terminal domain of titin,was identified by a yeast two-hybrid system. <ref>PMID: 12209887 </ref> It is presumed that myostatin has a putative role in the muscle Z-disk regulation.

[[Image:Myo1.gif]]
(Processing of myostatin protein. Lee,2004)

== Pathology ==
Mice lacking C-terminal domain of myostatin shows dramatic increases in skeletal muscle mass, which are observed for the entire life of mice. In addition, myostatin mutant mice fail to accumulate fat as a function of age and suppress the development of insulin resistance <ref>PMID: 11877467</ref>. Thus, the targeting myostatin pathway might be an effective way to promote muscle growth for the patients with muscle degenerative diseases, such as muscular dystrophy and to prevent obesity <ref>PMID: 15473835 </ref>.

== References ==
<references/>

File:Myostatin.jpg

2013-02-11T10:57:37Z

Jae-Geun Song: uploaded a new version of "Image:Myostatin.jpg"

Group:MUZIC:Myostatin

2013-02-11T10:56:56Z

Jae-Geun Song: /* Sequence annotation */

<Structure load='3hh2' size='400' frame='true' align='right' caption='The structure of myostatin:follistatin 288 (PDB 3HH2)' scene='Group:MUZIC:Myostatin/Myostatin/1'/>

== Introduction ==

Myostatin which is also known as growth and developmental factor-8(GDF-8) was originally identified in a screen for novel mammalian members of the transforming growth factor-ß (TGF-ß) superfamily of growth and differentiation factors.The phenotype of myostatin knock-out mice suggested that myostatin functions as a negative regulator of muscle growth, and it was on this basis that myostatin was given its name <ref>PMID:9139826</ref>. For these reasons, inhibitors targeting myostatin have been regarded as potential drugs in the treatment of muscle-wasting disorders such as muscular dystrophy <ref>PMID: 18425412 </ref>.

== Sequence annotation ==
Myostatin consists of three functional fragments: signal peptide, N-terminal and C-terminal fragments. Myostatin is synthesized as a precursor protein, N-terminal and C-terminal fragments are proteolytically cleaved. <ref>PMID: 9139826 </ref>.

[[Image:myostatin.jpg]]

== Structure ==
One structure of myostatin is currently available in Protein Data Bank.
The complex of two follistatin 288 molecules bound to one myostatin dimer was resolved to 2.15 Å using X-ray crystallography and deposited in PDB.
(Green:myostatin C-terminal dimer, yellow: follinstatin 288)

[[Image:Myo2.png]]

== Function and Interactions ==
Myostatin is initially formed as a precursor protein which undergoes two proteolytic processing events in order to generate the biologically active molecule. First the N-terminal signal sequence is removed, a second cleavage generates the C-terminal fragment, which possesses receptor-binding activity and modulates a signal transduction cascade in the target cell <ref>PMID:9139826</ref>.
The N-terminal fragment after proteolytic processing has been referred to as the propeptide (shown blue). One mechanism for activating myostatin latency appears to be proteolytic cleavage of the propeptide <ref>PMID: 14671324 </ref>. In addition to the regulation of intracellular myostation processing,follistatin has been known to be capable of binding and inhibiting the activity of the myostatin C-terminal dimer (shown yellow). <ref>PMID: 2106159 </ref>.

The interaction of myostatin with titin-cap(T-cap),a Z-disk protein which binds to N-terminal domain of titin,was identified by a yeast two-hybrid system. <ref>PMID: 12209887 </ref> It is presumed that myostatin has a putative role in the muscle Z-disk regulation.

[[Image:Myo1.gif]]
(Processing of myostatin protein. Lee,2004)

== Pathology ==
Mice lacking C-terminal domain of myostatin shows dramatic increases in skeletal muscle mass, which are observed for the entire life of mice. In addition, myostatin mutant mice fail to accumulate fat as a function of age and suppress the development of insulin resistance <ref>PMID: 11877467</ref>. Thus, the targeting myostatin pathway might be an effective way to promote muscle growth for the patients with muscle degenerative diseases, such as muscular dystrophy and to prevent obesity <ref>PMID: 15473835 </ref>.

== References ==
<references/>

Group:MUZIC:Myostatin

2013-02-11T10:46:50Z

Jae-Geun Song: /* Sequence annotation */

<Structure load='3hh2' size='400' frame='true' align='right' caption='The structure of myostatin:follistatin 288 (PDB 3HH2)' scene='Group:MUZIC:Myostatin/Myostatin/1'/>

== Introduction ==

Myostatin which is also known as growth and developmental factor-8(GDF-8) was originally identified in a screen for novel mammalian members of the transforming growth factor-ß (TGF-ß) superfamily of growth and differentiation factors.The phenotype of myostatin knock-out mice suggested that myostatin functions as a negative regulator of muscle growth, and it was on this basis that myostatin was given its name <ref>PMID:9139826</ref>. For these reasons, inhibitors targeting myostatin have been regarded as potential drugs in the treatment of muscle-wasting disorders such as muscular dystrophy <ref>PMID: 18425412 </ref>.

== Sequence annotation ==
Myostatin is synthesized as a precursor protein, which is activated by proteolytic cleavage. The first cleavage removes 24 amino acids from N-terminus and the second cleavage happens at the RSSR site(240-243 amino acids) <ref>PMID: 9139826 </ref>.

[[Image:myostatin.jpg]]

== Structure ==
One structure of myostatin is currently available in Protein Data Bank.
The complex of two follistatin 288 molecules bound to one myostatin dimer was resolved to 2.15 Å using X-ray crystallography and deposited in PDB.
(Green:myostatin C-terminal dimer, yellow: follinstatin 288)

[[Image:Myo2.png]]

== Function and Interactions ==
Myostatin is initially formed as a precursor protein which undergoes two proteolytic processing events in order to generate the biologically active molecule. First the N-terminal signal sequence is removed, a second cleavage generates the C-terminal fragment, which possesses receptor-binding activity and modulates a signal transduction cascade in the target cell <ref>PMID:9139826</ref>.
The N-terminal fragment after proteolytic processing has been referred to as the propeptide (shown blue). One mechanism for activating myostatin latency appears to be proteolytic cleavage of the propeptide <ref>PMID: 14671324 </ref>. In addition to the regulation of intracellular myostation processing,follistatin has been known to be capable of binding and inhibiting the activity of the myostatin C-terminal dimer (shown yellow). <ref>PMID: 2106159 </ref>.

The interaction of myostatin with titin-cap(T-cap),a Z-disk protein which binds to N-terminal domain of titin,was identified by a yeast two-hybrid system. <ref>PMID: 12209887 </ref> It is presumed that myostatin has a putative role in the muscle Z-disk regulation.

[[Image:Myo1.gif]]
(Processing of myostatin protein. Lee,2004)

== Pathology ==
Mice lacking C-terminal domain of myostatin shows dramatic increases in skeletal muscle mass, which are observed for the entire life of mice. In addition, myostatin mutant mice fail to accumulate fat as a function of age and suppress the development of insulin resistance <ref>PMID: 11877467</ref>. Thus, the targeting myostatin pathway might be an effective way to promote muscle growth for the patients with muscle degenerative diseases, such as muscular dystrophy and to prevent obesity <ref>PMID: 15473835 </ref>.

== References ==
<references/>

Group:MUZIC:Myostatin

2013-02-11T10:45:52Z

Jae-Geun Song: /* Sequence annotation */

<Structure load='3hh2' size='400' frame='true' align='right' caption='The structure of myostatin:follistatin 288 (PDB 3HH2)' scene='Group:MUZIC:Myostatin/Myostatin/1'/>

== Introduction ==

Myostatin which is also known as growth and developmental factor-8(GDF-8) was originally identified in a screen for novel mammalian members of the transforming growth factor-ß (TGF-ß) superfamily of growth and differentiation factors.The phenotype of myostatin knock-out mice suggested that myostatin functions as a negative regulator of muscle growth, and it was on this basis that myostatin was given its name <ref>PMID:9139826</ref>. For these reasons, inhibitors targeting myostatin have been regarded as potential drugs in the treatment of muscle-wasting disorders such as muscular dystrophy <ref>PMID: 18425412 </ref>.

== Sequence annotation ==
Myostatin is synthesized as a precursor protein, which is activated by proteolytic cleavage. The first cleavage removes 24 amino acids from N-terminus and second cleavage happens at RSSR site(240-243 amino acids)<ref>PMID: 9139826 </ref>.

[[Image:myostatin.jpg]]

== Structure ==
One structure of myostatin is currently available in Protein Data Bank.
The complex of two follistatin 288 molecules bound to one myostatin dimer was resolved to 2.15 Å using X-ray crystallography and deposited in PDB.
(Green:myostatin C-terminal dimer, yellow: follinstatin 288)

[[Image:Myo2.png]]

== Function and Interactions ==
Myostatin is initially formed as a precursor protein which undergoes two proteolytic processing events in order to generate the biologically active molecule. First the N-terminal signal sequence is removed, a second cleavage generates the C-terminal fragment, which possesses receptor-binding activity and modulates a signal transduction cascade in the target cell <ref>PMID:9139826</ref>.
The N-terminal fragment after proteolytic processing has been referred to as the propeptide (shown blue). One mechanism for activating myostatin latency appears to be proteolytic cleavage of the propeptide <ref>PMID: 14671324 </ref>. In addition to the regulation of intracellular myostation processing,follistatin has been known to be capable of binding and inhibiting the activity of the myostatin C-terminal dimer (shown yellow). <ref>PMID: 2106159 </ref>.

The interaction of myostatin with titin-cap(T-cap),a Z-disk protein which binds to N-terminal domain of titin,was identified by a yeast two-hybrid system. <ref>PMID: 12209887 </ref> It is presumed that myostatin has a putative role in the muscle Z-disk regulation.

[[Image:Myo1.gif]]
(Processing of myostatin protein. Lee,2004)

== Pathology ==
Mice lacking C-terminal domain of myostatin shows dramatic increases in skeletal muscle mass, which are observed for the entire life of mice. In addition, myostatin mutant mice fail to accumulate fat as a function of age and suppress the development of insulin resistance <ref>PMID: 11877467</ref>. Thus, the targeting myostatin pathway might be an effective way to promote muscle growth for the patients with muscle degenerative diseases, such as muscular dystrophy and to prevent obesity <ref>PMID: 15473835 </ref>.

== References ==
<references/>

File:Myostatin.jpg

2013-02-11T10:40:16Z

Jae-Geun Song: uploaded a new version of "Image:Myostatin.jpg"

Group:MUZIC:Myostatin

2013-02-11T10:39:43Z

Jae-Geun Song:

<Structure load='3hh2' size='400' frame='true' align='right' caption='The structure of myostatin:follistatin 288 (PDB 3HH2)' scene='Group:MUZIC:Myostatin/Myostatin/1'/>

== Introduction ==

Myostatin which is also known as growth and developmental factor-8(GDF-8) was originally identified in a screen for novel mammalian members of the transforming growth factor-ß (TGF-ß) superfamily of growth and differentiation factors.The phenotype of myostatin knock-out mice suggested that myostatin functions as a negative regulator of muscle growth, and it was on this basis that myostatin was given its name <ref>PMID:9139826</ref>. For these reasons, inhibitors targeting myostatin have been regarded as potential drugs in the treatment of muscle-wasting disorders such as muscular dystrophy <ref>PMID: 18425412 </ref>.

== Sequence annotation ==

[[Image:myostatin.jpg]]

== Structure ==
One structure of myostatin is currently available in Protein Data Bank.
The complex of two follistatin 288 molecules bound to one myostatin dimer was resolved to 2.15 Å using X-ray crystallography and deposited in PDB.
(Green:myostatin C-terminal dimer, yellow: follinstatin 288)

[[Image:Myo2.png]]

== Function and Interactions ==
Myostatin is initially formed as a precursor protein which undergoes two proteolytic processing events in order to generate the biologically active molecule. First the N-terminal signal sequence is removed, a second cleavage generates the C-terminal fragment, which possesses receptor-binding activity and modulates a signal transduction cascade in the target cell <ref>PMID:9139826</ref>.
The N-terminal fragment after proteolytic processing has been referred to as the propeptide (shown blue). One mechanism for activating myostatin latency appears to be proteolytic cleavage of the propeptide <ref>PMID: 14671324 </ref>. In addition to the regulation of intracellular myostation processing,follistatin has been known to be capable of binding and inhibiting the activity of the myostatin C-terminal dimer (shown yellow). <ref>PMID: 2106159 </ref>.

The interaction of myostatin with titin-cap(T-cap),a Z-disk protein which binds to N-terminal domain of titin,was identified by a yeast two-hybrid system. <ref>PMID: 12209887 </ref> It is presumed that myostatin has a putative role in the muscle Z-disk regulation.

[[Image:Myo1.gif]]
(Processing of myostatin protein. Lee,2004)

== Pathology ==
Mice lacking C-terminal domain of myostatin shows dramatic increases in skeletal muscle mass, which are observed for the entire life of mice. In addition, myostatin mutant mice fail to accumulate fat as a function of age and suppress the development of insulin resistance <ref>PMID: 11877467</ref>. Thus, the targeting myostatin pathway might be an effective way to promote muscle growth for the patients with muscle degenerative diseases, such as muscular dystrophy and to prevent obesity <ref>PMID: 15473835 </ref>.

== References ==
<references/>

File:Myostatin.jpg

2013-02-11T10:38:31Z

Jae-Geun Song:

Group:MUZIC:Myostatin

2013-02-11T09:57:57Z

Jae-Geun Song: /* Structure */

<Structure load='3hh2' size='400' frame='true' align='right' caption='The structure of myostatin:follistatin 288 (PDB 3HH2)' scene='Group:MUZIC:Myostatin/Myostatin/1'/>

== Introduction ==

Myostatin which is also known as growth and developmental factor-8(GDF-8) was originally identified in a screen for novel mammalian members of the transforming growth factor-ß (TGF-ß) superfamily of growth and differentiation factors.The phenotype of myostatin knock-out mice suggested that myostatin functions as a negative regulator of muscle growth, and it was on this basis that myostatin was given its name <ref>PMID:9139826</ref>. For these reasons, inhibitors targeting myostatin have been regarded as potential drugs in the treatment of muscle-wasting disorders such as muscular dystrophy <ref>PMID: 18425412 </ref>.

== Structure ==
One structure of myostatin is currently available in Protein Data Bank.
The complex of two follistatin 288 molecules bound to one myostatin dimer was resolved to 2.15 Å using X-ray crystallography and deposited in PDB.
(Green:myostatin C-terminal dimer, yellow: follinstatin 288)

[[Image:Myo2.png]]

== Function and Interactions ==
Myostatin is initially formed as a precursor protein which undergoes two proteolytic processing events in order to generate the biologically active molecule. First the N-terminal signal sequence is removed, a second cleavage generates the C-terminal fragment, which possesses receptor-binding activity and modulates a signal transduction cascade in the target cell <ref>PMID:9139826</ref>.
The N-terminal fragment after proteolytic processing has been referred to as the propeptide (shown blue). One mechanism for activating myostatin latency appears to be proteolytic cleavage of the propeptide <ref>PMID: 14671324 </ref>. In addition to the regulation of intracellular myostation processing,follistatin has been known to be capable of binding and inhibiting the activity of the myostatin C-terminal dimer (shown yellow). <ref>PMID: 2106159 </ref>.

The interaction of myostatin with titin-cap(T-cap),a Z-disk protein which binds to N-terminal domain of titin,was identified by a yeast two-hybrid system. <ref>PMID: 12209887 </ref> It is presumed that myostatin has a putative role in the muscle Z-disk regulation.

[[Image:Myo1.gif]]
(Processing of myostatin protein. Lee,2004)

== Pathology ==
Mice lacking C-terminal domain of myostatin shows dramatic increases in skeletal muscle mass, which are observed for the entire life of mice. In addition, myostatin mutant mice fail to accumulate fat as a function of age and suppress the development of insulin resistance <ref>PMID: 11877467</ref>. Thus, the targeting myostatin pathway might be an effective way to promote muscle growth for the patients with muscle degenerative diseases, such as muscular dystrophy and to prevent obesity <ref>PMID: 15473835 </ref>.

== References ==
<references/>

Group:MUZIC:Myostatin

2013-02-07T10:13:31Z

Jae-Geun Song:

<Structure load='3hh2' size='400' frame='true' align='right' caption='The structure of myostatin:follistatin 288 (PDB 3HH2)' scene='Group:MUZIC:Myostatin/Myostatin/1'/>

== Introduction ==

Myostatin which is also known as growth and developmental factor-8(GDF-8) was originally identified in a screen for novel mammalian members of the transforming growth factor-ß (TGF-ß) superfamily of growth and differentiation factors.The phenotype of myostatin knock-out mice suggested that myostatin functions as a negative regulator of muscle growth, and it was on this basis that myostatin was given its name <ref>PMID:9139826</ref>. For these reasons, inhibitors targeting myostatin have been regarded as potential drugs in the treatment of muscle-wasting disorders such as muscular dystrophy <ref>PMID: 18425412 </ref>.

== Structure ==
Only one structure of myostatin is currently available in Protein Data Bank.
The complex of two follistatin 288 molecules bound to one myostatin dimer was resolved to 2.15 Å using X-ray crystallography and deposited in PDB.
(Green:myostatin C-terminal dimer, yellow: follinstatin 288)

[[Image:Myo2.png]]

== Function and Interactions ==
Myostatin is initially formed as a precursor protein which undergoes two proteolytic processing events in order to generate the biologically active molecule. First the N-terminal signal sequence is removed, a second cleavage generates the C-terminal fragment, which possesses receptor-binding activity and modulates a signal transduction cascade in the target cell <ref>PMID:9139826</ref>.
The N-terminal fragment after proteolytic processing has been referred to as the propeptide (shown blue). One mechanism for activating myostatin latency appears to be proteolytic cleavage of the propeptide <ref>PMID: 14671324 </ref>. In addition to the regulation of intracellular myostation processing,follistatin has been known to be capable of binding and inhibiting the activity of the myostatin C-terminal dimer (shown yellow). <ref>PMID: 2106159 </ref>.

The interaction of myostatin with titin-cap(T-cap),a Z-disk protein which binds to N-terminal domain of titin,was identified by a yeast two-hybrid system. <ref>PMID: 12209887 </ref> It is presumed that myostatin has a putative role in the muscle Z-disk regulation.

[[Image:Myo1.gif]]
(Processing of myostatin protein. Lee,2004)

== Pathology ==
Mice lacking C-terminal domain of myostatin shows dramatic increases in skeletal muscle mass, which are observed for the entire life of mice. In addition, myostatin mutant mice fail to accumulate fat as a function of age and suppress the development of insulin resistance <ref>PMID: 11877467</ref>. Thus, the targeting myostatin pathway might be an effective way to promote muscle growth for the patients with muscle degenerative diseases, such as muscular dystrophy and to prevent obesity <ref>PMID: 15473835 </ref>.

== References ==
<references/>

Group:MUZIC:Plectin

2013-02-06T13:33:24Z

Jae-Geun Song: /* Introduction */

== Introduction ==
Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms.
Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain (isoform 1c),skeletal muscle (isoform 1d) and skin(isoform 1a). <ref>PMID:10556294</ref>.

[[Image:isoforms.gif]]

<Structure load='3PE0' size='300' frame='true' align='right' caption='Crystal structure of SR4-SR5-SH3 regions in the plakin domain (PDB:3PE0)' scene='User:Jae-Geun_Song/Workbench/plectin/Plakin/1'/>

== Sequence annotation ==
Human plectin contains 4,684 amino acids <ref>PMID:8633055</ref>. Plectin can be divided in three main sections; a central coiled-coil rod domain, N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region (2,828-4,684 aa) is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin <ref>PMID:3430617</ref>. N-terminal globular region contains actin binding domain comprising two calponin homology (180-396 aa) and plakin domain (659-944 aa).

[[Image:plectin.jpg]]

Schematic domain map of plectin (Winter, 2013)

== Structures ==

'''1. Actin Binding Domain (ABD)'''

<Structure load='1sh6' size='300' frame='true' align='right' caption='The actin binding domain of plectin (PDB:1SH6)' scene='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/1'/>

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain(<scene name='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/3'>CH1 and CH2</scene>)<ref>PMID:9164454</ref>. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported <ref>PMID: 15128297</ref>.

'''2. Plakin domain'''

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.<ref>PMID: 21288893 </ref>

'''3. Integrin β4-Plectin complex'''
The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.<ref>PMID: 19242489 </ref>

== Function and Interactions ==
Proteins coordinate various cytoskeletal networks are termed as cytolinkers, which are able to interlink different types of cytoskeletons. Plectin is one of the well-characterized cytolinker and expressed in diverse cell types and tissues, a number of different binding partners of plectin have been identified.

Intermediate filament(IF) binding sites of plectin is located between plakin repeats 5 and 6 in C-terminal globular domain. Several IF proteins were identified to interact with plectin such as vimentin, desmin, GFAP(glial fibrillary acidic protein) and cytokeratins <ref>PMID: 8830774 </ref> .

The actin binding domain(ABD)in N-terminal globular domain has a role to interact with integrin subunit beta 4 to establish mechanical stability in hemedesmosomes along with its function for binding to actin filament(F-actin). Calmodulin(CaM) is also known to bind the ABD of plectin to modulate the hemidesmosome disassembly <ref> PMID: 19419971 </ref>.

<Structure load='3F7P' size='300' frame='true' align='right' caption='Crystal structure of plectin ABD(magenta) and integrin beta 4 (green) complex (PDB:3F7P)' scene='Group:MUZIC:Plectin/Plecint/1' />

== Pathology ==
It has been reported that patients with EBS-MD (Epidermolysis bullosa simplex with muscular dystrophy),a genetic disorder characterized severe skin blistering disease combined with muscular dystrophy, have a muation on plectin gene(PLEC1). This mutation leads to premature termination of translation.<ref>PMID: 8941634 </ref>
In addition, site-specific missense mutation(R2110W) on plectin rod domain causes an autosomal dominant form of disease termed EBS-Ogna without muscular dystrophy.<ref>PMID: 9067706 </ref>
Plectin deficient(-/-) mice also exhibit similar skin and muscle phenotypes of human patients suffering from EBS-MD and died 2-3 days after birth. <ref>PMID: 9389647</ref>

== References ==

<references/>

Group:MUZIC:Plectin

2013-02-06T13:32:15Z

Jae-Geun Song: /* Introduction */

== Introduction ==
Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms.
Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain (isoforma 1c),skeletal muscle (isoform 1d) and skin(isoform 1a). <ref>PMID:10556294</ref>.

[[Image:isoforms.gif]]

<Structure load='3PE0' size='300' frame='true' align='right' caption='Crystal structure of SR4-SR5-SH3 regions in the plakin domain (PDB:3PE0)' scene='User:Jae-Geun_Song/Workbench/plectin/Plakin/1'/>

== Sequence annotation ==
Human plectin contains 4,684 amino acids <ref>PMID:8633055</ref>. Plectin can be divided in three main sections; a central coiled-coil rod domain, N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region (2,828-4,684 aa) is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin <ref>PMID:3430617</ref>. N-terminal globular region contains actin binding domain comprising two calponin homology (180-396 aa) and plakin domain (659-944 aa).

[[Image:plectin.jpg]]

Schematic domain map of plectin (Winter, 2013)

== Structures ==

'''1. Actin Binding Domain (ABD)'''

<Structure load='1sh6' size='300' frame='true' align='right' caption='The actin binding domain of plectin (PDB:1SH6)' scene='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/1'/>

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain(<scene name='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/3'>CH1 and CH2</scene>)<ref>PMID:9164454</ref>. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported <ref>PMID: 15128297</ref>.

'''2. Plakin domain'''

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.<ref>PMID: 21288893 </ref>

'''3. Integrin β4-Plectin complex'''
The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.<ref>PMID: 19242489 </ref>

== Function and Interactions ==
Proteins coordinate various cytoskeletal networks are termed as cytolinkers, which are able to interlink different types of cytoskeletons. Plectin is one of the well-characterized cytolinker and expressed in diverse cell types and tissues, a number of different binding partners of plectin have been identified.

Intermediate filament(IF) binding sites of plectin is located between plakin repeats 5 and 6 in C-terminal globular domain. Several IF proteins were identified to interact with plectin such as vimentin, desmin, GFAP(glial fibrillary acidic protein) and cytokeratins <ref>PMID: 8830774 </ref> .

The actin binding domain(ABD)in N-terminal globular domain has a role to interact with integrin subunit beta 4 to establish mechanical stability in hemedesmosomes along with its function for binding to actin filament(F-actin). Calmodulin(CaM) is also known to bind the ABD of plectin to modulate the hemidesmosome disassembly <ref> PMID: 19419971 </ref>.

<Structure load='3F7P' size='300' frame='true' align='right' caption='Crystal structure of plectin ABD(magenta) and integrin beta 4 (green) complex (PDB:3F7P)' scene='Group:MUZIC:Plectin/Plecint/1' />

== Pathology ==
It has been reported that patients with EBS-MD (Epidermolysis bullosa simplex with muscular dystrophy),a genetic disorder characterized severe skin blistering disease combined with muscular dystrophy, have a muation on plectin gene(PLEC1). This mutation leads to premature termination of translation.<ref>PMID: 8941634 </ref>
In addition, site-specific missense mutation(R2110W) on plectin rod domain causes an autosomal dominant form of disease termed EBS-Ogna without muscular dystrophy.<ref>PMID: 9067706 </ref>
Plectin deficient(-/-) mice also exhibit similar skin and muscle phenotypes of human patients suffering from EBS-MD and died 2-3 days after birth. <ref>PMID: 9389647</ref>

== References ==

<references/>

Group:MUZIC:Plectin

2013-02-06T13:26:15Z

Jae-Geun Song: /* Sequence annotation */

== Introduction ==
Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms.
Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain,skeletal muscle and skin . <ref>PMID:10556294</ref>.

[[Image:isoforms.gif]]

<Structure load='3PE0' size='300' frame='true' align='right' caption='Crystal structure of SR4-SR5-SH3 regions in the plakin domain (PDB:3PE0)' scene='User:Jae-Geun_Song/Workbench/plectin/Plakin/1'/>

== Sequence annotation ==
Human plectin contains 4,684 amino acids <ref>PMID:8633055</ref>. Plectin can be divided in three main sections; a central coiled-coil rod domain, N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region (2,828-4,684 aa) is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin <ref>PMID:3430617</ref>. N-terminal globular region contains actin binding domain comprising two calponin homology (180-396 aa) and plakin domain (659-944 aa).

[[Image:plectin.jpg]]

Schematic domain map of plectin (Winter, 2013)

== Structures ==

'''1. Actin Binding Domain (ABD)'''

<Structure load='1sh6' size='300' frame='true' align='right' caption='The actin binding domain of plectin (PDB:1SH6)' scene='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/1'/>

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain(<scene name='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/3'>CH1 and CH2</scene>)<ref>PMID:9164454</ref>. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported <ref>PMID: 15128297</ref>.

'''2. Plakin domain'''

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.<ref>PMID: 21288893 </ref>

'''3. Integrin β4-Plectin complex'''
The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.<ref>PMID: 19242489 </ref>

== Function and Interactions ==
Proteins coordinate various cytoskeletal networks are termed as cytolinkers, which are able to interlink different types of cytoskeletons. Plectin is one of the well-characterized cytolinker and expressed in diverse cell types and tissues, a number of different binding partners of plectin have been identified.

Intermediate filament(IF) binding sites of plectin is located between plakin repeats 5 and 6 in C-terminal globular domain. Several IF proteins were identified to interact with plectin such as vimentin, desmin, GFAP(glial fibrillary acidic protein) and cytokeratins <ref>PMID: 8830774 </ref> .

The actin binding domain(ABD)in N-terminal globular domain has a role to interact with integrin subunit beta 4 to establish mechanical stability in hemedesmosomes along with its function for binding to actin filament(F-actin). Calmodulin(CaM) is also known to bind the ABD of plectin to modulate the hemidesmosome disassembly <ref> PMID: 19419971 </ref>.

<Structure load='3F7P' size='300' frame='true' align='right' caption='Crystal structure of plectin ABD(magenta) and integrin beta 4 (green) complex (PDB:3F7P)' scene='Group:MUZIC:Plectin/Plecint/1' />

== Pathology ==
It has been reported that patients with EBS-MD (Epidermolysis bullosa simplex with muscular dystrophy),a genetic disorder characterized severe skin blistering disease combined with muscular dystrophy, have a muation on plectin gene(PLEC1). This mutation leads to premature termination of translation.<ref>PMID: 8941634 </ref>
In addition, site-specific missense mutation(R2110W) on plectin rod domain causes an autosomal dominant form of disease termed EBS-Ogna without muscular dystrophy.<ref>PMID: 9067706 </ref>
Plectin deficient(-/-) mice also exhibit similar skin and muscle phenotypes of human patients suffering from EBS-MD and died 2-3 days after birth. <ref>PMID: 9389647</ref>

== References ==

<references/>

Group:MUZIC:Plectin

2013-02-06T13:25:01Z

Jae-Geun Song: /* Sequence annotation */

== Introduction ==
Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms.
Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain,skeletal muscle and skin . <ref>PMID:10556294</ref>.

[[Image:isoforms.gif]]

<Structure load='3PE0' size='300' frame='true' align='right' caption='Crystal structure of SR4-SR5-SH3 regions in the plakin domain (PDB:3PE0)' scene='User:Jae-Geun_Song/Workbench/plectin/Plakin/1'/>

== Sequence annotation ==
Human plectin contains 4,684 amino acids. Plectin can be divided in three main sections; a central coiled-coil rod domain, N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region (2,828-4,684 aa) is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin <ref>PMID:3430617</ref>. N-terminal globular region contains actin binding domain comprising two calponin homology (180-396 aa) and plakin domain (659-944 aa).

[[Image:plectin.jpg]]

Schematic domain map of plectin (Winter, 2013)

== Structures ==

'''1. Actin Binding Domain (ABD)'''

<Structure load='1sh6' size='300' frame='true' align='right' caption='The actin binding domain of plectin (PDB:1SH6)' scene='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/1'/>

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain(<scene name='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/3'>CH1 and CH2</scene>)<ref>PMID:9164454</ref>. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported <ref>PMID: 15128297</ref>.

'''2. Plakin domain'''

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.<ref>PMID: 21288893 </ref>

'''3. Integrin β4-Plectin complex'''
The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.<ref>PMID: 19242489 </ref>

== Function and Interactions ==
Proteins coordinate various cytoskeletal networks are termed as cytolinkers, which are able to interlink different types of cytoskeletons. Plectin is one of the well-characterized cytolinker and expressed in diverse cell types and tissues, a number of different binding partners of plectin have been identified.

Intermediate filament(IF) binding sites of plectin is located between plakin repeats 5 and 6 in C-terminal globular domain. Several IF proteins were identified to interact with plectin such as vimentin, desmin, GFAP(glial fibrillary acidic protein) and cytokeratins <ref>PMID: 8830774 </ref> .

The actin binding domain(ABD)in N-terminal globular domain has a role to interact with integrin subunit beta 4 to establish mechanical stability in hemedesmosomes along with its function for binding to actin filament(F-actin). Calmodulin(CaM) is also known to bind the ABD of plectin to modulate the hemidesmosome disassembly <ref> PMID: 19419971 </ref>.

<Structure load='3F7P' size='300' frame='true' align='right' caption='Crystal structure of plectin ABD(magenta) and integrin beta 4 (green) complex (PDB:3F7P)' scene='Group:MUZIC:Plectin/Plecint/1' />

== Pathology ==
It has been reported that patients with EBS-MD (Epidermolysis bullosa simplex with muscular dystrophy),a genetic disorder characterized severe skin blistering disease combined with muscular dystrophy, have a muation on plectin gene(PLEC1). This mutation leads to premature termination of translation.<ref>PMID: 8941634 </ref>
In addition, site-specific missense mutation(R2110W) on plectin rod domain causes an autosomal dominant form of disease termed EBS-Ogna without muscular dystrophy.<ref>PMID: 9067706 </ref>
Plectin deficient(-/-) mice also exhibit similar skin and muscle phenotypes of human patients suffering from EBS-MD and died 2-3 days after birth. <ref>PMID: 9389647</ref>

== References ==

<references/>

Group:MUZIC:Plectin

2013-02-06T13:14:59Z

Jae-Geun Song: /* Sequence annotation */

== Introduction ==
Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms.
Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain,skeletal muscle and skin . <ref>PMID:10556294</ref>.

[[Image:isoforms.gif]]

<Structure load='3PE0' size='300' frame='true' align='right' caption='Crystal structure of SR4-SR5-SH3 regions in the plakin domain (PDB:3PE0)' scene='User:Jae-Geun_Song/Workbench/plectin/Plakin/1'/>

== Sequence annotation ==
Plectin can be divided in three main sections; a central coiled-coil rod domain, N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region (2,828-4,684 aa) is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin <ref>PMID:3430617</ref>. N-terminal globular region contains actin binding domain comprising two calponin homology (180-396 aa) and plakin domain (659-944 aa).

[[Image:plectin.jpg]]

Schematic domain map of plectin (Winter, 2013)

== Structures ==

'''1. Actin Binding Domain (ABD)'''

<Structure load='1sh6' size='300' frame='true' align='right' caption='The actin binding domain of plectin (PDB:1SH6)' scene='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/1'/>

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain(<scene name='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/3'>CH1 and CH2</scene>)<ref>PMID:9164454</ref>. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported <ref>PMID: 15128297</ref>.

'''2. Plakin domain'''

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.<ref>PMID: 21288893 </ref>

'''3. Integrin β4-Plectin complex'''
The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.<ref>PMID: 19242489 </ref>

== Function and Interactions ==
Proteins coordinate various cytoskeletal networks are termed as cytolinkers, which are able to interlink different types of cytoskeletons. Plectin is one of the well-characterized cytolinker and expressed in diverse cell types and tissues, a number of different binding partners of plectin have been identified.

Intermediate filament(IF) binding sites of plectin is located between plakin repeats 5 and 6 in C-terminal globular domain. Several IF proteins were identified to interact with plectin such as vimentin, desmin, GFAP(glial fibrillary acidic protein) and cytokeratins <ref>PMID: 8830774 </ref> .

The actin binding domain(ABD)in N-terminal globular domain has a role to interact with integrin subunit beta 4 to establish mechanical stability in hemedesmosomes along with its function for binding to actin filament(F-actin). Calmodulin(CaM) is also known to bind the ABD of plectin to modulate the hemidesmosome disassembly <ref> PMID: 19419971 </ref>.

<Structure load='3F7P' size='300' frame='true' align='right' caption='Crystal structure of plectin ABD(magenta) and integrin beta 4 (green) complex (PDB:3F7P)' scene='Group:MUZIC:Plectin/Plecint/1' />

== Pathology ==
It has been reported that patients with EBS-MD (Epidermolysis bullosa simplex with muscular dystrophy),a genetic disorder characterized severe skin blistering disease combined with muscular dystrophy, have a muation on plectin gene(PLEC1). This mutation leads to premature termination of translation.<ref>PMID: 8941634 </ref>
In addition, site-specific missense mutation(R2110W) on plectin rod domain causes an autosomal dominant form of disease termed EBS-Ogna without muscular dystrophy.<ref>PMID: 9067706 </ref>
Plectin deficient(-/-) mice also exhibit similar skin and muscle phenotypes of human patients suffering from EBS-MD and died 2-3 days after birth. <ref>PMID: 9389647</ref>

== References ==

<references/>

Group:MUZIC:Plectin

2013-02-06T13:14:40Z

Jae-Geun Song: /* Sequence annotation */

== Introduction ==
Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms.
Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain,skeletal muscle and skin . <ref>PMID:10556294</ref>.

[[Image:isoforms.gif]]

<Structure load='3PE0' size='300' frame='true' align='right' caption='Crystal structure of SR4-SR5-SH3 regions in the plakin domain (PDB:3PE0)' scene='User:Jae-Geun_Song/Workbench/plectin/Plakin/1'/>

== Sequence annotation ==
Plectin can be divided in three main sections; a central coiled-coil rod domain, N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region(2,828-4,684 aa) is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin <ref>PMID:3430617</ref>. N-terminal globular region contains actin binding domain comprising two calponin homology(180-396 aa) and plakin domain(659-944 aa).

[[Image:plectin.jpg]]

Schematic domain map of plectin (Winter, 2013)

== Structures ==

'''1. Actin Binding Domain (ABD)'''

<Structure load='1sh6' size='300' frame='true' align='right' caption='The actin binding domain of plectin (PDB:1SH6)' scene='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/1'/>

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain(<scene name='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/3'>CH1 and CH2</scene>)<ref>PMID:9164454</ref>. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported <ref>PMID: 15128297</ref>.

'''2. Plakin domain'''

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.<ref>PMID: 21288893 </ref>

'''3. Integrin β4-Plectin complex'''
The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.<ref>PMID: 19242489 </ref>

== Function and Interactions ==
Proteins coordinate various cytoskeletal networks are termed as cytolinkers, which are able to interlink different types of cytoskeletons. Plectin is one of the well-characterized cytolinker and expressed in diverse cell types and tissues, a number of different binding partners of plectin have been identified.

Intermediate filament(IF) binding sites of plectin is located between plakin repeats 5 and 6 in C-terminal globular domain. Several IF proteins were identified to interact with plectin such as vimentin, desmin, GFAP(glial fibrillary acidic protein) and cytokeratins <ref>PMID: 8830774 </ref> .

The actin binding domain(ABD)in N-terminal globular domain has a role to interact with integrin subunit beta 4 to establish mechanical stability in hemedesmosomes along with its function for binding to actin filament(F-actin). Calmodulin(CaM) is also known to bind the ABD of plectin to modulate the hemidesmosome disassembly <ref> PMID: 19419971 </ref>.

<Structure load='3F7P' size='300' frame='true' align='right' caption='Crystal structure of plectin ABD(magenta) and integrin beta 4 (green) complex (PDB:3F7P)' scene='Group:MUZIC:Plectin/Plecint/1' />

== Pathology ==
It has been reported that patients with EBS-MD (Epidermolysis bullosa simplex with muscular dystrophy),a genetic disorder characterized severe skin blistering disease combined with muscular dystrophy, have a muation on plectin gene(PLEC1). This mutation leads to premature termination of translation.<ref>PMID: 8941634 </ref>
In addition, site-specific missense mutation(R2110W) on plectin rod domain causes an autosomal dominant form of disease termed EBS-Ogna without muscular dystrophy.<ref>PMID: 9067706 </ref>
Plectin deficient(-/-) mice also exhibit similar skin and muscle phenotypes of human patients suffering from EBS-MD and died 2-3 days after birth. <ref>PMID: 9389647</ref>

== References ==

<references/>

Group:MUZIC:Plectin

2013-02-06T13:13:59Z

Jae-Geun Song: /* Sequence annotation */

== Introduction ==
Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms.
Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain,skeletal muscle and skin . <ref>PMID:10556294</ref>.

[[Image:isoforms.gif]]

<Structure load='3PE0' size='300' frame='true' align='right' caption='Crystal structure of SR4-SR5-SH3 regions in the plakin domain (PDB:3PE0)' scene='User:Jae-Geun_Song/Workbench/plectin/Plakin/1'/>

== Sequence annotation ==
Plectin can be divided in three main sections; a central coiled-coil rod domain, N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region(2,828-4,684 aa) is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin <ref>PMID:3430617</ref>. N-terminal globular region contains actin binding domain comprising two calponin homology(180-396 aa) and spectrin-like repeats(659-944 aa).

[[Image:plectin.jpg]]

Schematic domain map of plectin (Winter, 2013)

== Structures ==

'''1. Actin Binding Domain (ABD)'''

<Structure load='1sh6' size='300' frame='true' align='right' caption='The actin binding domain of plectin (PDB:1SH6)' scene='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/1'/>

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain(<scene name='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/3'>CH1 and CH2</scene>)<ref>PMID:9164454</ref>. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported <ref>PMID: 15128297</ref>.

'''2. Plakin domain'''

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.<ref>PMID: 21288893 </ref>

'''3. Integrin β4-Plectin complex'''
The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.<ref>PMID: 19242489 </ref>

== Function and Interactions ==
Proteins coordinate various cytoskeletal networks are termed as cytolinkers, which are able to interlink different types of cytoskeletons. Plectin is one of the well-characterized cytolinker and expressed in diverse cell types and tissues, a number of different binding partners of plectin have been identified.

Intermediate filament(IF) binding sites of plectin is located between plakin repeats 5 and 6 in C-terminal globular domain. Several IF proteins were identified to interact with plectin such as vimentin, desmin, GFAP(glial fibrillary acidic protein) and cytokeratins <ref>PMID: 8830774 </ref> .

The actin binding domain(ABD)in N-terminal globular domain has a role to interact with integrin subunit beta 4 to establish mechanical stability in hemedesmosomes along with its function for binding to actin filament(F-actin). Calmodulin(CaM) is also known to bind the ABD of plectin to modulate the hemidesmosome disassembly <ref> PMID: 19419971 </ref>.

<Structure load='3F7P' size='300' frame='true' align='right' caption='Crystal structure of plectin ABD(magenta) and integrin beta 4 (green) complex (PDB:3F7P)' scene='Group:MUZIC:Plectin/Plecint/1' />

== Pathology ==
It has been reported that patients with EBS-MD (Epidermolysis bullosa simplex with muscular dystrophy),a genetic disorder characterized severe skin blistering disease combined with muscular dystrophy, have a muation on plectin gene(PLEC1). This mutation leads to premature termination of translation.<ref>PMID: 8941634 </ref>
In addition, site-specific missense mutation(R2110W) on plectin rod domain causes an autosomal dominant form of disease termed EBS-Ogna without muscular dystrophy.<ref>PMID: 9067706 </ref>
Plectin deficient(-/-) mice also exhibit similar skin and muscle phenotypes of human patients suffering from EBS-MD and died 2-3 days after birth. <ref>PMID: 9389647</ref>

== References ==

<references/>

Group:MUZIC:Plectin

2013-02-06T13:05:08Z

Jae-Geun Song: qu

== Introduction ==
Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms.
Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain,skeletal muscle and skin . <ref>PMID:10556294</ref>.

[[Image:isoforms.gif]]

<Structure load='3PE0' size='300' frame='true' align='right' caption='Crystal structure of SR4-SR5-SH3 regions in the plakin domain (PDB:3PE0)' scene='User:Jae-Geun_Song/Workbench/plectin/Plakin/1'/>

== Sequence annotation ==
Plectin can be divided in three main sections; a central coiled-coil rod domain, N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin <ref>PMID:3430617</ref>. N-terminal globular region contains actin binding domain (ABD) comprising two calponin homology.

[[Image:plectin.jpg]]

Schematic domain map of plectin (Winter, 2013)

== Structures ==

'''1. Actin Binding Domain (ABD)'''

<Structure load='1sh6' size='300' frame='true' align='right' caption='The actin binding domain of plectin (PDB:1SH6)' scene='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/1'/>

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain(<scene name='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/3'>CH1 and CH2</scene>)<ref>PMID:9164454</ref>. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported <ref>PMID: 15128297</ref>.

'''2. Plakin domain'''

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.<ref>PMID: 21288893 </ref>

'''3. Integrin β4-Plectin complex'''
The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.<ref>PMID: 19242489 </ref>

== Function and Interactions ==
Proteins coordinate various cytoskeletal networks are termed as cytolinkers, which are able to interlink different types of cytoskeletons. Plectin is one of the well-characterized cytolinker and expressed in diverse cell types and tissues, a number of different binding partners of plectin have been identified.

Intermediate filament(IF) binding sites of plectin is located between plakin repeats 5 and 6 in C-terminal globular domain. Several IF proteins were identified to interact with plectin such as vimentin, desmin, GFAP(glial fibrillary acidic protein) and cytokeratins <ref>PMID: 8830774 </ref> .

The actin binding domain(ABD)in N-terminal globular domain has a role to interact with integrin subunit beta 4 to establish mechanical stability in hemedesmosomes along with its function for binding to actin filament(F-actin). Calmodulin(CaM) is also known to bind the ABD of plectin to modulate the hemidesmosome disassembly <ref> PMID: 19419971 </ref>.

<Structure load='3F7P' size='300' frame='true' align='right' caption='Crystal structure of plectin ABD(magenta) and integrin beta 4 (green) complex (PDB:3F7P)' scene='Group:MUZIC:Plectin/Plecint/1' />

== Pathology ==
It has been reported that patients with EBS-MD (Epidermolysis bullosa simplex with muscular dystrophy),a genetic disorder characterized severe skin blistering disease combined with muscular dystrophy, have a muation on plectin gene(PLEC1). This mutation leads to premature termination of translation.<ref>PMID: 8941634 </ref>
In addition, site-specific missense mutation(R2110W) on plectin rod domain causes an autosomal dominant form of disease termed EBS-Ogna without muscular dystrophy.<ref>PMID: 9067706 </ref>
Plectin deficient(-/-) mice also exhibit similar skin and muscle phenotypes of human patients suffering from EBS-MD and died 2-3 days after birth. <ref>PMID: 9389647</ref>

== References ==

<references/>

File:3HH2.pdb

2013-02-06T12:50:02Z

Jae-Geun Song:

Group:MUZIC:Plectin

2013-02-06T12:48:07Z

Jae-Geun Song:

== Introduction ==
Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms.
Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain,skeletal muscle and skin . <ref>PMID:10556294</ref>.

[[Image:isoforms.gif]]

<Structure load='3PE0' size='300' frame='true' align='right' caption='Crystal structure of SR4-SR5-SH3 regions in the plakin domain (PDB:3PE0)' scene='User:Jae-Geun_Song/Workbench/plectin/Plakin/1'/>

== Structures ==
Plectin can be divided in three main sections; a central coiled-coil rod domain, N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin <ref>PMID:3430617</ref>. N-terminal globular region contains actin binding domain (ABD) comprising two calponin homology.

[[Image:plectin.jpg]]

Schematic domain map of plectin (Winter, 2013)

'''1. Actin Binding Domain (ABD)'''

<Structure load='1sh6' size='300' frame='true' align='right' caption='The actin binding domain of plectin (PDB:1SH6)' scene='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/1'/>

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain(<scene name='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/3'>CH1 and CH2</scene>)<ref>PMID:9164454</ref>. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported <ref>PMID: 15128297</ref>.

'''2. Plakin domain'''

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.<ref>PMID: 21288893 </ref>

'''3. Integrin β4-Plectin complex'''
The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.<ref>PMID: 19242489 </ref>

== Function and Interactions ==
Proteins coordinate various cytoskeletal networks are termed as cytolinkers, which are able to interlink different types of cytoskeletons. Plectin is one of the well-characterized cytolinker and expressed in diverse cell types and tissues, a number of different binding partners of plectin have been identified.

Intermediate filament(IF) binding sites of plectin is located between plakin repeats 5 and 6 in C-terminal globular domain. Several IF proteins were identified to interact with plectin such as vimentin, desmin, GFAP(glial fibrillary acidic protein) and cytokeratins <ref>PMID: 8830774 </ref> .

The actin binding domain(ABD)in N-terminal globular domain has a role to interact with integrin subunit beta 4 to establish mechanical stability in hemedesmosomes along with its function for binding to actin filament(F-actin). Calmodulin(CaM) is also known to bind the ABD of plectin to modulate the hemidesmosome disassembly <ref> PMID: 19419971 </ref>.

<Structure load='3F7P' size='300' frame='true' align='right' caption='Crystal structure of plectin ABD(magenta) and integrin beta 4 (green) complex (PDB:3F7P)' scene='Group:MUZIC:Plectin/Plecint/1' />

== Pathology ==
It has been reported that patients with EBS-MD (Epidermolysis bullosa simplex with muscular dystrophy),a genetic disorder characterized severe skin blistering disease combined with muscular dystrophy, have a muation on plectin gene(PLEC1). This mutation leads to premature termination of translation.<ref>PMID: 8941634 </ref>
In addition, site-specific missense mutation(R2110W) on plectin rod domain causes an autosomal dominant form of disease termed EBS-Ogna without muscular dystrophy.<ref>PMID: 9067706 </ref>
Plectin deficient(-/-) mice also exhibit similar skin and muscle phenotypes of human patients suffering from EBS-MD and died 2-3 days after birth. <ref>PMID: 9389647</ref>

== References ==

<references/>

Group:MUZIC:Plectin

2013-02-06T12:47:15Z

Jae-Geun Song:

== Introduction ==
Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms.
Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain,skeletal muscle and skin . <ref>PMID:10556294</ref>.

[[Image:isoforms.gif]]

<Structure load='3PE0' size='300' frame='true' align='right' caption='Crystal structure of SR4-SR5-SH3 regions in the plakin domain (PDB:3PE0)' scene='User:Jae-Geun_Song/Workbench/plectin/Plakin/1'/>

== Structures ==
Plectin can be divided in three main sections; a central coiled-coil rod domain, N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin <ref>PMID:3430617</ref>. N-terminal globular region contains actin binding domain (ABD) comprising two calponin homology.

[[Image:plectin.jpg]]

Schematic domain map of plectin (Winter, 2013)

'''1. Actin Binding Domain (ABD)'''

<Structure load='1sh6' size='300' frame='true' align='right' caption='The actin binding domain of plectin (PDB:1SH6)' scene='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/1'/>

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain(<scene name='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/3'>CH1 and CH2</scene>)<ref>PMID:9164454</ref>. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported <ref>PMID: 15128297</ref>.

'''2. Plakin domain'''

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.<ref>PMID: 21288893 </ref>

'''3. Integrin β4-Plectin complex'''
The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.<ref>PMID: 19242489 </ref>

<Structure load='3F7P' size='300' frame='true' align='right' caption='Crystal structure of plectin ABD(magenta) and integrin beta 4 (green) complex (PDB:3F7P)' scene='Group:MUZIC:Plectin/Plecint/1' />

== Function and Interactions ==
Proteins coordinate various cytoskeletal networks are termed as cytolinkers, which are able to interlink different types of cytoskeletons. Plectin is one of the well-characterized cytolinker and expressed in diverse cell types and tissues, a number of different binding partners of plectin have been identified.

Intermediate filament(IF) binding sites of plectin is located between plakin repeats 5 and 6 in C-terminal globular domain. Several IF proteins were identified to interact with plectin such as vimentin, desmin, GFAP(glial fibrillary acidic protein) and cytokeratins <ref>PMID: 8830774 </ref> .

The actin binding domain(ABD)in N-terminal globular domain has a role to interact with integrin subunit beta 4 to establish mechanical stability in hemedesmosomes along with its function for binding to actin filament(F-actin). Calmodulin(CaM) is also known to bind the ABD of plectin to modulate the hemidesmosome disassembly <ref> PMID: 19419971 </ref>.

== Pathology ==
It has been reported that patients with EBS-MD (Epidermolysis bullosa simplex with muscular dystrophy),a genetic disorder characterized severe skin blistering disease combined with muscular dystrophy, have a muation on plectin gene(PLEC1). This mutation leads to premature termination of translation.<ref>PMID: 8941634 </ref>
In addition, site-specific missense mutation(R2110W) on plectin rod domain causes an autosomal dominant form of disease termed EBS-Ogna without muscular dystrophy.<ref>PMID: 9067706 </ref>
Plectin deficient(-/-) mice also exhibit similar skin and muscle phenotypes of human patients suffering from EBS-MD and died 2-3 days after birth. <ref>PMID: 9389647</ref>

== References ==

<references/>

Group:MUZIC:Plectin

2013-02-06T12:45:13Z

Jae-Geun Song:

<Structure load='1sh6' size='300' frame='true' align='right' caption='The actin binding domain of plectin (PDB:1SH6)' scene='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/1'/>

== Introduction ==
Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms.
Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain,skeletal muscle and skin . <ref>PMID:10556294</ref>.

[[Image:isoforms.gif]]

<Structure load='3PE0' size='300' frame='true' align='right' caption='Crystal structure of SR4-SR5-SH3 regions in the plakin domain (PDB:3PE0)' scene='User:Jae-Geun_Song/Workbench/plectin/Plakin/1'/>

== Structures ==
Plectin can be divided in three main sections; a central coiled-coil rod domain, N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin <ref>PMID:3430617</ref>. N-terminal globular region contains actin binding domain (ABD) comprising two calponin homology.

[[Image:plectin.jpg]]

Schematic domain map of plectin (Winter, 2013)

'''1. Actin Binding Domain (ABD)'''

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain(<scene name='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/3'>CH1 and CH2</scene>)<ref>PMID:9164454</ref>. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported <ref>PMID: 15128297</ref>.

'''2. Plakin domain'''

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.<ref>PMID: 21288893 </ref>

'''3. Integrin β4-Plectin complex'''
The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.<ref>PMID: 19242489 </ref>

<Structure load='3F7P' size='300' frame='true' align='right' caption='Crystal structure of plectin ABD(magenta) and integrin beta 4 (green) complex (PDB:3F7P)' scene='Group:MUZIC:Plectin/Plecint/1' />

== Function and Interactions ==
Proteins coordinate various cytoskeletal networks are termed as cytolinkers, which are able to interlink different types of cytoskeletons. Plectin is one of the well-characterized cytolinker and expressed in diverse cell types and tissues, a number of different binding partners of plectin have been identified.

Intermediate filament(IF) binding sites of plectin is located between plakin repeats 5 and 6 in C-terminal globular domain. Several IF proteins were identified to interact with plectin such as vimentin, desmin, GFAP(glial fibrillary acidic protein) and cytokeratins <ref>PMID: 8830774 </ref> .

The actin binding domain(ABD)in N-terminal globular domain has a role to interact with integrin subunit beta 4 to establish mechanical stability in hemedesmosomes along with its function for binding to actin filament(F-actin). Calmodulin(CaM) is also known to bind the ABD of plectin to modulate the hemidesmosome disassembly <ref> PMID: 19419971 </ref>.

== Pathology ==
It has been reported that patients with EBS-MD (Epidermolysis bullosa simplex with muscular dystrophy),a genetic disorder characterized severe skin blistering disease combined with muscular dystrophy, have a muation on plectin gene(PLEC1). This mutation leads to premature termination of translation.<ref>PMID: 8941634 </ref>
In addition, site-specific missense mutation(R2110W) on plectin rod domain causes an autosomal dominant form of disease termed EBS-Ogna without muscular dystrophy.<ref>PMID: 9067706 </ref>
Plectin deficient(-/-) mice also exhibit similar skin and muscle phenotypes of human patients suffering from EBS-MD and died 2-3 days after birth. <ref>PMID: 9389647</ref>

== References ==

<references/>

Group:MUZIC:Plectin

2013-02-06T12:44:40Z

Jae-Geun Song:

<Structure load='1sh6' size='300' frame='true' align='right' caption='The actin binding domain of plectin ([PDB:1SH6])' scene='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/1'/>

== Introduction ==
Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms.
Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain,skeletal muscle and skin . <ref>PMID:10556294</ref>.

[[Image:isoforms.gif]]

<Structure load='3PE0' size='300' frame='true' align='right' caption='Crystal structure of SR4-SR5-SH3 regions in the plakin domain (PDB:3PE0)' scene='User:Jae-Geun_Song/Workbench/plectin/Plakin/1'/>

== Structures ==
Plectin can be divided in three main sections; a central coiled-coil rod domain, N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin <ref>PMID:3430617</ref>. N-terminal globular region contains actin binding domain (ABD) comprising two calponin homology.

[[Image:plectin.jpg]]

Schematic domain map of plectin (Winter, 2013)

'''1. Actin Binding Domain (ABD)'''

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain(<scene name='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/3'>CH1 and CH2</scene>)<ref>PMID:9164454</ref>. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported <ref>PMID: 15128297</ref>.

'''2. Plakin domain'''

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.<ref>PMID: 21288893 </ref>

'''3. Integrin β4-Plectin complex'''
The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.<ref>PMID: 19242489 </ref>

<Structure load='3F7P' size='300' frame='true' align='right' caption='Crystal structure of plectin ABD(magenta) and integrin beta 4 (green) complex (PDB:3F7P)' scene='Group:MUZIC:Plectin/Plecint/1' />

== Function and Interactions ==
Proteins coordinate various cytoskeletal networks are termed as cytolinkers, which are able to interlink different types of cytoskeletons. Plectin is one of the well-characterized cytolinker and expressed in diverse cell types and tissues, a number of different binding partners of plectin have been identified.

Intermediate filament(IF) binding sites of plectin is located between plakin repeats 5 and 6 in C-terminal globular domain. Several IF proteins were identified to interact with plectin such as vimentin, desmin, GFAP(glial fibrillary acidic protein) and cytokeratins <ref>PMID: 8830774 </ref> .

The actin binding domain(ABD)in N-terminal globular domain has a role to interact with integrin subunit beta 4 to establish mechanical stability in hemedesmosomes along with its function for binding to actin filament(F-actin). Calmodulin(CaM) is also known to bind the ABD of plectin to modulate the hemidesmosome disassembly <ref> PMID: 19419971 </ref>.

== Pathology ==
It has been reported that patients with EBS-MD (Epidermolysis bullosa simplex with muscular dystrophy),a genetic disorder characterized severe skin blistering disease combined with muscular dystrophy, have a muation on plectin gene(PLEC1). This mutation leads to premature termination of translation.<ref>PMID: 8941634 </ref>
In addition, site-specific missense mutation(R2110W) on plectin rod domain causes an autosomal dominant form of disease termed EBS-Ogna without muscular dystrophy.<ref>PMID: 9067706 </ref>
Plectin deficient(-/-) mice also exhibit similar skin and muscle phenotypes of human patients suffering from EBS-MD and died 2-3 days after birth. <ref>PMID: 9389647</ref>

== References ==

<references/>

Group:MUZIC:Plectin

2013-02-06T12:43:47Z

Jae-Geun Song:

Group:MUZIC:Plectin

2013-02-06T12:42:29Z

Jae-Geun Song:

<Structure load='1sh6' size='300' frame='true' align='right' caption='The actin binding domain of plectin (PDB:1SH6)' scene='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/1'/>

== Introduction ==
Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms.
Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain,skeletal muscle and skin . <ref>PMID:10556294</ref>.

[[Image:isoforms.gif]]

<Structure load='3PE0' size='300' frame='true' align='right' caption='Crystal structure of SR4-SR5-SH3 regions in the plakin domain (PDB:3PE0)' scene='User:Jae-Geun_Song/Workbench/plectin/Plakin/1'/>

== Structures ==
Plectin can be divided in three main sections; a central coiled-coil rod domain, N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin <ref>PMID:3430617</ref>. N-terminal globular region contains actin binding domain (ABD) comprising two calponin homology.

[[Image:plectin.jpg]]

Schematic domain map of plectin (Winter, 2013)

'''1. Actin Binding Domain (ABD)'''

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain(<scene name='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/3'>CH1 and CH2</scene>)<ref>PMID:9164454</ref>. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported <ref>PMID: 15128297</ref>.

'''2. Plakin domain'''

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.<ref>PMID: 21288893 </ref>

'''3. Integrin β4-Plectin complex'''
The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.<ref>PMID: 19242489 </ref>

<Structure load='3F7P' size='300' frame='true' align='right' caption='Crystal structure of plectin ABD and integrin beta 4 complex (PDB:3F7P)' scene='Group:MUZIC:Plectin/Plecint/1' />

== Function and Interactions ==
Proteins coordinate various cytoskeletal networks are termed as cytolinkers, which are able to interlink different types of cytoskeletons. Plectin is one of the well-characterized cytolinker and expressed in diverse cell types and tissues, a number of different binding partners of plectin have been identified.

Intermediate filament(IF) binding sites of plectin is located between plakin repeats 5 and 6 in C-terminal globular domain. Several IF proteins were identified to interact with plectin such as vimentin, desmin, GFAP(glial fibrillary acidic protein) and cytokeratins <ref>PMID: 8830774 </ref> .

The actin binding domain(ABD)in N-terminal globular domain has a role to interact with integrin subunit beta 4 to establish mechanical stability in hemedesmosomes along with its function for binding to actin filament(F-actin). Calmodulin(CaM) is also known to bind the ABD of plectin to modulate the hemidesmosome disassembly <ref> PMID: 19419971 </ref>.

== Pathology ==
It has been reported that patients with EBS-MD (Epidermolysis bullosa simplex with muscular dystrophy),a genetic disorder characterized severe skin blistering disease combined with muscular dystrophy, have a muation on plectin gene(PLEC1). This mutation leads to premature termination of translation.<ref>PMID: 8941634 </ref>
In addition, site-specific missense mutation(R2110W) on plectin rod domain causes an autosomal dominant form of disease termed EBS-Ogna without muscular dystrophy.<ref>PMID: 9067706 </ref>
Plectin deficient(-/-) mice also exhibit similar skin and muscle phenotypes of human patients suffering from EBS-MD and died 2-3 days after birth. <ref>PMID: 9389647</ref>

== References ==

<references/>

Group:MUZIC:Plectin

2013-02-06T12:41:13Z

Jae-Geun Song:

<Structure load='1sh6' size='300' frame='true' align='right' caption='The actin binding domain of plectin (PDB:1SH6)' scene='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/1'/>

== Introduction ==
Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms.
Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain,skeletal muscle and skin . <ref>PMID:10556294</ref>.

[[Image:isoforms.gif]]

<Structure load='3PE0' size='300' frame='true' align='right' caption='Crystal structure of SR4-SR5-SH3 regions in the plakin domain (PDB:3PE0)' scene='User:Jae-Geun_Song/Workbench/plectin/Plakin/1'/>

== Structures ==
Plectin can be divided in three main sections; a central coiled-coil rod domain, N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin <ref>PMID:3430617</ref>. N-terminal globular region contains actin binding domain (ABD) comprising two calponin homology.

[[Image:plectin.jpg]]

Schematic domain map of plectin (Winter, 2013)

'''1. Actin Binding Domain (ABD)'''

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain(<scene name='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/3'>CH1 and CH2</scene>)<ref>PMID:9164454</ref>. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported <ref>PMID: 15128297</ref>.

'''2. Plakin domain'''

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.<ref>PMID: 21288893 </ref>

'''3. Integrin β4-Plectin complex'''
The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.<ref>PMID: 19242489 </ref>

<Structure load='3F7P' size='300' frame='true' align='right' caption='Crystal structure of plectin ABD and integrin beta 4 complex (PDB:3F7P)' <scene name='Group:MUZIC:Plectin/Plecint/1'>TextToBeDisplayed</scene> />

== Function and Interactions ==
Proteins coordinate various cytoskeletal networks are termed as cytolinkers, which are able to interlink different types of cytoskeletons. Plectin is one of the well-characterized cytolinker and expressed in diverse cell types and tissues, a number of different binding partners of plectin have been identified.

Intermediate filament(IF) binding sites of plectin is located between plakin repeats 5 and 6 in C-terminal globular domain. Several IF proteins were identified to interact with plectin such as vimentin, desmin, GFAP(glial fibrillary acidic protein) and cytokeratins <ref>PMID: 8830774 </ref> .

The actin binding domain(ABD)in N-terminal globular domain has a role to interact with integrin subunit beta 4 to establish mechanical stability in hemedesmosomes along with its function for binding to actin filament(F-actin). Calmodulin(CaM) is also known to bind the ABD of plectin to modulate the hemidesmosome disassembly <ref> PMID: 19419971 </ref>.

== Pathology ==
It has been reported that patients with EBS-MD (Epidermolysis bullosa simplex with muscular dystrophy),a genetic disorder characterized severe skin blistering disease combined with muscular dystrophy, have a muation on plectin gene(PLEC1). This mutation leads to premature termination of translation.<ref>PMID: 8941634 </ref>
In addition, site-specific missense mutation(R2110W) on plectin rod domain causes an autosomal dominant form of disease termed EBS-Ogna without muscular dystrophy.<ref>PMID: 9067706 </ref>
Plectin deficient(-/-) mice also exhibit similar skin and muscle phenotypes of human patients suffering from EBS-MD and died 2-3 days after birth. <ref>PMID: 9389647</ref>

== References ==

<references/>

File:3F7P.pdb

2013-02-06T12:35:41Z

Jae-Geun Song:

Group:MUZIC:Plectin

2013-02-04T14:36:09Z

Jae-Geun Song: /* Structures */

<Structure load='1sh6' size='300' frame='true' align='right' caption='The actin binding domain of plectin (PDB:1SH6)' scene='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/1'/>

== Introduction ==
Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms.
Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain,skeletal muscle and skin . <ref>PMID:10556294</ref>.

[[Image:isoforms.gif]]

<Structure load='3PE0' size='300' frame='true' align='right' caption='Crystal structure of SR4-SR5-SH3 regions in the plakin domain (PDB:3PE0)' scene='User:Jae-Geun_Song/Workbench/plectin/Plakin/1'/>

== Structures ==
Plectin can be divided in three main sections; a central coiled-coil rod domain, N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin <ref>PMID:3430617</ref>. N-terminal globular region contains actin binding domain (ABD) comprising two calponin homology.

[[Image:plectin.jpg]]

Schematic domain map of plectin (Winter, 2013)

'''1. Actin Binding Domain (ABD)'''

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain(<scene name='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/3'>CH1 and CH2</scene>)<ref>PMID:9164454</ref>. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported <ref>PMID: 15128297</ref>.

'''2. Plakin domain'''

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.<ref>PMID: 21288893 </ref>

'''3. Integrin β4-Plectin complex'''
The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.<ref>PMID: 19242489 </ref>

<Structure load='3F7P' size='300' frame='true' align='right' caption='Crystal structure of plectin ABD and integrin beta 4 complex (PDB:3F7P)' scene='Insert optional scene name here' />

== Function and Interactions ==
Proteins coordinate various cytoskeletal networks are termed as cytolinkers, which are able to interlink different types of cytoskeletons. Plectin is one of the well-characterized cytolinker and expressed in diverse cell types and tissues, a number of different binding partners of plectin have been identified.

Intermediate filament(IF) binding sites of plectin is located between plakin repeats 5 and 6 in C-terminal globular domain. Several IF proteins were identified to interact with plectin such as vimentin, desmin, GFAP(glial fibrillary acidic protein) and cytokeratins <ref>PMID: 8830774 </ref> .

The actin binding domain(ABD)in N-terminal globular domain has a role to interact with integrin subunit beta 4 to establish mechanical stability in hemedesmosomes along with its function for binding to actin filament(F-actin). Calmodulin(CaM) is also known to bind the ABD of plectin to modulate the hemidesmosome disassembly <ref> PMID: 19419971 </ref>.

== Pathology ==
It has been reported that patients with EBS-MD (Epidermolysis bullosa simplex with muscular dystrophy),a genetic disorder characterized severe skin blistering disease combined with muscular dystrophy, have a muation on plectin gene(PLEC1). This mutation leads to premature termination of translation.<ref>PMID: 8941634 </ref>
In addition, site-specific missense mutation(R2110W) on plectin rod domain causes an autosomal dominant form of disease termed EBS-Ogna without muscular dystrophy.<ref>PMID: 9067706 </ref>
Plectin deficient(-/-) mice also exhibit similar skin and muscle phenotypes of human patients suffering from EBS-MD and died 2-3 days after birth. <ref>PMID: 9389647</ref>

== References ==

<references/>

Group:MUZIC:Plectin

2013-02-04T14:27:58Z

Jae-Geun Song: /* Structures */

<Structure load='1sh6' size='300' frame='true' align='right' caption='The actin binding domain of plectin (PDB:1SH6)' scene='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/1'/>

== Introduction ==
Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms.
Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain,skeletal muscle and skin . <ref>PMID:10556294</ref>.

[[Image:isoforms.gif]]

<Structure load='3PE0' size='300' frame='true' align='right' caption='Crystal structure of SR4-SR5-SH3 regions in the plakin domain (PDB:3PE0)' scene='User:Jae-Geun_Song/Workbench/plectin/Plakin/1'/>

== Structures ==
Plectin can be divided in three main sections; a central coiled-coil rod domain, N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin <ref>PMID:3430617</ref>. N-terminal globular region contains actin binding domain (ABD) comprising two calponin homology.

[[Image:plectin.jpg]]

Schematic domain map of plectin (Winter, 2013)

'''1. Actin Binding Domain (ABD)'''

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain(<scene name='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/3'>CH1 and CH2</scene>)<ref>PMID:9164454</ref>. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported <ref>PMID: 15128297</ref>.

'''2. Plakin domain'''

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.<ref>PMID: 21288893 </ref>

'''3.Integrin β4-Plectin complex'''
The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.<ref>PMID: 19242489 </ref>

<Structure load='3F7P' size='300' frame='true' align='right' caption='Crystal structure of plectin ABD and integrin beta 4 complex (PDB:3F7P)' scene='Insert optional scene name here' />

== Function and Interactions ==
Proteins coordinate various cytoskeletal networks are termed as cytolinkers, which are able to interlink different types of cytoskeletons. Plectin is one of the well-characterized cytolinker and expressed in diverse cell types and tissues, a number of different binding partners of plectin have been identified.

Intermediate filament(IF) binding sites of plectin is located between plakin repeats 5 and 6 in C-terminal globular domain. Several IF proteins were identified to interact with plectin such as vimentin, desmin, GFAP(glial fibrillary acidic protein) and cytokeratins <ref>PMID: 8830774 </ref> .

The actin binding domain(ABD)in N-terminal globular domain has a role to interact with integrin subunit beta 4 to establish mechanical stability in hemedesmosomes along with its function for binding to actin filament(F-actin). Calmodulin(CaM) is also known to bind the ABD of plectin to modulate the hemidesmosome disassembly <ref> PMID: 19419971 </ref>.

== Pathology ==
It has been reported that patients with EBS-MD (Epidermolysis bullosa simplex with muscular dystrophy),a genetic disorder characterized severe skin blistering disease combined with muscular dystrophy, have a muation on plectin gene(PLEC1). This mutation leads to premature termination of translation.<ref>PMID: 8941634 </ref>
In addition, site-specific missense mutation(R2110W) on plectin rod domain causes an autosomal dominant form of disease termed EBS-Ogna without muscular dystrophy.<ref>PMID: 9067706 </ref>
Plectin deficient(-/-) mice also exhibit similar skin and muscle phenotypes of human patients suffering from EBS-MD and died 2-3 days after birth. <ref>PMID: 9389647</ref>

== References ==

<references/>

Group:MUZIC:Plectin

2013-02-04T14:27:29Z

Jae-Geun Song: /* Structures */

<Structure load='1sh6' size='300' frame='true' align='right' caption='The actin binding domain of plectin (PDB:1SH6)' scene='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/1'/>

== Introduction ==
Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms.
Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain,skeletal muscle and skin . <ref>PMID:10556294</ref>.

[[Image:isoforms.gif]]

<Structure load='3PE0' size='300' frame='true' align='right' caption='Crystal structure of SR4-SR5-SH3 regions in the plakin domain (PDB:3PE0)' scene='User:Jae-Geun_Song/Workbench/plectin/Plakin/1'/>

== Structures ==
Plectin can be divided in three main sections; a central coiled-coil rod domain, N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin <ref>PMID:3430617</ref>. N-terminal globular region contains actin binding domain (ABD) comprising two calponin homology.

[[Image:plectin.jpg]]

(Schematic domain map of plectin. Winter, 2013)

'''1. Actin Binding Domain (ABD)'''

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain(<scene name='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/3'>CH1 and CH2</scene>)<ref>PMID:9164454</ref>. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported <ref>PMID: 15128297</ref>.

'''2. Plakin domain'''

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.<ref>PMID: 21288893 </ref>

'''3.Integrin β4-Plectin complex'''
The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.<ref>PMID: 19242489 </ref>

<Structure load='3F7P' size='300' frame='true' align='right' caption='Crystal structure of plectin ABD and integrin beta 4 complex (PDB:3F7P)' scene='Insert optional scene name here' />

== Function and Interactions ==
Proteins coordinate various cytoskeletal networks are termed as cytolinkers, which are able to interlink different types of cytoskeletons. Plectin is one of the well-characterized cytolinker and expressed in diverse cell types and tissues, a number of different binding partners of plectin have been identified.

Intermediate filament(IF) binding sites of plectin is located between plakin repeats 5 and 6 in C-terminal globular domain. Several IF proteins were identified to interact with plectin such as vimentin, desmin, GFAP(glial fibrillary acidic protein) and cytokeratins <ref>PMID: 8830774 </ref> .

The actin binding domain(ABD)in N-terminal globular domain has a role to interact with integrin subunit beta 4 to establish mechanical stability in hemedesmosomes along with its function for binding to actin filament(F-actin). Calmodulin(CaM) is also known to bind the ABD of plectin to modulate the hemidesmosome disassembly <ref> PMID: 19419971 </ref>.

== Pathology ==
It has been reported that patients with EBS-MD (Epidermolysis bullosa simplex with muscular dystrophy),a genetic disorder characterized severe skin blistering disease combined with muscular dystrophy, have a muation on plectin gene(PLEC1). This mutation leads to premature termination of translation.<ref>PMID: 8941634 </ref>
In addition, site-specific missense mutation(R2110W) on plectin rod domain causes an autosomal dominant form of disease termed EBS-Ogna without muscular dystrophy.<ref>PMID: 9067706 </ref>
Plectin deficient(-/-) mice also exhibit similar skin and muscle phenotypes of human patients suffering from EBS-MD and died 2-3 days after birth. <ref>PMID: 9389647</ref>

== References ==

<references/>

File:Plectin.jpg

2013-02-04T14:27:05Z

Jae-Geun Song: uploaded a new version of "Image:Plectin.jpg"

File:Plectin.jpg

2013-02-04T14:25:35Z

Jae-Geun Song: uploaded a new version of "Image:Plectin.jpg"

Group:MUZIC:Plectin

2013-02-04T14:23:29Z

Jae-Geun Song: /* Structures */

<Structure load='1sh6' size='300' frame='true' align='right' caption='The actin binding domain of plectin (PDB:1SH6)' scene='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/1'/>

== Introduction ==
Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms.
Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain,skeletal muscle and skin . <ref>PMID:10556294</ref>.

[[Image:isoforms.gif]]

<Structure load='3PE0' size='300' frame='true' align='right' caption='Crystal structure of SR4-SR5-SH3 regions in the plakin domain (PDB:3PE0)' scene='User:Jae-Geun_Song/Workbench/plectin/Plakin/1'/>

== Structures ==
Plectin can be divided in three main sections; a central coiled-coil rod domain, N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin <ref>PMID:3430617</ref>. N-terminal globular region contains actin binding domain (ABD) comprising two calponin homology.

[[Image:plectin.jpg]]
(Schematic domain map of plectin. Winter, 2013)

'''1. Actin Binding Domain (ABD)'''

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain(<scene name='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/3'>CH1 and CH2</scene>)<ref>PMID:9164454</ref>. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported <ref>PMID: 15128297</ref>.

'''2. Plakin domain'''

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.<ref>PMID: 21288893 </ref>

'''3.Integrin β4-Plectin complex'''
The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.<ref>PMID: 19242489 </ref>

<Structure load='3F7P' size='300' frame='true' align='right' caption='Crystal structure of plectin ABD and integrin beta 4 complex (PDB:3F7P)' scene='Insert optional scene name here' />

== Function and Interactions ==
Proteins coordinate various cytoskeletal networks are termed as cytolinkers, which are able to interlink different types of cytoskeletons. Plectin is one of the well-characterized cytolinker and expressed in diverse cell types and tissues, a number of different binding partners of plectin have been identified.

Intermediate filament(IF) binding sites of plectin is located between plakin repeats 5 and 6 in C-terminal globular domain. Several IF proteins were identified to interact with plectin such as vimentin, desmin, GFAP(glial fibrillary acidic protein) and cytokeratins <ref>PMID: 8830774 </ref> .

The actin binding domain(ABD)in N-terminal globular domain has a role to interact with integrin subunit beta 4 to establish mechanical stability in hemedesmosomes along with its function for binding to actin filament(F-actin). Calmodulin(CaM) is also known to bind the ABD of plectin to modulate the hemidesmosome disassembly <ref> PMID: 19419971 </ref>.

== Pathology ==
It has been reported that patients with EBS-MD (Epidermolysis bullosa simplex with muscular dystrophy),a genetic disorder characterized severe skin blistering disease combined with muscular dystrophy, have a muation on plectin gene(PLEC1). This mutation leads to premature termination of translation.<ref>PMID: 8941634 </ref>
In addition, site-specific missense mutation(R2110W) on plectin rod domain causes an autosomal dominant form of disease termed EBS-Ogna without muscular dystrophy.<ref>PMID: 9067706 </ref>
Plectin deficient(-/-) mice also exhibit similar skin and muscle phenotypes of human patients suffering from EBS-MD and died 2-3 days after birth. <ref>PMID: 9389647</ref>

== References ==

<references/>

File:Plectin.jpg

2013-02-04T14:22:10Z

Jae-Geun Song:

Group:MUZIC:Plectin

2013-02-04T14:15:15Z

Jae-Geun Song:

<Structure load='1sh6' size='300' frame='true' align='right' caption='The actin binding domain of plectin (PDB:1SH6)' scene='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/1'/>

== Introduction ==
Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms.
Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain,skeletal muscle and skin . <ref>PMID:10556294</ref>.

[[Image:isoforms.gif]]

<Structure load='3PE0' size='300' frame='true' align='right' caption='Crystal structure of SR4-SR5-SH3 regions in the plakin domain (PDB:3PE0)' scene='User:Jae-Geun_Song/Workbench/plectin/Plakin/1'/>

== Structures ==
Plectin can be divided in three main sections; a central coiled-coil rod domain, N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin <ref>PMID:3430617</ref>. N-terminal globular region contains actin binding domain (ABD) comprising two calponin homology.

[[Image:plectin_structure.jpg]]
(Litjens, 2006)

'''1. Actin Binding Domain (ABD)'''

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain(<scene name='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/3'>CH1 and CH2</scene>)<ref>PMID:9164454</ref>. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported <ref>PMID: 15128297</ref>.

'''2. Plakin domain'''

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.<ref>PMID: 21288893 </ref>

'''3.Integrin β4-Plectin complex'''
The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.<ref>PMID: 19242489 </ref>

<Structure load='3F7P' size='300' frame='true' align='right' caption='Crystal structure of plectin ABD and integrin beta 4 complex (PDB:3F7P)' scene='Insert optional scene name here' />

== Function and Interactions ==
Proteins coordinate various cytoskeletal networks are termed as cytolinkers, which are able to interlink different types of cytoskeletons. Plectin is one of the well-characterized cytolinker and expressed in diverse cell types and tissues, a number of different binding partners of plectin have been identified.

Intermediate filament(IF) binding sites of plectin is located between plakin repeats 5 and 6 in C-terminal globular domain. Several IF proteins were identified to interact with plectin such as vimentin, desmin, GFAP(glial fibrillary acidic protein) and cytokeratins <ref>PMID: 8830774 </ref> .

The actin binding domain(ABD)in N-terminal globular domain has a role to interact with integrin subunit beta 4 to establish mechanical stability in hemedesmosomes along with its function for binding to actin filament(F-actin). Calmodulin(CaM) is also known to bind the ABD of plectin to modulate the hemidesmosome disassembly <ref> PMID: 19419971 </ref>.

== Pathology ==
It has been reported that patients with EBS-MD (Epidermolysis bullosa simplex with muscular dystrophy),a genetic disorder characterized severe skin blistering disease combined with muscular dystrophy, have a muation on plectin gene(PLEC1). This mutation leads to premature termination of translation.<ref>PMID: 8941634 </ref>
In addition, site-specific missense mutation(R2110W) on plectin rod domain causes an autosomal dominant form of disease termed EBS-Ogna without muscular dystrophy.<ref>PMID: 9067706 </ref>
Plectin deficient(-/-) mice also exhibit similar skin and muscle phenotypes of human patients suffering from EBS-MD and died 2-3 days after birth. <ref>PMID: 9389647</ref>

== References ==

<references/>

Group:MUZIC:Plectin

2013-02-04T14:14:17Z

Jae-Geun Song:

<Structure load='1sh6' size='300' frame='true' align='right' caption='The actin binding domain of plectin(PDB 1SH6)' scene='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/1'/>

== Introduction ==
Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms.
Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain,skeletal muscle and skin . <ref>PMID:10556294</ref>.

[[Image:isoforms.gif]]

<Structure load='3PE0' size='300' frame='true' align='right' caption='Crystal structure of SR4-SR5-SH3 regions in the plakin domain (PDB 3PE0)' scene='User:Jae-Geun_Song/Workbench/plectin/Plakin/1'/>

== Structures ==
Plectin can be divided in three main sections; a central coiled-coil rod domain, N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin <ref>PMID:3430617</ref>. N-terminal globular region contains actin binding domain (ABD) comprising two calponin homology.

[[Image:plectin_structure.jpg]]
(Litjens, 2006)

'''1. Actin Binding Domain (ABD)'''

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain(<scene name='User:Jae-Geun_Song/Workbench/plectin/Plecin_actin_binding_domain/3'>CH1 and CH2</scene>)<ref>PMID:9164454</ref>. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported <ref>PMID: 15128297</ref>.

'''2. Plakin domain'''

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.<ref>PMID: 21288893 </ref>

'''3.Integrin β4-Plectin complex'''
The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.<ref>PMID: 19242489 </ref>

<Structure load='3F7P' size='300' frame='true' align='right' caption='Crystal structure of plectin ABD and integrin beta 4 complex (PDB 3F7P)' scene='Insert optional scene name here' />

== Function and Interactions ==
Proteins coordinate various cytoskeletal networks are termed as cytolinkers, which are able to interlink different types of cytoskeletons. Plectin is one of the well-characterized cytolinker and expressed in diverse cell types and tissues, a number of different binding partners of plectin have been identified.

Intermediate filament(IF) binding sites of plectin is located between plakin repeats 5 and 6 in C-terminal globular domain. Several IF proteins were identified to interact with plectin such as vimentin, desmin, GFAP(glial fibrillary acidic protein) and cytokeratins <ref>PMID: 8830774 </ref> .

The actin binding domain(ABD)in N-terminal globular domain has a role to interact with integrin subunit beta 4 to establish mechanical stability in hemedesmosomes along with its function for binding to actin filament(F-actin). Calmodulin(CaM) is also known to bind the ABD of plectin to modulate the hemidesmosome disassembly <ref> PMID: 19419971 </ref>.

== Pathology ==
It has been reported that patients with EBS-MD (Epidermolysis bullosa simplex with muscular dystrophy),a genetic disorder characterized severe skin blistering disease combined with muscular dystrophy, have a muation on plectin gene(PLEC1). This mutation leads to premature termination of translation.<ref>PMID: 8941634 </ref>
In addition, site-specific missense mutation(R2110W) on plectin rod domain causes an autosomal dominant form of disease termed EBS-Ogna without muscular dystrophy.<ref>PMID: 9067706 </ref>
Plectin deficient(-/-) mice also exhibit similar skin and muscle phenotypes of human patients suffering from EBS-MD and died 2-3 days after birth. <ref>PMID: 9389647</ref>

== References ==

<references/>

Group:MUZIC:Myostatin

2013-02-04T12:14:27Z

Jae-Geun Song: /* Pathology */

<Structure load='3hh2' size='400' frame='true' align='right' caption='The structure of myostatin:follistatin 288 (PDB 3HH2)' scene='Insert optional scene name here' />

== Introduction ==

Myostatin which is also known as growth and developmental factor-8(GDF-8) was originally identified in a screen for novel mammalian members of the transforming growth factor-ß (TGF-ß) superfamily of growth and differentiation factors.The phenotype of myostatin knock-out mice suggested that myostatin functions as a negative regulator of muscle growth, and it was on this basis that myostatin was given its name <ref>PMID:9139826</ref>. For these reasons, inhibitors targeting myostatin have been regarded as potential drugs in the treatment of muscle-wasting disorders such as muscular dystrophy <ref>PMID: 18425412 </ref>.

== Structure ==
Only one structure of myostatin is currently available in Protein Data Bank.
The complex of two follistatin 288 molecules bound to one myostatin dimer was resolved to 2.15 Å using X-ray crystallography and deposited in PDB.
(Green:myostatin C-terminal dimer, yellow: follinstatin 288)

[[Image:Myo2.png]]

== Function and Interactions ==
Myostatin is initially formed as a precursor protein which undergoes two proteolytic processing events in order to generate the biologically active molecule. First the N-terminal signal sequence is removed, a second cleavage generates the C-terminal fragment, which possesses receptor-binding activity and modulates a signal transduction cascade in the target cell <ref>PMID:9139826</ref>.
The N-terminal fragment after proteolytic processing has been referred to as the propeptide (shown blue). One mechanism for activating myostatin latency appears to be proteolytic cleavage of the propeptide <ref>PMID: 14671324 </ref>. In addition to the regulation of intracellular myostation processing,follistatin has been known to be capable of binding and inhibiting the activity of the myostatin C-terminal dimer (shown yellow). <ref>PMID: 2106159 </ref>.

The interaction of myostatin with titin-cap(T-cap),a Z-disk protein which binds to N-terminal domain of titin,was identified by a yeast two-hybrid system. <ref>PMID: 12209887 </ref> It is presumed that myostatin has a putative role in the muscle Z-disk regulation.

[[Image:Myo1.gif]]
(Processing of myostatin protein. Lee,2004)

== Pathology ==
Mice lacking C-terminal domain of myostatin shows dramatic increases in skeletal muscle mass, which are observed for the entire life of mice. In addition, myostatin mutant mice fail to accumulate fat as a function of age and suppress the development of insulin resistance <ref>PMID: 11877467</ref>. Thus, the targeting myostatin pathway might be an effective way to promote muscle growth for the patients with muscle degenerative diseases, such as muscular dystrophy and to prevent obesity <ref>PMID: 15473835 </ref>.

== References ==
<references/>

Group:MUZIC:Myostatin

2013-02-04T12:13:46Z

Jae-Geun Song:

<Structure load='3hh2' size='400' frame='true' align='right' caption='The structure of myostatin:follistatin 288 (PDB 3HH2)' scene='Insert optional scene name here' />

== Introduction ==

Myostatin which is also known as growth and developmental factor-8(GDF-8) was originally identified in a screen for novel mammalian members of the transforming growth factor-ß (TGF-ß) superfamily of growth and differentiation factors.The phenotype of myostatin knock-out mice suggested that myostatin functions as a negative regulator of muscle growth, and it was on this basis that myostatin was given its name <ref>PMID:9139826</ref>. For these reasons, inhibitors targeting myostatin have been regarded as potential drugs in the treatment of muscle-wasting disorders such as muscular dystrophy <ref>PMID: 18425412 </ref>.

== Structure ==
Only one structure of myostatin is currently available in Protein Data Bank.
The complex of two follistatin 288 molecules bound to one myostatin dimer was resolved to 2.15 Å using X-ray crystallography and deposited in PDB.
(Green:myostatin C-terminal dimer, yellow: follinstatin 288)

[[Image:Myo2.png]]

== Function and Interactions ==
Myostatin is initially formed as a precursor protein which undergoes two proteolytic processing events in order to generate the biologically active molecule. First the N-terminal signal sequence is removed, a second cleavage generates the C-terminal fragment, which possesses receptor-binding activity and modulates a signal transduction cascade in the target cell <ref>PMID:9139826</ref>.
The N-terminal fragment after proteolytic processing has been referred to as the propeptide (shown blue). One mechanism for activating myostatin latency appears to be proteolytic cleavage of the propeptide <ref>PMID: 14671324 </ref>. In addition to the regulation of intracellular myostation processing,follistatin has been known to be capable of binding and inhibiting the activity of the myostatin C-terminal dimer (shown yellow). <ref>PMID: 2106159 </ref>.

The interaction of myostatin with titin-cap(T-cap),a Z-disk protein which binds to N-terminal domain of titin,was identified by a yeast two-hybrid system. <ref>PMID: 12209887 </ref> It is presumed that myostatin has a putative role in the muscle Z-disk regulation.

[[Image:Myo1.gif]]
(Processing of myostatin protein. Lee,2004)

== Pathology ==
Mice lacking C-terminal domain of myostatin shows dramatic increases in skeletal muscle mass, which are observed for the entire life of mice. In addition, myostatin mutant mice fail to accumulate fat as a function of age and suppress the development of insulin resistance <ref>PMID: 11877467</ref>. Thus, the targeting myostatin pathway might be a effective way to promote muscle growth for the patients with muscle degenerative diseases, such as muscular dystrophy and to prevent obesity <ref>PMID: 15473835 </ref>.

== References ==
<references/>

Group:MUZIC:Myostatin

2013-02-04T12:12:51Z

Jae-Geun Song: /* Function and Interactions */

<Structure load='3hh2' size='400' frame='true' align='right' caption='The structure of myostatin:follistatin 288' scene='Insert optional scene name here' />

== Introduction ==

Myostatin which is also known as growth and developmental factor-8(GDF-8) was originally identified in a screen for novel mammalian members of the transforming growth factor-ß (TGF-ß) superfamily of growth and differentiation factors.The phenotype of myostatin knock-out mice suggested that myostatin functions as a negative regulator of muscle growth, and it was on this basis that myostatin was given its name <ref>PMID:9139826</ref>. For these reasons, inhibitors targeting myostatin have been regarded as potential drugs in the treatment of muscle-wasting disorders such as muscular dystrophy <ref>PMID: 18425412 </ref>.

== Structure ==
Only one structure of myostatin is currently available in Protein Data Bank.
The complex of two follistatin 288 molecules bound to one myostatin dimer was resolved to 2.15 Å using X-ray crystallography and deposited in PDB.
(Green:myostatin C-terminal dimer, yellow: follinstatin 288)

[[Image:Myo2.png]]

== Function and Interactions ==
Myostatin is initially formed as a precursor protein which undergoes two proteolytic processing events in order to generate the biologically active molecule. First the N-terminal signal sequence is removed, a second cleavage generates the C-terminal fragment, which possesses receptor-binding activity and modulates a signal transduction cascade in the target cell <ref>PMID:9139826</ref>.
The N-terminal fragment after proteolytic processing has been referred to as the propeptide (shown blue). One mechanism for activating myostatin latency appears to be proteolytic cleavage of the propeptide <ref>PMID: 14671324 </ref>. In addition to the regulation of intracellular myostation processing,follistatin has been known to be capable of binding and inhibiting the activity of the myostatin C-terminal dimer (shown yellow). <ref>PMID: 2106159 </ref>.

The interaction of myostatin with titin-cap(T-cap),a Z-disk protein which binds to N-terminal domain of titin,was identified by a yeast two-hybrid system. <ref>PMID: 12209887 </ref> It is presumed that myostatin has a putative role in the muscle Z-disk regulation.

[[Image:Myo1.gif]]
(Processing of myostatin protein. Lee,2004)

== Pathology ==
Mice lacking C-terminal domain of myostatin shows dramatic increases in skeletal muscle mass, which are observed for the entire life of mice. In addition, myostatin mutant mice fail to accumulate fat as a function of age and suppress the development of insulin resistance <ref>PMID: 11877467</ref>. Thus, the targeting myostatin pathway might be a effective way to promote muscle growth for the patients with muscle degenerative diseases, such as muscular dystrophy and to prevent obesity <ref>PMID: 15473835 </ref>.

== References ==
<references/>

Group:MUZIC:Myostatin

2013-02-04T12:11:27Z

Jae-Geun Song: /* Function and Interactions */

<Structure load='3hh2' size='400' frame='true' align='right' caption='The structure of myostatin:follistatin 288' scene='Insert optional scene name here' />

== Introduction ==

Myostatin which is also known as growth and developmental factor-8(GDF-8) was originally identified in a screen for novel mammalian members of the transforming growth factor-ß (TGF-ß) superfamily of growth and differentiation factors.The phenotype of myostatin knock-out mice suggested that myostatin functions as a negative regulator of muscle growth, and it was on this basis that myostatin was given its name <ref>PMID:9139826</ref>. For these reasons, inhibitors targeting myostatin have been regarded as potential drugs in the treatment of muscle-wasting disorders such as muscular dystrophy <ref>PMID: 18425412 </ref>.

== Structure ==
Only one structure of myostatin is currently available in Protein Data Bank.
The complex of two follistatin 288 molecules bound to one myostatin dimer was resolved to 2.15 Å using X-ray crystallography and deposited in PDB.
(Green:myostatin C-terminal dimer, yellow: follinstatin 288)

[[Image:Myo2.png]]

== Function and Interactions ==
Myostatin is initially formed as a precursor protein which undergoes two proteolytic processing events in order to generate the biologically active molecule. First the N-terminal signal sequence is removed, a second cleavage generates the C-terminal fragment, which possesses receptor-binding activity and modulates a signal transduction cascade in the target cell <ref>PMID:9139826</ref>.
The N-terminal fragment after proteolytic processing has been referred to as the propeptide(shown blue). One mechanism for activating myostatin latency appears to be proteolytic cleavage of the propeptide <ref>PMID: 14671324 </ref>. In addition to the regulation of intracellular myostation processing,follistatin has been known to be capable of binding and inhibiting the activity of the myostatin C-terminal dimer(shown yellow). <ref>PMID: 2106159 </ref>.

The interaction of myostatin with titin-cap(T-cap),a Z-disk protein which binds to N-terminal domain of titin,was identified by a yeast two-hybrid system. <ref>PMID: 12209887 </ref> It is presumed that myostatin has a putative role in the muscle Z-disk regulation.

[[Image:Myo1.gif]]
(Processing of myostatin protein. Lee,2004)

== Pathology ==
Mice lacking C-terminal domain of myostatin shows dramatic increases in skeletal muscle mass, which are observed for the entire life of mice. In addition, myostatin mutant mice fail to accumulate fat as a function of age and suppress the development of insulin resistance <ref>PMID: 11877467</ref>. Thus, the targeting myostatin pathway might be a effective way to promote muscle growth for the patients with muscle degenerative diseases, such as muscular dystrophy and to prevent obesity <ref>PMID: 15473835 </ref>.

== References ==
<references/>

Group:MUZIC:Myostatin

2013-02-04T12:08:09Z

Jae-Geun Song: /* Pathology */

<Structure load='3hh2' size='400' frame='true' align='right' caption='The structure of myostatin:follistatin 288' scene='Insert optional scene name here' />

== Introduction ==

Myostatin which is also known as growth and developmental factor-8(GDF-8) was originally identified in a screen for novel mammalian members of the transforming growth factor-ß (TGF-ß) superfamily of growth and differentiation factors.The phenotype of myostatin knock-out mice suggested that myostatin functions as a negative regulator of muscle growth, and it was on this basis that myostatin was given its name <ref>PMID:9139826</ref>. For these reasons, inhibitors targeting myostatin have been regarded as potential drugs in the treatment of muscle-wasting disorders such as muscular dystrophy <ref>PMID: 18425412 </ref>.

== Structure ==
Only one structure of myostatin is currently available in Protein Data Bank.
The complex of two follistatin 288 molecules bound to one myostatin dimer was resolved to 2.15 Å using X-ray crystallography and deposited in PDB.
(Green:myostatin C-terminal dimer, yellow: follinstatin 288)

[[Image:Myo2.png]]

== Function and Interactions ==
Myostatin is initially formed as a precursor protein which undergoes two proteolytic processing events in order to generate the biologically active molecule. First the N-terminal signal sequence is removed, a second cleavage generates the C-terminal fragment, which possesses receptor-binding activity and modulates a signal transduction cascade in the target cell <ref>PMID:9139826</ref>.
The N-terminal fragment after proteolytic processing has been referred to as the propeptide. One mechanism for activating myostatin latency appears to be proteolytic cleavage of the propeptide <ref>PMID: 14671324 </ref>. In addition to the regulation of intracellular myostation processing,follistatin has been known to be capable of binding and inhibiting the activity of the myostatin C-terminal dimer. <ref>PMID: 2106159 </ref>.

The interaction of myostatin with titin-cap(T-cap),a Z-disk protein which binds to N-terminal domain of titin,was identified by a yeast two-hybrid system. <ref>PMID: 12209887 </ref> It is presumed that myostatin has a putative role in the muscle Z-disk regulation.

[[Image:Myo1.gif]]
(Lee,2004)

== Pathology ==
Mice lacking C-terminal domain of myostatin shows dramatic increases in skeletal muscle mass, which are observed for the entire life of mice. In addition, myostatin mutant mice fail to accumulate fat as a function of age and suppress the development of insulin resistance <ref>PMID: 11877467</ref>. Thus, the targeting myostatin pathway might be a effective way to promote muscle growth for the patients with muscle degenerative diseases, such as muscular dystrophy and to prevent obesity <ref>PMID: 15473835 </ref>.

== References ==
<references/>