{{Gallery
|width=100
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|Image:1eve.png|[http://proteopedia.org/wiki/index.php/1eve '''1EVE''']
|Image:1fss.png|[http://proteopedia.org/wiki/index.php/1fss '''1FSS''']
|Image:2d7m asym r 500.jpg|[http://proteopedia.org/wiki/index.php/1hbj '''2d7m''']
|Image:1vzj.png|[http://proteopedia.org/wiki/index.php/1vzj '''1VZJ''']
|Image:2ace.png|[http://proteopedia.org/wiki/index.php/2ace '''2ACE''']
|Image:2j25.png|[http://proteopedia.org/wiki/index.php/2j25 '''2J25''']
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{{TOC limit|limit=3}}

== '''Filamin C''' ==

In humans, 3 isoforms of Filamins exist that are coded by 3 different genes. While the genes for [[Filamin A]] and [[Filamin B]] are present on the X chromosome and chromosome 3 respectively, and both show a ubiquitous expression in many tissues, gene for Filamin C is located on the Chromosome 7 and the encoded protein is specifically expressed in muscles and has been predicted to have a Z disc targeting motif. <ref name="Van der"> PMID 11038172 </ref>

Filamin C is an actin binding homodimeric protein composed of two 290 kDa subunits. Each subunit is composed of an α actinin like N terminal actin binding domain (ABD) made up of 2 calponin homology tandem repeats followed by a flexible rod region containing 24 Immunoglobulin like domains (Ig- like) of around 96 residues each. The most C terminal domain (Ig 24) is the self association domain required for its dimerization ability. (Shown on right) The presence of 2 flexible calpain sensitive hinges, Hinge 1 between domain 15 and 16 divides the subunit into Rod 1 and Rod 2 domains and Hinge 2 between 23 and 24 separates the dimerization domain from the rest of domains. Each Ig domain is made of 7 β strands arranged antiparallel in group of 4 and 3 sheets forming a β sandwich.
As the three Filamin proteins share around 70% homology over the entire sequence with the exception of the hinges <ref name="Flier"> PMID 11336782 </ref>, not many structures of the Filamin C domains exist in the PDB.

== '''Sequence''' ==

[[Image:Figure 1.png|thumb|Left|400px| '''Figure 1''' Sequence annotation based on the tertiary structure of Human Filamin]]

[http://www.uniprot.org/uniprot/q14315 Amino acid sequence of Human Filamin C] is available from uniprot. The sequence annotation based on the tertiary structure is provided in Figure 1. Note that in Filamin C, Hinge 1 is absent.

== '''3D Structures''' ==
So far, only 7 3 dimensional structures of Filamin C domains exist in the protein database, out which only 2 are solved by X ray crystallography and the rest are solved by NMR.

[[2d7m]] - This is a solution structure of the 14th Filamin domain from human Filamin C solved by Solution NMR

[[2d7n]] - This is a solution structure of the 16th Filamin domain from human Filamin C solved by Solution NMR

[[2d7o]] - This is a solution structure of the 17th Filamin domain from human Filamin C solved by Solution NMR

[[2d7p]] - This is a solution structure of the 22th Filamin domain from human Filamin C solved by Solution NMR

[[2nqc]] - This is a structure of Ig-like domain 23 from human filamin C solved by X ray Crystallography

[[2d7q]] - This is a solution structure of the 23th Filamin domain from human Filamin C solved by Solution NMR

[[1v05]] - This is a structure of the Domain 24 (Dimerization domain) of human Filamin C solved by X ray Crystallography

== '''Functions and interaction partners of Filamin C''' ==
[[Image:700px-Myopodin_interaction_with_Filamin_C.jpg|thumb|Left|700px| '''Figure 2''' Interaction of Filamin C with Myopodin]]

Since its discovery in 1975 as one of the most potent crosslinkers of F- actin <ref> PMID 124734 </ref> , major efforts have been focused to elucidate the role of Filamins as scaffolding and signaling molecule in cells.
Its major functions include:

• Cross linking actin filaments to form Orthogonal branched networks

• Physically linking actin cytoskeleton to the membrane

• Localization of the membrane receptors and stabilization of the membrane

• Serving as scaffold for various interacting proteins which indicates its role in signalling

Some of the major interacting partners are shown in the diagram here.

• Integrin β1A - Domain 19-24 <ref> PMID 16076904 </ref>

• Migfilin - Domain 21 <ref> PMID 18829455 </ref>

• [[Group:MUZIC:Myotilin|Myotilin]] - Domain 19-21 <ref name="Van der" />

• FATZ-1 (myozenin-1, calsarcin 2) - Domain 20-24<ref> PMID 16076904 </ref>

• [[Group:MUZIC:Xin |Xin ]] - Domain 20 <ref> PMID 16631741 </ref>

• Gamma- and delta-sarcoglycans - Domain 23-24 <ref> PMID 10629222 </ref>

• [[Group:MUZIC:Myopodin|Myopodin]] - Domain 19-21 <ref> PMID 20554076 </ref> (Interaction shown in Figure 2)

== '''Pathology''' ==

Mutations in Filamin C gene form a rare cause Myofibrillar Myopathy (MFM) presenting a wide spectrum of clinical symptoms, mostly involving progressive muscle weakness in all limbs.

• First mutation identified in FLNc was in Ig domain 24 (Dimerization domain), caused by a non sense mutation of (8130G-->A; W2710X) <ref> PMID 15929027 </ref>

• Recently an in frame 6 amino acid deletion (Lys899-Val904) and 2 amino acid insertion (Val 899-Cys900) was identified in Ig domain 7 <ref> PMID 20417099 </ref>

• And another in frame 4 amino acid (Val930_Thr933) deletion mutation in Ig domain 7 has been found. <ref> PMID 19050726 </ref>

== '''References''' ==
<references />

<ref group="xtra">PMID:21524097</ref><ref group="xtra">PMID:16416311</ref><ref group="xtra">PMID:19830582</ref><ref group="xtra">PMID:18056414</ref><ref group="xtra">PMID:21169733</ref><ref group="xtra">PMID:19622754</ref><ref group="xtra">PMID:19050726 </ref><ref group="xtra">PMID:11252955</ref><ref group="xtra">PMID:9501083 </ref><references group="xtra"/>

File:2d7m asym r 500.jpg

2012-10-29T11:04:26Z

Ritika Sethi:

File:2d7n asym r 500.jpg

2012-10-29T11:04:16Z

Ritika Sethi:

2011-12-16T08:22:10Z

Ritika Sethi:

{{STRUCTURE_1v05| right| PDB=1v05 | SCENE=User:Ritika_Sethi/workbench/FilaminC/Domain_24_dimer/1 |CAPTION= Human Filamin C domain 24 dimer, [[1v05]] }}

<scene name='User:Ritika_Sethi/workbench/FilaminC/Domain_24_dimer/1'>TextToBeDisplayed</scene>

{{TOC limit|limit=3}}

== '''Filamin C''' ==

In humans, 3 isoforms of Filamins exist that are coded by 3 different genes. While the genes for [[Filamin A]] and [[Filamin B]] are present on the X chromosome and chromosome 3 respectively, and both show a ubiquitous expression in many tissues, gene for Filamin C is located on the Chromosome 7 and the encoded protein is specifically expressed in muscles and has been predicted to have a Z disc targeting motif. <ref name="Van der"> PMID 11038172 </ref>

Filamin C is an actin binding homodimeric protein composed of two 290 kDa subunits. Each subunit is composed of an α actinin like N terminal actin binding domain (ABD) made up of 2 calponin homology tandem repeats followed by a flexible rod region containing 24 Immunoglobulin like domains (Ig- like) of around 96 residues each. The most C terminal domain (Ig 24) is the self association domain required for its dimerization ability. (Shown on right) The presence of 2 flexible calpain sensitive hinges, Hinge 1 between domain 15 and 16 divides the subunit into Rod 1 and Rod 2 domains and Hinge 2 between 23 and 24 separates the dimerization domain from the rest of domains. Each Ig domain is made of 7 β strands arranged antiparallel in group of 4 and 3 sheets forming a β sandwich.
As the three Filamin proteins share around 70% homology over the entire sequence with the exception of the hinges <ref name="Flier"> PMID 11336782 </ref>, not many structures of the Filamin C domains exist in the PDB.

== '''Sequence''' ==

[[Image:FLN_Sequence_Annotation.JPG|thumb|Left|600px| '''Figure 1''' Sequence annotation based on the tertiary structure of Human Filamin]]

[http://www.uniprot.org/uniprot/q14315 Amino acid sequence of Human Filamin C] is available from uniprot. However, the sequence annotation based on the tertiary structure alignment with Dictyostelium gelation factor (ABP-120) <ref name="Flier" /> is provided in Figure 1. Note that in Filamin C, Hinge 1 is absent (Figure 2).

== '''3D Structures''' ==
So far, only 7 3 dimensional structures of Filamin C domains exist in the protein database, out which only 2 are solved by X ray crystallography and the rest are solved by NMR.

[[2d7m]] - This is a solution structure of the 14th Filamin domain from human Filamin C solved by Solution NMR

[[2d7n]] - This is a solution structure of the 16th Filamin domain from human Filamin C solved by Solution NMR

[[2d7o]] - This is a solution structure of the 17th Filamin domain from human Filamin C solved by Solution NMR

[[2d7p]] - This is a solution structure of the 22th Filamin domain from human Filamin C solved by Solution NMR

[[2nqc]] - This is a structure of Ig-like domain 23 from human filamin C solved by X ray Crystallography

[[2d7q]] - This is a solution structure of the 23th Filamin domain from human Filamin C solved by Solution NMR

[[1v05]] - This is a structure of the Domain 24 (Dimerization domain) of human Filamin C solved by X ray Crystallography

== '''Functions and interaction partners of Filamin C''' ==
[[Image:700px-Myopodin_interaction_with_Filamin_C.jpg|thumb|Left|700px| '''Figure 2''' Interaction of Filamin C with Myopodin]]

Since its discovery in 1975 as one of the most potent crosslinkers of F- actin <ref> PMID 124734 </ref> , major efforts have been focused to elucidate the role of Filamins as scaffolding and signaling molecule in cells.
Its major functions include:

• Cross linking actin filaments to form Orthogonal branched networks

• Physically linking actin cytoskeleton to the membrane

• Localization of the membrane receptors and stabilization of the membrane

• Serving as scaffold for various interacting proteins which indicates its role in signalling

Some of the major interacting partners are shown in the diagram here.

• Integrin β1A - Domain 19-24 <ref> PMID 16076904 </ref>

• Migfilin - Domain 21 <ref> PMID 18829455 </ref>

• [[Group:MUZIC:Myotilin|Myotilin]] - Domain 19-21 <ref name="Van der" />

• FATZ-1 (myozenin-1, calsarcin 2) - Domain 20-24<ref> PMID 16076904 </ref>

• [[Group:MUZIC:Xin |Xin ]] - Domain 20 <ref> PMID 16631741 </ref>

• Gamma- and delta-sarcoglycans - Domain 23-24 <ref> PMID 10629222 </ref>

• [[Group:MUZIC:Myopodin|Myopodin]] - Domain 19-21 <ref> PMID 20554076 </ref> (Interaction shown in Figure 2)

== '''Pathology''' ==

Mutations in Filamin C gene form a rare cause Myofibrillar Myopathy (MFM) presenting a wide spectrum of clinical symptoms, mostly involving progressive muscle weakness in all limbs.

• First mutation identified in FLNc was in Ig domain 24 (Dimerization domain), caused by a non sense mutation of (8130G-->A; W2710X) <ref> PMID 15929027 </ref>

• Recently an in frame 6 amino acid deletion (Lys899-Val904) and 2 amino acid insertion (Val 899-Cys900) was identified in Ig domain 7 <ref> PMID 20417099 </ref>

• And another in frame 4 amino acid (Val930_Thr933) deletion mutation in Ig domain 7 has been found. <ref> PMID 19050726 </ref>

== '''References''' ==
<references />

== '''Extra Reading''' ==

<ref group="xtra">PMID:21524097</ref><ref group="xtra">PMID:16416311</ref><ref group="xtra">PMID:19830582</ref><ref group="xtra">PMID:18056414</ref><ref group="xtra">PMID:21169733</ref><ref group="xtra">PMID:19622754</ref><ref group="xtra">PMID:19050726 </ref><ref group="xtra">PMID:11252955</ref><ref group="xtra">PMID:9501083 </ref><references group="xtra"/>

2011-12-01T08:32:10Z

Ritika Sethi: /* '''Sequence''' */

{{STRUCTURE_1v05| right| PDB=1v05 | SCENE=User:Ritika_Sethi/workbench/FilaminC/Flnc_ig_24/1 |CAPTION= Human Filamin C domain 24, [[1v05]] }}

{{TOC limit|limit=3}}

== '''Filamin C''' ==

In humans, 3 isoforms of Filamins exist that are coded by 3 different genes. While the genes for [[Filamin A]] and [[Filamin B]] are present on the X chromosome and chromosome 3 respectively, and both show a ubiquitous expression in many tissues, gene for Filamin C is located on the Chromosome 7 and the encoded protein is specifically expressed in muscles and has been predicted to have a Z disc targeting motif. <ref name="Van der"> PMID 11038172 </ref>

Filamin C is an actin binding homodimeric protein composed of two 290 kDa subunits. Each subunit is composed of an α actinin like N terminal actin binding domain (ABD) made up of 2 calponin homology tandem repeats followed by a flexible rod region containing 24 Immunoglobulin like domains (Ig- like) of around 96 residues each. The most C terminal domain (Ig 24) is the self association domain required for its dimerization ability. (Shown on right) The presence of 2 flexible calpain sensitive hinges, Hinge 1 between domain 15 and 16 divides the subunit into Rod 1 and Rod 2 domains and Hinge 2 between 23 and 24 separates the dimerization domain from the rest of domains. Each Ig domain is made of 7 β strands arranged antiparallel in group of 4 and 3 sheets forming a β sandwich.
As the three Filamin proteins share around 70% homology over the entire sequence with the exception of the hinges <ref name="Flier"> PMID 11336782 </ref>, not many structures of the Filamin C domains exist in the PDB.

== '''Sequence''' ==

[[Image:FLN_Sequence_Annotation.JPG|thumb|Left|600px|Sequence annotation based on the tertiary structure of Human Filamin]]

[http://www.uniprot.org/uniprot/q14315 Amino acid sequence of Human Filamin C] is available from uniprot. However, the sequence annotation based on the tertiary structure alignment with Dictyostelium gelation factor (ABP-120) <ref name="Flier" /> is provided here. Note that in Filamin C, hinge 1 is absent.

== '''3D Structures''' ==
So far, only 7 3 dimensional structures of Filamin C domains exist in the protein database, out which only 2 are solved by X ray crystallography and the rest are solved by NMR.

[[2d7m]] - This is a solution structure of the 14th Filamin domain from human Filamin C solved by Solution NMR

[[2d7n]] - This is a solution structure of the 16th Filamin domain from human Filamin C solved by Solution NMR

[[2d7o]] - This is a solution structure of the 17th Filamin domain from human Filamin C solved by Solution NMR

[[2d7p]] - This is a solution structure of the 22th Filamin domain from human Filamin C solved by Solution NMR

[[2nqc]] - This is a structure of Ig-like domain 23 from human filamin C solved by X ray Crystallography

[[2d7q]] - This is a solution structure of the 23th Filamin domain from human Filamin C solved by Solution NMR

[[1v05]] - This is a structure of the Domain 24 (Dimerization domain) of human Filamin C solved by X ray Crystallography

== '''Functions and interaction partners of Filamin C''' ==
[[Image:700px-Myopodin_interaction_with_Filamin_C.jpg|thumb|Left|700px|Interaction of Filamin C with Myopodin]]

Since its discovery in 1975 as one of the most potent crosslinkers of F- actin <ref> PMID 124734 </ref> , major efforts have been focused to elucidate the role of Filamins as scaffolding and signaling molecule in cells.
Its major functions include:

• Cross linking actin filaments to form Orthogonal branched networks

• Physically linking actin cytoskeleton to the membrane

• Localization of the membrane receptors and stabilization of the membrane

• Serving as scaffold for various interacting proteins which indicates its role in signalling

Some of the major interacting partners are shown in the diagram here.

• Integrin β1A - Domain 19-24 <ref> PMID 16076904 </ref>

• Migfilin - Domain 21 <ref> PMID 18829455 </ref>

• [[Group:MUZIC:Myotilin|Myotilin]] - Domain 19-21 <ref name="Van der" />

• FATZ-1 (myozenin-1, calsarcin 2) - Domain 20-24<ref> PMID 16076904 </ref>

• [[Group:MUZIC:Xin |Xin ]] - Domain 20 <ref> PMID 16631741 </ref>

• Gamma- and delta-sarcoglycans - Domain 23-24 <ref> PMID 10629222 </ref>

• [[Group:MUZIC:Myopodin|Myopodin]] - Domain 19-21 <ref> PMID 20554076 </ref> (Interaction shown in the figure on the right)

== '''Pathology''' ==

Mutations in Filamin C gene form a rare cause Myofibrillar Myopathy (MFM) presenting a wide spectrum of clinical symptoms, mostly involving progressive muscle weakness in all limbs.

• First mutation identified in FLNc was in Ig domain 24 (Dimerization domain), caused by a non sense mutation of (8130G-->A; W2710X) <ref> PMID 15929027 </ref>

• Recently an in frame 6 amino acid deletion (Lys899-Val904) and 2 amino acid insertion (Val 899-Cys900) was identified in Ig domain 7 <ref> PMID 20417099 </ref>

• And another in frame 4 amino acid (Val930_Thr933) deletion mutation in Ig domain 7 has been found. <ref> PMID 19050726 </ref>

== '''References''' ==
<references />

== '''Extra Reading''' ==

<ref group="xtra">PMID:21524097</ref><ref group="xtra">PMID:16416311</ref><ref group="xtra">PMID:19830582</ref><ref group="xtra">PMID:18056414</ref><ref group="xtra">PMID:21169733</ref><ref group="xtra">PMID:19622754</ref><ref group="xtra">PMID:19050726 </ref><ref group="xtra">PMID:11252955</ref><ref group="xtra">PMID:9501083 </ref><references group="xtra"/>

2011-12-01T08:04:43Z

Ritika Sethi:

{{STRUCTURE_1v05| right| PDB=1v05 | SCENE=User:Ritika_Sethi/workbench/FilaminC/Flnc_ig_24/1 |CAPTION= Human Filamin C domain 24, [[1v05]] }}

{{TOC limit|limit=3}}

== '''Filamin C''' ==

In humans, 3 isoforms of Filamins exist that are coded by 3 different genes. While the genes for [[Filamin A]] and [[Filamin B]] are present on the X chromosome and chromosome 3 respectively, and both show a ubiquitous expression in many tissues, gene for Filamin C is located on the Chromosome 7 and the encoded protein is specifically expressed in muscles and has been predicted to have a Z disc targeting motif. <ref name="Van der"> PMID 11038172 </ref>

Filamin C is an actin binding homodimeric protein composed of two 290 kDa subunits. Each subunit is composed of an α actinin like N terminal actin binding domain (ABD) made up of 2 calponin homology tandem repeats followed by a flexible rod region containing 24 Immunoglobulin like domains (Ig- like) of around 96 residues each. The most C terminal domain (Ig 24) is the self association domain required for its dimerization ability. (Shown on right) The presence of 2 flexible calpain sensitive hinges, Hinge 1 between domain 15 and 16 divides the subunit into Rod 1 and Rod 2 domains and Hinge 2 between 23 and 24 separates the dimerization domain from the rest of domains. Each Ig domain is made of 7 β strands arranged antiparallel in group of 4 and 3 sheets forming a β sandwich.
As the three Filamin proteins share around 70% homology over the entire sequence with the exception of the hinges <ref name="Flier"> PMID 11336782 </ref>, not many structures of the Filamin C domains exist in the PDB.

== '''Sequence''' ==

[[Image:FLN_Sequence_Annotation.JPG|thumb|Left|600px|Sequence annotation based on the tertiary structure of Human Filamin]]

[http://www.uniprot.org/uniprot/q14315 Amino acid sequence of Human Filamin C] is available from uniprot. However, the sequence annotation based on the tertiary structure alignment with Dictyostelium gelation factor (ABP-120) <ref name="Flier" /> is provided here.

== '''3D Structures''' ==
So far, only 7 3 dimensional structures of Filamin C domains exist in the protein database, out which only 2 are solved by X ray crystallography and the rest are solved by NMR.

[[2d7m]] - This is a solution structure of the 14th Filamin domain from human Filamin C solved by Solution NMR

[[2d7n]] - This is a solution structure of the 16th Filamin domain from human Filamin C solved by Solution NMR

[[2d7o]] - This is a solution structure of the 17th Filamin domain from human Filamin C solved by Solution NMR

[[2d7p]] - This is a solution structure of the 22th Filamin domain from human Filamin C solved by Solution NMR

[[2nqc]] - This is a structure of Ig-like domain 23 from human filamin C solved by X ray Crystallography

[[2d7q]] - This is a solution structure of the 23th Filamin domain from human Filamin C solved by Solution NMR

[[1v05]] - This is a structure of the Domain 24 (Dimerization domain) of human Filamin C solved by X ray Crystallography

== '''Functions and interaction partners of Filamin C''' ==
[[Image:700px-Myopodin_interaction_with_Filamin_C.jpg|thumb|Left|700px|Interaction of Filamin C with Myopodin]]

Since its discovery in 1975 as one of the most potent crosslinkers of F- actin <ref> PMID 124734 </ref> , major efforts have been focused to elucidate the role of Filamins as scaffolding and signaling molecule in cells.
Its major functions include:

• Cross linking actin filaments to form Orthogonal branched networks

• Physically linking actin cytoskeleton to the membrane

• Localization of the membrane receptors and stabilization of the membrane

• Serving as scaffold for various interacting proteins which indicates its role in signalling

Some of the major interacting partners are shown in the diagram here.

• Integrin β1A - Domain 19-24 <ref> PMID 16076904 </ref>

• Migfilin - Domain 21 <ref> PMID 18829455 </ref>

• [[Group:MUZIC:Myotilin|Myotilin]] - Domain 19-21 <ref name="Van der" />

• FATZ-1 (myozenin-1, calsarcin 2) - Domain 20-24<ref> PMID 16076904 </ref>

• [[Group:MUZIC:Xin |Xin ]] - Domain 20 <ref> PMID 16631741 </ref>

• Gamma- and delta-sarcoglycans - Domain 23-24 <ref> PMID 10629222 </ref>

• [[Group:MUZIC:Myopodin|Myopodin]] - Domain 19-21 <ref> PMID 20554076 </ref> (Interaction shown in the figure on the right)

== '''Pathology''' ==

Mutations in Filamin C gene form a rare cause Myofibrillar Myopathy (MFM) presenting a wide spectrum of clinical symptoms, mostly involving progressive muscle weakness in all limbs.

• First mutation identified in FLNc was in Ig domain 24 (Dimerization domain), caused by a non sense mutation of (8130G-->A; W2710X) <ref> PMID 15929027 </ref>

• Recently an in frame 6 amino acid deletion (Lys899-Val904) and 2 amino acid insertion (Val 899-Cys900) was identified in Ig domain 7 <ref> PMID 20417099 </ref>

• And another in frame 4 amino acid (Val930_Thr933) deletion mutation in Ig domain 7 has been found. <ref> PMID 19050726 </ref>

== '''References''' ==
<references />

== '''Extra Reading''' ==

<ref group="xtra">PMID:21524097</ref><ref group="xtra">PMID:16416311</ref><ref group="xtra">PMID:19830582</ref><ref group="xtra">PMID:18056414</ref><ref group="xtra">PMID:21169733</ref><ref group="xtra">PMID:19622754</ref><ref group="xtra">PMID:19050726 </ref><ref group="xtra">PMID:11252955</ref><ref group="xtra">PMID:9501083 </ref><references group="xtra"/>