Group:MUZIC:FilaminC: Difference between revisions

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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 (also known as FLNc/Gamma-Filamin/ ABPL) 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.~~ It is noteworthy to mention that the Hinge 1 is alternatively spliced and the majorly expressed variant of FLNc in striated muscles, lacks this hinge <ref> PMID 9791010 </ref>.

Filamin C (also known as FLNc/Gamma-Filamin/ ABPL) 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. Each Ig domain is made of 7 β strands arranged antiparallel in group of 4 and 3 sheets forming a β sandwich. 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. It is noteworthy to mention that the Hinge 1 is alternatively spliced and the majorly expressed variant of FLNc in striated muscles, lacks this hinge <ref> PMID 9791010 </ref>. Also, in FLNc, there is a unique insertion of 80 amino acid residues in domain 20, which is predicted to play a role in Z disc targeting. <ref> PMID 16631741 </ref>

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.

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 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 (also known as FLNc/Gamma-Filamin/ ABPL) 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. It is noteworthy to mention that the Hinge 1 is alternatively spliced and the majorly expressed variant of FLNc in striated muscles, lacks this hinge  <ref> PMID 9791010 </ref>.
+Filamin C (also known as FLNc/Gamma-Filamin/ ABPL) 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. Each Ig domain is made of 7 β strands arranged antiparallel in group of 4 and 3 sheets forming a β sandwich. 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.  It is noteworthy to mention that the Hinge 1 is alternatively spliced and the majorly expressed variant of FLNc in striated muscles, lacks this hinge  <ref> PMID 9791010 </ref>. Also, in FLNc, there is a unique insertion of 80 amino acid residues in domain 20, which is predicted to play a role in Z disc targeting. <ref> PMID  16631741 </ref>
 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.