Group:MUZIC:CARP: Difference between revisions

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Found on chromosome 10 in humans and 19 in mouse, the Ankrd1 gene structure is highly conserved, with nine exons and a canonical TATA box in the proximal promoter. Other canonical response elements identified in the 5' flanking sequence of CARP include GATA sites, E-box elements, a CCAC box, a CAGA box, and M-CAT, activator protein-1, SP-1, p53 binding sites <ref name='six'>PMID 10477291</ref>,<ref name='seven'>PMID 20599664</ref>. CARP protein sequence and domain organization is highly conserved among mammalian species: a bipartite nuclear localization signal, a PEST-like sequence, four highly conserved ankyrin-like repeats and another less conserved half repeat, and numerous potential modification sites for phosphorylation, glycosylation, and myristilation. Binding sites for sarcomeric proteins titin <ref name='one'>PMID 14583192</ref>, calsequestrin-2 (CASQ2)<ref name='eight'>PMID 15698842</ref> and telethonin/T-cap <ref name='nine'>PMID 22016770</ref> are located in ankyrin repeat region of Ankrd1. It possesses two PEST motifs. Mutations or deletion of the PEST region increase Ankrd1 protein stability in vivo <ref name='ten'>PMID 22016770</ref>.

== Gene Function ==

== Gene Function and Interactions ==

Ankrd1 plays a structural role by interacting with the Z disc protein titin. It is a part of the titin-mechanosensory signaling complex in the sarcomere and in response to stretch it translocates to the nucleus where it participates in the regulation of cardiac genes as a transcriptional co-repressor.<ref name='three'>PMID 9043061</ref>

Ankrd1 localizes in the central I-band region, co-localizes with the titin-N2A region, more specifically with a tyrosine-rich motif lying between two Ig-like motifs (I80 and I81). Ankrd1 protein contains a binding site for titin within its ankyrin repeat region.<ref name='one'>PMID 14583192</ref> The cleavage of Ankrd1 by calpain 3 disrupts the bipartite NLS potentially affecting its nuclear transport.<ref name='twenty one'>PMID 20860623</ref> The cleavage site for calpain 3 is at the N terminus of Ankrd1 between amino acids 30 and 71 <ref name='twenty two'>PMID 18310072</ref>.

CARP/Ankrd1 binds the sarcomeric protein cardiac calsequestrin-2, CASQ2. <ref name='eight'>PMID 15698842</ref> These interactions are mediated, at least partially, by the binding sites localized within the ankyrin repeats and coiled-coil domain. Ankrd1 can also interact with the sarcomeric proteins myopalladin <ref name='twenty three'>PMID 11309420</ref>., desmin <ref name='twenty four'>PMID 16450059</ref>, and muscle-specific RING finger proteins MuRF1/MuRF2 <ref name='twenty five'>PMID 18157088</ref> indicating its structural role. CARP/Ankrd1 also binds calpain 3 <ref name='twenty one'>PMID 20860623</ref> and several transcription factors such as YB1 and p53.

Ankrd1 plays a structural role by interacting with the Z disc protein titin. It is a part of the titin-mechanosensory signaling complex in the sarcomere and in response to stretch it translocates to the nucleus where it participates in the regulation of cardiac genes as a transcriptional co-repressor.<ref name=~~'three'>PMID 9043061</ref>~~

==Pathology ==

Ankrd1 has been found to be induced in the hypertrophy, during cardiac ventricle overload <ref name='eleven'>PMID 9043061</ref>, in the skeletal muscle under certain conditions such as exercise <ref name='twelve'>PMID 19150862</ref>, denervation <ref

name='thirteen'>PMID 12004005</ref>, work overload hypertrophy <ref name='fourteen'>PMID 11744623</ref> and muscle pathologies <ref name='fifteen'>PMID 12679596</ref>, <ref name='sixteen'>PMID 12746480 </ref>,<ref name='seventeen'>PMID 14516314 </ref>. Ankrd1 could be involved in muscle disuse atrophy, since it was identified as an indirect target gene of two transcription factors (p50 and Bcl-3) associated with muscle wasting <ref name='eighteen'>PMID 21249144 </ref>. Ankrd1 expression is increased in patients with left ventricular dilated and ischemic cardiomyopathies <ref name='ninteen'>PMID 12054667 </ref>, and it has been identified as a candidate gene with a role in congenital heart disease <ref name='twenty'>PMID 18273862 </ref>.

~~==Localization==~~

Ankrd1 localizes in the central I-band region, co-localizes with the titin-N2A region, more specifically with a tyrosine-rich motif lying between two Ig-like motifs (I80 and I81). Ankrd1 protein contains a binding site for titin within its ankyrin repeat region.<ref name='one'>PMID 14583192</ref> The cleavage of Ankrd1 by calpain 3 disrupts the bipartite NLS potentially affecting its nuclear transport.<ref name='twenty one'>PMID 20860623</ref> The cleavage site for calpain 3 is at the N terminus of Ankrd1 between amino acids 30 and 71 <ref name='twenty two'>PMID 18310072</ref>.

~~==CARP Interactions==~~

CARP/Ankrd1 binds the sarcomeric protein cardiac calsequestrin-2, CASQ2. <ref name='eight'>PMID 15698842</ref> These interactions are mediated, at least partially, by the binding sites localized within the ankyrin repeats and coiled-coil domain. Ankrd1 can also interact with the sarcomeric proteins myopalladin <ref name='twenty three'>PMID 11309420</ref>., desmin <ref name='twenty four'>PMID 16450059</ref>, and muscle-specific RING finger proteins MuRF1/MuRF2 <ref name='twenty five'>PMID 18157088</ref> indicating its structural role. CARP/Ankrd1 also binds calpain 3 <ref name='twenty one'>PMID 20860623</ref> and several transcription factors such as YB1 and p53.

== Refrences ==

@@ Line 13: / Line 13: @@
 Found on chromosome 10 in humans and 19 in mouse, the Ankrd1 gene structure is highly conserved, with nine exons and a canonical TATA box in the proximal promoter. Other canonical response elements identified in the 5' flanking sequence of CARP include GATA sites, E-box elements, a CCAC box, a CAGA box, and M-CAT, activator protein-1, SP-1, p53 binding sites <ref name='six'>PMID 10477291</ref>,<ref name='seven'>PMID 20599664</ref>. CARP protein sequence and domain organization is highly conserved among mammalian species: a bipartite nuclear localization signal, a PEST-like sequence, four highly conserved ankyrin-like repeats and another less conserved half repeat, and numerous potential modification sites for phosphorylation, glycosylation, and myristilation. Binding sites for sarcomeric proteins titin <ref name='one'>PMID 14583192</ref>, calsequestrin-2 (CASQ2)<ref name='eight'>PMID 15698842</ref> and telethonin/T-cap <ref name='nine'>PMID 22016770</ref>  are located in ankyrin repeat region of Ankrd1. It possesses two PEST motifs. Mutations or deletion of the PEST region increase Ankrd1 protein stability in vivo <ref name='ten'>PMID 22016770</ref>.
-== Gene Function ==
+== Gene Function and Interactions ==
+Ankrd1 plays a structural role by interacting with the Z disc protein titin. It is a part of the titin-mechanosensory signaling complex in the sarcomere and in response to stretch it translocates to the nucleus where it participates in the regulation of cardiac genes as a transcriptional co-repressor.<ref name='three'>PMID 9043061</ref>
+Ankrd1 localizes in the central I-band region, co-localizes with the titin-N2A region, more specifically with a tyrosine-rich motif lying between two Ig-like motifs (I80 and I81). Ankrd1 protein contains a binding site for titin within its ankyrin repeat region.<ref name='one'>PMID 14583192</ref> The cleavage of Ankrd1 by calpain 3 disrupts the bipartite NLS potentially affecting its nuclear transport.<ref name='twenty one'>PMID 20860623</ref> The cleavage site for calpain 3 is at the N terminus of Ankrd1 between amino acids 30 and 71 <ref name='twenty two'>PMID 18310072</ref>.
+CARP/Ankrd1 binds the sarcomeric protein cardiac calsequestrin-2, CASQ2. <ref name='eight'>PMID 15698842</ref> These interactions are mediated, at least partially, by the binding sites localized within the ankyrin repeats and coiled-coil domain. Ankrd1 can also interact with the sarcomeric proteins myopalladin <ref name='twenty three'>PMID 11309420</ref>., desmin <ref name='twenty four'>PMID 16450059</ref>, and muscle-specific RING finger proteins MuRF1/MuRF2 <ref name='twenty five'>PMID 18157088</ref> indicating its structural role. CARP/Ankrd1 also binds calpain 3 <ref name='twenty one'>PMID 20860623</ref> and several transcription factors such as YB1 and p53.
-Ankrd1 plays a structural role by interacting with the Z disc protein titin. It is a part of the titin-mechanosensory signaling complex in the sarcomere and in response to stretch it translocates to the nucleus where it participates in the regulation of cardiac genes as a transcriptional co-repressor.<ref name='three'>PMID 9043061</ref>
+==Pathology ==
 Ankrd1 has been found to be induced in the hypertrophy, during cardiac ventricle overload <ref name='eleven'>PMID 9043061</ref>, in the skeletal muscle under certain conditions such as exercise <ref name='twelve'>PMID 19150862</ref>, denervation <ref
 name='thirteen'>PMID 12004005</ref>, work overload hypertrophy <ref name='fourteen'>PMID 11744623</ref> and muscle pathologies <ref name='fifteen'>PMID 12679596</ref>, <ref name='sixteen'>PMID 12746480 </ref>,<ref name='seventeen'>PMID 14516314 </ref>. Ankrd1 could be involved in muscle disuse atrophy, since it was identified as an indirect target gene of two transcription factors (p50 and Bcl-3) associated with muscle wasting <ref name='eighteen'>PMID 21249144 </ref>. Ankrd1 expression is increased in patients with left ventricular dilated and ischemic cardiomyopathies <ref name='ninteen'>PMID 12054667  </ref>, and it has been identified as a candidate gene with a role in congenital heart disease <ref name='twenty'>PMID 18273862 </ref>.
-==Localization==
-Ankrd1 localizes in the central I-band region, co-localizes with the titin-N2A region, more specifically with a tyrosine-rich motif lying between two Ig-like motifs (I80 and I81). Ankrd1 protein contains a binding site for titin within its ankyrin repeat region.<ref name='one'>PMID 14583192</ref> The cleavage of Ankrd1 by calpain 3 disrupts the bipartite NLS potentially affecting its nuclear transport.<ref name='twenty one'>PMID 20860623</ref> The cleavage site for calpain 3 is at the N terminus of Ankrd1 between amino acids 30 and 71 <ref name='twenty two'>PMID 18310072</ref>.
-==CARP Interactions==
-CARP/Ankrd1 binds the sarcomeric protein cardiac calsequestrin-2, CASQ2. <ref name='eight'>PMID 15698842</ref> These interactions are mediated, at least partially, by the binding sites localized within the ankyrin repeats and coiled-coil domain. Ankrd1 can also interact with the sarcomeric proteins myopalladin <ref name='twenty three'>PMID 11309420</ref>., desmin <ref name='twenty four'>PMID 16450059</ref>, and muscle-specific RING finger proteins MuRF1/MuRF2 <ref name='twenty five'>PMID 18157088</ref> indicating its structural role. CARP/Ankrd1 also binds calpain 3 <ref name='twenty one'>PMID 20860623</ref> and several transcription factors such as YB1 and p53.
 == Refrences ==
 <references/>