https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Narendra+Kumar+VermaProteopedia - User contributions [en]2026-09-17T01:29:22ZUser contributionsMediaWiki 1.43.8https://proteopedia.org/index.php?title=Group:MUZIC:CARP&diff=1609290Group:MUZIC:CARP2012-11-16T10:55:12Z<p>Narendra Kumar Verma: </p>
<hr />
<div>== '''CARP''' ==<br />
<br />
'''Introduction'''<br />
<br />
Cardiac ankyrin repeat protein (CARP/Ankrd1) together with ankyrin repeat domain 2 (Ankrd2/Arpp) and with diabetes associated ankyrin repeat protein (DARP), belongs to a conserved muscle ankyrin repeat protein (MARP) family. <ref name='one'>PMID 14583192</ref> CARP/Ankrd1 has been independently identified by several groups as a cytokine-inducible transcriptional regulator, a protein interacting with transcriptional factor YB-1, and a cardiac doxorubicin-responsive protein <ref name='two'>PMID 7730328</ref>,<ref name='three'>PMID 9043061</ref>. In normal tissues, Ankrd1 is highly expressed in cardiac muscle and detectable in skeletal muscles [3]. It is an early differentiation marker during cardiogenesis with a high expression level in developing heart. <ref<br />
name='three'>PMID 9043061</ref>, <ref name='four'>PMID 9278441</ref>. Mutations in the ANKRD1 gene are responsible for human dilated cardiomyopathy. <ref name='five'>PMID 14561590</ref><br />
<br />
== Sequence Annotation ==<br />
CARP is comprised of 319 amino acids, the sequence of [http://http://www.uniprot.org/uniprot/ Q15327 human], [http://www.uniprot.org/uniprot/ Q9CR42 mouse], [http://www.uniprot.org/uniprot/ Q9TU71 rabbit],CARP is available from Uniprot. <br />
{{STRUCTURE_1n0r| PDB=1n11}}<br />
<br />
== Structure ==<br />
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>.<br />
<br />
== Gene Function and Interactions ==<br />
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><br />
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>.<br />
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.<br />
<br />
==Pathology ==<br />
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<br />
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>.<br />
<br />
<br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:ANKRD2&diff=1609289Group:MUZIC:ANKRD22012-11-16T10:45:28Z<p>Narendra Kumar Verma: </p>
<hr />
<div>== '''ANKRD2''' ==<br />
<br />
'''Introduction'''<br />
<br />
Ankyrin repeat-containing protein 2 (stretch responsive muscle) '''Ankrd2''' belongs to the conserved muscle ankyrin repeat protein (MARP) family,<ref name='one'>PMID 10873377</ref> Also known as Arpp.<ref name='two'>PMID 11453652</ref> It is more expressed in skeletal than cardiac muscle, preferentially in type 1 fibers.<ref name='three'>PMID 12004005</ref> Ankrd2 shares approximately 50% homology with the two more MARP family members: Cardiac ankyrin repeat protein (CARP/Ankrd1) and Diabetes related ankyrin repeat protein DARP.Expression of Ankrd2/Arpp is induced in response to various forms of stress and is highly responsive to muscle mechanical status both in vivo and in vitro <ref name='one'>PMID 10873377</ref>,<ref name='four'>PMID 14583192</ref>, as well as to muscle plasticity induced by physical exercise <ref name='five'>PMID 14561590</ref>,<ref name='six'>PMID 15677738</ref>. Apart from the mechanosensory function, Ankrd2/Arpp is a negative regulator of muscle differentiation.<ref name='seven'>PMID 18302940</ref><br />
<br />
== Sequence Annotation == <br />
Ankrd2 is comprised of 360 amino acids, the sequence of <br />
[http://http://www.uniprot.org/uniprot/ Q9GZV1 human], [http://www.uniprot.org/uniprot/ Q9WV06 mouse], [http://www.uniprot.org/uniprot/ F1MX12 bovine], Ankrd2 is available from Uniprot. <br />
<Structure load='2QYJ' size='300' frame='true' align='right' caption='Structure of a designed ankyrin repeat protein (DARPin) with five ankyrin repeat motifs [[2qyj]]' scene='User:Spyros_D._Chatziefthimiou/workbench/ANKRD2/2qyj/1' /><br />
<br />
== Structure ==<br />
<br />
Ankrd2 gene contains 9 exons and spans about 12 kb. The 280 bp long region upstream of the transcription initiation site of the human Ankrd2 gene is sufficient to confer spatial and temporal expression specificity, and contains mainly cis-elements specific for the muscle-specific transcription factor MyoD and for NF-kB. <ref name='eight'>PMID 11444853</ref> Ankrd2 promoter activity is significantly up-regulated by Nkx2.5 <ref name='nine'>PMID 22016770</ref>, upon longitudinal stretch by Akt-dependent NF-kB signaling pathway and in response to transverse stretch by Raf-1-dependent AP-1 signaling pathway. <ref name='ten'>PMID 20442316</ref> The major structural characteristic of the Ankrd2 protein is the presence in the middle portion of four conserved copies of 33-residue ankyrin repeats. In addition Ankrd2 contains a coiled-coil domain that contributes to its self-dimerization, a nuclear localization signal (NLS), allowing its sorting to the nucleus, PEST protein degradation sequence and numerous potential modification sites, mainly for phosphorylation. In particular the phosphorylation of Ankrd2 by the serine/threonine kinase Akt 2 is important for its function in muscle differentiation. <ref name='eleven'>PMID 21737686</ref> The position of Ankrd2 phosphorylation by Akt 2 is Ser 72 which is in close proximity of calpain 3 cleavage site (Arg 77). There are many other consensus phosphorylation sites for casein kinase I (CKI), casein kinase II (CKII), protein kinase C (PKC), extracellular signal regulated kinase (ERK), cAMP- dependent protein kinase, calmodulin-dependent protein kinase II and cGMP-dependent protein kinase <ref name='two'>PMID 11453652</ref>,<ref name='four'>PMID 14583192</ref><br />
<br />
<br />
[[Image:Ankrd.png|center|800px|thumb|Domain architecture and modification sites of '''Ankrd2''']]<br />
<br />
<br />
== Gene Function and Interactions ==<br />
<br />
Ankrd2 is involved in muscle stress response. It is up-regulated after chronic immobilization in a stretched position.<ref name='one'>PMID 10873377</ref> <ref name='six'>PMID 15677738</ref>, after eccentric contraction <ref name='five'>PMID 14561590</ref> , as well as in injured muscles.<ref name='eleven'>PMID 17926058</ref> Denervation of slow muscle decreases the level of Ankrd2 to below the detection limit in 4 weeks <ref name='six'>PMID 15677738</ref>, whereas denervation of fast muscle increases its expression.<ref name='three'>PMID 12004005</ref><br />
Ankrd2 is found in the central I-band of the sarcomere, where binds the N2A region of titin. In myoblasts Ankrd2 localizes both in the nuclei, in form of speckles and in the cytoplasm <ref name='seven'>PMID 18302940</ref>, with a diffused pattern. As the differentiation into multinucleated myotubes progresses, Ankrd2 seems to change localization and to accumulate mainly in the cytoplasm <ref>pmid 11444853 </ref>. In general, Ankrd2 protein functions by moving between the sarcomere and the nucleus, mainly in response to stress signals <ref name='fourteen'>PMID 15136035 </ref>.<br />
Ankrd2 is not essential for the basal functioning of skeletal muscle, but it is clear its influence on the gene expression program of skeletal muscle cells.<ref name='thirteen'>PMID 17392382</ref> Mainly the Ankrd2 protein has a major role in skeletal muscle formation as a myogenic regulator, since its over-expression in C2C12 myoblasts significantly affects and down-regulates MyoD, myogenin, and their target gene Myh1.<ref name='seven'>PMID 18302940</ref> <br />
<br />
<br />
==Pathology ==<br />
Altered expression of Ankrd2 has been found in patients suffering from inherited myopathies (muscular dystrophies (MD), congenital myopathies (CM)) and motor neuron diseases (spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS)).The Ankrd2/Arpp can interact with titin <ref name='four'>PMID 14583192</ref>, telethonin/T-cap <ref name='fourteen'>PMID 15136035 </ref>, calpain 3 <ref name='fifteen'>PMID 18310072 </ref>, promyelocytic leukemia protein (PML)<ref name='fourteen'>PMID 15136035 </ref>, YB-1 <ref name='fourteen'>PMID 15136035 </ref>, p53 <ref name='fourteen'>PMID 15136035 </ref>, Akt 2 <ref name='eleven'>PMID 21737686</ref> and zonula occludens 1 (ZO1).<ref name='nine'>PMID 22016770</ref><br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:ANKRD2&diff=1609288Group:MUZIC:ANKRD22012-11-16T10:44:47Z<p>Narendra Kumar Verma: </p>
<hr />
<div>== '''ANKRD2''' ==<br />
<br />
'''Introduction'''<br />
<br />
Ankyrin repeat-containing protein 2 (stretch responsive muscle) '''Ankrd2''' belongs to the conserved muscle ankyrin repeat protein (MARP) family,<ref name='one'>PMID 10873377</ref> Also known as Arpp.<ref name='two'>PMID 11453652</ref> It is more expressed in skeletal than cardiac muscle, preferentially in type 1 fibers.<ref name='three'>PMID 12004005</ref> Ankrd2 shares approximately 50% homology with the two more MARP family members: Cardiac ankyrin repeat protein (CARP/Ankrd1) and Diabetes related ankyrin repeat protein DARP.Expression of Ankrd2/Arpp is induced in response to various forms of stress and is highly responsive to muscle mechanical status both in vivo and in vitro <ref name='one'>PMID 10873377</ref>,<ref name='four'>PMID 14583192</ref>, as well as to muscle plasticity induced by physical exercise <ref name='five'>PMID 14561590</ref>,<ref name='six'>PMID 15677738</ref>. Apart from the mechanosensory function, Ankrd2/Arpp is a negative regulator of muscle differentiation.<ref name='seven'>PMID 18302940</ref><br />
<br />
== Sequence Annotation == <br />
Ankrd2 is comprised of 360 amino acids, the sequence of <br />
[http://http://www.uniprot.org/uniprot/ Q9GZV1 human], [http://www.uniprot.org/uniprot/ Q9WV06 mouse], [http://www.uniprot.org/uniprot/ F1MX12 bovine], [http://www.uniprot.org/uniprot/A4GR69 porcine] Ankrd2 is available from Uniprot. <br />
<Structure load='2QYJ' size='300' frame='true' align='right' caption='Structure of a designed ankyrin repeat protein (DARPin) with five ankyrin repeat motifs [[2qyj]]' scene='User:Spyros_D._Chatziefthimiou/workbench/ANKRD2/2qyj/1' /><br />
<br />
== Structure ==<br />
<br />
Ankrd2 gene contains 9 exons and spans about 12 kb. The 280 bp long region upstream of the transcription initiation site of the human Ankrd2 gene is sufficient to confer spatial and temporal expression specificity, and contains mainly cis-elements specific for the muscle-specific transcription factor MyoD and for NF-kB. <ref name='eight'>PMID 11444853</ref> Ankrd2 promoter activity is significantly up-regulated by Nkx2.5 <ref name='nine'>PMID 22016770</ref>, upon longitudinal stretch by Akt-dependent NF-kB signaling pathway and in response to transverse stretch by Raf-1-dependent AP-1 signaling pathway. <ref name='ten'>PMID 20442316</ref> The major structural characteristic of the Ankrd2 protein is the presence in the middle portion of four conserved copies of 33-residue ankyrin repeats. In addition Ankrd2 contains a coiled-coil domain that contributes to its self-dimerization, a nuclear localization signal (NLS), allowing its sorting to the nucleus, PEST protein degradation sequence and numerous potential modification sites, mainly for phosphorylation. In particular the phosphorylation of Ankrd2 by the serine/threonine kinase Akt 2 is important for its function in muscle differentiation. <ref name='eleven'>PMID 21737686</ref> The position of Ankrd2 phosphorylation by Akt 2 is Ser 72 which is in close proximity of calpain 3 cleavage site (Arg 77). There are many other consensus phosphorylation sites for casein kinase I (CKI), casein kinase II (CKII), protein kinase C (PKC), extracellular signal regulated kinase (ERK), cAMP- dependent protein kinase, calmodulin-dependent protein kinase II and cGMP-dependent protein kinase <ref name='two'>PMID 11453652</ref>,<ref name='four'>PMID 14583192</ref><br />
<br />
<br />
[[Image:Ankrd.png|center|800px|thumb|Domain architecture and modification sites of '''Ankrd2''']]<br />
<br />
<br />
== Gene Function and Interactions ==<br />
<br />
Ankrd2 is involved in muscle stress response. It is up-regulated after chronic immobilization in a stretched position.<ref name='one'>PMID 10873377</ref> <ref name='six'>PMID 15677738</ref>, after eccentric contraction <ref name='five'>PMID 14561590</ref> , as well as in injured muscles.<ref name='eleven'>PMID 17926058</ref> Denervation of slow muscle decreases the level of Ankrd2 to below the detection limit in 4 weeks <ref name='six'>PMID 15677738</ref>, whereas denervation of fast muscle increases its expression.<ref name='three'>PMID 12004005</ref><br />
Ankrd2 is found in the central I-band of the sarcomere, where binds the N2A region of titin. In myoblasts Ankrd2 localizes both in the nuclei, in form of speckles and in the cytoplasm <ref name='seven'>PMID 18302940</ref>, with a diffused pattern. As the differentiation into multinucleated myotubes progresses, Ankrd2 seems to change localization and to accumulate mainly in the cytoplasm <ref>pmid 11444853 </ref>. In general, Ankrd2 protein functions by moving between the sarcomere and the nucleus, mainly in response to stress signals <ref name='fourteen'>PMID 15136035 </ref>.<br />
Ankrd2 is not essential for the basal functioning of skeletal muscle, but it is clear its influence on the gene expression program of skeletal muscle cells.<ref name='thirteen'>PMID 17392382</ref> Mainly the Ankrd2 protein has a major role in skeletal muscle formation as a myogenic regulator, since its over-expression in C2C12 myoblasts significantly affects and down-regulates MyoD, myogenin, and their target gene Myh1.<ref name='seven'>PMID 18302940</ref> <br />
<br />
<br />
==Pathology ==<br />
Altered expression of Ankrd2 has been found in patients suffering from inherited myopathies (muscular dystrophies (MD), congenital myopathies (CM)) and motor neuron diseases (spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS)).The Ankrd2/Arpp can interact with titin <ref name='four'>PMID 14583192</ref>, telethonin/T-cap <ref name='fourteen'>PMID 15136035 </ref>, calpain 3 <ref name='fifteen'>PMID 18310072 </ref>, promyelocytic leukemia protein (PML)<ref name='fourteen'>PMID 15136035 </ref>, YB-1 <ref name='fourteen'>PMID 15136035 </ref>, p53 <ref name='fourteen'>PMID 15136035 </ref>, Akt 2 <ref name='eleven'>PMID 21737686</ref> and zonula occludens 1 (ZO1).<ref name='nine'>PMID 22016770</ref><br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1609287Group:MUZIC:DARP2012-11-16T10:03:14Z<p>Narendra Kumar Verma: </p>
<hr />
<div>== '''DARP''' ==<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
== Sequence Annotation ==<br />
http://www.uniprot.org/uniprot/Q812A3<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref> The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively.Silico analysis of promoter of DARP gene indicated the existence of binding site for PPARγ consensus sequence recognised by PPARγ is positioned upstream of transcriptional start site in the DARP gene from -18495 to -18517 base pair.<ref name='three'>PMID 915920</ref><br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function and Interactions ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts,indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
<br />
== Pathology ==<br />
Its altered expression in transgenic mice with increased or decreased PI3K(p110α) activity has a significant impact on functionality of the Z-disc and,subsequently,cardiac function.PI3K(p110α) protects the heart against myocardial infarction. Together with other genes encoding muscle structural/associated proteins, such as dystroglycan (Dag1), filamin C(Flnc), Rho-associated coiled-coil containing protein kinase 2(Rock2), crystallin, α B (Cryab), Cd151, integrin β 1 binding protein 2(Itgb1bp2/melusin), Lim domain binding 3(Ldb3/cypher), and synaptopodin 2 (Synpo2/myopodin), DARP/Ankrd23 was found up-and down-regulated respectively in the caPI3K (consitutively active PI3K)and dnPI3K(dominant negative PI3K.<ref name='six'>PMID PMC3162444 </ref><br />
DARP,calpain-10 and calpain-3 play an important role in the regulation of glucose utilization in skeletal muscle. Calpain-3 activity may be regulated by DARP.<ref name='one'>PMID 14583192 </ref<br />
<br />
<br />
<br />
<br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1609286Group:MUZIC:DARP2012-11-16T10:02:31Z<p>Narendra Kumar Verma: </p>
<hr />
<div>== '''DARP''' ==<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
== Sequence Annotation ==<br />
http://www.uniprot.org/uniprot/Q812A3<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref> The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively.Silico analysis of promoter of DARP gene indicated the existence of binding site for PPARγ consensus sequence recognised by PPARγ is positioned upstream of transcriptional start site in the DARP gene from -18495 to -18517 base pair.<ref name='three'>PMID 915920</ref><br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function and Interactions ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts,indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
<br />
DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
<br />
== Pathology ==<br />
Its altered expression in transgenic mice with increased or decreased PI3K(p110α) activity has a significant impact on functionality of the Z-disc and,subsequently,cardiac function.PI3K(p110α) protects the heart against myocardial infarction. Together with other genes encoding muscle structural/associated proteins, such as dystroglycan (Dag1), filamin C(Flnc), Rho-associated coiled-coil containing protein kinase 2(Rock2), crystallin, α B (Cryab), Cd151, integrin β 1 binding protein 2(Itgb1bp2/melusin), Lim domain binding 3(Ldb3/cypher), and synaptopodin 2 (Synpo2/myopodin), DARP/Ankrd23 was found up-and down-regulated respectively in the caPI3K (consitutively active PI3K)and dnPI3K(dominant negative PI3K.<ref name='six'>PMID PMC3162444 </ref><br />
DARP,calpain-10 and calpain-3 play an important role in the regulation of glucose utilization in skeletal muscle. Calpain-3 activity may be regulated by DARP.<ref name='one'>PMID 14583192 </ref<br />
<br />
<br />
<br />
<br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:CARP&diff=1609285Group:MUZIC:CARP2012-11-16T10:00:11Z<p>Narendra Kumar Verma: </p>
<hr />
<div>== '''CARP''' ==<br />
<br />
'''Introduction'''<br />
<br />
Cardiac ankyrin repeat protein (CARP/Ankrd1) together with ankyrin repeat domain 2 (Ankrd2/Arpp) and with diabetes associated ankyrin repeat protein (DARP), belongs to a conserved muscle ankyrin repeat protein (MARP) family. <ref name='one'>PMID 14583192</ref> CARP/Ankrd1 has been independently identified by several groups as a cytokine-inducible transcriptional regulator, a protein interacting with transcriptional factor YB-1, and a cardiac doxorubicin-responsive protein <ref name='two'>PMID 7730328</ref>,<ref name='three'>PMID 9043061</ref>. In normal tissues, Ankrd1 is highly expressed in cardiac muscle and detectable in skeletal muscles [3]. It is an early differentiation marker during cardiogenesis with a high expression level in developing heart. <ref<br />
name='three'>PMID 9043061</ref>, <ref name='four'>PMID 9278441</ref>. Mutations in the ANKRD1 gene are responsible for human dilated cardiomyopathy. <ref name='five'>PMID 14561590</ref><br />
<br />
== Sequence Annotation ==<br />
http://www.uniprot.org/uniprot/Q9CR42<br />
{{STRUCTURE_1n0r| PDB=1n11}}<br />
<br />
== Structure ==<br />
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>.<br />
<br />
== Gene Function and Interactions ==<br />
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><br />
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>.<br />
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.<br />
<br />
==Pathology ==<br />
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<br />
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>.<br />
<br />
<br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1609284Group:MUZIC:DARP2012-11-16T09:56:26Z<p>Narendra Kumar Verma: /* Pathology */</p>
<hr />
<div>__FORCETOC__<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
== Sequence Annotation ==<br />
http://www.uniprot.org/uniprot/Q812A3<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref> The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively.Silico analysis of promoter of DARP gene indicated the existence of binding site for PPARγ consensus sequence recognised by PPARγ is positioned upstream of transcriptional start site in the DARP gene from -18495 to -18517 base pair.<ref name='three'>PMID 915920</ref><br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function and Interactions ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts,indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
<br />
DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
<br />
== Pathology ==<br />
Its altered expression in transgenic mice with increased or decreased PI3K(p110α) activity has a significant impact on functionality of the Z-disc and,subsequently,cardiac function.PI3K(p110α) protects the heart against myocardial infarction. Together with other genes encoding muscle structural/associated proteins, such as dystroglycan (Dag1), filamin C(Flnc), Rho-associated coiled-coil containing protein kinase 2(Rock2), crystallin, α B (Cryab), Cd151, integrin β 1 binding protein 2(Itgb1bp2/melusin), Lim domain binding 3(Ldb3/cypher), and synaptopodin 2 (Synpo2/myopodin), DARP/Ankrd23 was found up-and down-regulated respectively in the caPI3K (consitutively active PI3K)and dnPI3K(dominant negative PI3K.<ref name='six'>PMID PMC3162444 </ref><br />
DARP,calpain-10 and calpain-3 play an important role in the regulation of glucose utilization in skeletal muscle. Calpain-3 activity may be regulated by DARP.<ref name='one'>PMID 14583192 </ref<br />
<br />
<br />
<br />
<br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1609283Group:MUZIC:DARP2012-11-16T09:54:53Z<p>Narendra Kumar Verma: </p>
<hr />
<div>__FORCETOC__<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
== Sequence Annotation ==<br />
http://www.uniprot.org/uniprot/Q812A3<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref> The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively.Silico analysis of promoter of DARP gene indicated the existence of binding site for PPARγ consensus sequence recognised by PPARγ is positioned upstream of transcriptional start site in the DARP gene from -18495 to -18517 base pair.<ref name='three'>PMID 915920</ref><br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function and Interactions ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts,indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
<br />
DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
<br />
== Pathology ==<br />
Its altered expression in transgenic mice with increased or decreased PI3K(p110α) activity has a significant impact on functionality of the Z-disc and,subsequently,cardiac function.PI3K(p110α) protects the heart against myocardial infarction. Togheter with other genes encoding muscle structural/associated proteins, such as dystroglycan (Dag1), filamin C(Flnc), Rho-associated coiled-coil containing protein kinase 2(Rock2), crystallin, α B (Cryab), Cd151, integrin β 1 binding protein 2(Itgb1bp2/melusin), Lim domain binding 3(Ldb3/cypher), and synaptopodin 2 (Synpo2/myopodin), DARP/Ankrd23 was found up-and down-regulated respectively in the caPI3K (consitutively active PI3K)and dnPI3K(dominant negative PI3K.<ref name='six'>PMID PMC3162444 </ref><br />
DARP,calpain-10 and calpain-3 play an important role in the regulation of glucose utilization in skeletal muscle. Calpain-3 activity may be regulated by DARP.<ref name='one'>PMID 14583192 </ref<br />
<br />
<br />
<br />
<br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:CARP&diff=1609282Group:MUZIC:CARP2012-11-16T09:48:44Z<p>Narendra Kumar Verma: </p>
<hr />
<div>__FORCETOC__<br />
<br />
'''Introduction'''<br />
<br />
Cardiac ankyrin repeat protein (CARP/Ankrd1) together with ankyrin repeat domain 2 (Ankrd2/Arpp) and with diabetes associated ankyrin repeat protein (DARP), belongs to a conserved muscle ankyrin repeat protein (MARP) family. <ref name='one'>PMID 14583192</ref> CARP/Ankrd1 has been independently identified by several groups as a cytokine-inducible transcriptional regulator, a protein interacting with transcriptional factor YB-1, and a cardiac doxorubicin-responsive protein <ref name='two'>PMID 7730328</ref>,<ref name='three'>PMID 9043061</ref>. In normal tissues, Ankrd1 is highly expressed in cardiac muscle and detectable in skeletal muscles [3]. It is an early differentiation marker during cardiogenesis with a high expression level in developing heart. <ref<br />
name='three'>PMID 9043061</ref>, <ref name='four'>PMID 9278441</ref>. Mutations in the ANKRD1 gene are responsible for human dilated cardiomyopathy. <ref name='five'>PMID 14561590</ref><br />
<br />
== Sequence Annotation ==<br />
http://www.uniprot.org/uniprot/Q9CR42<br />
{{STRUCTURE_1n0r| PDB=1n11}}<br />
<br />
== Structure ==<br />
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>.<br />
<br />
== Gene Function and Interactions ==<br />
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><br />
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>.<br />
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.<br />
<br />
==Pathology ==<br />
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<br />
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>.<br />
<br />
<br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:CARP&diff=1609281Group:MUZIC:CARP2012-11-16T09:44:48Z<p>Narendra Kumar Verma: </p>
<hr />
<div>__FORCETOC__<br />
<br />
'''Introduction'''<br />
<br />
Cardiac ankyrin repeat protein (CARP/Ankrd1) together with ankyrin repeat domain 2 (Ankrd2/Arpp) and with diabetes associated ankyrin repeat protein (DARP), belongs to a conserved muscle ankyrin repeat protein (MARP) family. <ref name='one'>PMID 14583192</ref> CARP/Ankrd1 has been independently identified by several groups as a cytokine-inducible transcriptional regulator, a protein interacting with transcriptional factor YB-1, and a cardiac doxorubicin-responsive protein <ref name='two'>PMID 7730328</ref>,<ref name='three'>PMID 9043061</ref>. In normal tissues, Ankrd1 is highly expressed in cardiac muscle and detectable in skeletal muscles [3]. It is an early differentiation marker during cardiogenesis with a high expression level in developing heart. <ref<br />
name='three'>PMID 9043061</ref>, <ref name='four'>PMID 9278441</ref>. Mutations in the ANKRD1 gene are responsible for human dilated cardiomyopathy. <ref name='five'>PMID 14561590</ref><br />
<br />
== Sequence Annotation ==<br />
http://www.uniprot.org/uniprot/Q9CR42<br />
{{STRUCTURE_1n0r| PDB=1n11}}<br />
<br />
== Structure ==<br />
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>.<br />
<br />
== Gene Function ==<br />
<br />
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> <br />
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<br />
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>.<br />
<br />
==Localization== <br />
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>.<br />
<br />
==CARP Interactions==<br />
<br />
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.<br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:ANKRD2&diff=1609280Group:MUZIC:ANKRD22012-11-16T09:40:37Z<p>Narendra Kumar Verma: </p>
<hr />
<div>== '''ANKRD2''' ==<br />
<br />
'''Introduction'''<br />
<br />
Ankyrin repeat-containing protein 2 (stretch responsive muscle) '''Ankrd2''' belongs to the conserved muscle ankyrin repeat protein (MARP) family,<ref name='one'>PMID 10873377</ref> Also known as Arpp.<ref name='two'>PMID 11453652</ref> It is more expressed in skeletal than cardiac muscle, preferentially in type 1 fibers.<ref name='three'>PMID 12004005</ref> Ankrd2 shares approximately 50% homology with the two more MARP family members: Cardiac ankyrin repeat protein (CARP/Ankrd1) and Diabetes related ankyrin repeat protein DARP.Expression of Ankrd2/Arpp is induced in response to various forms of stress and is highly responsive to muscle mechanical status both in vivo and in vitro <ref name='one'>PMID 10873377</ref>,<ref name='four'>PMID 14583192</ref>, as well as to muscle plasticity induced by physical exercise <ref name='five'>PMID 14561590</ref>,<ref name='six'>PMID 15677738</ref>. Apart from the mechanosensory function, Ankrd2/Arpp is a negative regulator of muscle differentiation.<ref name='seven'>PMID 18302940</ref><br />
<br />
== Sequence Annotation == <br />
http://www.uniprot.org/uniprot/Q9GZV1<br />
<Structure load='2QYJ' size='300' frame='true' align='right' caption='Structure of a designed ankyrin repeat protein (DARPin) with five ankyrin repeat motifs [[2qyj]]' scene='User:Spyros_D._Chatziefthimiou/workbench/ANKRD2/2qyj/1' /><br />
<br />
== Structure ==<br />
<br />
Ankrd2 gene contains 9 exons and spans about 12 kb. The 280 bp long region upstream of the transcription initiation site of the human Ankrd2 gene is sufficient to confer spatial and temporal expression specificity, and contains mainly cis-elements specific for the muscle-specific transcription factor MyoD and for NF-kB. <ref name='eight'>PMID 11444853</ref> Ankrd2 promoter activity is significantly up-regulated by Nkx2.5 <ref name='nine'>PMID 22016770</ref>, upon longitudinal stretch by Akt-dependent NF-kB signaling pathway and in response to transverse stretch by Raf-1-dependent AP-1 signaling pathway. <ref name='ten'>PMID 20442316</ref> The major structural characteristic of the Ankrd2 protein is the presence in the middle portion of four conserved copies of 33-residue ankyrin repeats. In addition Ankrd2 contains a coiled-coil domain that contributes to its self-dimerization, a nuclear localization signal (NLS), allowing its sorting to the nucleus, PEST protein degradation sequence and numerous potential modification sites, mainly for phosphorylation. In particular the phosphorylation of Ankrd2 by the serine/threonine kinase Akt 2 is important for its function in muscle differentiation. <ref name='eleven'>PMID 21737686</ref> The position of Ankrd2 phosphorylation by Akt 2 is Ser 72 which is in close proximity of calpain 3 cleavage site (Arg 77). There are many other consensus phosphorylation sites for casein kinase I (CKI), casein kinase II (CKII), protein kinase C (PKC), extracellular signal regulated kinase (ERK), cAMP- dependent protein kinase, calmodulin-dependent protein kinase II and cGMP-dependent protein kinase <ref name='two'>PMID 11453652</ref>,<ref name='four'>PMID 14583192</ref><br />
<br />
<br />
[[Image:Ankrd.png|center|800px|thumb|Domain architecture and modification sites of '''Ankrd2''']]<br />
<br />
<br />
== Gene Function and Interactions ==<br />
<br />
Ankrd2 is involved in muscle stress response. It is up-regulated after chronic immobilization in a stretched position.<ref name='one'>PMID 10873377</ref> <ref name='six'>PMID 15677738</ref>, after eccentric contraction <ref name='five'>PMID 14561590</ref> , as well as in injured muscles.<ref name='eleven'>PMID 17926058</ref> Denervation of slow muscle decreases the level of Ankrd2 to below the detection limit in 4 weeks <ref name='six'>PMID 15677738</ref>, whereas denervation of fast muscle increases its expression.<ref name='three'>PMID 12004005</ref><br />
Ankrd2 is found in the central I-band of the sarcomere, where binds the N2A region of titin. In myoblasts Ankrd2 localizes both in the nuclei, in form of speckles and in the cytoplasm <ref name='seven'>PMID 18302940</ref>, with a diffused pattern. As the differentiation into multinucleated myotubes progresses, Ankrd2 seems to change localization and to accumulate mainly in the cytoplasm <ref>pmid 11444853 </ref>. In general, Ankrd2 protein functions by moving between the sarcomere and the nucleus, mainly in response to stress signals <ref name='fourteen'>PMID 15136035 </ref>.<br />
Ankrd2 is not essential for the basal functioning of skeletal muscle, but it is clear its influence on the gene expression program of skeletal muscle cells.<ref name='thirteen'>PMID 17392382</ref> Mainly the Ankrd2 protein has a major role in skeletal muscle formation as a myogenic regulator, since its over-expression in C2C12 myoblasts significantly affects and down-regulates MyoD, myogenin, and their target gene Myh1.<ref name='seven'>PMID 18302940</ref> <br />
<br />
<br />
==Pathology ==<br />
Altered expression of Ankrd2 has been found in patients suffering from inherited myopathies (muscular dystrophies (MD), congenital myopathies (CM)) and motor neuron diseases (spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS)).The Ankrd2/Arpp can interact with titin <ref name='four'>PMID 14583192</ref>, telethonin/T-cap <ref name='fourteen'>PMID 15136035 </ref>, calpain 3 <ref name='fifteen'>PMID 18310072 </ref>, promyelocytic leukemia protein (PML)<ref name='fourteen'>PMID 15136035 </ref>, YB-1 <ref name='fourteen'>PMID 15136035 </ref>, p53 <ref name='fourteen'>PMID 15136035 </ref>, Akt 2 <ref name='eleven'>PMID 21737686</ref> and zonula occludens 1 (ZO1).<ref name='nine'>PMID 22016770</ref><br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:ANKRD2&diff=1609279Group:MUZIC:ANKRD22012-11-16T09:38:50Z<p>Narendra Kumar Verma: </p>
<hr />
<div>== '''ANKRD2''' ==<br />
<br />
'''Introduction'''<br />
<br />
Ankyrin repeat-containing protein 2 (stretch responsive muscle) '''Ankrd2''' belongs to the conserved muscle ankyrin repeat protein (MARP) family,<ref name='one'>PMID 10873377</ref> Also known as Arpp.<ref name='two'>PMID 11453652</ref> It is more expressed in skeletal than cardiac muscle, preferentially in type 1 fibers.<ref name='three'>PMID 12004005</ref> Ankrd2 shares approximately 50% homology with the two more MARP family members: Cardiac ankyrin repeat protein (CARP/Ankrd1) and Diabetes related ankyrin repeat protein DARP.Expression of Ankrd2/Arpp is induced in response to various forms of stress and is highly responsive to muscle mechanical status both in vivo and in vitro <ref name='one'>PMID 10873377</ref>,<ref name='four'>PMID 14583192</ref>, as well as to muscle plasticity induced by physical exercise <ref name='five'>PMID 14561590</ref>,<ref name='six'>PMID 15677738</ref>. Apart from the mechanosensory function, Ankrd2/Arpp is a negative regulator of muscle differentiation.<ref name='seven'>PMID 18302940</ref><br />
<br />
== Sequence Annotation == <br />
http://www.uniprot.org/uniprot/Q9GZV1<br />
<Structure load='2QYJ' size='300' frame='true' align='right' caption='Structure of a designed ankyrin repeat protein (DARPin) with five ankyrin repeat motifs [[2qyj]]' scene='User:Spyros_D._Chatziefthimiou/workbench/ANKRD2/2qyj/1' /><br />
<br />
== Structure ==<br />
<br />
Ankrd2 gene contains 9 exons and spans about 12 kb. The 280 bp long region upstream of the transcription initiation site of the human Ankrd2 gene is sufficient to confer spatial and temporal expression specificity, and contains mainly cis-elements specific for the muscle-specific transcription factor MyoD and for NF-kB. <ref name='eight'>PMID 11444853</ref> Ankrd2 promoter activity is significantly up-regulated by Nkx2.5 <ref name='nine'>PMID 22016770</ref>, upon longitudinal stretch by Akt-dependent NF-kB signaling pathway and in response to transverse stretch by Raf-1-dependent AP-1 signaling pathway. <ref name='ten'>PMID 20442316</ref> The major structural characteristic of the Ankrd2 protein is the presence in the middle portion of four conserved copies of 33-residue ankyrin repeats. In addition Ankrd2 contains a coiled-coil domain that contributes to its self-dimerization, a nuclear localization signal (NLS), allowing its sorting to the nucleus, PEST protein degradation sequence and numerous potential modification sites, mainly for phosphorylation. In particular the phosphorylation of Ankrd2 by the serine/threonine kinase Akt 2 is important for its function in muscle differentiation. <ref name='eleven'>PMID 21737686</ref> The position of Ankrd2 phosphorylation by Akt 2 is Ser 72 which is in close proximity of calpain 3 cleavage site (Arg 77). There are many other consensus phosphorylation sites for casein kinase I (CKI), casein kinase II (CKII), protein kinase C (PKC), extracellular signal regulated kinase (ERK), cAMP- dependent protein kinase, calmodulin-dependent protein kinase II and cGMP-dependent protein kinase <ref name='two'>PMID 11453652</ref>,<ref name='four'>PMID 14583192</ref><br />
<br />
<br />
[[Image:Ankrd.png|center|800px|thumb|Domain architecture and modification sites of '''Ankrd2''']]<br />
<br />
<br />
== Gene Function and Interactions ==<br />
<br />
Ankrd2 is involved in muscle stress response. It is up-regulated after chronic immobilization in a stretched position.<ref name='one'>PMID 10873377</ref> <ref name='six'>PMID 15677738</ref>, after eccentric contraction <ref name='five'>PMID 14561590</ref> , as well as in injured muscles.<ref name='eleven'>PMID 17926058</ref> Denervation of slow muscle decreases the level of Ankrd2 to below the detection limit in 4 weeks <ref name='six'>PMID 15677738</ref>, whereas denervation of fast muscle increases its expression.<ref name='three'>PMID 12004005</ref><br />
Ankrd2 is not essential for the basal functioning of skeletal muscle, but it is clear its influence on the gene expression program of skeletal muscle cells.<ref name='thirteen'>PMID 17392382</ref> Mainly the Ankrd2 protein has a major role in skeletal muscle formation as a myogenic regulator, since its over-expression in C2C12 myoblasts significantly affects and down-regulates MyoD, myogenin, and their target gene Myh1.<ref name='seven'>PMID 18302940</ref> <br />
<br />
<br />
==Localization== <br />
Ankrd2 is found in the central I-band of the sarcomere, where binds the N2A region of titin. In myoblasts Ankrd2 localizes both in the nuclei, in form of speckles and in the cytoplasm <ref name='seven'>PMID 18302940</ref>, with a diffused pattern. As the differentiation into multinucleated myotubes progresses, Ankrd2 seems to change localization and to accumulate mainly in the cytoplasm <ref>pmid 11444853 </ref>. In general, Ankrd2 protein functions by moving between the sarcomere and the nucleus, mainly in response to stress signals <ref name='fourteen'>PMID 15136035 </ref>.<br />
<br />
==Pathology ==<br />
Altered expression of Ankrd2 has been found in patients suffering from inherited myopathies (muscular dystrophies (MD), congenital myopathies (CM)) and motor neuron diseases (spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS)).The Ankrd2/Arpp can interact with titin <ref name='four'>PMID 14583192</ref>, telethonin/T-cap <ref name='fourteen'>PMID 15136035 </ref>, calpain 3 <ref name='fifteen'>PMID 18310072 </ref>, promyelocytic leukemia protein (PML)<ref name='fourteen'>PMID 15136035 </ref>, YB-1 <ref name='fourteen'>PMID 15136035 </ref>, p53 <ref name='fourteen'>PMID 15136035 </ref>, Akt 2 <ref name='eleven'>PMID 21737686</ref> and zonula occludens 1 (ZO1).<ref name='nine'>PMID 22016770</ref><br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:ANKRD2&diff=1609278Group:MUZIC:ANKRD22012-11-16T09:36:50Z<p>Narendra Kumar Verma: </p>
<hr />
<div>== '''ANKRD2''' ==<br />
<br />
'''Introduction'''<br />
<br />
Ankyrin repeat-containing protein 2 (stretch responsive muscle) '''Ankrd2''' belongs to the conserved muscle ankyrin repeat protein (MARP) family,<ref name='one'>PMID 10873377</ref> Also known as Arpp.<ref name='two'>PMID 11453652</ref> It is more expressed in skeletal than cardiac muscle, preferentially in type 1 fibers.<ref name='three'>PMID 12004005</ref> Ankrd2 shares approximately 50% homology with the two more MARP family members: Cardiac ankyrin repeat protein (CARP/Ankrd1) and Diabetes related ankyrin repeat protein DARP.Expression of Ankrd2/Arpp is induced in response to various forms of stress and is highly responsive to muscle mechanical status both in vivo and in vitro <ref name='one'>PMID 10873377</ref>,<ref name='four'>PMID 14583192</ref>, as well as to muscle plasticity induced by physical exercise <ref name='five'>PMID 14561590</ref>,<ref name='six'>PMID 15677738</ref>. Apart from the mechanosensory function, Ankrd2/Arpp is a negative regulator of muscle differentiation.<ref name='seven'>PMID 18302940</ref><br />
<br />
== Sequence Annotation == <br />
http://www.uniprot.org/uniprot/Q9GZV1<br />
<Structure load='2QYJ' size='300' frame='true' align='right' caption='Structure of a designed ankyrin repeat protein (DARPin) with five ankyrin repeat motifs [[2qyj]]' scene='User:Spyros_D._Chatziefthimiou/workbench/ANKRD2/2qyj/1' /><br />
<br />
== Structure ==<br />
<br />
Ankrd2 gene contains 9 exons and spans about 12 kb. The 280 bp long region upstream of the transcription initiation site of the human Ankrd2 gene is sufficient to confer spatial and temporal expression specificity, and contains mainly cis-elements specific for the muscle-specific transcription factor MyoD and for NF-kB. <ref name='eight'>PMID 11444853</ref> Ankrd2 promoter activity is significantly up-regulated by Nkx2.5 <ref name='nine'>PMID 22016770</ref>, upon longitudinal stretch by Akt-dependent NF-kB signaling pathway and in response to transverse stretch by Raf-1-dependent AP-1 signaling pathway. <ref name='ten'>PMID 20442316</ref> The major structural characteristic of the Ankrd2 protein is the presence in the middle portion of four conserved copies of 33-residue ankyrin repeats. In addition Ankrd2 contains a coiled-coil domain that contributes to its self-dimerization, a nuclear localization signal (NLS), allowing its sorting to the nucleus, PEST protein degradation sequence and numerous potential modification sites, mainly for phosphorylation. In particular the phosphorylation of Ankrd2 by the serine/threonine kinase Akt 2 is important for its function in muscle differentiation. <ref name='eleven'>PMID 21737686</ref> The position of Ankrd2 phosphorylation by Akt 2 is Ser 72 which is in close proximity of calpain 3 cleavage site (Arg 77). There are many other consensus phosphorylation sites for casein kinase I (CKI), casein kinase II (CKII), protein kinase C (PKC), extracellular signal regulated kinase (ERK), cAMP- dependent protein kinase, calmodulin-dependent protein kinase II and cGMP-dependent protein kinase <ref name='two'>PMID 11453652</ref>,<ref name='four'>PMID 14583192</ref><br />
<br />
<br />
[[Image:Ankrd.png|center|800px|thumb|Domain architecture and modification sites of '''Ankrd2''']]<br />
<br />
<br />
== Gene Function and Interactions ==<br />
<br />
Ankrd2 is involved in muscle stress response. It is up-regulated after chronic immobilization in a stretched position.<ref name='one'>PMID 10873377</ref> <ref name='six'>PMID 15677738</ref>, after eccentric contraction <ref name='five'>PMID 14561590</ref> , as well as in injured muscles.<ref name='eleven'>PMID 17926058</ref> Denervation of slow muscle decreases the level of Ankrd2 to below the detection limit in 4 weeks <ref name='six'>PMID 15677738</ref>, whereas denervation of fast muscle increases its expression.<ref name='three'>PMID 12004005</ref><br />
Ankrd2 is not essential for the basal functioning of skeletal muscle, but it is clear its influence on the gene expression program of skeletal muscle cells.<ref name='thirteen'>PMID 17392382</ref> Mainly the Ankrd2 protein has a major role in skeletal muscle formation as a myogenic regulator, since its over-expression in C2C12 myoblasts significantly affects and down-regulates MyoD, myogenin, and their target gene Myh1.<ref name='seven'>PMID 18302940</ref> Altered expression of Ankrd2 has been found in patients suffering from inherited myopathies (muscular dystrophies (MD), congenital myopathies (CM)) and motor neuron diseases (spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS)).The Ankrd2/Arpp can interact with titin <ref name='four'>PMID 14583192</ref>, telethonin/T-cap <ref name='fourteen'>PMID 15136035 </ref>, calpain 3 <ref name='fifteen'>PMID 18310072 </ref>, promyelocytic leukemia protein (PML)<ref name='fourteen'>PMID 15136035 </ref>, YB-1 <ref name='fourteen'>PMID 15136035 </ref>, p53 <ref name='fourteen'>PMID 15136035 </ref>, Akt 2 <ref name='eleven'>PMID 21737686</ref> and zonula occludens 1 (ZO1).<ref name='nine'>PMID 22016770</ref><br />
<br />
<br />
==Localization== <br />
Ankrd2 is found in the central I-band of the sarcomere, where binds the N2A region of titin. In myoblasts Ankrd2 localizes both in the nuclei, in form of speckles and in the cytoplasm <ref name='seven'>PMID 18302940</ref>, with a diffused pattern. As the differentiation into multinucleated myotubes progresses, Ankrd2 seems to change localization and to accumulate mainly in the cytoplasm <ref>pmid 11444853 </ref>. In general, Ankrd2 protein functions by moving between the sarcomere and the nucleus, mainly in response to stress signals <ref name='fourteen'>PMID 15136035 </ref>.<br />
<br />
==Pathology ==<br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:ANKRD2&diff=1609277Group:MUZIC:ANKRD22012-11-16T09:17:43Z<p>Narendra Kumar Verma: </p>
<hr />
<div>== '''ANKRD2''' ==<br />
<br />
'''Introduction'''<br />
<br />
Ankyrin repeat-containing protein 2 (stretch responsive muscle) '''Ankrd2''' belongs to the conserved muscle ankyrin repeat protein (MARP) family,<ref name='one'>PMID 10873377</ref> Also known as Arpp.<ref name='two'>PMID 11453652</ref> It is more expressed in skeletal than cardiac muscle, preferentially in type 1 fibers.<ref name='three'>PMID 12004005</ref> Ankrd2 shares approximately 50% homology with the two more MARP family members: Cardiac ankyrin repeat protein (CARP/Ankrd1) and Diabetes related ankyrin repeat protein DARP.Expression of Ankrd2/Arpp is induced in response to various forms of stress and is highly responsive to muscle mechanical status both in vivo and in vitro <ref name='one'>PMID 10873377</ref>,<ref name='four'>PMID 14583192</ref>, as well as to muscle plasticity induced by physical exercise <ref name='five'>PMID 14561590</ref>,<ref name='six'>PMID 15677738</ref>. Apart from the mechanosensory function, Ankrd2/Arpp is a negative regulator of muscle differentiation.<ref name='seven'>PMID 18302940</ref><br />
<br />
== Sequence Annotation == <br />
http://www.uniprot.org/uniprot/Q9GZV1<br />
<Structure load='2QYJ' size='300' frame='true' align='right' caption='Structure of a designed ankyrin repeat protein (DARPin) with five ankyrin repeat motifs [[2qyj]]' scene='User:Spyros_D._Chatziefthimiou/workbench/ANKRD2/2qyj/1' /><br />
<br />
== Structure ==<br />
<br />
Ankrd2 gene contains 9 exons and spans about 12 kb. The 280 bp long region upstream of the transcription initiation site of the human Ankrd2 gene is sufficient to confer spatial and temporal expression specificity, and contains mainly cis-elements specific for the muscle-specific transcription factor MyoD and for NF-kB. <ref name='eight'>PMID 11444853</ref> Ankrd2 promoter activity is significantly up-regulated by Nkx2.5 <ref name='nine'>PMID 22016770</ref>, upon longitudinal stretch by Akt-dependent NF-kB signaling pathway and in response to transverse stretch by Raf-1-dependent AP-1 signaling pathway. <ref name='ten'>PMID 20442316</ref> The major structural characteristic of the Ankrd2 protein is the presence in the middle portion of four conserved copies of 33-residue ankyrin repeats. In addition Ankrd2 contains a coiled-coil domain that contributes to its self-dimerization, a nuclear localization signal (NLS), allowing its sorting to the nucleus, PEST protein degradation sequence and numerous potential modification sites, mainly for phosphorylation. In particular the phosphorylation of Ankrd2 by the serine/threonine kinase Akt 2 is important for its function in muscle differentiation. <ref name='eleven'>PMID 21737686</ref> The position of Ankrd2 phosphorylation by Akt 2 is Ser 72 which is in close proximity of calpain 3 cleavage site (Arg 77). There are many other consensus phosphorylation sites for casein kinase I (CKI), casein kinase II (CKII), protein kinase C (PKC), extracellular signal regulated kinase (ERK), cAMP- dependent protein kinase, calmodulin-dependent protein kinase II and cGMP-dependent protein kinase <ref name='two'>PMID 11453652</ref>,<ref name='four'>PMID 14583192</ref><br />
<br />
<br />
[[Image:Ankrd.png|center|800px|thumb|Domain architecture and modification sites of '''Ankrd2''']]<br />
<br />
<br />
== Gene Function ==<br />
<br />
Ankrd2 is involved in muscle stress response. It is up-regulated after chronic immobilization in a stretched position.<ref name='one'>PMID 10873377</ref> <ref name='six'>PMID 15677738</ref>, after eccentric contraction <ref name='five'>PMID 14561590</ref> , as well as in injured muscles.<ref name='eleven'>PMID 17926058</ref> Denervation of slow muscle decreases the level of Ankrd2 to below the detection limit in 4 weeks <ref name='six'>PMID 15677738</ref>, whereas denervation of fast muscle increases its expression.<ref name='three'>PMID 12004005</ref><br />
Ankrd2 is not essential for the basal functioning of skeletal muscle, but it is clear its influence on the gene expression program of skeletal muscle cells.<ref name='thirteen'>PMID 17392382</ref> Mainly the Ankrd2 protein has a major role in skeletal muscle formation as a myogenic regulator, since its over-expression in C2C12 myoblasts significantly affects and down-regulates MyoD, myogenin, and their target gene Myh1.<ref name='seven'>PMID 18302940</ref> Altered expression of Ankrd2 has been found in patients suffering from inherited myopathies (muscular dystrophies (MD), congenital myopathies (CM)) and motor neuron diseases (spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS)).<br />
<br />
==Localization== <br />
Ankrd2 is found in the central I-band of the sarcomere, where binds the N2A region of titin. In myoblasts Ankrd2 localizes both in the nuclei, in form of speckles and in the cytoplasm <ref name='seven'>PMID 18302940</ref>, with a diffused pattern. As the differentiation into multinucleated myotubes progresses, Ankrd2 seems to change localization and to accumulate mainly in the cytoplasm <ref>pmid 11444853 </ref>. In general, Ankrd2 protein functions by moving between the sarcomere and the nucleus, mainly in response to stress signals <ref name='fourteen'>PMID 15136035 </ref>.<br />
<br />
==Ankrd2 Interactions==<br />
The Ankrd2/Arpp can interact with titin <ref name='four'>PMID 14583192</ref>, telethonin/T-cap <ref name='fourteen'>PMID 15136035 </ref>, calpain 3 <ref name='fifteen'>PMID 18310072 </ref>, promyelocytic leukemia protein (PML)<ref name='fourteen'>PMID 15136035 </ref>, YB-1 <ref name='fourteen'>PMID 15136035 </ref>, p53 <ref name='fourteen'>PMID 15136035 </ref>, Akt 2 <ref name='eleven'>PMID 21737686</ref> and zonula occludens 1 (ZO1).<ref name='nine'>PMID 22016770</ref><br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:ANKRD2&diff=1609276Group:MUZIC:ANKRD22012-11-16T09:17:02Z<p>Narendra Kumar Verma: </p>
<hr />
<div>== '''ANKRD2''' ==<br />
<br />
'''Introduction'''<br />
<br />
Ankyrin repeat-containing protein 2 (stretch responsive muscle) '''Ankrd2''' belongs to the conserved muscle ankyrin repeat protein (MARP) family,<ref name='one'>PMID 10873377</ref> Also known as Arpp.<ref name='two'>PMID 11453652</ref> It is more expressed in skeletal than cardiac muscle, preferentially in type 1 fibers.<ref name='three'>PMID 12004005</ref> Ankrd2 shares approximately 50% homology with the two more MARP family members: Cardiac ankyrin repeat protein (CARP/Ankrd1) and Diabetes related ankyrin repeat protein DARP.Expression of Ankrd2/Arpp is induced in response to various forms of stress and is highly responsive to muscle mechanical status both in vivo and in vitro <ref name='one'>PMID 10873377</ref>,<ref name='four'>PMID 14583192</ref>, as well as to muscle plasticity induced by physical exercise <ref name='five'>PMID 14561590</ref>,<ref name='six'>PMID 15677738</ref>. Apart from the mechanosensory function, Ankrd2/Arpp is a negative regulator of muscle differentiation.<ref name='seven'>PMID 18302940</ref><br />
<br />
== Sequence Annotation == <br />
uniprot/Q9GZV1<br />
<Structure load='2QYJ' size='300' frame='true' align='right' caption='Structure of a designed ankyrin repeat protein (DARPin) with five ankyrin repeat motifs [[2qyj]]' scene='User:Spyros_D._Chatziefthimiou/workbench/ANKRD2/2qyj/1' /><br />
<br />
== Structure ==<br />
<br />
Ankrd2 gene contains 9 exons and spans about 12 kb. The 280 bp long region upstream of the transcription initiation site of the human Ankrd2 gene is sufficient to confer spatial and temporal expression specificity, and contains mainly cis-elements specific for the muscle-specific transcription factor MyoD and for NF-kB. <ref name='eight'>PMID 11444853</ref> Ankrd2 promoter activity is significantly up-regulated by Nkx2.5 <ref name='nine'>PMID 22016770</ref>, upon longitudinal stretch by Akt-dependent NF-kB signaling pathway and in response to transverse stretch by Raf-1-dependent AP-1 signaling pathway. <ref name='ten'>PMID 20442316</ref> The major structural characteristic of the Ankrd2 protein is the presence in the middle portion of four conserved copies of 33-residue ankyrin repeats. In addition Ankrd2 contains a coiled-coil domain that contributes to its self-dimerization, a nuclear localization signal (NLS), allowing its sorting to the nucleus, PEST protein degradation sequence and numerous potential modification sites, mainly for phosphorylation. In particular the phosphorylation of Ankrd2 by the serine/threonine kinase Akt 2 is important for its function in muscle differentiation. <ref name='eleven'>PMID 21737686</ref> The position of Ankrd2 phosphorylation by Akt 2 is Ser 72 which is in close proximity of calpain 3 cleavage site (Arg 77). There are many other consensus phosphorylation sites for casein kinase I (CKI), casein kinase II (CKII), protein kinase C (PKC), extracellular signal regulated kinase (ERK), cAMP- dependent protein kinase, calmodulin-dependent protein kinase II and cGMP-dependent protein kinase <ref name='two'>PMID 11453652</ref>,<ref name='four'>PMID 14583192</ref><br />
<br />
<br />
[[Image:Ankrd.png|center|800px|thumb|Domain architecture and modification sites of '''Ankrd2''']]<br />
<br />
<br />
== Gene Function ==<br />
<br />
Ankrd2 is involved in muscle stress response. It is up-regulated after chronic immobilization in a stretched position.<ref name='one'>PMID 10873377</ref> <ref name='six'>PMID 15677738</ref>, after eccentric contraction <ref name='five'>PMID 14561590</ref> , as well as in injured muscles.<ref name='eleven'>PMID 17926058</ref> Denervation of slow muscle decreases the level of Ankrd2 to below the detection limit in 4 weeks <ref name='six'>PMID 15677738</ref>, whereas denervation of fast muscle increases its expression.<ref name='three'>PMID 12004005</ref><br />
Ankrd2 is not essential for the basal functioning of skeletal muscle, but it is clear its influence on the gene expression program of skeletal muscle cells.<ref name='thirteen'>PMID 17392382</ref> Mainly the Ankrd2 protein has a major role in skeletal muscle formation as a myogenic regulator, since its over-expression in C2C12 myoblasts significantly affects and down-regulates MyoD, myogenin, and their target gene Myh1.<ref name='seven'>PMID 18302940</ref> Altered expression of Ankrd2 has been found in patients suffering from inherited myopathies (muscular dystrophies (MD), congenital myopathies (CM)) and motor neuron diseases (spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS)).<br />
<br />
==Localization== <br />
Ankrd2 is found in the central I-band of the sarcomere, where binds the N2A region of titin. In myoblasts Ankrd2 localizes both in the nuclei, in form of speckles and in the cytoplasm <ref name='seven'>PMID 18302940</ref>, with a diffused pattern. As the differentiation into multinucleated myotubes progresses, Ankrd2 seems to change localization and to accumulate mainly in the cytoplasm <ref>pmid 11444853 </ref>. In general, Ankrd2 protein functions by moving between the sarcomere and the nucleus, mainly in response to stress signals <ref name='fourteen'>PMID 15136035 </ref>.<br />
<br />
==Ankrd2 Interactions==<br />
The Ankrd2/Arpp can interact with titin <ref name='four'>PMID 14583192</ref>, telethonin/T-cap <ref name='fourteen'>PMID 15136035 </ref>, calpain 3 <ref name='fifteen'>PMID 18310072 </ref>, promyelocytic leukemia protein (PML)<ref name='fourteen'>PMID 15136035 </ref>, YB-1 <ref name='fourteen'>PMID 15136035 </ref>, p53 <ref name='fourteen'>PMID 15136035 </ref>, Akt 2 <ref name='eleven'>PMID 21737686</ref> and zonula occludens 1 (ZO1).<ref name='nine'>PMID 22016770</ref><br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:ANKRD2&diff=1609275Group:MUZIC:ANKRD22012-11-16T09:15:08Z<p>Narendra Kumar Verma: </p>
<hr />
<div>== '''ANKRD2''' ==<br />
<br />
'''Introduction'''<br />
<br />
Ankyrin repeat-containing protein 2 (stretch responsive muscle) '''Ankrd2''' belongs to the conserved muscle ankyrin repeat protein (MARP) family,<ref name='one'>PMID 10873377</ref> Also known as Arpp.<ref name='two'>PMID 11453652</ref> It is more expressed in skeletal than cardiac muscle, preferentially in type 1 fibers.<ref name='three'>PMID 12004005</ref> Ankrd2 shares approximately 50% homology with the two more MARP family members: Cardiac ankyrin repeat protein (CARP/Ankrd1) and Diabetes related ankyrin repeat protein DARP.Expression of Ankrd2/Arpp is induced in response to various forms of stress and is highly responsive to muscle mechanical status both in vivo and in vitro <ref name='one'>PMID 10873377</ref>,<ref name='four'>PMID 14583192</ref>, as well as to muscle plasticity induced by physical exercise <ref name='five'>PMID 14561590</ref>,<ref name='six'>PMID 15677738</ref>. Apart from the mechanosensory function, Ankrd2/Arpp is a negative regulator of muscle differentiation.<ref name='seven'>PMID 18302940</ref><br />
<br />
== Sequence Annotation == <br />
Q9GZV1<br />
<Structure load='2QYJ' size='300' frame='true' align='right' caption='Structure of a designed ankyrin repeat protein (DARPin) with five ankyrin repeat motifs [[2qyj]]' scene='User:Spyros_D._Chatziefthimiou/workbench/ANKRD2/2qyj/1' /><br />
<br />
== Structure ==<br />
<br />
Ankrd2 gene contains 9 exons and spans about 12 kb. The 280 bp long region upstream of the transcription initiation site of the human Ankrd2 gene is sufficient to confer spatial and temporal expression specificity, and contains mainly cis-elements specific for the muscle-specific transcription factor MyoD and for NF-kB. <ref name='eight'>PMID 11444853</ref> Ankrd2 promoter activity is significantly up-regulated by Nkx2.5 <ref name='nine'>PMID 22016770</ref>, upon longitudinal stretch by Akt-dependent NF-kB signaling pathway and in response to transverse stretch by Raf-1-dependent AP-1 signaling pathway. <ref name='ten'>PMID 20442316</ref> The major structural characteristic of the Ankrd2 protein is the presence in the middle portion of four conserved copies of 33-residue ankyrin repeats. In addition Ankrd2 contains a coiled-coil domain that contributes to its self-dimerization, a nuclear localization signal (NLS), allowing its sorting to the nucleus, PEST protein degradation sequence and numerous potential modification sites, mainly for phosphorylation. In particular the phosphorylation of Ankrd2 by the serine/threonine kinase Akt 2 is important for its function in muscle differentiation. <ref name='eleven'>PMID 21737686</ref> The position of Ankrd2 phosphorylation by Akt 2 is Ser 72 which is in close proximity of calpain 3 cleavage site (Arg 77). There are many other consensus phosphorylation sites for casein kinase I (CKI), casein kinase II (CKII), protein kinase C (PKC), extracellular signal regulated kinase (ERK), cAMP- dependent protein kinase, calmodulin-dependent protein kinase II and cGMP-dependent protein kinase <ref name='two'>PMID 11453652</ref>,<ref name='four'>PMID 14583192</ref><br />
<br />
<br />
[[Image:Ankrd.png|center|800px|thumb|Domain architecture and modification sites of '''Ankrd2''']]<br />
<br />
<br />
== Gene Function ==<br />
<br />
Ankrd2 is involved in muscle stress response. It is up-regulated after chronic immobilization in a stretched position.<ref name='one'>PMID 10873377</ref> <ref name='six'>PMID 15677738</ref>, after eccentric contraction <ref name='five'>PMID 14561590</ref> , as well as in injured muscles.<ref name='eleven'>PMID 17926058</ref> Denervation of slow muscle decreases the level of Ankrd2 to below the detection limit in 4 weeks <ref name='six'>PMID 15677738</ref>, whereas denervation of fast muscle increases its expression.<ref name='three'>PMID 12004005</ref><br />
Ankrd2 is not essential for the basal functioning of skeletal muscle, but it is clear its influence on the gene expression program of skeletal muscle cells.<ref name='thirteen'>PMID 17392382</ref> Mainly the Ankrd2 protein has a major role in skeletal muscle formation as a myogenic regulator, since its over-expression in C2C12 myoblasts significantly affects and down-regulates MyoD, myogenin, and their target gene Myh1.<ref name='seven'>PMID 18302940</ref> Altered expression of Ankrd2 has been found in patients suffering from inherited myopathies (muscular dystrophies (MD), congenital myopathies (CM)) and motor neuron diseases (spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS)).<br />
<br />
==Localization== <br />
Ankrd2 is found in the central I-band of the sarcomere, where binds the N2A region of titin. In myoblasts Ankrd2 localizes both in the nuclei, in form of speckles and in the cytoplasm <ref name='seven'>PMID 18302940</ref>, with a diffused pattern. As the differentiation into multinucleated myotubes progresses, Ankrd2 seems to change localization and to accumulate mainly in the cytoplasm <ref>pmid 11444853 </ref>. In general, Ankrd2 protein functions by moving between the sarcomere and the nucleus, mainly in response to stress signals <ref name='fourteen'>PMID 15136035 </ref>.<br />
<br />
==Ankrd2 Interactions==<br />
The Ankrd2/Arpp can interact with titin <ref name='four'>PMID 14583192</ref>, telethonin/T-cap <ref name='fourteen'>PMID 15136035 </ref>, calpain 3 <ref name='fifteen'>PMID 18310072 </ref>, promyelocytic leukemia protein (PML)<ref name='fourteen'>PMID 15136035 </ref>, YB-1 <ref name='fourteen'>PMID 15136035 </ref>, p53 <ref name='fourteen'>PMID 15136035 </ref>, Akt 2 <ref name='eleven'>PMID 21737686</ref> and zonula occludens 1 (ZO1).<ref name='nine'>PMID 22016770</ref><br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:ANKRD2&diff=1609274Group:MUZIC:ANKRD22012-11-16T09:14:23Z<p>Narendra Kumar Verma: </p>
<hr />
<div>== '''ANKRD2''' ==<br />
<br />
'''Introduction'''<br />
<br />
Ankyrin repeat-containing protein 2 (stretch responsive muscle) '''Ankrd2''' belongs to the conserved muscle ankyrin repeat protein (MARP) family,<ref name='one'>PMID 10873377</ref> Also known as Arpp.<ref name='two'>PMID 11453652</ref> It is more expressed in skeletal than cardiac muscle, preferentially in type 1 fibers.<ref name='three'>PMID 12004005</ref> Ankrd2 shares approximately 50% homology with the two more MARP family members: Cardiac ankyrin repeat protein (CARP/Ankrd1) and Diabetes related ankyrin repeat protein DARP.Expression of Ankrd2/Arpp is induced in response to various forms of stress and is highly responsive to muscle mechanical status both in vivo and in vitro <ref name='one'>PMID 10873377</ref>,<ref name='four'>PMID 14583192</ref>, as well as to muscle plasticity induced by physical exercise <ref name='five'>PMID 14561590</ref>,<ref name='six'>PMID 15677738</ref>. Apart from the mechanosensory function, Ankrd2/Arpp is a negative regulator of muscle differentiation.<ref name='seven'>PMID 18302940</ref><br />
<br />
== Sequence Annotation ==<br />
http://www.uniprot.org/uniprot/Q9GZV1<br />
<Structure load='2QYJ' size='300' frame='true' align='right' caption='Structure of a designed ankyrin repeat protein (DARPin) with five ankyrin repeat motifs [[2qyj]]' scene='User:Spyros_D._Chatziefthimiou/workbench/ANKRD2/2qyj/1' /><br />
<br />
== Structure ==<br />
<br />
Ankrd2 gene contains 9 exons and spans about 12 kb. The 280 bp long region upstream of the transcription initiation site of the human Ankrd2 gene is sufficient to confer spatial and temporal expression specificity, and contains mainly cis-elements specific for the muscle-specific transcription factor MyoD and for NF-kB. <ref name='eight'>PMID 11444853</ref> Ankrd2 promoter activity is significantly up-regulated by Nkx2.5 <ref name='nine'>PMID 22016770</ref>, upon longitudinal stretch by Akt-dependent NF-kB signaling pathway and in response to transverse stretch by Raf-1-dependent AP-1 signaling pathway. <ref name='ten'>PMID 20442316</ref> The major structural characteristic of the Ankrd2 protein is the presence in the middle portion of four conserved copies of 33-residue ankyrin repeats. In addition Ankrd2 contains a coiled-coil domain that contributes to its self-dimerization, a nuclear localization signal (NLS), allowing its sorting to the nucleus, PEST protein degradation sequence and numerous potential modification sites, mainly for phosphorylation. In particular the phosphorylation of Ankrd2 by the serine/threonine kinase Akt 2 is important for its function in muscle differentiation. <ref name='eleven'>PMID 21737686</ref> The position of Ankrd2 phosphorylation by Akt 2 is Ser 72 which is in close proximity of calpain 3 cleavage site (Arg 77). There are many other consensus phosphorylation sites for casein kinase I (CKI), casein kinase II (CKII), protein kinase C (PKC), extracellular signal regulated kinase (ERK), cAMP- dependent protein kinase, calmodulin-dependent protein kinase II and cGMP-dependent protein kinase <ref name='two'>PMID 11453652</ref>,<ref name='four'>PMID 14583192</ref><br />
<br />
<br />
[[Image:Ankrd.png|center|800px|thumb|Domain architecture and modification sites of '''Ankrd2''']]<br />
<br />
<br />
== Gene Function ==<br />
<br />
Ankrd2 is involved in muscle stress response. It is up-regulated after chronic immobilization in a stretched position.<ref name='one'>PMID 10873377</ref> <ref name='six'>PMID 15677738</ref>, after eccentric contraction <ref name='five'>PMID 14561590</ref> , as well as in injured muscles.<ref name='eleven'>PMID 17926058</ref> Denervation of slow muscle decreases the level of Ankrd2 to below the detection limit in 4 weeks <ref name='six'>PMID 15677738</ref>, whereas denervation of fast muscle increases its expression.<ref name='three'>PMID 12004005</ref><br />
Ankrd2 is not essential for the basal functioning of skeletal muscle, but it is clear its influence on the gene expression program of skeletal muscle cells.<ref name='thirteen'>PMID 17392382</ref> Mainly the Ankrd2 protein has a major role in skeletal muscle formation as a myogenic regulator, since its over-expression in C2C12 myoblasts significantly affects and down-regulates MyoD, myogenin, and their target gene Myh1.<ref name='seven'>PMID 18302940</ref> Altered expression of Ankrd2 has been found in patients suffering from inherited myopathies (muscular dystrophies (MD), congenital myopathies (CM)) and motor neuron diseases (spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS)).<br />
<br />
==Localization== <br />
Ankrd2 is found in the central I-band of the sarcomere, where binds the N2A region of titin. In myoblasts Ankrd2 localizes both in the nuclei, in form of speckles and in the cytoplasm <ref name='seven'>PMID 18302940</ref>, with a diffused pattern. As the differentiation into multinucleated myotubes progresses, Ankrd2 seems to change localization and to accumulate mainly in the cytoplasm <ref>pmid 11444853 </ref>. In general, Ankrd2 protein functions by moving between the sarcomere and the nucleus, mainly in response to stress signals <ref name='fourteen'>PMID 15136035 </ref>.<br />
<br />
==Ankrd2 Interactions==<br />
The Ankrd2/Arpp can interact with titin <ref name='four'>PMID 14583192</ref>, telethonin/T-cap <ref name='fourteen'>PMID 15136035 </ref>, calpain 3 <ref name='fifteen'>PMID 18310072 </ref>, promyelocytic leukemia protein (PML)<ref name='fourteen'>PMID 15136035 </ref>, YB-1 <ref name='fourteen'>PMID 15136035 </ref>, p53 <ref name='fourteen'>PMID 15136035 </ref>, Akt 2 <ref name='eleven'>PMID 21737686</ref> and zonula occludens 1 (ZO1).<ref name='nine'>PMID 22016770</ref><br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:ANKRD2&diff=1609273Group:MUZIC:ANKRD22012-11-16T09:12:34Z<p>Narendra Kumar Verma: </p>
<hr />
<div>== '''ANKRD2''' ==<br />
<br />
'''Introduction'''<br />
<br />
Ankyrin repeat-containing protein 2 (stretch responsive muscle) '''Ankrd2''' belongs to the conserved muscle ankyrin repeat protein (MARP) family,<ref name='one'>PMID 10873377</ref> Also known as Arpp.<ref name='two'>PMID 11453652</ref> It is more expressed in skeletal than cardiac muscle, preferentially in type 1 fibers.<ref name='three'>PMID 12004005</ref> Ankrd2 shares approximately 50% homology with the two more MARP family members: Cardiac ankyrin repeat protein (CARP/Ankrd1) and Diabetes related ankyrin repeat protein DARP.Expression of Ankrd2/Arpp is induced in response to various forms of stress and is highly responsive to muscle mechanical status both in vivo and in vitro <ref name='one'>PMID 10873377</ref>,<ref name='four'>PMID 14583192</ref>, as well as to muscle plasticity induced by physical exercise <ref name='five'>PMID 14561590</ref>,<ref name='six'>PMID 15677738</ref>. Apart from the mechanosensory function, Ankrd2/Arpp is a negative regulator of muscle differentiation.<ref name='seven'>PMID 18302940</ref><br />
<br />
== Sequence Annotation ==<br />
<Structure load='2QYJ' size='300' frame='true' align='right' caption='Structure of a designed ankyrin repeat protein (DARPin) with five ankyrin repeat motifs [[2qyj]]' scene='User:Spyros_D._Chatziefthimiou/workbench/ANKRD2/2qyj/1' /><br />
<br />
== Structure ==<br />
<br />
Ankrd2 gene contains 9 exons and spans about 12 kb. The 280 bp long region upstream of the transcription initiation site of the human Ankrd2 gene is sufficient to confer spatial and temporal expression specificity, and contains mainly cis-elements specific for the muscle-specific transcription factor MyoD and for NF-kB. <ref name='eight'>PMID 11444853</ref> Ankrd2 promoter activity is significantly up-regulated by Nkx2.5 <ref name='nine'>PMID 22016770</ref>, upon longitudinal stretch by Akt-dependent NF-kB signaling pathway and in response to transverse stretch by Raf-1-dependent AP-1 signaling pathway. <ref name='ten'>PMID 20442316</ref> The major structural characteristic of the Ankrd2 protein is the presence in the middle portion of four conserved copies of 33-residue ankyrin repeats. In addition Ankrd2 contains a coiled-coil domain that contributes to its self-dimerization, a nuclear localization signal (NLS), allowing its sorting to the nucleus, PEST protein degradation sequence and numerous potential modification sites, mainly for phosphorylation. In particular the phosphorylation of Ankrd2 by the serine/threonine kinase Akt 2 is important for its function in muscle differentiation. <ref name='eleven'>PMID 21737686</ref> The position of Ankrd2 phosphorylation by Akt 2 is Ser 72 which is in close proximity of calpain 3 cleavage site (Arg 77). There are many other consensus phosphorylation sites for casein kinase I (CKI), casein kinase II (CKII), protein kinase C (PKC), extracellular signal regulated kinase (ERK), cAMP- dependent protein kinase, calmodulin-dependent protein kinase II and cGMP-dependent protein kinase <ref name='two'>PMID 11453652</ref>,<ref name='four'>PMID 14583192</ref><br />
<br />
<br />
[[Image:Ankrd.png|center|800px|thumb|Domain architecture and modification sites of '''Ankrd2''']]<br />
<br />
<br />
== Gene Function ==<br />
<br />
Ankrd2 is involved in muscle stress response. It is up-regulated after chronic immobilization in a stretched position.<ref name='one'>PMID 10873377</ref> <ref name='six'>PMID 15677738</ref>, after eccentric contraction <ref name='five'>PMID 14561590</ref> , as well as in injured muscles.<ref name='eleven'>PMID 17926058</ref> Denervation of slow muscle decreases the level of Ankrd2 to below the detection limit in 4 weeks <ref name='six'>PMID 15677738</ref>, whereas denervation of fast muscle increases its expression.<ref name='three'>PMID 12004005</ref><br />
Ankrd2 is not essential for the basal functioning of skeletal muscle, but it is clear its influence on the gene expression program of skeletal muscle cells.<ref name='thirteen'>PMID 17392382</ref> Mainly the Ankrd2 protein has a major role in skeletal muscle formation as a myogenic regulator, since its over-expression in C2C12 myoblasts significantly affects and down-regulates MyoD, myogenin, and their target gene Myh1.<ref name='seven'>PMID 18302940</ref> Altered expression of Ankrd2 has been found in patients suffering from inherited myopathies (muscular dystrophies (MD), congenital myopathies (CM)) and motor neuron diseases (spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS)).<br />
<br />
==Localization== <br />
Ankrd2 is found in the central I-band of the sarcomere, where binds the N2A region of titin. In myoblasts Ankrd2 localizes both in the nuclei, in form of speckles and in the cytoplasm <ref name='seven'>PMID 18302940</ref>, with a diffused pattern. As the differentiation into multinucleated myotubes progresses, Ankrd2 seems to change localization and to accumulate mainly in the cytoplasm <ref>pmid 11444853 </ref>. In general, Ankrd2 protein functions by moving between the sarcomere and the nucleus, mainly in response to stress signals <ref name='fourteen'>PMID 15136035 </ref>.<br />
<br />
==Ankrd2 Interactions==<br />
The Ankrd2/Arpp can interact with titin <ref name='four'>PMID 14583192</ref>, telethonin/T-cap <ref name='fourteen'>PMID 15136035 </ref>, calpain 3 <ref name='fifteen'>PMID 18310072 </ref>, promyelocytic leukemia protein (PML)<ref name='fourteen'>PMID 15136035 </ref>, YB-1 <ref name='fourteen'>PMID 15136035 </ref>, p53 <ref name='fourteen'>PMID 15136035 </ref>, Akt 2 <ref name='eleven'>PMID 21737686</ref> and zonula occludens 1 (ZO1).<ref name='nine'>PMID 22016770</ref><br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=User:Narendra_Kumar_Verma&diff=1601298User:Narendra Kumar Verma2012-11-05T15:42:26Z<p>Narendra Kumar Verma: </p>
<hr />
<div>Narendra Kumar Verma<br />
PhD Student (Marie Curie)<br />
FP7-MUZIC<br />
Narendra Kumar Verma<br />
c/o Lab Lanfranchi<br />
Dipartimento di Biologia<br />
via U. Bassi 58/b<br />
35121 Padova, Italy<br />
e-mail: verm.narendra@gmail.com</div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=User:Narendra_Kumar_Verma&diff=1601297User:Narendra Kumar Verma2012-11-05T15:40:36Z<p>Narendra Kumar Verma: </p>
<hr />
<div>Narendra Kumar Verma<br />
PhD Student (Marie Curie)<br />
FP7-MUZIC<br />
Narendra Kumar Verma<br />
c/o Lab Lanfranchi<br />
Dipartimento di Biologia<br />
via U. Bassi 58/b<br />
35121 Padova, Italy<br />
Tel: 049 8276368<br />
Fax: 049 8276280<br />
e-mail: verm.narendra@gmail.com</div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1600914Group:MUZIC:DARP2012-10-31T10:40:12Z<p>Narendra Kumar Verma: </p>
<hr />
<div>__FORCETOC__<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
'''Sequence Annotation'''<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref> The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively.Silico analysis of promoter of DARP gene indicated the existence of binding site for PPARγ consensus sequence recognised by PPARγ is positioned upstream of transcriptional start site in the DARP gene from -18495 to -18517 base pair.<ref name='three'>PMID 915920</ref><br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts,indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
Its altered expression in transgenic mice with increased or decreased PI3K(p110α) activity has a significant impact on functionality of the Z-disc and,subsequently,cardiac function.PI3K(p110α) protects the heart against myocardial infarction. Togheter with other genes encoding muscle structural/associated proteins, such as dystroglycan (Dag1), filamin C(Flnc), Rho-associated coiled-coil containing protein kinase 2(Rock2), crystallin, α B (Cryab), Cd151, integrin β 1 binding protein 2(Itgb1bp2/melusin), Lim domain binding 3(Ldb3/cypher), and synaptopodin 2 (Synpo2/myopodin), DARP/Ankrd23 was found up-and down-regulated respectively in the caPI3K (consitutively active PI3K)and dnPI3K(dominant negative PI3K.<ref name='six'>PMID PMC3162444 </ref><br />
DARP,calpain-10 and calpain-3 play an important role in the regulation of glucose utilization in skeletal muscle. Calpain-3 activity may be regulated by DARP.<ref name='one'>PMID 14583192 </ref><br />
<br />
== DARP Interactions ==<br />
DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:ANKRD2&diff=1600913Group:MUZIC:ANKRD22012-10-31T10:21:11Z<p>Narendra Kumar Verma: </p>
<hr />
<div>== '''ANKRD2''' ==<br />
<br />
'''Introduction'''<br />
<br />
Ankyrin repeat-containing protein 2 (stretch responsive muscle) '''Ankrd2''' belongs to the conserved muscle ankyrin repeat protein (MARP) family,<ref name='one'>PMID 10873377</ref> Also known as Arpp.<ref name='two'>PMID 11453652</ref> It is more expressed in skeletal than cardiac muscle, preferentially in type 1 fibers.<ref name='three'>PMID 12004005</ref> Ankrd2 shares approximately 50% homology with the two more MARP family members: Cardiac ankyrin repeat protein (CARP/Ankrd1) and Diabetes related ankyrin repeat protein DARP.Expression of Ankrd2/Arpp is induced in response to various forms of stress and is highly responsive to muscle mechanical status both in vivo and in vitro <ref name='one'>PMID 10873377</ref>,<ref name='four'>PMID 14583192</ref>, as well as to muscle plasticity induced by physical exercise <ref name='five'>PMID 14561590</ref>,<ref name='six'>PMID 15677738</ref>. Apart from the mechanosensory function, Ankrd2/Arpp is a negative regulator of muscle differentiation.<ref name='seven'>PMID 18302940</ref><br />
<br />
'''Sequence Annotation''' <br />
<Structure load='2QYJ' size='300' frame='true' align='right' caption='Structure of a designed ankyrin repeat protein (DARPin) with five ankyrin repeat motifs [[2qyj]]' scene='User:Spyros_D._Chatziefthimiou/workbench/ANKRD2/2qyj/1' /><br />
<br />
== Structure ==<br />
<br />
Ankrd2 gene contains 9 exons and spans about 12 kb. The 280 bp long region upstream of the transcription initiation site of the human Ankrd2 gene is sufficient to confer spatial and temporal expression specificity, and contains mainly cis-elements specific for the muscle-specific transcription factor MyoD and for NF-kB. <ref name='eight'>PMID 11444853</ref> Ankrd2 promoter activity is significantly up-regulated by Nkx2.5 <ref name='nine'>PMID 22016770</ref>, upon longitudinal stretch by Akt-dependent NF-kB signaling pathway and in response to transverse stretch by Raf-1-dependent AP-1 signaling pathway. <ref name='ten'>PMID 20442316</ref> The major structural characteristic of the Ankrd2 protein is the presence in the middle portion of four conserved copies of 33-residue ankyrin repeats. In addition Ankrd2 contains a coiled-coil domain that contributes to its self-dimerization, a nuclear localization signal (NLS), allowing its sorting to the nucleus, PEST protein degradation sequence and numerous potential modification sites, mainly for phosphorylation. In particular the phosphorylation of Ankrd2 by the serine/threonine kinase Akt 2 is important for its function in muscle differentiation. <ref name='eleven'>PMID 21737686</ref> The position of Ankrd2 phosphorylation by Akt 2 is Ser 72 which is in close proximity of calpain 3 cleavage site (Arg 77). There are many other consensus phosphorylation sites for casein kinase I (CKI), casein kinase II (CKII), protein kinase C (PKC), extracellular signal regulated kinase (ERK), cAMP- dependent protein kinase, calmodulin-dependent protein kinase II and cGMP-dependent protein kinase <ref name='two'>PMID 11453652</ref>,<ref name='four'>PMID 14583192</ref><br />
<br />
<br />
[[Image:Ankrd.png|center|800px|thumb|Domain architecture and modification sites of '''Ankrd2''']]<br />
<br />
<br />
== Gene Function ==<br />
<br />
Ankrd2 is involved in muscle stress response. It is up-regulated after chronic immobilization in a stretched position.<ref name='one'>PMID 10873377</ref> <ref name='six'>PMID 15677738</ref>, after eccentric contraction <ref name='five'>PMID 14561590</ref> , as well as in injured muscles.<ref name='eleven'>PMID 17926058</ref> Denervation of slow muscle decreases the level of Ankrd2 to below the detection limit in 4 weeks <ref name='six'>PMID 15677738</ref>, whereas denervation of fast muscle increases its expression.<ref name='three'>PMID 12004005</ref><br />
Ankrd2 is not essential for the basal functioning of skeletal muscle, but it is clear its influence on the gene expression program of skeletal muscle cells.<ref name='thirteen'>PMID 17392382</ref> Mainly the Ankrd2 protein has a major role in skeletal muscle formation as a myogenic regulator, since its over-expression in C2C12 myoblasts significantly affects and down-regulates MyoD, myogenin, and their target gene Myh1.<ref name='seven'>PMID 18302940</ref> Altered expression of Ankrd2 has been found in patients suffering from inherited myopathies (muscular dystrophies (MD), congenital myopathies (CM)) and motor neuron diseases (spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS)).<br />
<br />
==Localization== <br />
Ankrd2 is found in the central I-band of the sarcomere, where binds the N2A region of titin. In myoblasts Ankrd2 localizes both in the nuclei, in form of speckles and in the cytoplasm <ref name='seven'>PMID 18302940</ref>, with a diffused pattern. As the differentiation into multinucleated myotubes progresses, Ankrd2 seems to change localization and to accumulate mainly in the cytoplasm <ref>pmid 11444853 </ref>. In general, Ankrd2 protein functions by moving between the sarcomere and the nucleus, mainly in response to stress signals <ref name='fourteen'>PMID 15136035 </ref>.<br />
<br />
==Ankrd2 Interactions==<br />
The Ankrd2/Arpp can interact with titin <ref name='four'>PMID 14583192</ref>, telethonin/T-cap <ref name='fourteen'>PMID 15136035 </ref>, calpain 3 <ref name='fifteen'>PMID 18310072 </ref>, promyelocytic leukemia protein (PML)<ref name='fourteen'>PMID 15136035 </ref>, YB-1 <ref name='fourteen'>PMID 15136035 </ref>, p53 <ref name='fourteen'>PMID 15136035 </ref>, Akt 2 <ref name='eleven'>PMID 21737686</ref> and zonula occludens 1 (ZO1).<ref name='nine'>PMID 22016770</ref><br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:ANKRD2&diff=1600912Group:MUZIC:ANKRD22012-10-31T10:18:30Z<p>Narendra Kumar Verma: </p>
<hr />
<div>== '''ANKRD2''' ==<br />
<br />
'''Introduction'''<br />
<br />
Ankyrin repeat-containing protein 2 (stretch responsive muscle) '''Ankrd2''' belongs to the conserved muscle ankyrin repeat protein (MARP) family,<ref name='one'>PMID 10873377</ref> Also known as Arpp.<ref name='two'>PMID 11453652</ref> It is more expressed in skeletal than cardiac muscle, preferentially in type 1 fibers.<ref name='three'>PMID 12004005</ref> Ankrd2 shares approximately 50% homology with the two more MARP family members: Cardiac ankyrin repeat protein (CARP/Ankrd1) and Diabetes related ankyrin repeat protein DARP.Expression of Ankrd2/Arpp is induced in response to various forms of stress and is highly responsive to muscle mechanical status both in vivo and in vitro <ref name='one'>PMID 10873377</ref>,<ref name='four'>PMID 14583192</ref>, as well as to muscle plasticity induced by physical exercise <ref name='five'>PMID 14561590</ref>,<ref name='six'>PMID 15677738</ref>. Apart from the mechanosensory function, Ankrd2/Arpp is a negative regulator of muscle differentiation.<ref name='seven'>PMID 18302940</ref><br />
'''Sequence Annotation''' <br />
<Structure load='2QYJ' size='300' frame='true' align='right' caption='Structure of a designed ankyrin repeat protein (DARPin) with five ankyrin repeat motifs [[2qyj]]' scene='User:Spyros_D._Chatziefthimiou/workbench/ANKRD2/2qyj/1' /><br />
<br />
== Structure ==<br />
<br />
Ankrd2 gene contains 9 exons and spans about 12 kb. The 280 bp long region upstream of the transcription initiation site of the human Ankrd2 gene is sufficient to confer spatial and temporal expression specificity, and contains mainly cis-elements specific for the muscle-specific transcription factor MyoD and for NF-kB. <ref name='eight'>PMID 11444853</ref> Ankrd2 promoter activity is significantly up-regulated by Nkx2.5 <ref name='nine'>PMID 22016770</ref>, upon longitudinal stretch by Akt-dependent NF-kB signaling pathway and in response to transverse stretch by Raf-1-dependent AP-1 signaling pathway. <ref name='ten'>PMID 20442316</ref> The major structural characteristic of the Ankrd2 protein is the presence in the middle portion of four conserved copies of 33-residue ankyrin repeats. In addition Ankrd2 contains a coiled-coil domain that contributes to its self-dimerization, a nuclear localization signal (NLS), allowing its sorting to the nucleus, PEST protein degradation sequence and numerous potential modification sites, mainly for phosphorylation. In particular the phosphorylation of Ankrd2 by the serine/threonine kinase Akt 2 is important for its function in muscle differentiation. <ref name='eleven'>PMID 21737686</ref> The position of Ankrd2 phosphorylation by Akt 2 is Ser 72 which is in close proximity of calpain 3 cleavage site (Arg 77). There are many other consensus phosphorylation sites for casein kinase I (CKI), casein kinase II (CKII), protein kinase C (PKC), extracellular signal regulated kinase (ERK), cAMP- dependent protein kinase, calmodulin-dependent protein kinase II and cGMP-dependent protein kinase <ref name='two'>PMID 11453652</ref>,<ref name='four'>PMID 14583192</ref><br />
<br />
<br />
[[Image:Ankrd.png|center|800px|thumb|Domain architecture and modification sites of '''Ankrd2''']]<br />
<br />
<br />
== Gene Function ==<br />
<br />
Ankrd2 is involved in muscle stress response. It is up-regulated after chronic immobilization in a stretched position.<ref name='one'>PMID 10873377</ref> <ref name='six'>PMID 15677738</ref>, after eccentric contraction <ref name='five'>PMID 14561590</ref> , as well as in injured muscles.<ref name='eleven'>PMID 17926058</ref> Denervation of slow muscle decreases the level of Ankrd2 to below the detection limit in 4 weeks <ref name='six'>PMID 15677738</ref>, whereas denervation of fast muscle increases its expression.<ref name='three'>PMID 12004005</ref><br />
Ankrd2 is not essential for the basal functioning of skeletal muscle, but it is clear its influence on the gene expression program of skeletal muscle cells.<ref name='thirteen'>PMID 17392382</ref> Mainly the Ankrd2 protein has a major role in skeletal muscle formation as a myogenic regulator, since its over-expression in C2C12 myoblasts significantly affects and down-regulates MyoD, myogenin, and their target gene Myh1.<ref name='seven'>PMID 18302940</ref> Altered expression of Ankrd2 has been found in patients suffering from inherited myopathies (muscular dystrophies (MD), congenital myopathies (CM)) and motor neuron diseases (spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS)).<br />
<br />
==Localization== <br />
Ankrd2 is found in the central I-band of the sarcomere, where binds the N2A region of titin. In myoblasts Ankrd2 localizes both in the nuclei, in form of speckles and in the cytoplasm <ref name='seven'>PMID 18302940</ref>, with a diffused pattern. As the differentiation into multinucleated myotubes progresses, Ankrd2 seems to change localization and to accumulate mainly in the cytoplasm <ref>pmid 11444853 </ref>. In general, Ankrd2 protein functions by moving between the sarcomere and the nucleus, mainly in response to stress signals <ref name='fourteen'>PMID 15136035 </ref>.<br />
<br />
==Ankrd2 Interactions==<br />
The Ankrd2/Arpp can interact with titin <ref name='four'>PMID 14583192</ref>, telethonin/T-cap <ref name='fourteen'>PMID 15136035 </ref>, calpain 3 <ref name='fifteen'>PMID 18310072 </ref>, promyelocytic leukemia protein (PML)<ref name='fourteen'>PMID 15136035 </ref>, YB-1 <ref name='fourteen'>PMID 15136035 </ref>, p53 <ref name='fourteen'>PMID 15136035 </ref>, Akt 2 <ref name='eleven'>PMID 21737686</ref> and zonula occludens 1 (ZO1).<ref name='nine'>PMID 22016770</ref><br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:CARP&diff=1597349Group:MUZIC:CARP2012-10-29T15:51:30Z<p>Narendra Kumar Verma: </p>
<hr />
<div>__FORCETOC__<br />
<br />
'''Introduction'''<br />
<br />
Cardiac ankyrin repeat protein (CARP/Ankrd1) together with ankyrin repeat domain 2 (Ankrd2/Arpp) and with diabetes associated ankyrin repeat protein (DARP), belongs to a conserved muscle ankyrin repeat protein (MARP) family. <ref name='one'>PMID 14583192</ref> CARP/Ankrd1 has been independently identified by several groups as a cytokine-inducible transcriptional regulator, a protein interacting with transcriptional factor YB-1, and a cardiac doxorubicin-responsive protein <ref name='two'>PMID 7730328</ref>,<ref name='three'>PMID 9043061</ref>. In normal tissues, Ankrd1 is highly expressed in cardiac muscle and detectable in skeletal muscles [3]. It is an early differentiation marker during cardiogenesis with a high expression level in developing heart. <ref<br />
name='three'>PMID 9043061</ref>, <ref name='four'>PMID 9278441</ref>. Mutations in the ANKRD1 gene are responsible for human dilated cardiomyopathy. <ref name='five'>PMID 14561590</ref><br />
<br />
'''Sequence Annotation'''<br />
{{STRUCTURE_1n0r| PDB=1n11}}<br />
<br />
== Structure ==<br />
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>.<br />
<br />
== Gene Function ==<br />
<br />
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> <br />
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<br />
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>.<br />
<br />
==Localization== <br />
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>.<br />
<br />
==CARP Interactions==<br />
<br />
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.<br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:CARP&diff=1597348Group:MUZIC:CARP2012-10-29T15:48:53Z<p>Narendra Kumar Verma: </p>
<hr />
<div>__FORCETOC__<br />
<br />
'''Introduction'''<br />
<br />
Cardiac ankyrin repeat protein (CARP/Ankrd1) together with ankyrin repeat domain 2 (Ankrd2/Arpp) and with diabetes associated ankyrin repeat protein (DARP), belongs to a conserved muscle ankyrin repeat protein (MARP) family. <ref name='one'>PMID 14583192</ref> CARP/Ankrd1 has been independently identified by several groups as a cytokine-inducible transcriptional regulator, a protein interacting with transcriptional factor YB-1, and a cardiac doxorubicin-responsive protein <ref name='two'>PMID 7730328</ref>,<ref name='three'>PMID 9043061</ref>. In normal tissues, Ankrd1 is highly expressed in cardiac muscle and detectable in skeletal muscles [3]. It is an early differentiation marker during cardiogenesis with a high expression level in developing heart. <ref<br />
name='three'>PMID 9043061</ref>, <ref name='four'>PMID 9278441</ref>. Mutations in the ANKRD1 gene are responsible for human dilated cardiomyopathy. <ref name='five'>PMID 14561590</ref><br />
<br />
''Sequence Annotation'''<br />
{{STRUCTURE_1n0r| PDB=1n11}}<br />
<br />
== Structure ==<br />
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>.<br />
<br />
== Gene Function ==<br />
<br />
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> <br />
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<br />
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>.<br />
<br />
==Localization== <br />
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>.<br />
<br />
==CARP Interactions==<br />
<br />
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.<br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:CARP&diff=1597295Group:MUZIC:CARP2012-10-29T10:06:36Z<p>Narendra Kumar Verma: </p>
<hr />
<div>__FORCETOC__<br />
<br />
'''Introduction'''<br />
<br />
Cardiac ankyrin repeat protein (CARP/Ankrd1) together with ankyrin repeat domain 2 (Ankrd2/Arpp) and with diabetes associated ankyrin repeat protein (DARP), belongs to a conserved muscle ankyrin repeat protein (MARP) family. <ref name='one'>PMID 14583192</ref> CARP/Ankrd1 has been independently identified by several groups as a cytokine-inducible transcriptional regulator, a protein interacting with transcriptional factor YB-1, and a cardiac doxorubicin-responsive protein <ref name='two'>PMID 7730328</ref>,<ref name='three'>PMID 9043061</ref>. In normal tissues, Ankrd1 is highly expressed in cardiac muscle and detectable in skeletal muscles [3]. It is an early differentiation marker during cardiogenesis with a high expression level in developing heart. <ref<br />
name='three'>PMID 9043061</ref>, <ref name='four'>PMID 9278441</ref>. Mutations in the ANKRD1 gene are responsible for human dilated cardiomyopathy. <ref name='five'>PMID 14561590</ref><br />
{{STRUCTURE_1n0r| PDB=1n11}}<br />
<br />
== Structure ==<br />
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>.<br />
<br />
== Gene Function ==<br />
<br />
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> <br />
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<br />
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>.<br />
<br />
==Localization== <br />
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>.<br />
<br />
==CARP Interactions==<br />
<br />
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.<br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1541361Group:MUZIC:DARP2012-10-08T08:07:57Z<p>Narendra Kumar Verma: </p>
<hr />
<div>__FORCETOC__<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref> The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively.Silico analysis of promoter of DARP gene indicated the existence of binding site for PPARγ consensus sequence recognised by PPARγ is positioned upstream of transcriptional start site in the DARP gene from -18495 to -18517 base pair.<ref name='three'>PMID 915920</ref><br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts,indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
Its altered expression in transgenic mice with increased or decreased PI3K(p110α) activity has a significant impact on functionality of the Z-disc and,subsequently,cardiac function.PI3K(p110α) protects the heart against myocardial infarction. Togheter with other genes encoding muscle structural/associated proteins, such as dystroglycan (Dag1), filamin C(Flnc), Rho-associated coiled-coil containing protein kinase 2(Rock2), crystallin, α B (Cryab), Cd151, integrin β 1 binding protein 2(Itgb1bp2/melusin), Lim domain binding 3(Ldb3/cypher), and synaptopodin 2 (Synpo2/myopodin), DARP/Ankrd23 was found up-and down-regulated respectively in the caPI3K (consitutively active PI3K)and dnPI3K(dominant negative PI3K.<ref name='six'>PMID PMC3162444 </ref><br />
DARP,calpain-10 and calpain-3 play an important role in the regulation of glucose utilization in skeletal muscle. Calpain-3 activity may be regulated by DARP.<ref name='one'>PMID 14583192 </ref><br />
<br />
== DARP Interactions ==<br />
DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1541256Group:MUZIC:DARP2012-10-03T21:16:11Z<p>Narendra Kumar Verma: /* Gene Function */</p>
<hr />
<div>__FORCETOC__<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref> The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively.Silico analysis of promoter of DARP gene indicated the existence of binding site for PPARγ consensus sequence recognised by PPARγ is positioned upstream of transcriptional start site in the DARP gene from -18495 to -18517 bp.<ref name='three'>PMID 915920</ref><br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
Its altered expression in transgenic mice with increased or decreased PI3K(p110α) activity has a significant impact on functionality of the Z-disc and,subsequently,cardiac function.PI3K(p110α) protects the heart against myocardial infarction. Togheter with other genes encoding muscle structural/associated proteins, such as dystroglycan (Dag1), filamin C(Flnc), Rho-associated coiled-coil containing protein kinase 2(Rock2), crystallin, α B (Cryab), Cd151, integrin β 1 binding protein 2(Itgb1bp2/melusin), Lim domain binding 3(Ldb3/cypher), and synaptopodin 2 (Synpo2/myopodin), DARP/Ankrd23 was found up-and down-regulated respectively in the caPI3K (consitutively active PI3K)and dnPI3K(dominant negative PI3K.<ref name='six'>PMID PMC3162444 </ref><br />
DARP,calpain-10 and calpain-3 play an important role in theregulation of glucose utilization in skeletal muscle. Calpain-3 activity may be regulated by DARP.<ref name='one'>PMID 14583192 </ref><br />
<br />
== DARP Interactions ==<br />
DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1541254Group:MUZIC:DARP2012-10-03T21:07:06Z<p>Narendra Kumar Verma: /* DARP Interactions */</p>
<hr />
<div>__FORCETOC__<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref> The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively.Silico analysis of promoter of DARP gene indicated the existence of binding site for PPARγ consensus sequence recognised by PPARγ is positioned upstream of transcriptional start site in the DARP gene from -18495 to -18517 bp.<ref name='three'>PMID 915920</ref><br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
Its altered expression in transgenic mice with increased or decreased PI3K(p110α) activity has a significant impact on functionality of the Z-disc and,subsequently,cardiac function.PI3K(p110α) protects the heart against myocardial infarction. Togheter with other genes encoding muscle structural/associated proteins, such as dystroglycan (Dag1), filamin C(Flnc), Rho-associated coiled-coil containing protein kinase 2(Rock2), crystallin, α B (Cryab), Cd151, integrin β 1 binding protein 2(Itgb1bp2/melusin), Lim domain binding 3(Ldb3/cypher), and synaptopodin 2 (Synpo2/myopodin), DARP/Ankrd23 was found up-and down-regulated respectively in the caPI3K (consitutively active PI3K)and dnPI3K(dominant negative PI3K.<br />
DARP,calpain-10 and calpain-3 play an important role in theregulation of glucose utilization in skeletal muscle. Calpain-3 activity may be regulated by DARP.<ref name='one'>PMID 14583192 </ref><br />
<br />
== DARP Interactions ==<br />
DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1541253Group:MUZIC:DARP2012-10-03T21:06:14Z<p>Narendra Kumar Verma: /* Structure */</p>
<hr />
<div>__FORCETOC__<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref> The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively.Silico analysis of promoter of DARP gene indicated the existence of binding site for PPARγ consensus sequence recognised by PPARγ is positioned upstream of transcriptional start site in the DARP gene from -18495 to -18517 bp.<ref name='three'>PMID 915920</ref><br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
Its altered expression in transgenic mice with increased or decreased PI3K(p110α) activity has a significant impact on functionality of the Z-disc and,subsequently,cardiac function.PI3K(p110α) protects the heart against myocardial infarction. Togheter with other genes encoding muscle structural/associated proteins, such as dystroglycan (Dag1), filamin C(Flnc), Rho-associated coiled-coil containing protein kinase 2(Rock2), crystallin, α B (Cryab), Cd151, integrin β 1 binding protein 2(Itgb1bp2/melusin), Lim domain binding 3(Ldb3/cypher), and synaptopodin 2 (Synpo2/myopodin), DARP/Ankrd23 was found up-and down-regulated respectively in the caPI3K (consitutively active PI3K)and dnPI3K(dominant negative PI3K.<br />
DARP,calpain-10 and calpain-3 play an important role in theregulation of glucose utilization in skeletal muscle. Calpain-3 activity may be regulated by DARP.<ref name='one'>PMID 14583192 </ref><br />
<br />
== DARP Interactions ==<br />
DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref> In<br />
<br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1541252Group:MUZIC:DARP2012-10-03T21:04:46Z<p>Narendra Kumar Verma: </p>
<hr />
<div>__FORCETOC__<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref>The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively.Silico analysis of promoter of DARP gene indicated the existence of binding site for PPARγ consensus sequence recognised by PPARγ is positioned upstream of transcriptional start site in the DARP gene from -18495 to -18517 bp.<ref name='three'>PMID 915920</ref><br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
Its altered expression in transgenic mice with increased or decreased PI3K(p110α) activity has a significant impact on functionality of the Z-disc and,subsequently,cardiac function.PI3K(p110α) protects the heart against myocardial infarction. Togheter with other genes encoding muscle structural/associated proteins, such as dystroglycan (Dag1), filamin C(Flnc), Rho-associated coiled-coil containing protein kinase 2(Rock2), crystallin, α B (Cryab), Cd151, integrin β 1 binding protein 2(Itgb1bp2/melusin), Lim domain binding 3(Ldb3/cypher), and synaptopodin 2 (Synpo2/myopodin), DARP/Ankrd23 was found up-and down-regulated respectively in the caPI3K (consitutively active PI3K)and dnPI3K(dominant negative PI3K.<br />
DARP,calpain-10 and calpain-3 play an important role in theregulation of glucose utilization in skeletal muscle. Calpain-3 activity may be regulated by DARP.<ref name='one'>PMID 14583192 </ref><br />
<br />
== DARP Interactions ==<br />
DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref> In<br />
<br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1541251Group:MUZIC:DARP2012-10-03T21:02:47Z<p>Narendra Kumar Verma: /* Structure */</p>
<hr />
<div>__FORCETOC__<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref>The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively.Silico analysis of promoter of DARP gene indicated the existence of binding site for PPARγ consensus sequence recognised by PPARγ is positioned upstream of transcriptional start site in the DARP gene(from -18495 to -18517 bp).<ref name='three'>PMID 915920</ref><br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
Its altered expression in transgenic mice with increased or decreased PI3K(p110α) activity has a significant impact on functionality of the Z-disc and,subsequently,cardiac function.PI3K(p110α) protects the heart against myocardial infarction. Togheter with other genes encoding muscle structural/associated proteins, such as dystroglycan (Dag1), filamin C(Flnc), Rho-associated coiled-coil containing protein kinase 2(Rock2), crystallin, α B (Cryab), Cd151, integrin β 1 binding protein 2(Itgb1bp2/melusin), Lim domain binding 3(Ldb3/cypher), and synaptopodin 2 (Synpo2/myopodin), DARP/Ankrd23 was found up-and down-regulated respectively in the caPI3K (consitutively active PI3K)and dnPI3K(dominant negative PI3K.<br />
DARP,calpain-10 and calpain-3 play an important role in theregulation of glucose utilization in skeletal muscle. Calpain-3 activity may be regulated by DARP.<ref name='two'>PMID 14583192 </ref><br />
<br />
== DARP Interactions ==<br />
DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref> In<br />
<br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1541249Group:MUZIC:DARP2012-10-03T21:01:09Z<p>Narendra Kumar Verma: /* Gene Function */</p>
<hr />
<div>__FORCETOC__<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref>The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively.Silico analysis of promoter of DARP gene indicated the existence of binding site for PPARγ consensus sequence recognised by PPARγ is positioned upstream of transcriptional start site in the DARP gene(from -18495 to -18517 bp.<ref name='three'>PMID 915920</ref><br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
Its altered expression in transgenic mice with increased or decreased PI3K(p110α) activity has a significant impact on functionality of the Z-disc and,subsequently,cardiac function.PI3K(p110α) protects the heart against myocardial infarction. Togheter with other genes encoding muscle structural/associated proteins, such as dystroglycan (Dag1), filamin C(Flnc), Rho-associated coiled-coil containing protein kinase 2(Rock2), crystallin, α B (Cryab), Cd151, integrin β 1 binding protein 2(Itgb1bp2/melusin), Lim domain binding 3(Ldb3/cypher), and synaptopodin 2 (Synpo2/myopodin), DARP/Ankrd23 was found up-and down-regulated respectively in the caPI3K (consitutively active PI3K)and dnPI3K(dominant negative PI3K.<br />
DARP,calpain-10 and calpain-3 play an important role in theregulation of glucose utilization in skeletal muscle. Calpain-3 activity may be regulated by DARP.<ref name='two'>PMID 14583192 </ref><br />
<br />
== DARP Interactions ==<br />
DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref> In<br />
<br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1541242Group:MUZIC:DARP2012-10-03T20:51:57Z<p>Narendra Kumar Verma: </p>
<hr />
<div>__FORCETOC__<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref>The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively.Silico analysis of promoter of DARP gene indicated the existence of binding site for PPARγ consensus sequence recognised by PPARγ is positioned upstream of transcriptional start site in the DARP gene(from -18495 to -18517 bp.<ref name='three'>PMID 915920</ref><br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
Its altered expression in transgenic mice with increased or decreased PI3K(p110α) activity has a significant impact on functionality of the Z-disc and,subsequently,cardiac function.PI3K(p110α) protects the heart against myocardial infarction. Togheter with other genes encoding muscle structural/associated proteins, such as dystroglycan (Dag1), filamin C(Flnc), Rho-associated coiled-coil containing protein kinase 2(Rock2), crystallin, α B (Cryab), Cd151, integrin β 1 binding protein 2(Itgb1bp2/melusin), Lim domain binding 3(Ldb3/cypher), and synaptopodin 2 (Synpo2/myopodin), DARP/Ankrd23 was found up-and down-regulated respectively in the caPI3K (consitutively active PI3K)and dnPI3K(dominant negative PI3K.<br />
<br />
== DARP Interactions ==<br />
DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref> In<br />
<br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1539007Group:MUZIC:DARP2012-10-02T17:06:49Z<p>Narendra Kumar Verma: /* Gene Function */</p>
<hr />
<div>__FORCETOC__<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref>The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively<br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
Its altered expression in transgenic mice with increased or decreased PI3K(p110α) activity has a significant impact on functionality of the Z-disc and,subsequently,cardiac function.PI3K(p110α) protects the heart against myocardial infarction. Togheter with other genes encoding muscle structural/associated proteins, such as dystroglycan (Dag1), filamin C(Flnc), Rho-associated coiled-coil containing protein kinase 2(Rock2), crystallin, α B (Cryab), Cd151, integrin β 1 binding protein 2(Itgb1bp2/melusin), Lim domain binding 3(Ldb3/cypher), and synaptopodin 2 (Synpo2/myopodin), DARP/Ankrd23 was found up-and down-regulated respectively in the caPI3K (consitutively active PI3K)and dnPI3K(dominant negative PI3K.<br />
<br />
== DARP Interactions ==<br />
DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1539006Group:MUZIC:DARP2012-10-02T17:05:20Z<p>Narendra Kumar Verma: </p>
<hr />
<div>__FORCETOC__<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref>The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively<br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
Its altered expression in transgenic mice with increased or decreased PI3K(p110α) activity has a significant impact on functionality of the Z-disc and,subsequently,cardiac function.PI3K(p110α) protects the heart against<br />
myocardial infarction. Togheter with other genes encoding muscle structural/associated proteins, such as dystroglycan (Dag1), filamin C(Flnc), Rho-associated coiled-coil containing protein kinase 2(Rock2), crystallin, α B (Cryab), Cd151, integrin β 1 binding protein<br />
2(Itgb1bp2/melusin), Lim domain binding 3 (Ldb3/cypher), and synaptopodin 2 (Synpo2/myopodin), DARP/Ankrd23 was found up-and<br />
down-regulated respectively in the caPI3K (consitutively active PI3K)and dnPI3K(dominant negative PI3K.<br />
<br />
== DARP Interactions ==<br />
DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1539005Group:MUZIC:DARP2012-10-02T16:35:43Z<p>Narendra Kumar Verma: </p>
<hr />
<div>__FORCETOC__<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref>The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively<br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
Its altered expression in transgenic mice with increased or decreased PI3K(p110α) activity has a significant impact on functionality of the Z-disc and,subsequently,cardiac function.<br />
<br />
== DARP Interactions ==<br />
DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1538680Group:MUZIC:DARP2012-09-27T14:52:50Z<p>Narendra Kumar Verma: /* Interaction */</p>
<hr />
<div>__FORCETOC__<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref>The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively<br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
<br />
== DARP Interactions ==<br />
DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1538678Group:MUZIC:DARP2012-09-27T14:36:18Z<p>Narendra Kumar Verma: /* Gene Function */</p>
<hr />
<div>__FORCETOC__<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref>The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively<br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
<br />
== Interaction ==<br />
DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1538677Group:MUZIC:DARP2012-09-27T14:35:37Z<p>Narendra Kumar Verma: /* Interaction */</p>
<hr />
<div>__FORCETOC__<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref>The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively<br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
<br />
== Interaction ==<br />
DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1538676Group:MUZIC:DARP2012-09-27T14:34:44Z<p>Narendra Kumar Verma: </p>
<hr />
<div>__FORCETOC__<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref>The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively<br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
<br />
== Interaction ==<br />
DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
<br />
<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1538675Group:MUZIC:DARP2012-09-27T14:34:04Z<p>Narendra Kumar Verma: </p>
<hr />
<div>__FORCETOC__<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref>The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively<br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
<br />
== Interaction ==<br />
.DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
<br />
<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1538674Group:MUZIC:DARP2012-09-27T14:30:20Z<p>Narendra Kumar Verma: /* Structure */</p>
<hr />
<div>__FORCETOC__<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref>The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively.DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1538673Group:MUZIC:DARP2012-09-27T14:28:27Z<p>Narendra Kumar Verma: </p>
<hr />
<div>__FORCETOC__<br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref>The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively.DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
<br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=File:DARP.png&diff=1538672File:DARP.png2012-09-27T13:53:57Z<p>Narendra Kumar Verma: </p>
<hr />
<div>== Licensing ==<br />
{{self|cc-by-sa-3.0|GFDL}}</div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1538671Group:MUZIC:DARP2012-09-27T13:53:17Z<p>Narendra Kumar Verma: /* Structure */</p>
<hr />
<div>__FORCETOC__<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref>The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively.DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
<br />
[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1536599Group:MUZIC:DARP2012-09-26T16:21:07Z<p>Narendra Kumar Verma: /* Structure */</p>
<hr />
<div>__FORCETOC__<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref>The amino acid sequence of DARP showed high similarity to cardiac ankyrin-repeat protein (CARP) and ankyrin-repeat domain 2 (Ankrd2) with 45 and 36% identities, respectively.DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
<br />
[[Image:DARP.jpg|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1536598Group:MUZIC:DARP2012-09-26T12:20:24Z<p>Narendra Kumar Verma: /* Structure */</p>
<hr />
<div>__FORCETOC__<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref> DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
<br />
[[Image:DARP.jpg|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
<br />
== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
<br />
== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:DARP&diff=1536596Group:MUZIC:DARP2012-09-26T09:51:03Z<p>Narendra Kumar Verma: /* Structure */</p>
<hr />
<div>__FORCETOC__<br />
<br />
'''Introduction'''<br />
<br />
Diabetes related ankyrin repeat protein DARP (Ankrd23) and its two close homologs Ankrd2/Arpp and Ankrd1/CARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). <ref name='one'>PMID 14583192</ref> DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism. <ref name='two'>PMID 12456686 </ref><br />
{{STRUCTURE_1n0r | PDB=1svx}}<br />
<br />
== Structure ==<br />
DARP contains putative nuclear localization signals,four tandem ankyrin-like repeats, potential coiled-coil dimerization motif within its unique aminoterminal domain that mediates the formation of homodimers. <ref name='three'>PMID 16450059</ref> DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref><br />
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[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']]<br />
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== Gene Function ==<br />
DARP knock out muscle fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that this protein may play a role in the passive mechanical behavior of muscle. <ref name='four'>PMID 17392382 </ref> DARP expression is altered by a change of energy supply and energy metabolic condition, induced by excess fatty acid treatment in vitro and fasting in vivo. <ref name='two'>PMID 12456686 </ref> The expression of DARP is induced during recovery following starvation.<br />
In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of DARP: staining for DARP was increased in the nucleus, at the I-band region of myofibrils and also at intercalated discs. <ref name='one'>PMID 14583192</ref><br />
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref><br />
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== Refrences ==<br />
<references/></div>Narendra Kumar Vermahttps://proteopedia.org/index.php?title=Group:MUZIC:ANKRD2&diff=1536595Group:MUZIC:ANKRD22012-09-26T09:38:42Z<p>Narendra Kumar Verma: /* Gene Function */</p>
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<div><Structure load='2QYJ' size='300' frame='true' align='right' caption='Structure of a designed ankyrin repeat protein (DARPin) with five ankyrin repeat motifs [[2qyj]]' scene='User:Spyros_D._Chatziefthimiou/workbench/ANKRD2/2qyj/1' /><br />
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== '''ANKRD2''' ==<br />
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'''Introduction'''<br />
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Ankyrin repeat-containing protein 2 (stretch responsive muscle) '''Ankrd2''' belongs to the conserved muscle ankyrin repeat protein (MARP) family,<ref name='one'>PMID 10873377</ref> Also known as Arpp.<ref name='two'>PMID 11453652</ref> It is more expressed in skeletal than cardiac muscle, preferentially in type 1 fibers.<ref name='three'>PMID 12004005</ref> Ankrd2 shares approximately 50% homology with the two more MARP family members: Cardiac ankyrin repeat protein (CARP/Ankrd1) and Diabetes related ankyrin repeat protein DARP.Expression of Ankrd2/Arpp is induced in response to various forms of stress and is highly responsive to muscle mechanical status both in vivo and in vitro <ref name='one'>PMID 10873377</ref>,<ref name='four'>PMID 14583192</ref>, as well as to muscle plasticity induced by physical exercise <ref name='five'>PMID 14561590</ref>,<ref name='six'>PMID 15677738</ref>. Apart from the mechanosensory function, Ankrd2/Arpp is a negative regulator of muscle differentiation.<ref name='seven'>PMID 18302940</ref> <br />
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== Structure ==<br />
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Ankrd2 gene contains 9 exons and spans about 12 kb. The 280 bp long region upstream of the transcription initiation site of the human Ankrd2 gene is sufficient to confer spatial and temporal expression specificity, and contains mainly cis-elements specific for the muscle-specific transcription factor MyoD and for NF-kB. <ref name='eight'>PMID 11444853</ref> Ankrd2 promoter activity is significantly up-regulated by Nkx2.5 <ref name='nine'>PMID 22016770</ref>, upon longitudinal stretch by Akt-dependent NF-kB signaling pathway and in response to transverse stretch by Raf-1-dependent AP-1 signaling pathway. <ref name='ten'>PMID 20442316</ref> The major structural characteristic of the Ankrd2 protein is the presence in the middle portion of four conserved copies of 33-residue ankyrin repeats. In addition Ankrd2 contains a coiled-coil domain that contributes to its self-dimerization, a nuclear localization signal (NLS), allowing its sorting to the nucleus, PEST protein degradation sequence and numerous potential modification sites, mainly for phosphorylation. In particular the phosphorylation of Ankrd2 by the serine/threonine kinase Akt 2 is important for its function in muscle differentiation. <ref name='eleven'>PMID 21737686</ref> The position of Ankrd2 phosphorylation by Akt 2 is Ser 72 which is in close proximity of calpain 3 cleavage site (Arg 77). There are many other consensus phosphorylation sites for casein kinase I (CKI), casein kinase II (CKII), protein kinase C (PKC), extracellular signal regulated kinase (ERK), cAMP- dependent protein kinase, calmodulin-dependent protein kinase II and cGMP-dependent protein kinase <ref name='two'>PMID 11453652</ref>,<ref name='four'>PMID 14583192</ref><br />
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[[Image:Ankrd.png|center|800px|thumb|Domain architecture and modification sites of '''Ankrd2''']]<br />
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== Gene Function ==<br />
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Ankrd2 is involved in muscle stress response. It is up-regulated after chronic immobilization in a stretched position.<ref name='one'>PMID 10873377</ref> <ref name='six'>PMID 15677738</ref>, after eccentric contraction <ref name='five'>PMID 14561590</ref> , as well as in injured muscles.<ref name='eleven'>PMID 17926058</ref> Denervation of slow muscle decreases the level of Ankrd2 to below the detection limit in 4 weeks <ref name='six'>PMID 15677738</ref>, whereas denervation of fast muscle increases its expression.<ref name='three'>PMID 12004005</ref><br />
Ankrd2 is not essential for the basal functioning of skeletal muscle, but it is clear its influence on the gene expression program of skeletal muscle cells.<ref name='thirteen'>PMID 17392382</ref> Mainly the Ankrd2 protein has a major role in skeletal muscle formation as a myogenic regulator, since its over-expression in C2C12 myoblasts significantly affects and down-regulates MyoD, myogenin, and their target gene Myh1.<ref name='seven'>PMID 18302940</ref> Altered expression of Ankrd2 has been found in patients suffering from inherited myopathies (muscular dystrophies (MD), congenital myopathies (CM)) and motor neuron diseases (spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS)).<br />
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==Localization== <br />
Ankrd2 is found in the central I-band of the sarcomere, where binds the N2A region of titin. In myoblasts Ankrd2 localizes both in the nuclei, in form of speckles and in the cytoplasm <ref name='seven'>PMID 18302940</ref>, with a diffused pattern. As the differentiation into multinucleated myotubes progresses, Ankrd2 seems to change localization and to accumulate mainly in the cytoplasm <ref>pmid 11444853 </ref>. In general, Ankrd2 protein functions by moving between the sarcomere and the nucleus, mainly in response to stress signals <ref name='fourteen'>PMID 15136035 </ref>.<br />
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==Ankrd2 Interactions==<br />
The Ankrd2/Arpp can interact with titin <ref name='four'>PMID 14583192</ref>, telethonin/T-cap <ref name='fourteen'>PMID 15136035 </ref>, calpain 3 <ref name='fifteen'>PMID 18310072 </ref>, promyelocytic leukemia protein (PML)<ref name='fourteen'>PMID 15136035 </ref>, YB-1 <ref name='fourteen'>PMID 15136035 </ref>, p53 <ref name='fourteen'>PMID 15136035 </ref>, Akt 2 <ref name='eleven'>PMID 21737686</ref> and zonula occludens 1 (ZO1).<ref name='nine'>PMID 22016770</ref><br />
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== References ==<br />
<references/></div>Narendra Kumar Verma