Group:MUZIC:DARP: Difference between revisions
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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> | 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> | ||
== Sequence Annotation == | |||
http://www.uniprot.org/uniprot/Q812A3 | |||
{{STRUCTURE_1n0r | PDB=1svx}} | {{STRUCTURE_1n0r | PDB=1svx}} | ||
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[[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']] | [[Image:DARP.png|center|800px|thumb|Domain architecture and modification sites of '''DARP''']] | ||
== Gene Function == | == Gene Function and Interactions == | ||
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. | 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. | ||
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> | 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> | ||
Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref> | Differently from its homolog genes, DARP is not upregulated after ECs.<ref name='five'>PMID 14561590 </ref> | ||
DARP interacts with a tyrosine-rich binding motif between Ig80 and Ig81 of titin and with myopalladin. <ref name='one'>PMID 14583192</ref> | |||
== Pathology == | |||
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> | 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> | ||
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 | 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 | ||
== Refrences == | == Refrences == | ||
<references/> | <references/> | ||
