Group:MUZIC:CARP

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Introduction

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 CARDIAC ANKYRIN REPEAT PROTEIN; CARP belongs to the conserved muscle ankyrin repeat protein (MARP) family.[1] 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 [2],[3]. In normal tissues, Ankrd1 is highly expressed in cardiac muscle and detectable in skeletal muscles. [4] It is an early differentiation marker during cardiogenesis with a high expression level in developing heart [5],[6]. Mutations in the ANKRD1 gene are responsible for human dilated cardiomyopathy.[7]

PDB ID 1n11

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1n0r, resolution 1.50Å ()
Ligands:
Related: 1n0q
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

Structure

ANKRD1 was cloned by using the N2A region of titin as bait in a yeast 2-hybrid screen of a skeletal muscle cDNA library,which is also called CARP. [8] full-length cDNA encoding ANKRD1 contains a nuclear localization signal, 4 tandem ankyrin-like repeats, multiple phosphorylation sites, and a PEST-rich region, which is typically found in rapidly degraded proteins.[9]

Gene Function

CARP plays a structural role by interacting with the Z disc protein titin. Ankrd1/CARP 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.Ankrd1/CARP has a role in the propagation of signals initiated by myogenic regulatory factors (MRFs) during myogenesis.[10] CARP overexpression in muscle fibres fails to affect their calibre, indicating that CARP per se cannot initiate atrophy. However, a switch towards fast-twitch fibres is observed, suggesting that CARP plays a role in skeletal muscle plasticity.[11] Mutations in the ANKRD1 gene encoding CARP are responsible for human dilated cardiomyopathy.[12]

Localization

Ankrd1/CARP 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..[13] cardiac ankyrin repeat protein Ankrd1/CARP as a co-activator of the p53 tumor suppressor protein.[14]

CARP Interactions

CARP has been shown to interacts with the Titin [15] and MYPN. [16]



Refrences

  1. ↑ Miller MK, Bang ML, Witt CC, Labeit D, Trombitas C, Watanabe K, Granzier H, McElhinny AS, Gregorio CC, Labeit S. The muscle ankyrin repeat proteins: CARP, ankrd2/Arpp and DARP as a family of titin filament-based stress response molecules. J Mol Biol. 2003 Nov 7;333(5):951-64. PMID:14583192
  2. ↑ Miller MK, Bang ML, Witt CC, Labeit D, Trombitas C, Watanabe K, Granzier H, McElhinny AS, Gregorio CC, Labeit S. The muscle ankyrin repeat proteins: CARP, ankrd2/Arpp and DARP as a family of titin filament-based stress response molecules. J Mol Biol. 2003 Nov 7;333(5):951-64. PMID:14583192
  3. ↑ Zou Y, Evans S, Chen J, Kuo HC, Harvey RP, Chien KR. CARP, a cardiac ankyrin repeat protein, is downstream in the Nkx2-5 homeobox gene pathway. Development. 1997 Feb;124(4):793-804. PMID:9043061
  4. ↑ Zou Y, Evans S, Chen J, Kuo HC, Harvey RP, Chien KR. CARP, a cardiac ankyrin repeat protein, is downstream in the Nkx2-5 homeobox gene pathway. Development. 1997 Feb;124(4):793-804. PMID:9043061
  5. ↑ Zou Y, Evans S, Chen J, Kuo HC, Harvey RP, Chien KR. CARP, a cardiac ankyrin repeat protein, is downstream in the Nkx2-5 homeobox gene pathway. Development. 1997 Feb;124(4):793-804. PMID:9043061
  6. ↑ Jeyaseelan R, Poizat C, Baker RK, Abdishoo S, Isterabadi LB, Lyons GE, Kedes L. A novel cardiac-restricted target for doxorubicin. CARP, a nuclear modulator of gene expression in cardiac progenitor cells and cardiomyocytes. J Biol Chem. 1997 Sep 5;272(36):22800-8. PMID:9278441
  7. ↑ Duboscq-Bidot L, Charron P, Ruppert V, Fauchier L, Richter A, Tavazzi L, Arbustini E, Wichter T, Maisch B, Komajda M, Isnard R, Villard E. Mutations in the ANKRD1 gene encoding CARP are responsible for human dilated cardiomyopathy. Eur Heart J. 2009 Sep;30(17):2128-36. Epub 2009 Jun 12. PMID:19525294 doi:10.1093/eurheartj/ehp225
  8. ↑ Miller MK, Bang ML, Witt CC, Labeit D, Trombitas C, Watanabe K, Granzier H, McElhinny AS, Gregorio CC, Labeit S. The muscle ankyrin repeat proteins: CARP, ankrd2/Arpp and DARP as a family of titin filament-based stress response molecules. J Mol Biol. 2003 Nov 7;333(5):951-64. PMID:14583192
  9. ↑ Chu W, Burns DK, Swerlick RA, Presky DH. Identification and characterization of a novel cytokine-inducible nuclear protein from human endothelial cells. J Biol Chem. 1995 Apr 28;270(17):10236-45. PMID:7730328
  10. ↑ Kojic S, Nestorovic A, Rakicevic L, Belgrano A, Stankovic M, Divac A, Faulkner G. A novel role for cardiac ankyrin repeat protein Ankrd1/CARP as a co-activator of the p53 tumor suppressor protein. Arch Biochem Biophys. 2010 Oct 1;502(1):60-7. Epub 2010 Jul 3. PMID:20599664 doi:10.1016/j.abb.2010.06.029
  11. ↑ Laure L, Suel L, Roudaut C, Bourg N, Ouali A, Bartoli M, Richard I, Daniele N. Cardiac ankyrin repeat protein is a marker of skeletal muscle pathological remodelling. FEBS J. 2009 Feb;276(3):669-84. PMID:19143834 doi:10.1111/j.1742-4658.2008.06814.x
  12. ↑ Duboscq-Bidot L, Charron P, Ruppert V, Fauchier L, Richter A, Tavazzi L, Arbustini E, Wichter T, Maisch B, Komajda M, Isnard R, Villard E. Mutations in the ANKRD1 gene encoding CARP are responsible for human dilated cardiomyopathy. Eur Heart J. 2009 Sep;30(17):2128-36. Epub 2009 Jun 12. PMID:19525294 doi:10.1093/eurheartj/ehp225
  13. ↑ Park JH, Liu L, Kim IH, Kim JH, You KR, Kim DG. Identification of the genes involved in enhanced fenretinide-induced apoptosis by parthenolide in human hepatoma cells. Cancer Res. 2005 Apr 1;65(7):2804-14. PMID:15805281 doi:65/7/2804
  14. ↑ Kojic S, Nestorovic A, Rakicevic L, Belgrano A, Stankovic M, Divac A, Faulkner G. A novel role for cardiac ankyrin repeat protein Ankrd1/CARP as a co-activator of the p53 tumor suppressor protein. Arch Biochem Biophys. 2010 Oct 1;502(1):60-7. Epub 2010 Jul 3. PMID:20599664 doi:10.1016/j.abb.2010.06.029
  15. ↑ Miller MK, Bang ML, Witt CC, Labeit D, Trombitas C, Watanabe K, Granzier H, McElhinny AS, Gregorio CC, Labeit S. The muscle ankyrin repeat proteins: CARP, ankrd2/Arpp and DARP as a family of titin filament-based stress response molecules. J Mol Biol. 2003 Nov 7;333(5):951-64. PMID:14583192
  16. ↑ Bang ML, Mudry RE, McElhinny AS, Trombitas K, Geach AJ, Yamasaki R, Sorimachi H, Granzier H, Gregorio CC, Labeit S. Myopalladin, a novel 145-kilodalton sarcomeric protein with multiple roles in Z-disc and I-band protein assemblies. J Cell Biol. 2001 Apr 16;153(2):413-27. PMID:11309420

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