Group:MUZIC:CARP

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== Structure ==
== Structure ==
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Found on chromosome 10 in humans and 19 in mouse, the ankrd1 gene structure is highly conserved, with nine exons and a canonical TATA box in the proximal promoter. Other canonical response elements identified in the 5' flanking sequence of CARP include GATA sites, E-box elements, a CCAC box, a CAGA box, and M-CAT, activator protein-1, SP-1, p53 binding sites.<ref>pmid 10477291 </ref>, <ref>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 ref>pmid 9278441 </ref>
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Found on chromosome 10 in humans and 19 in mouse, the ankrd1 gene structure is highly conserved, with nine exons and a canonical TATA box in the proximal promoter. Other canonical response elements identified in the 5' flanking sequence of CARP include GATA sites, E-box elements, a CCAC box, a CAGA box, and M-CAT, activator protein-1, SP-1, p53 binding sites.<ref>pmid 10477291 </ref>, <ref>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 <ref>pmid 9278441 </ref>
== Gene Function ==
== Gene Function ==

Revision as of 10:30, 15 August 2011


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

Drag the structure with the mouse to rotate
1n0r, resolution 1.50Å ()
Ligands:
Related: 1n0q
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

Structure

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.[8], [9] 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 [10]

Gene Function

CARP/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>pmid 9043061 </ref> ref>pmid 9278441 </ref>. CARP/Ankrd1 has been found to be induced in the hypertrophy, during cardiac ventricle overload.</ref> ref>pmid 10904011 </ref> and in denervated skeletal muscle </ref> ref>pmid 9382869 </ref> ,</ref> ref>pmid 12004005 </ref>. In skeletal muscle, CARP/Ankrd1 is up-regulated in response to a variety of mechanical stresses, including acute resistance exercise.</ref> ref>pmid 11758972 </ref> and work overload hypertrophy. </ref> ref>pmid 11744623 </ref> CARP/Ankrd1 expression is increased in patients with left ventricular dilated and ischemic cardiomyopathies </ref> ref>pmid 12054667 </ref>, and it has been identified as a candidate gene with a role in congenital heart disease.</ref> ref>pmid 18273862 </ref>

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..[11] cardiac ankyrin repeat protein Ankrd1/CARP as a co-activator of the p53 tumor suppressor protein.[12]

CARP Interactions

CARP has been shown to interacts with the Titin [13] and MYPN. [14]



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. ↑ Kuo H, Chen J, Ruiz-Lozano P, Zou Y, Nemer M, Chien KR. Control of segmental expression of the cardiac-restricted ankyrin repeat protein gene by distinct regulatory pathways in murine cardiogenesis. Development. 1999 Oct;126(19):4223-34. PMID:10477291
  9. ↑ 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
  10. ↑ 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
  11. ↑ 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
  12. ↑ 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
  13. ↑ 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
  14. ↑ 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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