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| ==Pseudo-atomic model of the AKAP18-PKA Complex in a linear conformation derived from electron microscopy== | | ==Pseudo-atomic model of the AKAP18-PKA Complex in a linear conformation derived from electron microscopy== |
| <StructureSection load='3j4r' size='340' side='right' caption='[[3j4r]], [[Resolution|resolution]] 35.00Å' scene=''> | | <SX load='3j4r' size='340' side='right' viewer='molstar' caption='[[3j4r]], [[Resolution|resolution]] 35.00Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[3j4r]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3J4R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3J4R FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3j4r]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3J4R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3J4R FirstGlance]. <br> |
| </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3j4q|3j4q]]</td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 35Å</td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Prkar2a, mCG_16488 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Prkaca, Pkaca ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3j4r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3j4r OCA], [https://pdbe.org/3j4r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3j4r RCSB], [https://www.ebi.ac.uk/pdbsum/3j4r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3j4r ProSAT]</span></td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/cAMP-dependent_protein_kinase cAMP-dependent protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.11 2.7.11.11] </span></td></tr>
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| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3j4r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3j4r OCA], [http://pdbe.org/3j4r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3j4r RCSB], [http://www.ebi.ac.uk/pdbsum/3j4r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3j4r ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/KAPCA_MOUSE KAPCA_MOUSE]] Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, TRPC1 and VASP. RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP. Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+). TRPC1 activation by phosphorylation promotes Ca(2+) influx, essential for the increase in permeability induced by thrombin in confluent endothelial monolayers. PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Regulates negatively tight junction (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT).<ref>PMID:15340140</ref> <ref>PMID:19223768</ref> <ref>PMID:19560455</ref> | | [https://www.uniprot.org/uniprot/AKA7G_RAT AKA7G_RAT] Probably targets cAMP-dependent protein kinase (PKA) to the cellular membrane or cytoskeletal structures. The membrane-associated form reduces epithelial sodium channel (ENaC) activity, whereas the free cytoplasmic form may negatively regulate ENaC channel feedback inhibition by intracellular sodium (By similarity). Isoform Delta may be involved in shuttling aquaporin-2 (AQP2) to the plasma membrane.[UniProtKB:Q9P0M2]<ref>PMID:15037626</ref> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Anchoring proteins sequester kinases with their substrates to locally disseminate intracellular signals and avert indiscriminate transmission of these responses throughout the cell. Mechanistic understanding of this process is hampered by limited structural information on these macromolecular complexes. A-kinase anchoring proteins (AKAPs) spatially constrain phosphorylation by cAMP-dependent protein kinases (PKA). Electron microscopy and three-dimensional reconstructions of type-II PKA-AKAP18gamma complexes reveal hetero-pentameric assemblies that adopt a range of flexible tripartite configurations. Intrinsically disordered regions within each PKA regulatory subunit impart the molecular plasticity that affords an approximately 16 nanometer radius of motion to the associated catalytic subunits. Manipulating flexibility within the PKA holoenzyme augmented basal and cAMP responsive phosphorylation of AKAP-associated substrates. Cell-based analyses suggest that the catalytic subunit remains within type-II PKA-AKAP18gamma complexes upon cAMP elevation. We propose that the dynamic movement of kinase sub-structures, in concert with the static AKAP-regulatory subunit interface, generates a solid-state signaling microenvironment for substrate phosphorylation. DOI: http://dx.doi.org/10.7554/eLife.01319.001.
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| Intrinsic disorder within an AKAP-protein kinase A complex guides local substrate phosphorylation.,Smith FD, Reichow SL, Esseltine JL, Shi D, Langeberg LK, Scott JD, Gonen T Elife. 2013 Nov 5;2(0). pii: e01319. doi: 10.7554/eLife.01319. PMID:24192038<ref>PMID:24192038</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 3j4r" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[A-kinase anchor protein|A-kinase anchor protein]] | | *[[A-kinase anchor protein 3D structures|A-kinase anchor protein 3D structures]] |
| *[[CAMP-dependent protein kinase|CAMP-dependent protein kinase]] | | *[[CAMP-dependent protein kinase 3D structures|CAMP-dependent protein kinase 3D structures]] |
| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </SX> |
| [[Category: Human]] | | [[Category: Homo sapiens]] |
| [[Category: Lk3 transgenic mice]] | | [[Category: Large Structures]] |
| [[Category: CAMP-dependent protein kinase]] | | [[Category: Mus musculus]] |
| [[Category: Gonen, T]] | | [[Category: Gonen T]] |
| [[Category: Reichow, S L]] | | [[Category: Reichow SL]] |
| [[Category: A-kinase anchoring protein]]
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| [[Category: Anchoring]]
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| [[Category: Camp-dependent kinase]]
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| [[Category: Intrinsic disorder]]
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| [[Category: Phosphorylation]]
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| [[Category: Pka regulatory subunit ii]]
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| [[Category: Rii]]
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| [[Category: Transferase]]
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