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PRKAR1A
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<h2 id="function">Function</h2> <p><a href="/facts/Cyclic_adenosine_monophosphate/flK2vwUe">cAMP</a> is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase A (<a href="/facts/Protein_kinase_A/kaKoYfbp">PKA</a>), which transduces the signal through <a href="/facts/Phosphorylation/LXUEEeIL">phosphorylation</a> of different target proteins. The inactive holoenzyme of PKA is a tetramer composed of two regulatory and two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits of PKA have been identified in humans. The protein encoded by this gene is one of the regulatory subunits. This protein was found to be a tissue-specific extinguisher that downregulates the expression of seven liver genes in hepatoma x fibroblast hybrids Three alternatively spliced transcript variants encoding the same protein have been observed.<a class="footnote-ref" id="fnref:2" href="#fn:2"><sup>2</sup></a> </p> <h2 id="clinical-significance">Clinical significance</h2> <p>Functional null mutations in this gene cause <a href="/facts/Carney_complex/twXYKx2z">Carney complex</a> (CNC), an autosomal dominant multiple neoplasia syndrome. This gene can fuse to the RET protooncogene by gene rearrangement and form the thyroid tumor-specific chimeric oncogene known as PTC2.<a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a> </p><p>Mutation of PRKAR1A leads to the Carney complex, associating multiple endocrine tumors. </p> <h2 id="interactions">Interactions</h2> <p>PRKAR1A has been shown to <a href="/facts/Protein-protein_interaction/etvm9Wmg">interact</a> with: </p> <ul><li><a href="/facts/AKAP10/VBwuG3h7">AKAP10</a>,<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a><a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a></li> <li><a href="/facts/AKAP1/QmQCozvN">AKAP1</a>,<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a><a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a></li> <li><a href="/facts/AKAP4/AzwPtVGI">AKAP4</a>,<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a><a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a></li> <li><a href="/facts/ARFGEF1/Xz8kCnW3">ARFGEF1</a>,<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a></li> <li><a href="/facts/ARFGEF2/BfJ6jzwR">ARFGEF2</a>,<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a></li> <li><a href="/facts/Grb2/uaFzqAbM">Grb2</a>,<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a></li> <li><a href="/facts/MYO7A/NuhwlACg">MYO7A</a>,<a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a></li> <li><a href="/facts/PRKAR1B/qs1Y8GvP">PRKAR1B</a>,<a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a><a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a> and</li> <li><a href="/facts/UBE2M/lTkqSMl5">UBE2M</a>.<a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a></li></ul> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/CAMP-dependent_protein_kinase/kaKoYfbp">cAMP-dependent protein kinase</a></li></ul> <h2 id="further-reading">Further reading</h2> <ul><li>Stratakis CA (2002). "Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit (PRKAR1A) in patients with the "complex of spotty skin pigmentation, myxomas, endocrine overactivity, and schwannomas" (Carney complex)". <i>Ann. N. Y. Acad. Sci</i>. 968 (1): 3–21. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/2002NYASA.968....3S">2002NYASA.968....3S</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1111%2Fj.1749-6632.2002.tb04323.x">10.1111/j.1749-6632.2002.tb04323.x</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12119264">12119264</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:26108486">26108486</a>.</li> <li>Bourdeau I, Stratakis CA (2002). "Cyclic AMP-dependent signaling aberrations in macronodular adrenal disease". <i>Ann. N. Y. Acad. Sci</i>. 968 (1): 240–55. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/2002NYASA.968..240B">2002NYASA.968..240B</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1111%2Fj.1749-6632.2002.tb04339.x">10.1111/j.1749-6632.2002.tb04339.x</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12119280">12119280</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:22397904">22397904</a>.</li> <li>Alto N, Carlisle Michel JJ, Dodge KL, Langeberg LK, Scott JD (2003). <a href="https://doi.org/10.2337%2Fdiabetes.51.2007.s385">"Intracellular targeting of protein kinases and phosphatases"</a>. <i>Diabetes</i>. 51 (Suppl 3): S385–8. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.2337%2Fdiabetes.51.2007.s385">10.2337/diabetes.51.2007.s385</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12475780">12475780</a>.</li> <li>Stergiopoulos SG, Stratakis CA (2003). "Human tumors associated with Carney complex and germline PRKAR1A mutations: a protein kinase A disease!". <i>FEBS Lett</i>. 546 (1): 59–64. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0014-5793%2803%2900452-6">10.1016/S0014-5793(03)00452-6</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12829237">12829237</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:37055425">37055425</a>.</li> <li>Bossis I, Stratakis CA (2004). <a href="https://doi.org/10.1210%2Fen.2004-0900">"Minireview: PRKAR1A: normal and abnormal functions"</a>. <i>Endocrinology</i>. 145 (12): 5452–8. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1210%2Fen.2004-0900">10.1210/en.2004-0900</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/15331577">15331577</a>.</li> <li>Cho-Chung YS, Nesterova MV (2006). <a href="https://zenodo.org/record/1235884">"Tumor reversion: protein kinase A isozyme switching"</a>. <i>Ann. N. Y. Acad. Sci</i>. 1058: 76–86. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1196%2Fannals.1359.014">10.1196/annals.1359.014</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/16394127">16394127</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:45471438">45471438</a>.</li> <li>Lytras A, Tolis G (2006). "Growth hormone-secreting tumors: genetic aspects and data from animal models". <i>Neuroendocrinology</i>. 83 (3–4): 166–78. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1159%2F000095525">10.1159/000095525</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/17047380">17047380</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:45606794">45606794</a>.</li> <li>Harrich D, McMillan N, Munoz L, Apolloni A, Meredith L (2007). "Will diverse Tat interactions lead to novel antiretroviral drug targets?". <i>Current Drug Targets</i>. 7 (12): 1595–606. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.2174%2F138945006779025338">10.2174/138945006779025338</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/17168834">17168834</a>.</li> <li>Boshart M, Weih F, Nichols M, Schütz G (1991). <a href="https://epub.ub.uni-muenchen.de/3205/1/010.pdf">"The tissue-specific extinguisher locus TSE1 encodes a regulatory subunit of cAMP-dependent protein kinase"</a> (PDF). <i>Cell</i>. 66 (5): 849–59. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2F0092-8674%2891%2990432-X">10.1016/0092-8674(91)90432-X</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/1832337">1832337</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:8277752">8277752</a>.</li> <li>Jones KW, Shapero MH, Chevrette M, Fournier RE (1991). "Subtractive hybridization cloning of a tissue-specific extinguisher: TSE1 encodes a regulatory subunit of protein kinase A". <i>Cell</i>. 66 (5): 861–72. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2F0092-8674%2891%2990433-Y">10.1016/0092-8674(91)90433-Y</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/1889088">1889088</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:24273073">24273073</a>.</li> <li>Hofmann B, Nishanian P, Baldwin RL, Insixiengmay P, Nel A, Fahey JL (1991). <a href="https://doi.org/10.4049%2Fjimmunol.145.11.3699">"HIV inhibits the early steps of lymphocyte activation, including initiation of inositol phospholipid metabolism"</a>. <i>J. Immunol</i>. 145 (11): 3699–705. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.4049%2Fjimmunol.145.11.3699">10.4049/jimmunol.145.11.3699</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/1978848">1978848</a>.</li> <li>Sandberg M, Skålhegg B, Jahnsen T (1990). "The two mRNA forms for the type I alpha regulatory subunit of cAMP-dependent protein kinase from human testis are due to the use of different polyadenylation site signals". <i>Biochem. Biophys. Res. Commun</i>. 167 (1): 323–30. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2F0006-291X%2890%2991768-N">10.1016/0006-291X(90)91768-N</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/2310396">2310396</a>.</li> <li>Lem J, Chin AC, Thayer MJ, Leach RJ, Fournier RE (1988). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC282174">"Coordinate regulation of two genes encoding gluconeogenic enzymes by the trans-dominant locus Tse-1"</a>. <i>Proc. Natl. Acad. Sci. U.S.A</i>. 85 (19): 7302–6. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/1988PNAS...85.7302L">1988PNAS...85.7302L</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1073%2Fpnas.85.19.7302">10.1073/pnas.85.19.7302</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC282174">282174</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/2902627">2902627</a>.</li> <li>Sandberg M, Taskén K, Oyen O, Hansson V, Jahnsen T (1988). "Molecular cloning, cDNA structure and deduced amino acid sequence for a type I regulatory subunit of cAMP-dependent protein kinase from human testis". <i>Biochem. Biophys. Res. Commun</i>. 149 (3): 939–45. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2F0006-291X%2887%2990499-2">10.1016/0006-291X(87)90499-2</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/3426618">3426618</a>.</li> <li>Geahlen RL, Carmichael DF, Hashimoto E, Krebs EG (1982). "Phosphorylation of cAMP-dependent protein kinase subunits". <i>Adv. Enzyme Regul</i>. 20: 195–209. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2F0065-2571%2882%2990016-4">10.1016/0065-2571(82)90016-4</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/6287816">6287816</a>.</li> <li>Guild BC, Strominger JL (1984). <a href="https://doi.org/10.1016%2FS0021-9258%2818%2990722-2">"HLA-A2 antigen phosphorylation in vitro by cyclic AMP-dependent protein kinase. Sites of phosphorylation and segmentation in class i major histocompatibility complex gene structure"</a>. <i>J. Biol. Chem</i>. 259 (21): 13504–10. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0021-9258%2818%2990722-2">10.1016/S0021-9258(18)90722-2</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/6333425">6333425</a>.</li> <li>Bongarzone I, Monzini N, Borrello MG, Carcano C, Ferraresi G, Arighi E, Mondellini P, Della Porta G, Pierotti MA (1993). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC358915">"Molecular characterization of a thyroid tumor-specific transforming sequence formed by the fusion of ret tyrosine kinase and the regulatory subunit RI alpha of cyclic AMP-dependent protein kinase A"</a>. <i>Mol. Cell. Biol</i>. 13 (1): 358–66. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1128%2FMCB.13.1.358">10.1128/MCB.13.1.358</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC358915">358915</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/7678053">7678053</a>.</li> <li>Hofmann B, Nishanian P, Nguyen T, Insixiengmay P, Fahey JL (1993). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC46995">"Human immunodeficiency virus proteins induce the inhibitory cAMP/protein kinase A pathway in normal lymphocytes"</a>. <i>Proc. Natl. Acad. Sci. U.S.A</i>. 90 (14): 6676–80. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/1993PNAS...90.6676H">1993PNAS...90.6676H</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1073%2Fpnas.90.14.6676">10.1073/pnas.90.14.6676</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC46995">46995</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/7688126">7688126</a>.</li> <li>Hofmann B, Nishanian P, Fan J, Nguyen T, Fahey JL (1994). "HIV Gag p17 protein impairs proliferation of normal lymphocytes in vitro". <i>AIDS</i>. 8 (7): 1016–7. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1097%2F00002030-199407000-00025">10.1097/00002030-199407000-00025</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/7946090">7946090</a>.</li></ul> <h2 id="external-links">External links</h2> <ul><li><a href="https://www.ebi.ac.uk/pdbe/pdbe-kb/proteins/P10644">PDBe-KB</a> provides an overview of all the structure information available in the PDB for Human cAMP-dependent protein kinase type I-alpha regulatory subunit (PRKAR1A)</li></ul> <p><i>This article incorporates text from the <a href="/facts/United_States_National_Library_of_Medicine/Hzty0MCX">United States National Library of Medicine</a>, which is in the <a href="/facts/Public_domain/YWKMDKw4">public domain</a>.</i> </p> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Scambler P, Oyen O, Wainwright B, Farrall M, Law HY, Estivill X, Sandberg M, Williamson R, Jahnsen T (December 1987). "Exclusion of catalytic and regulatory subunits of cAMP-dependent protein kinase as candidate genes for the defect causing cystic fibrosis". Am J Hum Genet. 41 (5): 925–32. PMC 1684338. PMID 3479018. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1684338" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1684338</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>"Entrez Gene: PRKAR1A protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1)". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5573" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5573</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>"Entrez Gene: PRKAR1A protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1)". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5573" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5573</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Huang LJ, Durick K, Weiner JA, Chun J, Taylor SS (October 1997). "D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain". Proc. Natl. Acad. Sci. U.S.A. 94 (21): 11184–9. Bibcode:1997PNAS...9411184J. doi:10.1073/pnas.94.21.11184. PMC 23409. PMID 9326583. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC23409" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC23409</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026. <a href="/wiki/Bibcode_(identifier)" target="_blank">/wiki/Bibcode_(identifier)</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Carlson CR, Ruppelt A, Taskén K (March 2003). "A kinase anchoring protein (AKAP) interaction and dimerization of the RIalpha and RIbeta regulatory subunits of protein kinase a in vivo by the yeast two hybrid system". J. Mol. Biol. 327 (3): 609–18. doi:10.1016/s0022-2836(03)00093-7. PMID 12634056. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Herberg FW, Maleszka A, Eide T, Vossebein L, Tasken K (April 2000). "Analysis of A-kinase anchoring protein (AKAP) interaction with protein kinase A (PKA) regulatory subunits: PKA isoform specificity in AKAP binding". J. Mol. Biol. 298 (2): 329–39. doi:10.1006/jmbi.2000.3662. 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