KAP0_HUMAN
ID KAP0_HUMAN Reviewed; 381 AA.
AC P10644; K7ER48; Q567S7;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 241.
DE RecName: Full=cAMP-dependent protein kinase type I-alpha regulatory subunit;
DE AltName: Full=Tissue-specific extinguisher 1;
DE Short=TSE1;
GN Name=PRKAR1A; Synonyms=PKR1, PRKAR1, TSE1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=3426618; DOI=10.1016/0006-291x(87)90499-2;
RA Sandberg M., Tasken K., Oeyen O., Hansson V., Jahnsen T.;
RT "Molecular cloning, cDNA structure and deduced amino acid sequence for a
RT type I regulatory subunit of cAMP-dependent protein kinase from human
RT testis.";
RL Biochem. Biophys. Res. Commun. 149:939-945(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=2310396; DOI=10.1016/0006-291x(90)91768-n;
RA Sandberg M., Skalhegg B., Jahnsen T.;
RT "The two mRNA forms for the type I alpha regulatory subunit of cAMP-
RT dependent protein kinase from human testis are due to the use of different
RT polyadenylation site signals.";
RL Biochem. Biophys. Res. Commun. 167:323-330(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1889088; DOI=10.1016/0092-8674(91)90433-y;
RA Jones K.W., Shapero M.H., Chevrette M., Fournier R.E.;
RT "Subtractive hybridization cloning of a tissue-specific extinguisher: TSE1
RT encodes a regulatory subunit of protein kinase A.";
RL Cell 66:861-872(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=8977401; DOI=10.1210/endo.138.1.4864;
RA Solberg R., Sandberg M., Natarajan V., Torjesen P.A., Hansson V.,
RA Jahnsen T., Tasken K.;
RT "The human gene for the regulatory subunit RI alpha of cyclic adenosine 3',
RT 5'-monophosphate-dependent protein kinase: two distinct promoters provide
RT differential regulation of alternately spliced messenger ribonucleic
RT acids.";
RL Endocrinology 138:169-181(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 1-13, AND ACETYLATION AT MET-1.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [8]
RP INVOLVEMENT IN PPNAD1.
RX PubMed=12213893; DOI=10.1210/jc.2002-020592;
RA Groussin L., Jullian E., Perlemoine K., Louvel A., Leheup B., Luton J.P.,
RA Bertagna X., Bertherat J.;
RT "Mutations of the PRKAR1A gene in Cushing's syndrome due to sporadic
RT primary pigmented nodular adrenocortical disease.";
RL J. Clin. Endocrinol. Metab. 87:4324-4329(2002).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [10]
RP INTERACTION WITH RFC2.
RX PubMed=15655353;
RA Gupte R.S., Weng Y., Liu L., Lee M.Y.;
RT "The second subunit of the replication factor C complex (RFC40) and the
RT regulatory subunit (RIalpha) of protein kinase A form a protein complex
RT promoting cell survival.";
RL Cell Cycle 4:323-329(2005).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [12]
RP FUNCTION, AND INTERACTION WITH PRKX.
RX PubMed=16491121; DOI=10.1038/sj.onc.1209436;
RA Glesne D., Huberman E.;
RT "Smad6 is a protein kinase X phosphorylation substrate and is required for
RT HL-60 cell differentiation.";
RL Oncogene 25:4086-4098(2006).
RN [13]
RP INTERACTION WITH AICDA.
RX PubMed=16387847; DOI=10.1073/pnas.0509969103;
RA Pasqualucci L., Kitaura Y., Gu H., Dalla-Favera R.;
RT "PKA-mediated phosphorylation regulates the function of activation-induced
RT deaminase (AID) in B cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:395-400(2006).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using sequential
RT IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment
RT and fractionation of phosphopeptides with strong anion exchange
RT chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [22]
RP INTERACTION WITH RARA, AND FUNCTION.
RX PubMed=20215566; DOI=10.1210/en.2009-1338;
RA Santos N.C., Kim K.H.;
RT "Activity of retinoic acid receptor-alpha is directly regulated at its
RT protein kinase A sites in response to follicle-stimulating hormone
RT signaling.";
RL Endocrinology 151:2361-2372(2010).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [25]
RP INVOLVEMENT IN ACRDYS1, AND MUTAGENESIS OF TYR-373.
RX PubMed=21651393; DOI=10.1056/nejmoa1012717;
RA Linglart A., Menguy C., Couvineau A., Auzan C., Gunes Y., Cancel M.,
RA Motte E., Pinto G., Chanson P., Bougneres P., Clauser E., Silve C.;
RT "Recurrent PRKAR1A mutation in acrodysostosis with hormone resistance.";
RL N. Engl. J. Med. 364:2218-2226(2011).
RN [26]
RP INTERACTION WITH PJA2.
RX PubMed=21423175; DOI=10.1038/ncb2209;
RA Lignitto L., Carlucci A., Sepe M., Stefan E., Cuomo O., Nistico R.,
RA Scorziello A., Savoia C., Garbi C., Annunziato L., Feliciello A.;
RT "Control of PKA stability and signalling by the RING ligase praja2.";
RL Nat. Cell Biol. 13:412-422(2011).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [28]
RP INVOLVEMENT IN CNC1.
RX PubMed=22785148; DOI=10.1507/endocrj.ej12-0040;
RA Tung S.C., Hwang D.Y., Yang J.W., Chen W.J., Lee C.T.;
RT "An unusual presentation of Carney complex with diffuse primary pigmented
RT nodular adrenocortical disease on one adrenal gland and a nonpigmented
RT adrenocortical adenoma and focal primary pigmented nodular adrenocortical
RT disease on the other.";
RL Endocr. J. 59:823-830(2012).
RN [29]
RP INTERACTION WITH C2ORF88/SMAKAP, AND SUBCELLULAR LOCATION.
RX PubMed=23115245; DOI=10.1074/jbc.m112.395970;
RA Burgers P.P., Ma Y., Margarucci L., Mackey M., van der Heyden M.A.,
RA Ellisman M., Scholten A., Taylor S.S., Heck A.J.;
RT "A small novel A-kinase anchoring protein (AKAP) that localizes
RT specifically protein kinase A-regulatory subunit I (PKA-RI) to the plasma
RT membrane.";
RL J. Biol. Chem. 287:43789-43797(2012).
RN [30]
RP INVOLVEMENT IN CNC1.
RX PubMed=23323113; DOI=10.4132/koreanjpathol.2012.46.6.595;
RA Park K.U., Kim H.S., Lee S.K., Jung W.W., Park Y.K.;
RT "Novel Mutation in PRKAR1A in Carney Complex.";
RL Korean J. Pathol. 46:595-600(2012).
RN [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [32]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [34]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-75; SER-77 AND SER-83, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [35]
RP INTERACTION WITH PRKACA AND PRKACB.
RX PubMed=33058759; DOI=10.1016/j.ajhg.2020.09.005;
RA Palencia-Campos A., Aoto P.C., Machal E.M.F., Rivera-Barahona A.,
RA Soto-Bielicka P., Bertinetti D., Baker B., Vu L., Piceci-Sparascio F.,
RA Torrente I., Boudin E., Peeters S., Van Hul W., Huber C., Bonneau D.,
RA Hildebrand M.S., Coleman M., Bahlo M., Bennett M.F., Schneider A.L.,
RA Scheffer I.E., Kibaek M., Kristiansen B.S., Issa M.Y., Mehrez M.I.,
RA Ismail S., Tenorio J., Li G., Skaalhegg B.S., Otaify G.A., Temtamy S.,
RA Aglan M., Joench A.E., De Luca A., Mortier G., Cormier-Daire V.,
RA Ziegler A., Wallis M., Lapunzina P., Herberg F.W., Taylor S.S.,
RA Ruiz-Perez V.L.;
RT "Germline and Mosaic Variants in PRKACA and PRKACB Cause a Multiple
RT Congenital Malformation Syndrome.";
RL Am. J. Hum. Genet. 107:977-988(2020).
RN [36]
RP VARIANT CNC1 CYS-74.
RX PubMed=15371594; DOI=10.1073/pnas.0405535101;
RA Veugelers M., Wilkes D., Burton K., McDermott D.A., Song Y.,
RA Goldstein M.M., La Perle K., Vaughan C.J., O'Hagan A., Bennett K.R.,
RA Meyer B.J., Legius E., Karttunen M., Norio R., Kaariainen H., Lavyne M.,
RA Neau J.-P., Richter G., Kirali K., Farnsworth A., Stapleton K., Morelli P.,
RA Takanashi Y., Bamforth J.-S., Eitelberger F., Noszian I., Manfroi W.,
RA Powers J., Mochizuki Y., Imai T., Ko G.T.C., Driscoll D.A., Goldmuntz E.,
RA Edelberg J.M., Collins A., Eccles D., Irvine A.D., McKnight G.S.,
RA Basson C.T.;
RT "Comparative PRKAR1A genotype-phenotype analyses in humans with Carney
RT complex and prkar1a haploinsufficient mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:14222-14227(2004).
RN [37]
RP VARIANTS CNC1 ASN-9; SER-146; TYR-183; ASP-213 AND TRP-289, AND
RP CHARACTERIZATION OF VARIANTS CNC1 ASN-9; CYS-74; SER-146; TYR-183; ASP-213
RP AND TRP-289.
RX PubMed=18241045; DOI=10.1002/humu.20688;
RA Greene E.L., Horvath A.D., Nesterova M., Giatzakis C., Bossis I.,
RA Stratakis C.A.;
RT "In vitro functional studies of naturally occurring pathogenic PRKAR1A
RT mutations that are not subject to nonsense mRNA decay.";
RL Hum. Mutat. 29:633-639(2008).
RN [38]
RP VARIANT ACRDYS1 HIS-373.
RX PubMed=22464250; DOI=10.1016/j.ajhg.2012.03.003;
RA Michot C., Le Goff C., Goldenberg A., Abhyankar A., Klein C., Kinning E.,
RA Guerrot A.M., Flahaut P., Duncombe A., Baujat G., Lyonnet S.,
RA Thalassinos C., Nitschke P., Casanova J.L., Le Merrer M., Munnich A.,
RA Cormier-Daire V.;
RT "Exome sequencing identifies PDE4D mutations as another cause of
RT acrodysostosis.";
RL Am. J. Hum. Genet. 90:740-745(2012).
RN [39]
RP VARIANTS ACRDYS1 THR-327 AND PRO-335.
RX PubMed=22464252; DOI=10.1016/j.ajhg.2012.03.004;
RA Lee H., Graham J.M. Jr., Rimoin D.L., Lachman R.S., Krejci P.,
RA Tompson S.W., Nelson S.F., Krakow D., Cohn D.H.;
RT "Exome sequencing identifies PDE4D mutations in acrodysostosis.";
RL Am. J. Hum. Genet. 90:746-751(2012).
RN [40]
RP VARIANTS ACRDYS1 ARG-285; GLU-289; VAL-328 AND LEU-335.
RX PubMed=23043190; DOI=10.1210/jc.2012-2326;
RA Linglart A., Fryssira H., Hiort O., Holterhus P.M., Perez de Nanclares G.,
RA Argente J., Heinrichs C., Kuechler A., Mantovani G., Leheup B., Wicart P.,
RA Chassot V., Schmidt D., Rubio-Cabezas O., Richter-Unruh A., Berrade S.,
RA Pereda A., Boros E., Munoz-Calvo M.T., Castori M., Gunes Y., Bertrand G.,
RA Bougneres P., Clauser E., Silve C.;
RT "PRKAR1A and PDE4D mutations cause acrodysostosis but two distinct
RT syndromes with or without GPCR-signaling hormone resistance.";
RL J. Clin. Endocrinol. Metab. 97:E2328-E2338(2012).
RN [41]
RP VARIANT ACRDYS1 ALA-239, AND CHARACTERIZATION OF VARIANT ACRDYS1 ALA-239.
RX PubMed=22723333; DOI=10.1210/jc.2012-1369;
RA Nagasaki K., Iida T., Sato H., Ogawa Y., Kikuchi T., Saitoh A., Ogata T.,
RA Fukami M.;
RT "PRKAR1A mutation affecting cAMP-mediated G protein-coupled receptor
RT signaling in a patient with acrodysostosis and hormone resistance.";
RL J. Clin. Endocrinol. Metab. 97:E1808-E1813(2012).
RN [42]
RP VARIANTS ACRDYS1 THR-213 AND CYS-373, AND VARIANT ASN-227.
RX PubMed=23425300; DOI=10.1111/cge.12106;
RA Muhn F., Klopocki E., Graul-Neumann L., Uhrig S., Colley A., Castori M.,
RA Lankes E., Henn W., Gruber-Sedlmayr U., Seifert W., Horn D.;
RT "Novel mutations of the PRKAR1A gene in patients with acrodysostosis.";
RL Clin. Genet. 84:531-538(2013).
RN [43]
RP VARIANT ACRDYS1 CYS-175, CHARACTERIZATION OF VARIANTS ACRDYS1 CYS-175;
RP THR-213; ARG-285; GLU-289; VAL-328 AND LEU-335, CHARACTERIZATION OF
RP VARIANTS CNC1 ASP-213 AND TRP-289, AND FUNCTION.
RX PubMed=26405036; DOI=10.1074/jbc.m115.656553;
RA Rhayem Y., Le Stunff C., Abdel Khalek W., Auzan C., Bertherat J.,
RA Linglart A., Couvineau A., Silve C., Clauser E.;
RT "Functional characterization of PRKAR1A mutations reveals a unique
RT molecular mechanism causing acrodysostosis but multiple mechanisms causing
RT carney complex.";
RL J. Biol. Chem. 290:27816-27828(2015).
CC -!- FUNCTION: Regulatory subunit of the cAMP-dependent protein kinases
CC involved in cAMP signaling in cells. {ECO:0000269|PubMed:16491121,
CC ECO:0000269|PubMed:20215566, ECO:0000269|PubMed:26405036}.
CC -!- SUBUNIT: The inactive holoenzyme is composed of two regulatory chains
CC and two catalytic chains. Activation by cAMP releases the two active
CC catalytic monomers and the regulatory dimer. Interacts with PRKACA and
CC PRKACB (PubMed:33058759). PRKAR1A also interacts with RFC2; the complex
CC may be involved in cell survival. Interacts with AKAP4. Interacts with
CC RARA; the interaction occurs in the presence of cAMP or FSH and
CC regulates RARA transcriptional activity. Interacts with the
CC phosphorylated form of PJA2. Interacts with CBFA2T3 (By similarity).
CC Interacts with PRKX; regulates this cAMP-dependent protein kinase.
CC Interacts with C2orf88/smAKAP; this interaction may target PRKAR1A to
CC the plasma membrane. Interacts with AICDA. {ECO:0000250,
CC ECO:0000269|PubMed:15655353, ECO:0000269|PubMed:16387847,
CC ECO:0000269|PubMed:16491121, ECO:0000269|PubMed:20215566,
CC ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:23115245,
CC ECO:0000269|PubMed:33058759}.
CC -!- INTERACTION:
CC P10644; Q9GZX7: AICDA; NbExp=5; IntAct=EBI-476431, EBI-3834328;
CC P10644; P24588: AKAP5; NbExp=3; IntAct=EBI-476431, EBI-703640;
CC P10644; O43687-2: AKAP7; NbExp=3; IntAct=EBI-476431, EBI-10185182;
CC P10644; Q9H6J7-2: C11orf49; NbExp=3; IntAct=EBI-476431, EBI-13328871;
CC P10644; Q9BSF0: C2orf88; NbExp=9; IntAct=EBI-476431, EBI-744298;
CC P10644; Q86Y01: DTX1; NbExp=3; IntAct=EBI-476431, EBI-1755174;
CC P10644; P0C7A2-2: FAM153B; NbExp=3; IntAct=EBI-476431, EBI-12940382;
CC P10644; Q9H0R8: GABARAPL1; NbExp=2; IntAct=EBI-476431, EBI-746969;
CC P10644; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-476431, EBI-742388;
CC P10644; P17612: PRKACA; NbExp=13; IntAct=EBI-476431, EBI-476586;
CC P10644; P31321: PRKAR1B; NbExp=6; IntAct=EBI-476431, EBI-2805516;
CC P10644; P51817: PRKX; NbExp=2; IntAct=EBI-476431, EBI-4302903;
CC P10644; P35250: RFC2; NbExp=7; IntAct=EBI-476431, EBI-476409;
CC P10644; Q86UC2: RSPH3; NbExp=3; IntAct=EBI-476431, EBI-6873025;
CC P10644; Q01105: SET; NbExp=2; IntAct=EBI-476431, EBI-1053182;
CC P10644; Q8N0X7: SPART; NbExp=3; IntAct=EBI-476431, EBI-2643803;
CC P10644; P03259-2; Xeno; NbExp=5; IntAct=EBI-476431, EBI-7225021;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23115245}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P10644-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P10644-2; Sequence=VSP_054833, VSP_054834;
CC -!- TISSUE SPECIFICITY: Four types of regulatory chains are found: I-alpha,
CC I-beta, II-alpha, and II-beta. Their expression varies among tissues
CC and is in some cases constitutive and in others inducible.
CC -!- PTM: The pseudophosphorylation site binds to the substrate-binding
CC region of the catalytic chain, resulting in the inhibition of its
CC activity.
CC -!- DISEASE: Carney complex 1 (CNC1) [MIM:160980]: CNC is a multiple
CC neoplasia syndrome characterized by spotty skin pigmentation, cardiac
CC and other myxomas, endocrine tumors, and psammomatous melanotic
CC schwannomas. {ECO:0000269|PubMed:15371594, ECO:0000269|PubMed:18241045,
CC ECO:0000269|PubMed:22785148, ECO:0000269|PubMed:23323113,
CC ECO:0000269|PubMed:26405036}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Intracardiac myxoma (INTMYX) [MIM:255960]: Inheritance is
CC autosomal recessive. Note=The disease is caused by variants affecting
CC the gene represented in this entry.
CC -!- DISEASE: Primary pigmented nodular adrenocortical disease 1 (PPNAD1)
CC [MIM:610489]: A rare bilateral adrenal defect causing ACTH-independent
CC Cushing syndrome. Macroscopic appearance of the adrenals is
CC characteristic with small pigmented micronodules observed in the
CC cortex. Clinical manifestations of Cushing syndrome include facial and
CC truncal obesity, abdominal striae, muscular weakness, osteoporosis,
CC arterial hypertension, diabetes. PPNAD1 is most often diagnosed in
CC patients with Carney complex, a multiple neoplasia syndrome. However it
CC can also be observed in patients without other manifestations.
CC {ECO:0000269|PubMed:12213893}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Acrodysostosis 1, with or without hormone resistance (ACRDYS1)
CC [MIM:101800]: A form of skeletal dysplasia characterized by short
CC stature, severe brachydactyly, facial dysostosis, and nasal hypoplasia.
CC Affected individuals often have advanced bone age and obesity.
CC Laboratory studies show resistance to multiple hormones, including
CC parathyroid, thyrotropin, calcitonin, growth hormone-releasing hormone,
CC and gonadotropin. However, not all patients show endocrine
CC abnormalities. {ECO:0000269|PubMed:21651393,
CC ECO:0000269|PubMed:22464250, ECO:0000269|PubMed:22464252,
CC ECO:0000269|PubMed:22723333, ECO:0000269|PubMed:23043190,
CC ECO:0000269|PubMed:23425300, ECO:0000269|PubMed:26405036}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the cAMP-dependent kinase regulatory chain
CC family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PRKAR1AID387.html";
CC ---------------------------------------------------------------------------
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DR EMBL; M18468; AAB50922.1; -; mRNA.
DR EMBL; M33336; AAB50921.1; -; mRNA.
DR EMBL; S54705; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; S54707; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; S54709; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; S54711; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; Y07642; CAA68925.1; -; mRNA.
DR EMBL; AC079210; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC036285; AAH36285.1; -; mRNA.
DR EMBL; BC093042; AAH93042.1; -; mRNA.
DR CCDS; CCDS11678.1; -. [P10644-1]
DR CCDS; CCDS62307.1; -. [P10644-2]
DR PIR; A34627; OKHU1R.
DR RefSeq; NP_001263218.1; NM_001276289.1. [P10644-1]
DR RefSeq; NP_001263219.1; NM_001276290.1. [P10644-2]
DR RefSeq; NP_001265362.1; NM_001278433.1. [P10644-1]
DR RefSeq; NP_002725.1; NM_002734.4. [P10644-1]
DR RefSeq; NP_997636.1; NM_212471.2. [P10644-1]
DR RefSeq; NP_997637.1; NM_212472.2. [P10644-1]
DR RefSeq; XP_011523285.1; XM_011524983.2.
DR RefSeq; XP_011523286.1; XM_011524984.2. [P10644-1]
DR RefSeq; XP_011523287.1; XM_011524985.2.
DR PDB; 5KJX; X-ray; 1.90 A; A=234-381.
DR PDB; 5KJY; X-ray; 2.00 A; A=234-381.
DR PDB; 5KJZ; X-ray; 1.35 A; A=234-381.
DR PDBsum; 5KJX; -.
DR PDBsum; 5KJY; -.
DR PDBsum; 5KJZ; -.
DR AlphaFoldDB; P10644; -.
DR SMR; P10644; -.
DR BioGRID; 111559; 218.
DR DIP; DIP-34368N; -.
DR IntAct; P10644; 193.
DR MINT; P10644; -.
DR STRING; 9606.ENSP00000376475; -.
DR BindingDB; P10644; -.
DR ChEMBL; CHEMBL4928; -.
DR DrugBank; DB01790; (Rp)-cAMPS.
DR DrugBank; DB02527; Cyclic adenosine monophosphate.
DR DrugBank; DB02315; Cyclic GMP.
DR DrugBank; DB05798; GEM-231.
DR GuidetoPHARMACOLOGY; 1472; -.
DR iPTMnet; P10644; -.
DR MetOSite; P10644; -.
DR PhosphoSitePlus; P10644; -.
DR SwissPalm; P10644; -.
DR BioMuta; PRKAR1A; -.
DR DMDM; 125193; -.
DR OGP; P10644; -.
DR REPRODUCTION-2DPAGE; IPI00021831; -.
DR EPD; P10644; -.
DR jPOST; P10644; -.
DR MassIVE; P10644; -.
DR MaxQB; P10644; -.
DR PaxDb; P10644; -.
DR PeptideAtlas; P10644; -.
DR PRIDE; P10644; -.
DR ProteomicsDB; 52634; -. [P10644-1]
DR Antibodypedia; 31783; 378 antibodies from 35 providers.
DR DNASU; 5573; -.
DR Ensembl; ENST00000358598.6; ENSP00000351410.1; ENSG00000108946.16. [P10644-1]
DR Ensembl; ENST00000392711.5; ENSP00000376475.1; ENSG00000108946.16. [P10644-1]
DR Ensembl; ENST00000536854.6; ENSP00000445625.1; ENSG00000108946.16. [P10644-1]
DR Ensembl; ENST00000585427.6; ENSP00000464715.2; ENSG00000108946.16. [P10644-1]
DR Ensembl; ENST00000585981.6; ENSP00000467311.2; ENSG00000108946.16. [P10644-2]
DR Ensembl; ENST00000586397.5; ENSP00000466459.1; ENSG00000108946.16. [P10644-1]
DR Ensembl; ENST00000588178.6; ENSP00000465013.2; ENSG00000108946.16. [P10644-1]
DR Ensembl; ENST00000588188.6; ENSP00000468106.2; ENSG00000108946.16. [P10644-2]
DR Ensembl; ENST00000589017.6; ENSP00000465445.2; ENSG00000108946.16. [P10644-1]
DR Ensembl; ENST00000589228.6; ENSP00000464977.2; ENSG00000108946.16. [P10644-1]
DR Ensembl; ENST00000589480.6; ENSP00000466649.2; ENSG00000108946.16. [P10644-1]
DR GeneID; 5573; -.
DR KEGG; hsa:5573; -.
DR MANE-Select; ENST00000589228.6; ENSP00000464977.2; NM_002734.5; NP_002725.1.
DR UCSC; uc002jhg.5; human. [P10644-1]
DR CTD; 5573; -.
DR DisGeNET; 5573; -.
DR GeneCards; PRKAR1A; -.
DR GeneReviews; PRKAR1A; -.
DR HGNC; HGNC:9388; PRKAR1A.
DR HPA; ENSG00000108946; Low tissue specificity.
DR MalaCards; PRKAR1A; -.
DR MIM; 101800; phenotype.
DR MIM; 160980; phenotype.
DR MIM; 188830; gene.
DR MIM; 255960; phenotype.
DR MIM; 610489; phenotype.
DR neXtProt; NX_P10644; -.
DR OpenTargets; ENSG00000108946; -.
DR Orphanet; 950; Acrodysostosis.
DR Orphanet; 280651; Acrodysostosis with multiple hormone resistance.
DR Orphanet; 520; Acute promyelocytic leukemia.
DR Orphanet; 1359; Carney complex.
DR Orphanet; 615; Familial atrial myxoma.
DR Orphanet; 189439; Primary pigmented nodular adrenocortical disease.
DR PharmGKB; PA33754; -.
DR VEuPathDB; HostDB:ENSG00000108946; -.
DR eggNOG; KOG1113; Eukaryota.
DR GeneTree; ENSGT00940000155148; -.
DR HOGENOM; CLU_018310_1_0_1; -.
DR InParanoid; P10644; -.
DR OMA; VESSFWA; -.
DR PhylomeDB; P10644; -.
DR TreeFam; TF314920; -.
DR PathwayCommons; P10644; -.
DR Reactome; R-HSA-163615; PKA activation.
DR Reactome; R-HSA-164378; PKA activation in glucagon signalling.
DR Reactome; R-HSA-180024; DARPP-32 events.
DR Reactome; R-HSA-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
DR Reactome; R-HSA-432040; Vasopressin regulates renal water homeostasis via Aquaporins.
DR Reactome; R-HSA-442720; CREB1 phosphorylation through the activation of Adenylate Cyclase.
DR Reactome; R-HSA-5610787; Hedgehog 'off' state.
DR Reactome; R-HSA-9634597; GPER1 signaling.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR Reactome; R-HSA-9664323; FCGR3A-mediated IL10 synthesis.
DR Reactome; R-HSA-9700645; ALK mutants bind TKIs.
DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants.
DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production.
DR SignaLink; P10644; -.
DR SIGNOR; P10644; -.
DR BioGRID-ORCS; 5573; 100 hits in 1085 CRISPR screens.
DR ChiTaRS; PRKAR1A; human.
DR GenomeRNAi; 5573; -.
DR Pharos; P10644; Tbio.
DR PRO; PR:P10644; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P10644; protein.
DR Bgee; ENSG00000108946; Expressed in mucosa of paranasal sinus and 205 other tissues.
DR ExpressionAtlas; P10644; baseline and differential.
DR Genevisible; P10644; HS.
DR GO; GO:0005952; C:cAMP-dependent protein kinase complex; IBA:GO_Central.
DR GO; GO:0005813; C:centrosome; IEA:Ensembl.
DR GO; GO:0097546; C:ciliary base; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005771; C:multivesicular body; IEA:Ensembl.
DR GO; GO:0031594; C:neuromuscular junction; IEA:Ensembl.
DR GO; GO:0031588; C:nucleotide-activated protein kinase complex; IDA:BHF-UCL.
DR GO; GO:0044853; C:plasma membrane raft; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0097224; C:sperm connecting piece; IEA:Ensembl.
DR GO; GO:0030552; F:cAMP binding; IBA:GO_Central.
DR GO; GO:0004862; F:cAMP-dependent protein kinase inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0008603; F:cAMP-dependent protein kinase regulator activity; IDA:BHF-UCL.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0034236; F:protein kinase A catalytic subunit binding; IPI:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IDA:UniProtKB.
DR GO; GO:0060038; P:cardiac muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; TAS:ProtInc.
DR GO; GO:0001707; P:mesoderm formation; IEA:Ensembl.
DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; IMP:UniProtKB.
DR GO; GO:2000480; P:negative regulation of cAMP-dependent protein kinase activity; IDA:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; TAS:ProtInc.
DR GO; GO:0045214; P:sarcomere organization; IEA:Ensembl.
DR CDD; cd00038; CAP_ED; 2.
DR Gene3D; 2.60.120.10; -; 2.
DR InterPro; IPR012198; cAMP_dep_PK_reg_su.
DR InterPro; IPR003117; cAMP_dep_PK_reg_su_I/II_a/b.
DR InterPro; IPR018490; cNMP-bd-like.
DR InterPro; IPR018488; cNMP-bd_CS.
DR InterPro; IPR000595; cNMP-bd_dom.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR Pfam; PF00027; cNMP_binding; 2.
DR Pfam; PF02197; RIIa; 1.
DR PIRSF; PIRSF000548; PK_regulatory; 1.
DR SMART; SM00100; cNMP; 2.
DR SMART; SM00394; RIIa; 1.
DR SUPFAM; SSF51206; SSF51206; 2.
DR PROSITE; PS00888; CNMP_BINDING_1; 2.
DR PROSITE; PS00889; CNMP_BINDING_2; 2.
DR PROSITE; PS50042; CNMP_BINDING_3; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; cAMP; cAMP-binding;
KW Cell membrane; Cushing syndrome; Direct protein sequencing;
KW Disease variant; Disulfide bond; Membrane; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..381
FT /note="cAMP-dependent protein kinase type I-alpha
FT regulatory subunit"
FT /id="PRO_0000205377"
FT REGION 1..136
FT /note="Dimerization and phosphorylation"
FT REGION 64..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 96..100
FT /note="Pseudophosphorylation motif"
FT BINDING 137..254
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT BINDING 202
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT BINDING 211
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT BINDING 255..381
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="2"
FT BINDING 326
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="2"
FT BINDING 335
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="2"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|PubMed:12665801,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 3
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09456"
FT MOD_RES 75
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 77
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 83
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18318008, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19367720, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 101
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBC7"
FT MOD_RES 258
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09456"
FT DISULFID 18
FT /note="Interchain (with C-39)"
FT /evidence="ECO:0000250"
FT DISULFID 39
FT /note="Interchain (with C-18)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 326..337
FT /note="EIALLMNRPRAA -> HLIISRRSIPLG (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_054833"
FT VAR_SEQ 338..381
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_054834"
FT VARIANT 9
FT /note="S -> N (in CNC1; exhibits increased PKA activity
FT which is attributed to decreased binding to cAMP and/or the
FT catalytic subunit)"
FT /evidence="ECO:0000269|PubMed:18241045"
FT /id="VAR_046894"
FT VARIANT 74
FT /note="R -> C (in CNC1; exhibits increased PKA activity
FT which is attributed to decreased binding to cAMP and/or the
FT catalytic subunit; dbSNP:rs137853303)"
FT /evidence="ECO:0000269|PubMed:15371594,
FT ECO:0000269|PubMed:18241045"
FT /id="VAR_046895"
FT VARIANT 146
FT /note="R -> S (in CNC1; exhibits increased PKA activity
FT which is attributed to decreased binding to cAMP and/or the
FT catalytic subunit)"
FT /evidence="ECO:0000269|PubMed:18241045"
FT /id="VAR_046896"
FT VARIANT 175
FT /note="Y -> C (in ACRDYS1; reduces PKA activity; decreases
FT cAMP binding)"
FT /evidence="ECO:0000269|PubMed:26405036"
FT /id="VAR_075533"
FT VARIANT 183
FT /note="D -> Y (in CNC1; exhibits increased PKA activity
FT which is attributed to decreased binding to cAMP and/or the
FT catalytic subunit)"
FT /evidence="ECO:0000269|PubMed:18241045"
FT /id="VAR_046897"
FT VARIANT 213
FT /note="A -> D (in CNC1; exhibits increased PKA activity
FT which is attributed to decreased binding to cAMP and/or the
FT catalytic subunit; reduces protein degradation;
FT dbSNP:rs281864786)"
FT /evidence="ECO:0000269|PubMed:18241045,
FT ECO:0000269|PubMed:26405036"
FT /id="VAR_046898"
FT VARIANT 213
FT /note="A -> T (in ACRDYS1; reduces PKA activity; decreases
FT cAMP binding; reduces protein degradation)"
FT /evidence="ECO:0000269|PubMed:23425300,
FT ECO:0000269|PubMed:26405036"
FT /id="VAR_069456"
FT VARIANT 227
FT /note="D -> N"
FT /evidence="ECO:0000269|PubMed:23425300"
FT /id="VAR_069457"
FT VARIANT 239
FT /note="T -> A (in ACRDYS1; impairs response of PKA to c-
FT AMP)"
FT /evidence="ECO:0000269|PubMed:22723333"
FT /id="VAR_069458"
FT VARIANT 285
FT /note="Q -> R (in ACRDYS1; reduces PKA activity; decreases
FT cAMP binding; dbSNP:rs1555814719)"
FT /evidence="ECO:0000269|PubMed:23043190,
FT ECO:0000269|PubMed:26405036"
FT /id="VAR_069459"
FT VARIANT 289
FT /note="G -> E (in ACRDYS1; reduces PKA activity; decreases
FT cAMP binding; reduces protein degradation)"
FT /evidence="ECO:0000269|PubMed:23043190,
FT ECO:0000269|PubMed:26405036"
FT /id="VAR_069460"
FT VARIANT 289
FT /note="G -> W (in CNC1; exhibits increased PKA activity
FT which is attributed to decreased binding to cAMP and/or the
FT catalytic subunit; accelerates protein degradation)"
FT /evidence="ECO:0000269|PubMed:18241045,
FT ECO:0000269|PubMed:26405036"
FT /id="VAR_046899"
FT VARIANT 327
FT /note="I -> T (in ACRDYS1; dbSNP:rs387906695)"
FT /evidence="ECO:0000269|PubMed:22464252"
FT /id="VAR_069461"
FT VARIANT 328
FT /note="A -> V (in ACRDYS1; disrupts cAMP binding)"
FT /evidence="ECO:0000269|PubMed:23043190,
FT ECO:0000269|PubMed:26405036"
FT /id="VAR_069462"
FT VARIANT 335
FT /note="R -> L (in ACRDYS1; disrupts cAMP binding)"
FT /evidence="ECO:0000269|PubMed:23043190,
FT ECO:0000269|PubMed:26405036"
FT /id="VAR_069464"
FT VARIANT 335
FT /note="R -> P (in ACRDYS1; dbSNP:rs387906694)"
FT /evidence="ECO:0000269|PubMed:22464252"
FT /id="VAR_069463"
FT VARIANT 373
FT /note="Y -> C (in ACRDYS1)"
FT /evidence="ECO:0000269|PubMed:23425300"
FT /id="VAR_069465"
FT VARIANT 373
FT /note="Y -> H (in ACRDYS1; dbSNP:rs387906693)"
FT /evidence="ECO:0000269|PubMed:22464250"
FT /id="VAR_068241"
FT MUTAGEN 373
FT /note="Y->A: Impairs response of PKA to c-AMP."
FT /evidence="ECO:0000269|PubMed:21651393"
FT HELIX 237..250
FT /evidence="ECO:0007829|PDB:5KJZ"
FT HELIX 254..256
FT /evidence="ECO:0007829|PDB:5KJZ"
FT HELIX 261..270
FT /evidence="ECO:0007829|PDB:5KJZ"
FT STRAND 272..276
FT /evidence="ECO:0007829|PDB:5KJZ"
FT STRAND 281..283
FT /evidence="ECO:0007829|PDB:5KJZ"
FT STRAND 291..304
FT /evidence="ECO:0007829|PDB:5KJZ"
FT STRAND 313..318
FT /evidence="ECO:0007829|PDB:5KJZ"
FT HELIX 326..330
FT /evidence="ECO:0007829|PDB:5KJZ"
FT STRAND 336..351
FT /evidence="ECO:0007829|PDB:5KJZ"
FT HELIX 352..358
FT /evidence="ECO:0007829|PDB:5KJZ"
FT HELIX 360..362
FT /evidence="ECO:0007829|PDB:5KJZ"
FT HELIX 363..370
FT /evidence="ECO:0007829|PDB:5KJZ"
FT TURN 371..376
FT /evidence="ECO:0007829|PDB:5KJZ"
SQ SEQUENCE 381 AA; 42982 MW; 2D04F08CE8857A6D CRC64;
MESGSTAASE EARSLRECEL YVQKHNIQAL LKDSIVQLCT ARPERPMAFL REYFERLEKE
EAKQIQNLQK AGTRTDSRED EISPPPPNPV VKGRRRRGAI SAEVYTEEDA ASYVRKVIPK
DYKTMAALAK AIEKNVLFSH LDDNERSDIF DAMFSVSFIA GETVIQQGDE GDNFYVIDQG
ETDVYVNNEW ATSVGEGGSF GELALIYGTP RAATVKAKTN VKLWGIDRDS YRRILMGSTL
RKRKMYEEFL SKVSILESLD KWERLTVADA LEPVQFEDGQ KIVVQGEPGD EFFIILEGSA
AVLQRRSENE EFVEVGRLGP SDYFGEIALL MNRPRAATVV ARGPLKCVKL DRPRFERVLG
PCSDILKRNI QQYNSFVSLS V
