KAPCA_HUMAN
ID KAPCA_HUMAN Reviewed; 351 AA.
AC P17612; Q32P54; Q9H2Y0; Q9NRB4; Q9NRH9;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 241.
DE RecName: Full=cAMP-dependent protein kinase catalytic subunit alpha;
DE Short=PKA C-alpha;
DE EC=2.7.11.11;
GN Name=PRKACA; Synonyms=PKACA;
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).
RX PubMed=2843813; DOI=10.1093/nar/16.16.8189;
RA Maldonado F., Hanks S.K.;
RT "A cDNA clone encoding human cAMP-dependent protein kinase catalytic
RT subunit C alpha.";
RL Nucleic Acids Res. 16:8189-8190(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye, and Testis;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-189 (ISOFORM 2), SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=10906071; DOI=10.1095/biolreprod63.2.607;
RA Reinton N., Orstavik S., Haugen T.B., Jahnsen T., Tasken K., Skalhegg B.S.;
RT "A novel isoform of human cyclic 3',5'-adenosine monophosphate-dependent
RT protein kinase, c alpha-s, localizes to sperm midpiece.";
RL Biol. Reprod. 63:607-611(2000).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-152 (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=10982398; DOI=10.1091/mbc.11.9.3031;
RA San Agustin J.T., Wilkerson C.G., Witman G.B.;
RT "The unique catalytic subunit of sperm cAMP-dependent protein kinase is the
RT product of an alternative C-alpha mRNA expressed specifically in
RT spermatogenic cells.";
RL Mol. Biol. Cell 11:3031-3044(2000).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-39 (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=10841548; DOI=10.1073/pnas.97.12.6433;
RA Desseyn J.-L., Burton K.A., McKnight G.S.;
RT "Expression of a nonmyristylated variant of the catalytic subunit of
RT protein kinase A during male germ-cell development.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:6433-6438(2000).
RN [9]
RP AUTOPHOSPHORYLATION, PHOSPHORYLATION AT THR-196, PHOSPHORYLATION AT THR-198
RP BY PDK1, AND MUTAGENESIS OF ARG-195; GLY-201 AND THR-202.
RX PubMed=12372837; DOI=10.1074/jbc.m204970200;
RA Moore M.J., Kanter J.R., Jones K.C., Taylor S.S.;
RT "Phosphorylation of the catalytic subunit of protein kinase A.
RT Autophosphorylation versus phosphorylation by phosphoinositide-dependent
RT kinase-1.";
RL J. Biol. Chem. 277:47878-47884(2002).
RN [10]
RP INTERACTION WITH RAB13.
RX PubMed=15096524; DOI=10.1083/jcb.200312118;
RA Koehler K., Louvard D., Zahraoui A.;
RT "Rab13 regulates PKA signaling during tight junction assembly.";
RL J. Cell Biol. 165:175-180(2004).
RN [11]
RP FUNCTION AS NFKB1 KINASE.
RX PubMed=15642694; DOI=10.1074/jbc.m412180200;
RA Guan H., Hou S., Ricciardi R.P.;
RT "DNA binding of repressor nuclear factor-kappaB p50/p50 depends on
RT phosphorylation of Ser337 by the protein kinase A catalytic subunit.";
RL J. Biol. Chem. 280:9957-9962(2005).
RN [12]
RP FUNCTION AS CLDN3 KINASE.
RX PubMed=15905176; DOI=10.1074/jbc.m502003200;
RA D'Souza T., Agarwal R., Morin P.J.;
RT "Phosphorylation of claudin-3 at threonine 192 by cAMP-dependent protein
RT kinase regulates tight junction barrier function in ovarian cancer cells.";
RL J. Biol. Chem. 280:26233-26240(2005).
RN [13]
RP FUNCTION, AND 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 FUNCTION IN PROTEASOME REGULATION, AND FUNCTION AS PSMC5/RPT6 KINASE.
RX PubMed=17565987; DOI=10.1074/jbc.m702439200;
RA Zhang F., Hu Y., Huang P., Toleman C.A., Paterson A.J., Kudlow J.E.;
RT "Proteasome function is regulated by cyclic AMP-dependent protein kinase
RT through phosphorylation of Rpt6.";
RL J. Biol. Chem. 282:22460-22471(2007).
RN [15]
RP FUNCTION AS RYR2 KINASE.
RX PubMed=17693412; DOI=10.1074/jbc.m703510200;
RA Xiao B., Tian X., Xie W., Jones P.P., Cai S., Wang X., Jiang D., Kong H.,
RA Zhang L., Chen K., Walsh M.P., Cheng H., Chen S.R.W.;
RT "Functional consequence of protein kinase A-dependent phosphorylation of
RT the cardiac ryanodine receptor: sensitization of store overload-induced
RT Ca2+ release.";
RL J. Biol. Chem. 282:30256-30264(2007).
RN [16]
RP PHOSPHORYLATION, AND ACTIVITY REGULATION.
RX PubMed=17909264; DOI=10.1677/jme-07-0048;
RA Ichikawa T., Horie-Inoue K., Ikeda K., Blumberg B., Inoue S.;
RT "Vitamin K2 induces phosphorylation of protein kinase A and expression of
RT novel target genes in osteoblastic cells.";
RL J. Mol. Endocrinol. 39:239-247(2007).
RN [17]
RP FUNCTION AS ALPHA-DIFLUOROMETHYLORNITHINE ANTAGONIST.
RX PubMed=17333334; DOI=10.1007/s10549-007-9536-5;
RA Xu H., Washington S., Verderame M.F., Manni A.;
RT "Activation of protein kinase A (PKA) signaling mitigates the
RT antiproliferative and antiinvasive effects of alpha-difluoromethylornithine
RT in breast cancer cells.";
RL Breast Cancer Res. Treat. 107:63-70(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-49 AND SER-339, AND
RP IDENTIFICATION BY 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 [19]
RP FUNCTION, AND INTERACTION WITH APOBEC3G.
RX PubMed=18836454; DOI=10.1038/nsmb.1497;
RA Shirakawa K., Takaori-Kondo A., Yokoyama M., Izumi T., Matsui M., Io K.,
RA Sato T., Sato H., Uchiyama T.;
RT "Phosphorylation of APOBEC3G by protein kinase A regulates its interaction
RT with HIV-1 Vif.";
RL Nat. Struct. Mol. Biol. 15:1184-1191(2008).
RN [20]
RP ACTIVITY REGULATION, AND MUTAGENESIS OF TYR-205.
RX PubMed=18178622; DOI=10.1073/pnas.0709214104;
RA Masterson L.R., Mascioni A., Traaseth N.J., Taylor S.S., Veglia G.;
RT "Allosteric cooperativity in protein kinase A.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:506-511(2008).
RN [21]
RP SUBCELLULAR LOCATION.
RX PubMed=19210988; DOI=10.1016/j.yexcr.2008.12.026;
RA Yan X., Walkiewicz M., Carlson J., Leiphon L., Grove B.;
RT "Gravin dynamics regulates the subcellular distribution of PKA.";
RL Exp. Cell Res. 315:1247-1259(2009).
RN [22]
RP IDENTIFICATION BY 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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339, 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 [24]
RP FUNCTION IN PLATELETS, FUNCTION AS VASP KINASE, AND INTERACTION WITH NFKB1;
RP NFKB2 AND NFKBIA.
RX PubMed=20356841; DOI=10.1074/jbc.m109.077602;
RA Gambaryan S., Kobsar A., Rukoyatkina N., Herterich S., Geiger J.,
RA Smolenski A., Lohmann S.M., Walter U.;
RT "Thrombin and collagen induce a feedback inhibitory signaling pathway in
RT platelets involving dissociation of the catalytic subunit of protein kinase
RT A from an NFkappaB-IkappaB complex.";
RL J. Biol. Chem. 285:18352-18363(2010).
RN [25]
RP FUNCTION IN OSTEOBLAST DIFFERENTIATION, AND ACTIVITY REGULATION.
RX PubMed=19949837; DOI=10.1007/s11010-009-0344-6;
RA Wang W., Zhang X., Zheng J., Yang J.;
RT "High glucose stimulates adipogenic and inhibits osteogenic differentiation
RT in MG-63 cells through cAMP/protein kinase A/extracellular signal-regulated
RT kinase pathway.";
RL Mol. Cell. Biochem. 338:115-122(2010).
RN [26]
RP FUNCTION IN PHOSPHORYLATION OF HSF1, INTERACTION WITH HSF1, AND SUBCELLULAR
RP LOCATION.
RX PubMed=21085490; DOI=10.1371/journal.pone.0013830;
RA Murshid A., Chou S.D., Prince T., Zhang Y., Bharti A., Calderwood S.K.;
RT "Protein kinase A binds and activates heat shock factor 1.";
RL PLoS ONE 5:E13830-E13830(2010).
RN [27]
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 [28]
RP FUNCTION AS RORA KINASE.
RX PubMed=21514275; DOI=10.1016/j.bbrc.2011.04.046;
RA Ermisch M., Firla B., Steinhilber D.;
RT "Protein kinase A activates and phosphorylates ROR?4 in vitro and takes
RT part in ROR? activation by CaMK-IV.";
RL Biochem. Biophys. Res. Commun. 408:442-446(2011).
RN [29]
RP FUNCTION AS KINASE, TISSUE SPECIFICITY, AND INTERACTION WITH PRKAR1A/PKR1
RP AND PRKAR2A/PKR2.
RX PubMed=21812984; DOI=10.1186/1471-2091-12-40;
RA Vetter M.M., Zenn H.-M., Mendez E., van den Boom H., Herberg F.W.,
RA Skaalhegg B.S.;
RT "The testis-specific C?2 subunit of PKA is kinetically indistinguishable
RT from the common C?1 subunit of PKA.";
RL BMC Biochem. 12:40-40(2011).
RN [30]
RP FUNCTION, AND SUBCELLULAR LOCATION.
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 [31]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339, AND IDENTIFICATION BY
RP 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 [32]
RP MYRISTOYLATION AT GLY-2, CLEAVAGE OF INITIATOR METHIONINE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=25255805; DOI=10.1038/ncomms5919;
RA Thinon E., Serwa R.A., Broncel M., Brannigan J.A., Brassat U., Wright M.H.,
RA Heal W.P., Wilkinson A.J., Mann D.J., Tate E.W.;
RT "Global profiling of co- and post-translationally N-myristoylated proteomes
RT in human cells.";
RL Nat. Commun. 5:4919-4919(2014).
RN [33]
RP INVOLVEMENT IN PPNAD4, VARIANT PPNAD4 ARG-206, AND CHARACTERIZATION OF
RP VARIANT PPNAD4 ARG-206.
RX PubMed=24747643; DOI=10.1038/ng.2956;
RA Goh G., Scholl U.I., Healy J.M., Choi M., Prasad M.L., Nelson-Williams C.,
RA Kunstman J.W., Kuntsman J.W., Korah R., Suttorp A.C., Dietrich D.,
RA Haase M., Willenberg H.S., Staalberg P., Hellman P., Akerstroem G.,
RA Bjoerklund P., Carling T., Lifton R.P.;
RT "Recurrent activating mutation in PRKACA in cortisol-producing adrenal
RT tumors.";
RL Nat. Genet. 46:613-617(2014).
RN [34]
RP MYRISTOYLATION AT GLY-2, CLEAVAGE OF INITIATOR METHIONINE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=25807930; DOI=10.1002/anie.201500342;
RA Broncel M., Serwa R.A., Ciepla P., Krause E., Dallman M.J., Magee A.I.,
RA Tate E.W.;
RT "Multifunctional reagents for quantitative proteome-wide analysis of
RT protein modification in human cells and dynamic profiling of protein
RT lipidation during vertebrate development.";
RL Angew. Chem. Int. Ed. 54:5948-5951(2015).
RN [35]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 15-351, AND PHOSPHORYLATION AT
RP THR-198 AND SER-339.
RX PubMed=16765046; DOI=10.1016/j.bmcl.2006.05.092;
RA Lin X., Murray J.M., Rico A.C., Wang M.X., Chu D.T., Zhou Y.,
RA Del Rosario M., Kaufman S., Ma S., Fang E., Crawford K., Jefferson A.B.;
RT "Discovery of 2-pyrimidyl-5-amidothiophenes as potent inhibitors for AKT:
RT synthesis and SAR studies.";
RL Bioorg. Med. Chem. Lett. 16:4163-4168(2006).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS), PHOSPHORYLATION AT THR-198 AND
RP SER-339, AND ACTIVITY REGULATION.
RX PubMed=20137943; DOI=10.1016/j.bmcl.2010.01.067;
RA Zeng Q., Allen J.G., Bourbeau M.P., Wang X., Yao G., Tadesse S.,
RA Rider J.T., Yuan C.C., Hong F.-T., Lee M.R., Zhang S., Lofgren J.A.,
RA Freeman D.J., Yang S., Li C., Tominey E., Huang X., Hoffman D.,
RA Yamane H.K., Fotsch C., Dominguez C., Hungate R., Zhang X.;
RT "Azole-based inhibitors of AKT/PKB for the treatment of cancer.";
RL Bioorg. Med. Chem. Lett. 20:1559-1564(2010).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (2.49 ANGSTROMS), PHOSPHORYLATION AT THR-198 AND
RP SER-339, AND ACTIVITY REGULATION.
RX PubMed=20481595; DOI=10.1021/jm1003842;
RA Freeman-Cook K.D., Autry C., Borzillo G., Gordon D., Barbacci-Tobin E.,
RA Bernardo V., Briere D., Clark T., Corbett M., Jakubczak J., Kakar S.,
RA Knauth E., Lippa B., Luzzio M.J., Mansour M., Martinelli G., Marx M.,
RA Nelson K., Pandit J., Rajamohan F., Robinson S., Subramanyam C., Wei L.,
RA Wythes M., Morris J.;
RT "Design of selective, ATP-competitive inhibitors of Akt.";
RL J. Med. Chem. 53:4615-4622(2010).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH ADENOSINE ANALOG,
RP PHOSPHORYLATION AT SER-11; THR-198 AND SER-339, AND ACTIVITY REGULATION.
RX PubMed=20732331; DOI=10.1016/j.jmb.2010.08.028;
RA Pflug A., Rogozina J., Lavogina D., Enkvist E., Uri A., Engh R.A.,
RA Bossemeyer D.;
RT "Diversity of bisubstrate binding modes of adenosine analogue-oligoarginine
RT conjugates in protein kinase a and implications for protein substrate
RT interactions.";
RL J. Mol. Biol. 403:66-77(2010).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH AURORA KINASE
RP INHIBITORS, PHOSPHORYLATION AT SER-11; THR-198 AND SER-339, AND MUTAGENESIS
RP OF LYS-48; LEU-96; MET-121; VAL-124; GLN-182 AND THR-184.
RX PubMed=21774789; DOI=10.1042/bj20110592;
RA Pflug A., de Oliveira T.M., Bossemeyer D., Engh R.A.;
RT "Mutants of protein kinase A that mimic the ATP-binding site of Aurora
RT kinase.";
RL Biochem. J. 440:85-93(2011).
RN [41]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS), AND PHOSPHORYLATION AT THR-198 AND
RP SER-339.
RA Behnen J., Koester H., Ritschel T., Neudert G., Heine A., Klebe G.;
RT "Experimental active site mapping as a starting point to fragment-based
RT lead discovery.";
RL Submitted (JUL-2010) to the PDB data bank.
RN [42]
RP X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS).
RA Koester H., Craan T., Brass S., Heine A., Klebe G.;
RT "Fragment based drug design on PKA.";
RL Submitted (SEP-2010) to the PDB data bank.
RN [43]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-41; GLN-46 AND CYS-264.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [44]
RP VARIANT PPNAD4 ARG-206, AND CHARACTERIZATION OF VARIANT PPNAD4 ARG-206.
RX PubMed=24571724; DOI=10.1056/nejmoa1310359;
RA Beuschlein F., Fassnacht M., Assie G., Calebiro D., Stratakis C.A.,
RA Osswald A., Ronchi C.L., Wieland T., Sbiera S., Faucz F.R., Schaak K.,
RA Schmittfull A., Schwarzmayr T., Barreau O., Vezzosi D., Rizk-Rabin M.,
RA Zabel U., Szarek E., Salpea P., Forlino A., Vetro A., Zuffardi O.,
RA Kisker C., Diener S., Meitinger T., Lohse M.J., Reincke M., Bertherat J.,
RA Strom T.M., Allolio B.;
RT "Constitutive activation of PKA catalytic subunit in adrenal Cushing's
RT syndrome.";
RL N. Engl. J. Med. 370:1019-1028(2014).
RN [45]
RP VARIANT PPNAD4 ARG-206, AND CHARACTERIZATION OF VARIANT PPNAD4 ARG-206.
RX PubMed=24700472; DOI=10.1126/science.1249480;
RA Cao Y., He M., Gao Z., Peng Y., Li Y., Li L., Zhou W., Li X., Zhong X.,
RA Lei Y., Su T., Wang H., Jiang Y., Yang L., Wei W., Yang X., Jiang X.,
RA Liu L., He J., Ye J., Wei Q., Li Y., Wang W., Wang J., Ning G.;
RT "Activating hotspot L205R mutation in PRKACA and adrenal Cushing's
RT syndrome.";
RL Science 344:913-917(2014).
RN [46]
RP VARIANT PPNAD4 ARG-206, AND CHARACTERIZATION OF VARIANT PPNAD4 ARG-206.
RX PubMed=24855271; DOI=10.1126/science.1252328;
RA Sato Y., Maekawa S., Ishii R., Sanada M., Morikawa T., Shiraishi Y.,
RA Yoshida K., Nagata Y., Sato-Otsubo A., Yoshizato T., Suzuki H.,
RA Shiozawa Y., Kataoka K., Kon A., Aoki K., Chiba K., Tanaka H., Kume H.,
RA Miyano S., Fukayama M., Nureki O., Homma Y., Ogawa S.;
RT "Recurrent somatic mutations underlie corticotropin-independent Cushing's
RT syndrome.";
RL Science 344:917-920(2014).
RN [47]
RP VARIANT CAFD1 ARG-137, CHARACTERIZATION OF VARIANT CAFD1 ARG-137,
RP INVOLVEMENT IN CAFD1, AND INTERACTION WITH PRKAR1A AND PRKAR2B.
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).
CC -!- FUNCTION: Phosphorylates a large number of substrates in the cytoplasm
CC and the nucleus (PubMed:15642694, PubMed:15905176, PubMed:16387847,
CC PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454,
CC PubMed:19949837, PubMed:20356841, PubMed:21085490, PubMed:21514275,
CC PubMed:21812984). Phosphorylates CDC25B, ABL1, NFKB1, CLDN3,
CC PSMC5/RPT6, PJA2, RYR2, RORA, SOX9 and VASP (PubMed:15642694,
CC PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987,
CC PubMed:17693412, PubMed:18836454, PubMed:19949837, PubMed:20356841,
CC PubMed:21085490, PubMed:21514275, PubMed:21812984). Regulates the
CC abundance of compartmentalized pools of its regulatory subunits through
CC phosphorylation of PJA2 which binds and ubiquitinates these subunits,
CC leading to their subsequent proteolysis (PubMed:21423175). RORA is
CC activated by phosphorylation (PubMed:21514275). Required for glucose-
CC mediated adipogenic differentiation increase and osteogenic
CC differentiation inhibition from osteoblasts (PubMed:19949837). Involved
CC in chondrogenesis by mediating phosphorylation of SOX9 (By similarity).
CC Involved in the regulation of platelets in response to thrombin and
CC collagen; maintains circulating platelets in a resting state by
CC phosphorylating proteins in numerous platelet inhibitory pathways when
CC in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha
CC (NFKBIA), but thrombin and collagen disrupt these complexes and free
CC active PRKACA stimulates platelets and leads to platelet aggregation by
CC phosphorylating VASP (PubMed:15642694, PubMed:20356841). Prevents the
CC antiproliferative and anti-invasive effects of alpha-
CC difluoromethylornithine in breast cancer cells when activated
CC (PubMed:17333334). RYR2 channel activity is potentiated by
CC phosphorylation in presence of luminal Ca(2+), leading to reduced
CC amplitude and increased frequency of store overload-induced Ca(2+)
CC release (SOICR) characterized by an increased rate of Ca(2+) release
CC and propagation velocity of spontaneous Ca(2+) waves, despite reduced
CC wave amplitude and resting cytosolic Ca(2+) (PubMed:17693412).
CC PSMC5/RPT6 activation by phosphorylation stimulates proteasome
CC (PubMed:17565987). Negatively regulates tight junctions (TJs) in
CC ovarian cancer cells via CLDN3 phosphorylation (PubMed:15905176). NFKB1
CC phosphorylation promotes NF-kappa-B p50-p50 DNA binding
CC (PubMed:15642694). Involved in embryonic development by down-regulating
CC the Hedgehog (Hh) signaling pathway that determines embryo pattern
CC formation and morphogenesis. Prevents meiosis resumption in prophase-
CC arrested oocytes via CDC25B inactivation by phosphorylation (By
CC similarity). May also regulate rapid eye movement (REM) sleep in the
CC pedunculopontine tegmental (PPT) (By similarity). Phosphorylates
CC APOBEC3G and AICDA (PubMed:16387847, PubMed:18836454). Phosphorylates
CC HSF1; this phosphorylation promotes HSF1 nuclear localization and
CC transcriptional activity upon heat shock (PubMed:21085490).
CC {ECO:0000250|UniProtKB:P05132, ECO:0000250|UniProtKB:P27791,
CC ECO:0000269|PubMed:15642694, ECO:0000269|PubMed:15905176,
CC ECO:0000269|PubMed:16387847, ECO:0000269|PubMed:17333334,
CC ECO:0000269|PubMed:17565987, ECO:0000269|PubMed:17693412,
CC ECO:0000269|PubMed:18836454, ECO:0000269|PubMed:19949837,
CC ECO:0000269|PubMed:20356841, ECO:0000269|PubMed:21085490,
CC ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:21514275,
CC ECO:0000269|PubMed:21812984}.
CC -!- FUNCTION: [Isoform 2]: Phosphorylates and activates ABL1 in sperm
CC flagellum to promote spermatozoa capacitation.
CC {ECO:0000250|UniProtKB:P05132}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.11;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.11;
CC -!- ACTIVITY REGULATION: Allosterically activated by various compounds,
CC including ATP. Activated by cAMP; the nucleotide acts as a dynamic and
CC allosteric activator by coupling the two lobes of apo PKA, enhancing
CC the enzyme dynamics synchronously and priming it for catalysis.
CC Inhibited by H89 (N-[2-[[3-(4-Bromophenyl)-2-propenyl]amino]ethyl]-5-
CC isoquinolinesulfonamide), spiroindoline, azole-based inhibitors, (3s)-
CC amino-aminomethylbenzamide analogs, ARC-1032 (6-{[(2S,3S,4R,5R)-5-(6-
CC amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-4-
CC carbamimidamido-1-carbamoylbutyl]hexanamide), ARC-1034
CC (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-
CC yl]formamido}-N-[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-
CC carbamoylbutyl]carbamoyl}butyl]hexanamide), ARC-582, ARC-902 (Adc-6-
CC aminohexanoic acid-(D-Arg)(6)-NH(2)), ARC-1012 ((2R)-6-amino-2-
CC (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-
CC yl]formamido}hexanamido)-N-(5-{[(1R)-4-carbamimidamido-1-{[(1R)-4-
CC carbamimidamido-1-
CC carbamoylbutyl]carbamoyl}butyl]carbamoyl}pentyl)hexanamide) and ARC-
CC 1039 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-
CC 2-yl]formamido}-N-[(1R)-1-[(5-{[(1R)-4-carbamimidamido-1-{[(1R)-4-
CC carbamimidamido-1-
CC carbamoylbutyl]carbamoyl}butyl]carbamoyl}pentyl)carbamoyl]ethyl]he
CC xanamide). {ECO:0000269|PubMed:17909264, ECO:0000269|PubMed:18178622,
CC ECO:0000269|PubMed:19949837, ECO:0000269|PubMed:20137943,
CC ECO:0000269|PubMed:20481595, ECO:0000269|PubMed:20732331}.
CC -!- SUBUNIT: A number of inactive tetrameric holoenzymes are produced by
CC the combination of homo- or heterodimers of the different regulatory
CC subunits associated with two catalytic subunits. cAMP causes the
CC dissociation of the inactive holoenzyme into a dimer of regulatory
CC subunits bound to four cAMP and two free monomeric catalytic subunits.
CC The cAMP-dependent protein kinase catalytic subunit binds PJA2. Both
CC isoforms 1 and 2 forms activate cAMP-sensitive PKAI and PKAII
CC holoenzymes by interacting with regulatory subunit (R) of PKA,
CC PRKAR1A/PKR1 and PRKAR2A/PKR2, respectively. Interacts with PRKAR1A and
CC PRKAR2B (PubMed:33058759). Interacts with NFKB1, NFKB2 and NFKBIA in
CC platelets; these interactions are disrupted by thrombin and collagen.
CC Binds to ABL1 in spermatozoa and with CDC25B in oocytes. Interacts with
CC APOBEC3G and AICDA. Interacts with RAB13; downstream effector of RAB13
CC involved in tight junction assembly. Found in a complex at least
CC composed of MROH2B, PRKACA isoform 2 and TCP11 (By similarity).
CC Interacts with MROH2B (By similarity). Isoform 2 interacts with TCP11
CC (By similarity). Interacts with HSF1 (PubMed:21085490).
CC {ECO:0000250|UniProtKB:P05132, ECO:0000269|PubMed:15096524,
CC ECO:0000269|PubMed:16387847, ECO:0000269|PubMed:18836454,
CC ECO:0000269|PubMed:20356841, ECO:0000269|PubMed:20732331,
CC ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:21774789,
CC ECO:0000269|PubMed:21812984, ECO:0000269|PubMed:33058759}.
CC -!- INTERACTION:
CC P17612; Q9GZX7: AICDA; NbExp=3; IntAct=EBI-476586, EBI-3834328;
CC P17612; P54819: AK2; NbExp=3; IntAct=EBI-476586, EBI-1056291;
CC P17612; Q9NQ31: AKIP1; NbExp=4; IntAct=EBI-476586, EBI-517035;
CC P17612; P31749: AKT1; NbExp=3; IntAct=EBI-476586, EBI-296087;
CC P17612; P09917: ALOX5; NbExp=2; IntAct=EBI-476586, EBI-79934;
CC P17612; Q92870-2: APBB2; NbExp=3; IntAct=EBI-476586, EBI-21535880;
CC P17612; Q9HC16: APOBEC3G; NbExp=6; IntAct=EBI-476586, EBI-717839;
CC P17612; P05067: APP; NbExp=3; IntAct=EBI-476586, EBI-77613;
CC P17612; P54253: ATXN1; NbExp=3; IntAct=EBI-476586, EBI-930964;
CC P17612; P54252: ATXN3; NbExp=3; IntAct=EBI-476586, EBI-946046;
CC P17612; Q4VBR4: ATXN3; NbExp=3; IntAct=EBI-476586, EBI-12928880;
CC P17612; Q5T686: AVPI1; NbExp=3; IntAct=EBI-476586, EBI-8640233;
CC P17612; P23560-2: BDNF; NbExp=3; IntAct=EBI-476586, EBI-12275524;
CC P17612; P35520: CBS; NbExp=3; IntAct=EBI-476586, EBI-740135;
CC P17612; P40227: CCT6A; NbExp=3; IntAct=EBI-476586, EBI-356687;
CC P17612; P12830: CDH1; NbExp=3; IntAct=EBI-476586, EBI-727477;
CC P17612; Q8NE08: COL25A1; NbExp=3; IntAct=EBI-476586, EBI-25836642;
CC P17612; P48730-2: CSNK1D; NbExp=3; IntAct=EBI-476586, EBI-9087876;
CC P17612; O14531: DPYSL4; NbExp=3; IntAct=EBI-476586, EBI-719542;
CC P17612; P26378-2: ELAVL4; NbExp=3; IntAct=EBI-476586, EBI-21603100;
CC P17612; P15036: ETS2; NbExp=3; IntAct=EBI-476586, EBI-1646991;
CC P17612; Q969W3: FAM104A; NbExp=3; IntAct=EBI-476586, EBI-10281506;
CC P17612; P04406: GAPDH; NbExp=3; IntAct=EBI-476586, EBI-354056;
CC P17612; P49841: GSK3B; NbExp=7; IntAct=EBI-476586, EBI-373586;
CC P17612; P07900: HSP90AA1; NbExp=4; IntAct=EBI-476586, EBI-296047;
CC P17612; P42858: HTT; NbExp=3; IntAct=EBI-476586, EBI-466029;
CC P17612; O75874: IDH1; NbExp=3; IntAct=EBI-476586, EBI-715695;
CC P17612; P06756: ITGAV; NbExp=3; IntAct=EBI-476586, EBI-298282;
CC P17612; P23276: KEL; NbExp=3; IntAct=EBI-476586, EBI-746662;
CC P17612; Q5S007: LRRK2; NbExp=6; IntAct=EBI-476586, EBI-5323863;
CC P17612; Q13387-4: MAPK8IP2; NbExp=3; IntAct=EBI-476586, EBI-12345753;
CC P17612; Q16549: PCSK7; NbExp=3; IntAct=EBI-476586, EBI-8059854;
CC P17612; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-476586, EBI-9090282;
CC P17612; Q9C010-2: PKIB; NbExp=3; IntAct=EBI-476586, EBI-12886396;
CC P17612; O14494: PLPP1; NbExp=3; IntAct=EBI-476586, EBI-2865290;
CC P17612; P00491: PNP; NbExp=3; IntAct=EBI-476586, EBI-712238;
CC P17612; P10644: PRKAR1A; NbExp=13; IntAct=EBI-476586, EBI-476431;
CC P17612; P31321: PRKAR1B; NbExp=8; IntAct=EBI-476586, EBI-2805516;
CC P17612; P31323: PRKAR2B; NbExp=15; IntAct=EBI-476586, EBI-2930670;
CC P17612; Q13200: PSMD2; NbExp=3; IntAct=EBI-476586, EBI-357648;
CC P17612; P21246: PTN; NbExp=3; IntAct=EBI-476586, EBI-473725;
CC P17612; Q6NTF9-3: RHBDD2; NbExp=3; IntAct=EBI-476586, EBI-17589229;
CC P17612; P61513: RPL37A; NbExp=3; IntAct=EBI-476586, EBI-356793;
CC P17612; P04271: S100B; NbExp=3; IntAct=EBI-476586, EBI-458391;
CC P17612; Q99720-4: SIGMAR1; NbExp=3; IntAct=EBI-476586, EBI-25831036;
CC P17612; P84022: SMAD3; NbExp=3; IntAct=EBI-476586, EBI-347161;
CC P17612; Q16560-2: SNRNP35; NbExp=3; IntAct=EBI-476586, EBI-12938570;
CC P17612; Q3SY56: SP6; NbExp=3; IntAct=EBI-476586, EBI-11175533;
CC P17612; Q9UNE7: STUB1; NbExp=3; IntAct=EBI-476586, EBI-357085;
CC P17612; O60784-2: TOM1; NbExp=3; IntAct=EBI-476586, EBI-12117154;
CC P17612; Q9Y228: TRAF3IP3; NbExp=3; IntAct=EBI-476586, EBI-765817;
CC P17612; Q9UHP3: USP25; NbExp=3; IntAct=EBI-476586, EBI-2513462;
CC P17612; Q9UBQ0-2: VPS29; NbExp=3; IntAct=EBI-476586, EBI-11141397;
CC P17612; P59215: Gnao1; Xeno; NbExp=4; IntAct=EBI-476586, EBI-8071125;
CC P17612; P12369: Prkar2b; Xeno; NbExp=2; IntAct=EBI-476586, EBI-6096160;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Nucleus {ECO:0000250}.
CC Mitochondrion {ECO:0000250}. Membrane {ECO:0000305}; Lipid-anchor
CC {ECO:0000305}. Note=Translocates into the nucleus (monomeric catalytic
CC subunit). The inactive holoenzyme is found in the cytoplasm.
CC Distributed throughout the cytoplasm in meiotically incompetent
CC oocytes. Associated to mitochondrion as meiotic competence is acquired.
CC Aggregates around the germinal vesicles (GV) at the immature GV stage
CC oocytes (By similarity). Colocalizes with HSF1 in nuclear stress bodies
CC (nSBs) upon heat shock (PubMed:21085490). {ECO:0000250,
CC ECO:0000269|PubMed:21085490}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell projection, cilium, flagellum
CC {ECO:0000269|PubMed:10906071}. Cytoplasmic vesicle, secretory vesicle,
CC acrosome {ECO:0000250|UniProtKB:P05132}. Note=Expressed in the midpiece
CC region of the sperm flagellum (PubMed:10906071). Colocalizes with
CC MROH2B and TCP11 on the acrosome and tail regions in round spermatids
CC and spermatozoa regardless of the capacitation status of the sperm (By
CC similarity). {ECO:0000250|UniProtKB:P05132,
CC ECO:0000269|PubMed:10906071}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=C-alpha-1;
CC IsoId=P17612-1; Sequence=Displayed;
CC Name=2; Synonyms=C-alpha-2, C-alpha-S, C(s);
CC IsoId=P17612-2; Sequence=VSP_004759;
CC -!- TISSUE SPECIFICITY: Isoform 1 is ubiquitous. Isoform 2 is sperm-
CC specific and is enriched in pachytene spermatocytes but is not detected
CC in round spermatids. {ECO:0000269|PubMed:10906071,
CC ECO:0000269|PubMed:21812984}.
CC -!- PTM: Asn-3 is partially deaminated to Asp giving rise to 2 major
CC isoelectric variants, called CB and CA respectively. {ECO:0000250}.
CC -!- PTM: Autophosphorylated. Phosphorylation is enhanced by vitamin K(2).
CC Phosphorylated on threonine and serine residues. Phosphorylation on
CC Thr-198 is required for full activity. {ECO:0000269|PubMed:12372837,
CC ECO:0000269|PubMed:16765046, ECO:0000269|PubMed:17909264,
CC ECO:0000269|PubMed:20137943, ECO:0000269|PubMed:20481595,
CC ECO:0000269|PubMed:20732331, ECO:0000269|PubMed:21774789,
CC ECO:0000269|Ref.41}.
CC -!- PTM: Phosphorylated at Tyr-331 by activated receptor tyrosine kinases
CC EGFR and PDGFR; this increases catalytic efficiency. {ECO:0000250}.
CC -!- DISEASE: Primary pigmented nodular adrenocortical disease 4 (PPNAD4)
CC [MIM:615830]: 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. Adrenal glands show overall normal size and weight, and
CC multiple small yellow-to-dark brown nodules surrounded by a cortex with
CC a uniform appearance. Microscopically, there are moderate diffuse
CC cortical hyperplasia with mostly nonpigmented nodules, multiple
CC capsular deficits and massive circumscribed and infiltrating extra-
CC adrenal cortical excrescences with micronodules. Clinical
CC manifestations of Cushing syndrome include facial and truncal obesity,
CC abdominal striae, muscular weakness, osteoporosis, arterial
CC hypertension, diabetes. {ECO:0000269|PubMed:24571724,
CC ECO:0000269|PubMed:24700472, ECO:0000269|PubMed:24747643,
CC ECO:0000269|PubMed:24855271}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Cardioacrofacial dysplasia 1 (CAFD1) [MIM:619142]: An
CC autosomal dominant disease characterized by dysmorphic facial features,
CC congenital cardiac defects, primarily common atrium or atrioventricular
CC septal defect, and limb anomalies, including short limbs, brachydactyly
CC and postaxial polydactyly. {ECO:0000269|PubMed:33058759}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. cAMP subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/prkaca/";
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DR EMBL; X07767; CAA30597.1; -; mRNA.
DR EMBL; AK290147; BAF82836.1; -; mRNA.
DR EMBL; DQ667173; ABG25918.1; -; Genomic_DNA.
DR EMBL; CH471106; EAW84399.1; -; Genomic_DNA.
DR EMBL; BC039846; AAH39846.1; -; mRNA.
DR EMBL; BC108259; AAI08260.1; -; mRNA.
DR EMBL; AF208004; AAG35720.1; -; mRNA.
DR EMBL; AF239744; AAF76426.1; -; mRNA.
DR EMBL; AF224718; AAF75622.1; -; mRNA.
DR CCDS; CCDS12304.1; -. [P17612-1]
DR CCDS; CCDS12305.1; -. [P17612-2]
DR PIR; S01404; OKHU2C.
DR RefSeq; NP_001291278.1; NM_001304349.1.
DR RefSeq; NP_002721.1; NM_002730.3. [P17612-1]
DR RefSeq; NP_997401.1; NM_207518.2. [P17612-2]
DR PDB; 2GU8; X-ray; 2.20 A; A=15-351.
DR PDB; 3AGL; X-ray; 2.10 A; A/B=1-351.
DR PDB; 3AGM; X-ray; 2.00 A; A=1-351.
DR PDB; 3AMA; X-ray; 1.75 A; A=1-351.
DR PDB; 3AMB; X-ray; 2.25 A; A=1-351.
DR PDB; 3L9L; X-ray; 2.00 A; A/B=1-351.
DR PDB; 3L9M; X-ray; 1.90 A; A/B=1-351.
DR PDB; 3L9N; X-ray; 2.00 A; A=1-351.
DR PDB; 3MVJ; X-ray; 2.49 A; A/B/E=1-351.
DR PDB; 3NX8; X-ray; 2.00 A; A=1-351.
DR PDB; 3OOG; X-ray; 2.00 A; A=1-351.
DR PDB; 3OVV; X-ray; 1.58 A; A=1-351.
DR PDB; 3OWP; X-ray; 1.88 A; A=1-351.
DR PDB; 3OXT; X-ray; 2.20 A; A=1-351.
DR PDB; 3P0M; X-ray; 2.03 A; A=1-351.
DR PDB; 3POO; X-ray; 1.60 A; A=1-351.
DR PDB; 3VQH; X-ray; 1.95 A; A=1-351.
DR PDB; 4AE6; X-ray; 2.10 A; A/B=16-351.
DR PDB; 4AE9; X-ray; 2.30 A; A/B=16-351.
DR PDB; 4UJ1; X-ray; 1.77 A; A=1-351.
DR PDB; 4UJ2; X-ray; 2.02 A; A=1-351.
DR PDB; 4UJ9; X-ray; 1.87 A; A=1-351.
DR PDB; 4UJA; X-ray; 1.93 A; A=1-351.
DR PDB; 4UJB; X-ray; 1.95 A; A=1-351.
DR PDB; 4WB5; X-ray; 1.64 A; A=2-351.
DR PDB; 4WB6; X-ray; 2.10 A; A/B=2-351.
DR PDB; 4WB7; X-ray; 1.90 A; A/B=16-351.
DR PDB; 4WB8; X-ray; 1.55 A; A=16-351.
DR PDB; 5BX6; X-ray; 1.89 A; A=1-351.
DR PDB; 5BX7; X-ray; 1.89 A; A=1-350.
DR PDB; 5IZF; X-ray; 2.10 A; A=1-351.
DR PDB; 5IZJ; X-ray; 1.85 A; A/B=1-351.
DR PDB; 5J5X; X-ray; 2.60 A; A=1-351.
DR PDB; 5N23; X-ray; 2.09 A; A=1-351.
DR PDB; 5UZK; X-ray; 2.30 A; A=1-351.
DR PDB; 6BYR; X-ray; 3.66 A; A/C=16-351.
DR PDB; 6BYS; X-ray; 4.75 A; A/C/E/G=2-351.
DR PDB; 6C0U; X-ray; 2.65 A; A=1-351.
DR PDB; 6FRX; X-ray; 1.88 A; A=1-351.
DR PDB; 6NO7; X-ray; 3.55 A; A/C/E/G=2-351.
DR PDB; 6QJ7; X-ray; 1.69 A; A=1-351.
DR PDB; 6WJF; EM; 7.50 A; A/B=16-351.
DR PDB; 6WJG; EM; 6.20 A; A/B=16-351.
DR PDBsum; 2GU8; -.
DR PDBsum; 3AGL; -.
DR PDBsum; 3AGM; -.
DR PDBsum; 3AMA; -.
DR PDBsum; 3AMB; -.
DR PDBsum; 3L9L; -.
DR PDBsum; 3L9M; -.
DR PDBsum; 3L9N; -.
DR PDBsum; 3MVJ; -.
DR PDBsum; 3NX8; -.
DR PDBsum; 3OOG; -.
DR PDBsum; 3OVV; -.
DR PDBsum; 3OWP; -.
DR PDBsum; 3OXT; -.
DR PDBsum; 3P0M; -.
DR PDBsum; 3POO; -.
DR PDBsum; 3VQH; -.
DR PDBsum; 4AE6; -.
DR PDBsum; 4AE9; -.
DR PDBsum; 4UJ1; -.
DR PDBsum; 4UJ2; -.
DR PDBsum; 4UJ9; -.
DR PDBsum; 4UJA; -.
DR PDBsum; 4UJB; -.
DR PDBsum; 4WB5; -.
DR PDBsum; 4WB6; -.
DR PDBsum; 4WB7; -.
DR PDBsum; 4WB8; -.
DR PDBsum; 5BX6; -.
DR PDBsum; 5BX7; -.
DR PDBsum; 5IZF; -.
DR PDBsum; 5IZJ; -.
DR PDBsum; 5J5X; -.
DR PDBsum; 5N23; -.
DR PDBsum; 5UZK; -.
DR PDBsum; 6BYR; -.
DR PDBsum; 6BYS; -.
DR PDBsum; 6C0U; -.
DR PDBsum; 6FRX; -.
DR PDBsum; 6NO7; -.
DR PDBsum; 6QJ7; -.
DR PDBsum; 6WJF; -.
DR PDBsum; 6WJG; -.
DR AlphaFoldDB; P17612; -.
DR BMRB; P17612; -.
DR SMR; P17612; -.
DR BioGRID; 111553; 297.
DR CORUM; P17612; -.
DR DIP; DIP-33878N; -.
DR ELM; P17612; -.
DR IntAct; P17612; 154.
DR MINT; P17612; -.
DR STRING; 9606.ENSP00000309591; -.
DR BindingDB; P17612; -.
DR ChEMBL; CHEMBL4101; -.
DR DrugBank; DB07204; (1S)-1-(1H-INDOL-3-YLMETHYL)-2-(2-PYRIDIN-4-YL-[1,7]NAPHTYRIDIN-5-YLOXY)-EHYLAMINE.
DR DrugBank; DB07107; (1S)-2-(1H-INDOL-3-YL)-1-[({5-[(E)-2-PYRIDIN-4-YLVINYL]PYRIDIN-3-YL}OXY)METHYL]ETHYLAMINE.
DR DrugBank; DB07857; (2R)-2-(4-chlorophenyl)-2-[4-(1H-pyrazol-4-yl)phenyl]ethanamine.
DR DrugBank; DB07860; (2R)-2-(4-CHLOROPHENYL)-2-PHENYLETHANAMINE.
DR DrugBank; DB08073; (2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE.
DR DrugBank; DB06959; (2S)-1-(3H-Indol-3-yl)-3-{[5-(6-isoquinolinyl)-3-pyridinyl]oxy}-2-propanamine.
DR DrugBank; DB07124; (2S)-1-(6H-INDOL-3-YL)-3-{[5-(7H-PYRAZOLO[3,4-C]PYRIDIN-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE.
DR DrugBank; DB06977; (2S)-1-{[5-(1H-Indazol-5-yl)-3-pyridinyl]oxy}-3-(7aH-indol-3-yl)-2-propanamine.
DR DrugBank; DB07858; (2S)-2-(4-chlorophenyl)-2-[4-(1H-pyrazol-4-yl)phenyl]ethanamine.
DR DrugBank; DB07583; (4R,2S)-5'-(4-(4-CHLOROBENZYLOXY)PYRROLIDIN-2-YLMETHANESULFONYL)ISOQUINOLINE.
DR DrugBank; DB07855; (S)-1-PHENYL-1-[4-(9H-PURIN-6-YL)PHENYL]METHANAMINE.
DR DrugBank; DB07876; (S)-2-METHYL-1-[(4-METHYL-5-ISOQUINOLINE)SULFONYL]-HOMOPIPERAZINE.
DR DrugBank; DB08149; 1-[4-(4-chlorobenzyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl]methanamine.
DR DrugBank; DB08148; 1-[4-(4-chlorophenyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl]methanamine.
DR DrugBank; DB08070; 2-[4-(3-METHYL-1H-PYRAZOL-4-YL)PHENYL]ETHANAMINE.
DR DrugBank; DB03374; 3,5-Diiodotyrosine.
DR DrugBank; DB07458; 3-(1H-indol-3-yl)-4-{1-[2-(1-methylpyrrolidin-2-yl)ethyl]-1H-indol-3-yl}-1H-pyrrole-2,5-dione.
DR DrugBank; DB02155; 3-[(3-sec-butyl-4-hydroxybenzoyl)amino]azepan-4-yl 4-(2-hydroxy-5-methoxybenzoyl)benzoate.
DR DrugBank; DB08113; 3-pyridin-4-yl-1H-indazole.
DR DrugBank; DB08569; 3-PYRIDIN-4-YL-2,4-DIHYDRO-INDENO[1,2-.C.] PYRAZOLE.
DR DrugBank; DB08150; 4-(4-chlorobenzyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-aminium.
DR DrugBank; DB07859; 4-(4-CHLOROPHENYL)-4-[4-(1H-PYRAZOL-4-YL)PHENYL]PIPERIDINE.
DR DrugBank; DB07996; 5-(2-methylpiperazine-1-sulfonyl)isoquinoline.
DR DrugBank; DB08114; 5-benzyl-1,3-thiazol-2-amine.
DR DrugBank; DB07856; 6-{4-[4-(4-CHLOROPHENYL)PIPERIDIN-4-YL]PHENYL}-9H-PURINE.
DR DrugBank; DB08568; A-674563.
DR DrugBank; DB04098; Balanol.
DR DrugBank; DB02611; Balanol Analog 1.
DR DrugBank; DB01940; Balanol Analog 2.
DR DrugBank; DB04522; Dexfosfoserine.
DR DrugBank; DB08846; Ellagic acid.
DR DrugBank; DB08162; Fasudil.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB07995; H-89.
DR DrugBank; DB04707; Hydroxyfasudil.
DR DrugBank; DB07947; ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY)ETHYLAMINO)ETHYL)AMIDE.
DR DrugBank; DB08231; Myristic acid.
DR DrugBank; DB07235; N-[(1S)-2-AMINO-1-(2,4-DICHLOROBENZYL)ETHYL]-5-[2-(METHYLAMINO)PYRIMIDIN-4-YL]THIOPHENE-2-CARBOXAMIDE.
DR DrugBank; DB07997; N-[2-(METHYLAMINO)ETHYL]-5-ISOQUINOLINESULFONAMIDE.
DR DrugBank; DB07854; N-METHYL-1-[4-(9H-PURIN-6-YL)PHENYL]METHANAMINE.
DR DrugBank; DB01919; Pentanal.
DR DrugBank; DB02482; Phosphonothreonine.
DR DrugBank; DB04530; S,S-(2-Hydroxyethyl)Thiocysteine.
DR DrugBank; DB08756; Y-27632.
DR DrugCentral; P17612; -.
DR GuidetoPHARMACOLOGY; 1476; -.
DR GlyGen; P17612; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P17612; -.
DR PhosphoSitePlus; P17612; -.
DR SwissPalm; P17612; -.
DR BioMuta; PRKACA; -.
DR DMDM; 125205; -.
DR EPD; P17612; -.
DR jPOST; P17612; -.
DR MassIVE; P17612; -.
DR MaxQB; P17612; -.
DR PaxDb; P17612; -.
DR PeptideAtlas; P17612; -.
DR PRIDE; P17612; -.
DR ProteomicsDB; 53496; -. [P17612-1]
DR ProteomicsDB; 53497; -. [P17612-2]
DR Antibodypedia; 4159; 526 antibodies from 41 providers.
DR DNASU; 5566; -.
DR Ensembl; ENST00000308677.9; ENSP00000309591.3; ENSG00000072062.15. [P17612-1]
DR Ensembl; ENST00000589994.6; ENSP00000466651.1; ENSG00000072062.15. [P17612-2]
DR Ensembl; ENST00000672938.1; ENSP00000500293.1; ENSG00000288516.1. [P17612-2]
DR Ensembl; ENST00000673550.1; ENSP00000499940.1; ENSG00000288516.1. [P17612-1]
DR GeneID; 5566; -.
DR KEGG; hsa:5566; -.
DR MANE-Select; ENST00000308677.9; ENSP00000309591.3; NM_002730.4; NP_002721.1.
DR UCSC; uc002myb.4; human. [P17612-1]
DR CTD; 5566; -.
DR DisGeNET; 5566; -.
DR GeneCards; PRKACA; -.
DR HGNC; HGNC:9380; PRKACA.
DR HPA; ENSG00000072062; Tissue enhanced (skeletal).
DR MalaCards; PRKACA; -.
DR MIM; 601639; gene.
DR MIM; 615830; phenotype.
DR MIM; 619142; phenotype.
DR neXtProt; NX_P17612; -.
DR OpenTargets; ENSG00000072062; -.
DR Orphanet; 401920; Fibrolamellar hepatocellular carcinoma.
DR Orphanet; 189439; Primary pigmented nodular adrenocortical disease.
DR PharmGKB; PA33748; -.
DR VEuPathDB; HostDB:ENSG00000072062; -.
DR eggNOG; KOG0616; Eukaryota.
DR GeneTree; ENSGT00940000162186; -.
DR InParanoid; P17612; -.
DR OMA; WQDSRNL; -.
DR OrthoDB; 963519at2759; -.
DR PhylomeDB; P17612; -.
DR TreeFam; TF313399; -.
DR BRENDA; 2.7.11.11; 2681.
DR PathwayCommons; P17612; -.
DR Reactome; R-HSA-111931; PKA-mediated phosphorylation of CREB.
DR Reactome; R-HSA-163358; PKA-mediated phosphorylation of key metabolic factors.
DR Reactome; R-HSA-163560; Triglyceride catabolism.
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-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR Reactome; R-HSA-380259; Loss of Nlp from mitotic centrosomes.
DR Reactome; R-HSA-380270; Recruitment of mitotic centrosome proteins and complexes.
DR Reactome; R-HSA-380284; Loss of proteins required for interphase microtubule organization from the centrosome.
DR Reactome; R-HSA-380320; Recruitment of NuMA to mitotic centrosomes.
DR Reactome; R-HSA-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
DR Reactome; R-HSA-392517; Rap1 signalling.
DR Reactome; R-HSA-422356; Regulation of insulin secretion.
DR Reactome; R-HSA-432040; Vasopressin regulates renal water homeostasis via Aquaporins.
DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-HSA-442720; CREB1 phosphorylation through the activation of Adenylate Cyclase.
DR Reactome; R-HSA-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
DR Reactome; R-HSA-5578775; Ion homeostasis.
DR Reactome; R-HSA-5610780; Degradation of GLI1 by the proteasome.
DR Reactome; R-HSA-5610783; Degradation of GLI2 by the proteasome.
DR Reactome; R-HSA-5610785; GLI3 is processed to GLI3R by the proteasome.
DR Reactome; R-HSA-5610787; Hedgehog 'off' state.
DR Reactome; R-HSA-5620912; Anchoring of the basal body to the plasma membrane.
DR Reactome; R-HSA-5621575; CD209 (DC-SIGN) signaling.
DR Reactome; R-HSA-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-HSA-8853659; RET signaling.
DR Reactome; R-HSA-8854518; AURKA Activation by TPX2.
DR Reactome; R-HSA-8963896; HDL assembly.
DR Reactome; R-HSA-9010642; ROBO receptors bind AKAP5.
DR Reactome; R-HSA-9022535; Loss of phosphorylation of MECP2 at T308.
DR Reactome; R-HSA-9022692; Regulation of MECP2 expression and activity.
DR Reactome; R-HSA-9634597; GPER1 signaling.
DR Reactome; R-HSA-9634600; Regulation of glycolysis by fructose 2,6-bisphosphate metabolism.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR Reactome; R-HSA-9664323; FCGR3A-mediated IL10 synthesis.
DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production.
DR SABIO-RK; P17612; -.
DR SignaLink; P17612; -.
DR SIGNOR; P17612; -.
DR BioGRID-ORCS; 5566; 45 hits in 1122 CRISPR screens.
DR ChiTaRS; PRKACA; human.
DR EvolutionaryTrace; P17612; -.
DR GeneWiki; PRKACA; -.
DR GenomeRNAi; 5566; -.
DR Pharos; P17612; Tchem.
DR PRO; PR:P17612; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P17612; protein.
DR Bgee; ENSG00000072062; Expressed in gastrocnemius and 102 other tissues.
DR ExpressionAtlas; P17612; baseline and differential.
DR Genevisible; P17612; HS.
DR GO; GO:0001669; C:acrosomal vesicle; ISS:UniProtKB.
DR GO; GO:0034704; C:calcium channel complex; TAS:BHF-UCL.
DR GO; GO:0005952; C:cAMP-dependent protein kinase complex; IDA:UniProtKB.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
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:0043197; C:dendritic spine; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:BHF-UCL.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0031594; C:neuromuscular junction; IEA:Ensembl.
DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0031588; C:nucleotide-activated protein kinase complex; IDA:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0044853; C:plasma membrane raft; IDA:UniProtKB.
DR GO; GO:0036126; C:sperm flagellum; IEA:Ensembl.
DR GO; GO:0097225; C:sperm midpiece; IDA:UniProtKB.
DR GO; GO:0004679; F:AMP-activated protein kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004691; F:cAMP-dependent protein kinase activity; IDA:BHF-UCL.
DR GO; GO:0000287; F:magnesium ion binding; IEA:Ensembl.
DR GO; GO:0030145; F:manganese ion binding; IEA:Ensembl.
DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR GO; GO:0034237; F:protein kinase A regulatory subunit binding; IPI:BHF-UCL.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IDA:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IDA:UniProtKB.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; TAS:BHF-UCL.
DR GO; GO:0086064; P:cell communication by electrical coupling involved in cardiac conduction; TAS:BHF-UCL.
DR GO; GO:0070417; P:cellular response to cold; IEA:Ensembl.
DR GO; GO:0071872; P:cellular response to epinephrine stimulus; TAS:BHF-UCL.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IDA:UniProtKB.
DR GO; GO:0034605; P:cellular response to heat; IDA:UniProtKB.
DR GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; IEA:Ensembl.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0034380; P:high-density lipoprotein particle assembly; TAS:Reactome.
DR GO; GO:0001707; P:mesoderm formation; IEA:Ensembl.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IEA:Ensembl.
DR GO; GO:0006397; P:mRNA processing; IDA:UniProtKB.
DR GO; GO:1901621; P:negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning; IEA:Ensembl.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IEA:Ensembl.
DR GO; GO:0046827; P:positive regulation of protein export from nucleus; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; IEA:Ensembl.
DR GO; GO:0006611; P:protein export from nucleus; IEA:Ensembl.
DR GO; GO:0010737; P:protein kinase A signaling; IBA:GO_Central.
DR GO; GO:1990044; P:protein localization to lipid droplet; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:2000810; P:regulation of bicellular tight junction assembly; IDA:UniProtKB.
DR GO; GO:1903779; P:regulation of cardiac conduction; TAS:Reactome.
DR GO; GO:0055117; P:regulation of cardiac muscle contraction; TAS:BHF-UCL.
DR GO; GO:0010881; P:regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; TAS:BHF-UCL.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; TAS:BHF-UCL.
DR GO; GO:0002027; P:regulation of heart rate; TAS:BHF-UCL.
DR GO; GO:0016241; P:regulation of macroautophagy; TAS:ParkinsonsUK-UCL.
DR GO; GO:0045667; P:regulation of osteoblast differentiation; IDA:UniProtKB.
DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; IDA:UniProtKB.
DR GO; GO:0043393; P:regulation of protein binding; TAS:BHF-UCL.
DR GO; GO:0070613; P:regulation of protein processing; IEA:Ensembl.
DR GO; GO:0060314; P:regulation of ryanodine-sensitive calcium-release channel activity; TAS:BHF-UCL.
DR GO; GO:0003091; P:renal water homeostasis; TAS:Reactome.
DR GO; GO:0048240; P:sperm capacitation; ISS:UniProtKB.
DR CDD; cd14209; STKc_PKA; 1.
DR IDEAL; IID00366; -.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR044109; STKc_PKA.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; cAMP; Cell membrane;
KW Cell projection; Cilium; Cushing syndrome; Cytoplasm; Cytoplasmic vesicle;
KW Disease variant; Flagellum; Kinase; Lipoprotein; Membrane; Mitochondrion;
KW Myristate; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:25255805,
FT ECO:0000269|PubMed:25807930"
FT CHAIN 2..351
FT /note="cAMP-dependent protein kinase catalytic subunit
FT alpha"
FT /id="PRO_0000086052"
FT DOMAIN 44..298
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 299..351
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT ACT_SITE 167
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 50..58
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 73
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 122..128
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 169..172
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 3
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250"
FT MOD_RES 11
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P05132"
FT MOD_RES 49
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 140
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05132"
FT MOD_RES 196
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:12372837"
FT MOD_RES 198
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000269|PubMed:12372837,
FT ECO:0000269|PubMed:16765046, ECO:0000269|PubMed:20137943,
FT ECO:0000269|PubMed:20481595, ECO:0000269|PubMed:20732331,
FT ECO:0000269|PubMed:21774789, ECO:0000269|Ref.41"
FT MOD_RES 331
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P05132"
FT MOD_RES 339
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16765046,
FT ECO:0000269|PubMed:20137943, ECO:0000269|PubMed:20481595,
FT ECO:0000269|PubMed:20732331, ECO:0000269|PubMed:21774789,
FT ECO:0000269|Ref.41, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:24275569"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:25255805,
FT ECO:0000269|PubMed:25807930"
FT VAR_SEQ 1..15
FT /note="MGNAAAAKKGSEQES -> MASNSSD (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10841548,
FT ECO:0000303|PubMed:10906071, ECO:0000303|PubMed:10982398"
FT /id="VSP_004759"
FT VARIANT 41
FT /note="L -> V (in dbSNP:rs56029020)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040591"
FT VARIANT 46
FT /note="R -> Q (in dbSNP:rs56085217)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040592"
FT VARIANT 137
FT /note="G -> R (in CAFD1; decreased interaction with
FT regulatory subunit PRKAR2B)"
FT /evidence="ECO:0000269|PubMed:33058759"
FT /id="VAR_085198"
FT VARIANT 206
FT /note="L -> R (in PPNAD4; somatic mutation; the mutation
FT results in cAMP-independent basal protein kinase activity
FT and constitutive activation of protein kinase A;
FT dbSNP:rs386352352)"
FT /evidence="ECO:0000269|PubMed:24571724,
FT ECO:0000269|PubMed:24700472, ECO:0000269|PubMed:24747643,
FT ECO:0000269|PubMed:24855271"
FT /id="VAR_071707"
FT VARIANT 264
FT /note="S -> C (in dbSNP:rs35635531)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040593"
FT MUTAGEN 48
FT /note="K->R: Enhanced basal kinase activity; when
FT associated with Q-96, L-121, A-124, K-182 and A-184."
FT /evidence="ECO:0000269|PubMed:21774789"
FT MUTAGEN 96
FT /note="L->Q: Enhanced basal kinase activity; when
FT associated with R-48, L-121, A-124, K-182 and A-184."
FT /evidence="ECO:0000269|PubMed:21774789"
FT MUTAGEN 121
FT /note="M->L: Enhanced basal kinase activity; when
FT associated with R-48, Q-96, A-124, K-182 and A-184."
FT /evidence="ECO:0000269|PubMed:21774789"
FT MUTAGEN 124
FT /note="V->A: Enhanced basal kinase activity; when
FT associated with R-48, Q-96, L-121, K-182 and A-184."
FT /evidence="ECO:0000269|PubMed:21774789"
FT MUTAGEN 182
FT /note="Q->K: Enhanced basal kinase activity; when
FT associated with R-48, Q-96, L-121, A-124 and A-184."
FT /evidence="ECO:0000269|PubMed:21774789"
FT MUTAGEN 184
FT /note="T->A: Enhanced basal kinase activity; when
FT associated with R-48, Q-96, L-121, A-124 and K-182."
FT /evidence="ECO:0000269|PubMed:21774789"
FT MUTAGEN 195
FT /note="R->A: No phosphorylation."
FT /evidence="ECO:0000269|PubMed:12372837"
FT MUTAGEN 201
FT /note="G->A: No phosphorylation."
FT /evidence="ECO:0000269|PubMed:12372837"
FT MUTAGEN 202
FT /note="T->A: No phosphorylation."
FT /evidence="ECO:0000269|PubMed:12372837"
FT MUTAGEN 205
FT /note="Y->A: Loss of allosteric regulation."
FT /evidence="ECO:0000269|PubMed:18178622"
FT HELIX 3..6
FT /evidence="ECO:0007829|PDB:3AMA"
FT HELIX 16..32
FT /evidence="ECO:0007829|PDB:4WB8"
FT HELIX 41..43
FT /evidence="ECO:0007829|PDB:4WB8"
FT STRAND 44..52
FT /evidence="ECO:0007829|PDB:4WB8"
FT STRAND 57..63
FT /evidence="ECO:0007829|PDB:4WB8"
FT TURN 64..66
FT /evidence="ECO:0007829|PDB:4WB8"
FT STRAND 69..76
FT /evidence="ECO:0007829|PDB:4WB8"
FT HELIX 77..82
FT /evidence="ECO:0007829|PDB:4WB8"
FT HELIX 86..98
FT /evidence="ECO:0007829|PDB:4WB8"
FT STRAND 107..112
FT /evidence="ECO:0007829|PDB:4WB8"
FT STRAND 114..122
FT /evidence="ECO:0007829|PDB:4WB8"
FT HELIX 129..136
FT /evidence="ECO:0007829|PDB:4WB8"
FT HELIX 141..160
FT /evidence="ECO:0007829|PDB:4WB8"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:4WB8"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:4WB8"
FT STRAND 181..183
FT /evidence="ECO:0007829|PDB:4WB8"
FT HELIX 186..188
FT /evidence="ECO:0007829|PDB:4UJ2"
FT HELIX 203..205
FT /evidence="ECO:0007829|PDB:4WB8"
FT HELIX 208..211
FT /evidence="ECO:0007829|PDB:4WB8"
FT STRAND 212..214
FT /evidence="ECO:0007829|PDB:5IZJ"
FT HELIX 219..234
FT /evidence="ECO:0007829|PDB:4WB8"
FT HELIX 244..253
FT /evidence="ECO:0007829|PDB:4WB8"
FT HELIX 264..273
FT /evidence="ECO:0007829|PDB:4WB8"
FT TURN 278..280
FT /evidence="ECO:0007829|PDB:4WB8"
FT TURN 282..284
FT /evidence="ECO:0007829|PDB:5IZF"
FT TURN 286..289
FT /evidence="ECO:0007829|PDB:4WB8"
FT HELIX 290..293
FT /evidence="ECO:0007829|PDB:4WB8"
FT HELIX 296..298
FT /evidence="ECO:0007829|PDB:4WB8"
FT HELIX 303..307
FT /evidence="ECO:0007829|PDB:4WB8"
FT TURN 345..350
FT /evidence="ECO:0007829|PDB:4WB8"
SQ SEQUENCE 351 AA; 40590 MW; BF6D3ECD2614E5AB CRC64;
MGNAAAAKKG SEQESVKEFL AKAKEDFLKK WESPAQNTAH LDQFERIKTL GTGSFGRVML
VKHKETGNHY AMKILDKQKV VKLKQIEHTL NEKRILQAVN FPFLVKLEFS FKDNSNLYMV
MEYVPGGEMF SHLRRIGRFS EPHARFYAAQ IVLTFEYLHS LDLIYRDLKP ENLLIDQQGY
IQVTDFGFAK RVKGRTWTLC GTPEYLAPEI ILSKGYNKAV DWWALGVLIY EMAAGYPPFF
ADQPIQIYEK IVSGKVRFPS HFSSDLKDLL RNLLQVDLTK RFGNLKNGVN DIKNHKWFAT
TDWIAIYQRK VEAPFIPKFK GPGDTSNFDD YEEEEIRVSI NEKCGKEFSE F
