ID KAPCB_HUMAN Reviewed; 351 AA. AC P22694; B1APG4; B4DKB0; B4E2Q1; Q14VH1; Q59GC0; Q5BNE9; Q5BNF0; Q5BNF1; AC Q5BNF2; Q5BNF3; Q5CZ92; Q5T1K3; Q7Z3M1; Q8IYR5; Q8IZQ0; Q96B09; DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 27-MAR-2024, entry version 231. DE RecName: Full=cAMP-dependent protein kinase catalytic subunit beta; DE Short=PKA C-beta; DE EC=2.7.11.11 {ECO:0000269|PubMed:12420224, ECO:0000269|PubMed:31112131}; GN Name=PRKACB; 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=2342480; DOI=10.1210/mend-4-3-465; RA Beebe S.J., Oyen O., Sandberg M., Froysa A., Hansson V., Jahnsen T.; RT "Molecular cloning of a tissue-specific protein kinase (C gamma) from human RT testis -- representing a third isoform for the catalytic subunit of cAMP- RT dependent protein kinase."; RL Mol. Endocrinol. 4:465-475(1990). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 7). RC TISSUE=Retina, and Salivary gland; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3; 9 AND 10). RC TISSUE=Brain, Thalamus, and Trachea; 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 [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG SeattleSNPs variation discovery resource; RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [7] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 8). RC TISSUE=Brain; 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 [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-30 (ISOFORMS 2; 5 AND 6), NUCLEOTIDE RP SEQUENCE [MRNA] OF 1-16 (ISOFORM 3), NUCLEOTIDE SEQUENCE [MRNA] OF 1-13 RP (ISOFORM 4), AND TISSUE SPECIFICITY. RX PubMed=11589697; DOI=10.1046/j.0014-2956.2001.02429.x; RA Orstavik S., Reinton N., Frengen E., Langeland B.T., Jahnsen T., RA Skalhegg B.S.; RT "Identification of novel splice variants of the human catalytic subunit RT Cbeta of cAMP-dependent protein kinase."; RL Eur. J. Biochem. 268:5066-5073(2001). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-15 (ISOFORM 1), FUNCTION, CATALYTIC RP ACTIVITY, AND COFACTOR. RX PubMed=12420224; DOI=10.1038/sj.onc.1205986; RA Wu K.-J., Mattioli M., Morse H.C., Dalla-Favera R.; RT "c-MYC activates protein kinase A (PKA) by direct transcriptional RT activation of the PKA catalytic subunit beta (PKA-CB) gene."; RL Oncogene 21:7872-7882(2002). RN [11] RP IDENTIFICATION BY 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 [12] 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 [13] RP FUNCTION, AND INTERACTION WITH GPKOW. RX PubMed=21880142; DOI=10.1186/1750-2187-6-10; RA Aksaas A.K., Larsen A.C., Rogne M., Rosendal K., Kvissel A.K., RA Skaalhegg B.S.; RT "G-patch domain and KOW motifs-containing protein, GPKOW; a nuclear RNA- RT binding protein regulated by protein kinase A."; RL J. Mol. Signal. 6:10-10(2011). RN [14] RP FUNCTION, SUBCELLULAR LOCATION, AND 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 [15] 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 [16] 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 [17] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=31112131; DOI=10.7554/elife.43038; RA Jewell J.L., Fu V., Hong A.W., Yu F.X., Meng D., Melick C.H., Wang H., RA Lam W.M., Yuan H.X., Taylor S.S., Guan K.L.; RT "GPCR signaling inhibits mTORC1 via PKA phosphorylation of Raptor."; RL Elife 8:0-0(2019). RN [18] RP VARIANT [LARGE SCALE ANALYSIS] GLN-106. 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 [19] RP VARIANTS CAFD2 LEU-54; ARG-88; ASN-88 AND ARG-235, INVOLVEMENT IN CAFD2, RP CHARACTERIZATION OF VARIANTS CAFD2 ARG-88 AND ARG-235, INTERACTION WITH RP PRKAR1A AND PRKAR2B, AND ACTIVITY REGULATION. 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: Mediates cAMP-dependent signaling triggered by receptor CC binding to GPCRs (PubMed:12420224, PubMed:21423175, PubMed:31112131). CC PKA activation regulates diverse cellular processes such as cell CC proliferation, the cell cycle, differentiation and regulation of CC microtubule dynamics, chromatin condensation and decondensation, CC nuclear envelope disassembly and reassembly, as well as regulation of CC intracellular transport mechanisms and ion flux (PubMed:12420224, CC PubMed:21423175). Regulates the abundance of compartmentalized pools of CC its regulatory subunits through phosphorylation of PJA2 which binds and CC ubiquitinates these subunits, leading to their subsequent proteolysis CC (PubMed:12420224, PubMed:21423175). Phosphorylates GPKOW which CC regulates its ability to bind RNA (PubMed:21880142). Acts as a negative CC regulator of mTORC1 by mediating phosphorylation of RPTOR CC (PubMed:31112131). {ECO:0000269|PubMed:12420224, CC ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:21880142, CC ECO:0000269|PubMed:31112131}. 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 Evidence={ECO:0000269|PubMed:12420224}; 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; Evidence={ECO:0000269|PubMed:12420224}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:12420224}; CC -!- ACTIVITY REGULATION: Activated by cAMP. {ECO:0000269|PubMed:33058759}. 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 (By similarity). Interacts with PRKAR1A and PRKAR2B (PubMed:33058759). CC The cAMP-dependent protein kinase catalytic subunit binds PJA2 CC (PubMed:21423175). Interacts with GPKOW (PubMed:21880142). CC {ECO:0000250|UniProtKB:P05132, ECO:0000269|PubMed:21423175, CC ECO:0000269|PubMed:21880142, ECO:0000269|PubMed:33058759}. CC -!- INTERACTION: CC P22694; P05067: APP; NbExp=3; IntAct=EBI-2679622, EBI-77613; CC P22694; Q92624: APPBP2; NbExp=3; IntAct=EBI-2679622, EBI-743771; CC P22694; Q5T686: AVPI1; NbExp=3; IntAct=EBI-2679622, EBI-8640233; CC P22694; P08238: HSP90AB1; NbExp=2; IntAct=EBI-2679622, EBI-352572; CC P22694; P61925: PKIA; NbExp=5; IntAct=EBI-2679622, EBI-2682139; CC P22694-2; Q92917: GPKOW; NbExp=4; IntAct=EBI-5258763, EBI-746309; CC P22694-8; P05067: APP; NbExp=3; IntAct=EBI-25937151, EBI-77613; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21423175}. Cell CC membrane {ECO:0000269|PubMed:21423175}. Membrane {ECO:0000305}; Lipid- CC anchor {ECO:0000305}. Nucleus {ECO:0000250|UniProtKB:P05131}. CC Note=Translocates into the nucleus (monomeric catalytic subunit). The CC inactive holoenzyme is found in the cytoplasm. CC {ECO:0000250|UniProtKB:P05131}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=10; CC Name=1; Synonyms=Beta1; CC IsoId=P22694-1; Sequence=Displayed; CC Name=2; Synonyms=Beta2; CC IsoId=P22694-2; Sequence=VSP_017364; CC Name=3; Synonyms=Beta3; CC IsoId=P22694-3; Sequence=VSP_017369, VSP_017370; CC Name=4; Synonyms=Beta4; CC IsoId=P22694-4; Sequence=VSP_017368, VSP_017371; CC Name=5; Synonyms=Beta4ab; CC IsoId=P22694-5; Sequence=VSP_017366; CC Name=6; Synonyms=Beta4abc; CC IsoId=P22694-6; Sequence=VSP_017365; CC Name=7; CC IsoId=P22694-7; Sequence=VSP_017367; CC Name=8; CC IsoId=P22694-8; Sequence=VSP_036556, VSP_036557; CC Name=9; CC IsoId=P22694-9; Sequence=VSP_043372; CC Name=10; CC IsoId=P22694-10; Sequence=VSP_017366, VSP_046238; CC -!- TISSUE SPECIFICITY: Isoform 1 is most abundant in the brain, with low CC level expression in kidney. Isoform 2 is predominantly expressed in CC thymus, spleen and kidney. Isoform 3 and isoform 4 are only expressed CC in the brain. {ECO:0000269|PubMed:11589697}. CC -!- PTM: Asn-3 is partially deaminated to Asp giving rise to 2 major CC isoelectric variants, called CB and CA respectively. CC {ECO:0000250|UniProtKB:P05383}. CC -!- DISEASE: Cardioacrofacial dysplasia 2 (CAFD2) [MIM:619143]: 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. CAFD2 patients may show developmental delay CC of variable severity, intellectual disability, autistic features and CC focal seizures. {ECO:0000269|PubMed:33058759}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 3]: Incomplete sequence. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 4]: Incomplete sequence. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 5]: Incomplete sequence. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr CC protein kinase family. cAMP subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAD92426.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/prkacb/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M34181; AAA60170.1; -; mRNA. DR EMBL; BX537705; CAD97818.1; -; mRNA. DR EMBL; BX641026; CAE46017.1; -; mRNA. DR EMBL; AB209189; BAD92426.1; ALT_SEQ; mRNA. DR EMBL; CR936631; CAI56774.1; -; mRNA. DR EMBL; AK091420; BAG52356.1; -; mRNA. DR EMBL; AK296482; BAG59122.1; -; mRNA. DR EMBL; AK304375; BAG65213.1; -; mRNA. DR EMBL; DQ667174; ABG25919.1; -; Genomic_DNA. DR EMBL; AL359504; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL450063; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471097; EAW73248.1; -; Genomic_DNA. DR EMBL; BC016285; AAH16285.1; -; mRNA. DR EMBL; BC035058; AAH35058.1; -; mRNA. DR EMBL; AY927364; AAX19487.1; -; mRNA. DR EMBL; AY927365; AAX19488.1; -; mRNA. DR EMBL; AY927366; AAX19489.1; -; mRNA. DR EMBL; AY927367; AAX19490.1; -; mRNA. DR EMBL; AY927368; AAX19491.1; -; mRNA. DR EMBL; AF538872; AAN16454.1; -; Genomic_DNA. DR CCDS; CCDS55609.1; -. [P22694-9] DR CCDS; CCDS55610.1; -. [P22694-7] DR CCDS; CCDS55611.1; -. [P22694-10] DR CCDS; CCDS691.1; -. [P22694-1] DR CCDS; CCDS692.1; -. [P22694-8] DR CCDS; CCDS693.1; -. [P22694-2] DR CCDS; CCDS72813.1; -. [P22694-3] DR CCDS; CCDS72815.1; -. [P22694-6] DR PIR; A34724; OKHUCB. DR RefSeq; NP_001229786.1; NM_001242857.2. [P22694-9] DR RefSeq; NP_001229787.1; NM_001242858.2. [P22694-3] DR RefSeq; NP_001229788.1; NM_001242859.2. [P22694-7] DR RefSeq; NP_001229789.1; NM_001242860.2. [P22694-6] DR RefSeq; NP_001229790.1; NM_001242861.2. [P22694-10] DR RefSeq; NP_001229791.1; NM_001242862.2. DR RefSeq; NP_001287844.1; NM_001300915.1. DR RefSeq; NP_001287845.1; NM_001300916.1. DR RefSeq; NP_001287846.1; NM_001300917.1. DR RefSeq; NP_002722.1; NM_002731.3. [P22694-1] DR RefSeq; NP_891993.1; NM_182948.3. [P22694-2] DR RefSeq; NP_997461.1; NM_207578.2. [P22694-8] DR RefSeq; XP_005271076.1; XM_005271019.1. DR RefSeq; XP_006710821.1; XM_006710758.1. DR AlphaFoldDB; P22694; -. DR SMR; P22694; -. DR BioGRID; 111554; 179. DR IntAct; P22694; 85. DR MINT; P22694; -. DR STRING; 9606.ENSP00000359719; -. DR BindingDB; P22694; -. DR ChEMBL; CHEMBL2918; -. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB02482; Phosphonothreonine. DR DrugCentral; P22694; -. DR GuidetoPHARMACOLOGY; 1477; -. DR GlyGen; P22694; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P22694; -. DR MetOSite; P22694; -. DR PhosphoSitePlus; P22694; -. DR SwissPalm; P22694; -. DR BioMuta; PRKACB; -. DR DMDM; 125210; -. DR CPTAC; non-CPTAC-3182; -. DR EPD; P22694; -. DR jPOST; P22694; -. DR MassIVE; P22694; -. DR MaxQB; P22694; -. DR PaxDb; 9606-ENSP00000359719; -. DR PeptideAtlas; P22694; -. DR ProteomicsDB; 3296; -. DR ProteomicsDB; 54019; -. [P22694-1] DR ProteomicsDB; 54020; -. [P22694-2] DR ProteomicsDB; 54021; -. [P22694-3] DR ProteomicsDB; 54022; -. [P22694-4] DR ProteomicsDB; 54023; -. [P22694-5] DR ProteomicsDB; 54024; -. [P22694-6] DR ProteomicsDB; 54025; -. [P22694-7] DR ProteomicsDB; 54026; -. [P22694-8] DR ProteomicsDB; 54027; -. [P22694-9] DR Pumba; P22694; -. DR Antibodypedia; 4160; 485 antibodies from 36 providers. DR DNASU; 5567; -. DR Ensembl; ENST00000370685.7; ENSP00000359719.3; ENSG00000142875.21. [P22694-2] DR Ensembl; ENST00000370688.7; ENSP00000359722.3; ENSG00000142875.21. [P22694-8] DR Ensembl; ENST00000370689.6; ENSP00000359723.2; ENSG00000142875.21. [P22694-1] DR Ensembl; ENST00000394839.6; ENSP00000378315.2; ENSG00000142875.21. [P22694-10] DR Ensembl; ENST00000436133.6; ENSP00000390906.2; ENSG00000142875.21. [P22694-7] DR Ensembl; ENST00000446538.5; ENSP00000401252.2; ENSG00000142875.21. [P22694-9] DR Ensembl; ENST00000610703.4; ENSP00000481980.1; ENSG00000142875.21. [P22694-3] DR Ensembl; ENST00000614872.4; ENSP00000479722.1; ENSG00000142875.21. [P22694-6] DR GeneID; 5567; -. DR KEGG; hsa:5567; -. DR MANE-Select; ENST00000370685.7; ENSP00000359719.3; NM_182948.4; NP_891993.1. [P22694-2] DR UCSC; uc001dji.4; human. [P22694-1] DR AGR; HGNC:9381; -. DR CTD; 5567; -. DR DisGeNET; 5567; -. DR GeneCards; PRKACB; -. DR GeneReviews; PRKACB; -. DR HGNC; HGNC:9381; PRKACB. DR HPA; ENSG00000142875; Tissue enhanced (brain). DR MalaCards; PRKACB; -. DR MIM; 176892; gene. DR MIM; 619143; phenotype. DR neXtProt; NX_P22694; -. DR OpenTargets; ENSG00000142875; -. DR Orphanet; 289; Ellis Van Creveld syndrome. DR PharmGKB; PA33749; -. DR VEuPathDB; HostDB:ENSG00000142875; -. DR eggNOG; KOG0616; Eukaryota. DR GeneTree; ENSGT00940000161169; -. DR HOGENOM; CLU_000288_63_5_1; -. DR InParanoid; P22694; -. DR OMA; FAKEVQD; -. DR OrthoDB; 10768at2759; -. DR PhylomeDB; P22694; -. DR TreeFam; TF313399; -. DR BRENDA; 2.7.11.11; 2681. DR PathwayCommons; P22694; -. 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-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-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-5621575; CD209 (DC-SIGN) signaling. DR Reactome; R-HSA-5687128; MAPK6/MAPK4 signaling. DR Reactome; R-HSA-8853659; RET signaling. DR Reactome; R-HSA-8963896; HDL assembly. DR Reactome; R-HSA-9010642; ROBO receptors bind AKAP5. 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; P22694; -. DR SignaLink; P22694; -. DR SIGNOR; P22694; -. DR BioGRID-ORCS; 5567; 20 hits in 1191 CRISPR screens. DR ChiTaRS; PRKACB; human. DR GeneWiki; PRKACB; -. DR GenomeRNAi; 5567; -. DR Pharos; P22694; Tchem. DR PRO; PR:P22694; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P22694; Protein. DR Bgee; ENSG00000142875; Expressed in endothelial cell and 213 other cell types or tissues. DR ExpressionAtlas; P22694; baseline and differential. DR GO; GO:0005952; C:cAMP-dependent protein kinase complex; IBA:GO_Central. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0097546; C:ciliary base; TAS:Reactome. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0004679; F:AMP-activated protein kinase activity; IEA:UniProtKB-EC. DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB. DR GO; GO:0004691; F:cAMP-dependent protein kinase activity; IDA:UniProtKB. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; TAS:Reactome. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IDA:UniProtKB. DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; TAS:UniProtKB. DR GO; GO:0034380; P:high-density lipoprotein particle assembly; TAS:Reactome. DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IEA:Ensembl. DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IDA:UniProtKB. DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl. DR GO; GO:0010737; P:protein kinase A signaling; IBA:GO_Central. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0070613; P:regulation of protein processing; IEA:Ensembl. DR GO; GO:0003091; P:renal water homeostasis; TAS:Reactome. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR CDD; cd14209; STKc_PKA; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR24353:SF116; CAMP-DEPENDENT PROTEIN KINASE CATALYTIC SUBUNIT BETA; 1. DR PANTHER; PTHR24353; CYCLIC NUCLEOTIDE-DEPENDENT PROTEIN KINASE; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00133; S_TK_X; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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. DR Genevisible; P22694; HS. PE 1: Evidence at protein level; KW Alternative splicing; ATP-binding; cAMP; Cell membrane; Cytoplasm; KW Disease variant; Kinase; Lipoprotein; Membrane; Myristate; KW 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 CHAIN 2..351 FT /note="cAMP-dependent protein kinase catalytic subunit FT beta" FT /id="PRO_0000086060" 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 /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 73 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|UniProtKB:P05383" FT MOD_RES 11 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P05132" FT MOD_RES 69 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P68181" FT MOD_RES 140 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P05132" FT MOD_RES 198 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P05132" FT MOD_RES 322 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P68182" FT MOD_RES 331 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P05132" FT MOD_RES 339 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P68182" FT LIPID 2 FT /note="N-myristoyl glycine" FT /evidence="ECO:0000269|PubMed:25255805" FT VAR_SEQ 1..16 FT /note="MGNAATAKKGSEVESV -> MAAYREPPCNQYTGTTTALQKLEGFASRLFHR FT HSKGTAHDQKTALENDSLHFSEHTALWDRSM (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11589697, FT ECO:0000303|PubMed:17974005" FT /id="VSP_017364" FT VAR_SEQ 1..15 FT /note="MGNAATAKKGSEVES -> MSARKSSDASACSSSEISDSF (in isoform FT 6)" FT /evidence="ECO:0000303|PubMed:11589697, ECO:0000303|Ref.3" FT /id="VSP_017365" FT VAR_SEQ 1..15 FT /note="MGNAATAKKGSEVES -> MGLSRKSSDASACSSSEISDSF (in FT isoform 9)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043372" FT VAR_SEQ 1..14 FT /note="MGNAATAKKGSEVE -> MSARKSSDASACSSSEI (in isoform 5 FT and isoform 10)" FT /evidence="ECO:0000303|PubMed:11589697, FT ECO:0000303|PubMed:14702039" FT /id="VSP_017366" FT VAR_SEQ 1..14 FT /note="MGNAATAKKGSEVE -> MGLSRKSSDASACSSSEI (in isoform 7)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_017367" FT VAR_SEQ 1..13 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:11589697" FT /id="VSP_017368" FT VAR_SEQ 1..12 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:11589697, FT ECO:0000303|PubMed:14702039" FT /id="VSP_017369" FT VAR_SEQ 13..16 FT /note="VESV -> MGLL (in isoform 3)" FT /evidence="ECO:0000303|PubMed:11589697, FT ECO:0000303|PubMed:14702039" FT /id="VSP_017370" FT VAR_SEQ 14 FT /note="E -> M (in isoform 4)" FT /evidence="ECO:0000303|PubMed:11589697" FT /id="VSP_017371" FT VAR_SEQ 79..111 FT /note="Missing (in isoform 10)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046238" FT VAR_SEQ 256..257 FT /note="VR -> NF (in isoform 8)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_036556" FT VAR_SEQ 258..351 FT /note="Missing (in isoform 8)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_036557" FT VARIANT 54 FT /note="S -> L (in CAFD2; dbSNP:rs1663748771)" FT /evidence="ECO:0000269|PubMed:33058759" FT /id="VAR_085199" FT VARIANT 88 FT /note="H -> N (in CAFD2)" FT /evidence="ECO:0000269|PubMed:33058759" FT /id="VAR_085200" FT VARIANT 88 FT /note="H -> R (in CAFD2; increased sensitivity to cAMP FT activation; dbSNP:rs768056300)" FT /evidence="ECO:0000269|PubMed:33058759" FT /id="VAR_085201" FT VARIANT 106 FT /note="R -> Q (in dbSNP:rs36117118)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040594" FT VARIANT 235 FT /note="G -> R (in CAFD2; increased sensitivity to cAMP FT activation; decreased interaction with regulatory subunits FT PRKAR1A and PRKAR2B; dbSNP:rs1670492319)" FT /evidence="ECO:0000269|PubMed:33058759" FT /id="VAR_085202" FT CONFLICT 80 FT /note="V -> G (in Ref. 3; CAI56774)" FT /evidence="ECO:0000305" FT CONFLICT 159 FT /note="H -> N (in Ref. 8; AAH35058)" FT /evidence="ECO:0000305" FT CONFLICT 163 FT /note="L -> I (in Ref. 8; AAH35058)" FT /evidence="ECO:0000305" FT CONFLICT 233 FT /note="A -> V (in Ref. 3; CAI56774)" FT /evidence="ECO:0000305" FT CONFLICT 261 FT /note="H -> N (in Ref. 8; AAH35058)" FT /evidence="ECO:0000305" SQ SEQUENCE 351 AA; 40623 MW; 5C7443FBBA1C9BEC CRC64; MGNAATAKKG SEVESVKEFL AKAKEDFLKK WENPTQNNAG LEDFERKKTL GTGSFGRVML VKHKATEQYY AMKILDKQKV VKLKQIEHTL NEKRILQAVN FPFLVRLEYA FKDNSNLYMV MEYVPGGEMF SHLRRIGRFS EPHARFYAAQ IVLTFEYLHS LDLIYRDLKP ENLLIDHQGY IQVTDFGFAK RVKGRTWTLC GTPEYLAPEI ILSKGYNKAV DWWALGVLIY EMAAGYPPFF ADQPIQIYEK IVSGKVRFPS HFSSDLKDLL RNLLQVDLTK RFGNLKNGVS DIKTHKWFAT TDWIAIYQRK VEAPFIPKFR GSGDTSNFDD YEEEDIRVSI TEKCAKEFGE F //