KAPCB_HUMAN
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 03-AUG-2022, entry version 222.
DE RecName: Full=cAMP-dependent protein kinase catalytic subunit beta;
DE Short=PKA C-beta;
DE EC=2.7.11.11;
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), AND FUNCTION.
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 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 [18]
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. PKA activation regulates diverse cellular processes
CC such as cell proliferation, the cell cycle, differentiation and
CC regulation of microtubule dynamics, chromatin condensation and
CC decondensation, nuclear envelope disassembly and reassembly, as well as
CC regulation of intracellular transport mechanisms and ion flux.
CC Regulates the abundance of compartmentalized pools of its regulatory
CC subunits through phosphorylation of PJA2 which binds and ubiquitinates
CC these subunits, leading to their subsequent proteolysis
CC (PubMed:12420224, PubMed:21423175). Phosphorylates GPKOW which
CC regulates its ability to bind RNA (PubMed:21880142).
CC {ECO:0000269|PubMed:12420224, ECO:0000269|PubMed:21423175,
CC ECO:0000269|PubMed:21880142}.
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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
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}. Note=Translocates into the
CC nucleus (monomeric catalytic subunit). The inactive holoenzyme is found
CC in the cytoplasm. {ECO:0000250}.
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. {ECO:0000250}.
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/";
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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; 126.
DR IntAct; P22694; 83.
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 EPD; P22694; -.
DR jPOST; P22694; -.
DR MassIVE; P22694; -.
DR MaxQB; P22694; -.
DR PaxDb; P22694; -.
DR PeptideAtlas; P22694; -.
DR PRIDE; 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 Antibodypedia; 4160; 420 antibodies from 36 providers.
DR DNASU; 5567; -.
DR Ensembl; ENST00000370682.7; ENSP00000359716.3; ENSG00000142875.20. [P22694-7]
DR Ensembl; ENST00000370685.7; ENSP00000359719.3; ENSG00000142875.20. [P22694-2]
DR Ensembl; ENST00000370688.7; ENSP00000359722.3; ENSG00000142875.20. [P22694-8]
DR Ensembl; ENST00000370689.6; ENSP00000359723.2; ENSG00000142875.20. [P22694-1]
DR Ensembl; ENST00000394839.6; ENSP00000378315.2; ENSG00000142875.20. [P22694-10]
DR Ensembl; ENST00000446538.5; ENSP00000401252.2; ENSG00000142875.20. [P22694-9]
DR Ensembl; ENST00000610703.4; ENSP00000481980.1; ENSG00000142875.20. [P22694-3]
DR Ensembl; ENST00000614872.4; ENSP00000479722.1; ENSG00000142875.20. [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 CTD; 5567; -.
DR DisGeNET; 5567; -.
DR GeneCards; 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 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; GNARYNK; -.
DR OrthoDB; 963519at2759; -.
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; 19 hits in 1110 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 211 other tissues.
DR ExpressionAtlas; P22694; baseline and differential.
DR Genevisible; P22694; HS.
DR GO; GO:0005952; C:cAMP-dependent protein kinase complex; TAS:UniProtKB.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0097546; C:ciliary base; TAS:Reactome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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: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: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 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 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"
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)"
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)"
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
