ID KAPCB_RAT Reviewed; 351 AA. AC P68182; P05206; DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 27-MAR-2024, entry version 157. DE RecName: Full=cAMP-dependent protein kinase catalytic subunit beta; DE Short=PKA C-beta; DE EC=2.7.11.11; GN Name=Prkacb; Synonyms=Pkacb; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Brain; RX PubMed=1610898; DOI=10.1016/0167-4781(92)90073-9; RA Shuntoh H., Sakamoto N., Matsuyama S., Saitoh M., Tanaka C.; RT "Molecular structure of the C beta catalytic subunit of rat cAMP-dependent RT protein kinase and differential expression of C alpha and C beta isoforms RT in rat tissues and cultured cells."; RL Biochim. Biophys. Acta 1131:175-180(1992). RN [2] RP PROTEIN SEQUENCE OF 2-8, AND DEAMIDATION AT ASN-3. RX PubMed=9521123; DOI=10.1002/pro.5560070227; RA Jedrzejewski P.T., Girod A., Tholey A., Koenig N., Thullner S., Kinzel V., RA Bossemeyer D.; RT "A conserved deamidation site at Asn 2 in the catalytic subunit of RT mammalian cAMP-dependent protein kinase detected by capillary LC-MS and RT tandem mass spectrometry."; RL Protein Sci. 7:457-469(1998). RN [3] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-322 AND SER-339, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). 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. Phosphorylates CC GPKOW which regulates its ability to bind RNA. Acts as a negative CC regulator of mTORC1 by mediating phosphorylation of RPTOR. CC {ECO:0000250|UniProtKB:P22694}. 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; Evidence={ECO:0000250}; CC -!- ACTIVITY REGULATION: Activated by cAMP. {ECO:0000250|UniProtKB:P22694}. 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 Interacts with PRKAR1A and PRKAR2B (By similarity). The cAMP-dependent CC protein kinase catalytic subunit binds PJA2. Interacts with GPKOW. CC {ECO:0000250|UniProtKB:P05132, ECO:0000250|UniProtKB:P22694}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P22694}. Cell CC membrane {ECO:0000250|UniProtKB:P22694}. Membrane CC {ECO:0000250|UniProtKB:P22694}; Lipid-anchor CC {ECO:0000250|UniProtKB:P22694}. 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 -!- PTM: Asn-3 is deaminated to Asp in more than 25% of the proteins, CC giving rise to 2 major isoelectric variants, called CB and CA CC respectively (0.4 pH unit change). Deamidation proceeds via the so- CC called beta-aspartyl shift mechanism and yields either 'D-Asp-2' CC (major) or 'D-isoAsp-2' (minor), in addition to L-isomers. Deamidation CC occurs after the addition of myristate. The Asn-3 form reaches a CC significantly larger nuclear/cytoplasmic ratio than the 'Asp-2' form. CC {ECO:0000269|PubMed:9521123}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr CC protein kinase family. cAMP subfamily. {ECO:0000305}. 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; D10770; BAA01601.1; -; mRNA. DR PIR; JQ1139; OKRTCB. DR RefSeq; NP_001071113.1; NM_001077645.1. DR AlphaFoldDB; P68182; -. DR SMR; P68182; -. DR BioGRID; 254303; 1. DR IntAct; P68182; 2. DR MINT; P68182; -. DR STRING; 10116.ENSRNOP00000062228; -. DR BindingDB; P68182; -. DR GuidetoPHARMACOLOGY; 1477; -. DR GlyGen; P68182; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P68182; -. DR PhosphoSitePlus; P68182; -. DR jPOST; P68182; -. DR PaxDb; 10116-ENSRNOP00000062228; -. DR Ensembl; ENSRNOT00000068739.2; ENSRNOP00000062228.1; ENSRNOG00000004978.7. DR Ensembl; ENSRNOT00055041233; ENSRNOP00055033550; ENSRNOG00055023932. DR Ensembl; ENSRNOT00060001112; ENSRNOP00060000416; ENSRNOG00060000873. DR Ensembl; ENSRNOT00065021101; ENSRNOP00065016277; ENSRNOG00065012881. DR GeneID; 293508; -. DR KEGG; rno:293508; -. DR AGR; RGD:1310574; -. DR CTD; 5567; -. DR RGD; 1310574; Prkacb. DR eggNOG; KOG0616; Eukaryota. DR GeneTree; ENSGT00940000161169; -. DR HOGENOM; CLU_000288_63_5_1; -. DR InParanoid; P68182; -. DR OrthoDB; 10768at2759; -. DR PhylomeDB; P68182; -. DR Reactome; R-RNO-163615; PKA activation. DR Reactome; R-RNO-164378; PKA activation in glucagon signalling. DR Reactome; R-RNO-180024; DARPP-32 events. DR Reactome; R-RNO-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion. DR Reactome; R-RNO-392517; Rap1 signalling. DR Reactome; R-RNO-422356; Regulation of insulin secretion. DR Reactome; R-RNO-432040; Vasopressin regulates renal water homeostasis via Aquaporins. DR Reactome; R-RNO-4420097; VEGFA-VEGFR2 Pathway. DR Reactome; R-RNO-442720; CREB1 phosphorylation through the activation of Adenylate Cyclase. DR Reactome; R-RNO-5610785; GLI3 is processed to GLI3R by the proteasome. DR Reactome; R-RNO-5610787; Hedgehog 'off' state. DR Reactome; R-RNO-5687128; MAPK6/MAPK4 signaling. DR Reactome; R-RNO-8853659; RET signaling. DR Reactome; R-RNO-8963896; HDL assembly. DR Reactome; R-RNO-9634597; GPER1 signaling. DR Reactome; R-RNO-983231; Factors involved in megakaryocyte development and platelet production. DR PRO; PR:P68182; -. DR Proteomes; UP000002494; Chromosome 2. DR Bgee; ENSRNOG00000004978; Expressed in frontal cortex and 18 other cell types or tissues. DR GO; GO:0005952; C:cAMP-dependent protein kinase complex; IDA:RGD. DR GO; GO:0005813; C:centrosome; ISO:RGD. DR GO; GO:0097546; C:ciliary base; ISO:RGD. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD. 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; ISS:UniProtKB. DR GO; GO:0004691; F:cAMP-dependent protein kinase activity; IDA:RGD. DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB. DR GO; GO:0034237; F:protein kinase A regulatory subunit binding; IC:RGD. 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; ISO:RGD. DR GO; GO:0051447; P:negative regulation of meiotic cell cycle; IDA:RGD. DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; ISO:RGD. DR GO; GO:1904262; P:negative regulation of TORC1 signaling; ISS:UniProtKB. DR GO; GO:0001843; P:neural tube closure; ISO:RGD. DR GO; GO:0010737; P:protein kinase A signaling; IBA:GO_Central. DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB. DR GO; GO:0070613; P:regulation of protein processing; ISO:RGD. 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; P68182; RN. PE 1: Evidence at protein level; KW ATP-binding; cAMP; Cell membrane; Cytoplasm; Direct protein sequencing; KW Kinase; Lipoprotein; Membrane; Myristate; Nucleotide-binding; Nucleus; KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; KW Transferase. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:9521123" FT CHAIN 2..351 FT /note="cAMP-dependent protein kinase catalytic subunit FT beta" FT /id="PRO_0000086063" 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:0000269|PubMed:9521123" 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:0007744|PubMed:22673903" FT MOD_RES 331 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P05132" FT MOD_RES 339 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT LIPID 2 FT /note="N-myristoyl glycine" FT /evidence="ECO:0000250|UniProtKB:P22694" SQ SEQUENCE 351 AA; 40708 MW; EBAC9B8041DF9F47 CRC64; MGNTAIAKKG SEVESVKEFL AKAKEDFLRK WENPPPSNAG LEDFERKKTL GTGSFGRVML VKHKATEQYY AMKILDKQKV VKLKQIEHTL NEKRILQAVE FPFLVRLEYS FKDNSNLYMV MEYVPGGEMF SHLRRIGRFS EPHARFYAAQ IVLTFEYLHS LDLIYRDLKP ENLLIDHQGY IQVTDFGFAK RVKGRTWTLC GTPEYLAPEI ILSKGYNKAV DWWALGVLIY EMAAGYPPFF ADQPIQIYEK IVSGKVRFPS HFSSDLKDLL RNLLQVDLTK RFGNLKNGVS DIKTHKWFAT TDWIAIYQRK VEAPFIPKFR GSGDTSNFDD YEEEEIRVSI TEKCGKEFCE F //