ID KAPCB_PIG Reviewed; 351 AA. AC P05383; DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 24-JAN-2024, entry version 159. 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 Sus scrofa (Pig). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus. OX NCBI_TaxID=9823; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] OF 14-251. RX PubMed=2441988; DOI=10.1111/j.1432-1033.1987.tb13326.x; RA Adavani S.R., Schwarz M., Showers M.O., Maurer R.A., Hemmings B.A.; RT "Multiple mRNA species code for the catalytic subunit of the cAMP-dependent RT protein kinase from LLC-PK1 cells. Evidence for two forms of the catalytic RT subunit."; RL Eur. J. Biochem. 167:221-226(1987). RN [2] RP PROTEIN SEQUENCE OF 2-8; 10-22 AND 30-47, MYRISTOYLATION AT GLY-2, AND RP 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 DEAMIDATION AT ASN-3, AND SUBCELLULAR LOCATION. RX PubMed=10684253; DOI=10.1083/jcb.148.4.715; RA Pepperkok R., Hotz-Wagenblatt A., Koenig N., Girod A., Bossemeyer D., RA Kinzel V.; RT "Intracellular distribution of mammalian protein kinase A catalytic subunit RT altered by conserved Asn2 deamidation."; RL J. Cell Biol. 148:715-726(2000). 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:10684253, 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; X05998; CAA29415.1; -; mRNA. DR PIR; S00085; S00085. DR AlphaFoldDB; P05383; -. DR SMR; P05383; -. DR STRING; 9823.ENSSSCP00000058922; -. DR iPTMnet; P05383; -. DR PeptideAtlas; P05383; -. DR InParanoid; P05383; -. DR Proteomes; UP000008227; Unplaced. DR Proteomes; UP000314985; Unplaced. DR Proteomes; UP000694570; Unplaced. DR Proteomes; UP000694571; Unplaced. DR Proteomes; UP000694720; Unplaced. DR Proteomes; UP000694722; Unplaced. DR Proteomes; UP000694723; Unplaced. DR Proteomes; UP000694724; Unplaced. DR Proteomes; UP000694725; Unplaced. DR Proteomes; UP000694726; Unplaced. DR Proteomes; UP000694727; Unplaced. DR Proteomes; UP000694728; Unplaced. DR GO; GO:0005952; C:cAMP-dependent protein kinase complex; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. 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; ISS:UniProtKB. DR GO; GO:0004691; F:cAMP-dependent protein kinase activity; ISS:UniProtKB. DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:1904262; P:negative regulation of TORC1 signaling; ISS:UniProtKB. DR GO; GO:0010737; P:protein kinase A signaling; IBA:GO_Central. DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB. 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:SF150; 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. 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_0000086062" 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; partial" FT /evidence="ECO:0000269|PubMed:10684253, FT 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: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:9521123" SQ SEQUENCE 351 AA; 40594 MW; 384A1EB1FC198B61 CRC64; MGNAATAKKG SEVESVKEFL AKAKEDFLKK WENPAPNNAG LEDFERKKTL GTGSFGRVML VKHKATEQYY AMKILDKQKV VKLKQIEHTL NEKRILQAVN FPFLVRLEFS FKDNSNLYMV MEYVPGGEMF SHLRRIGRFS EPHARFYAAQ IVLTFEYLHS LDLIYRDLKP ENLLIDHQGY IQVTDFGFAK RVKGRTWTLC GTPEYLAPEI ILSKGYNKAV DWWALGVLIY EMAAGYPPFF ADQPIQIYEK IVSGKVRFPS HFSSDLKDLL RNLLQVDLTK RFGNLKNGVS DIKTHKWFAT TDWIAIYQRK VEAPFIPKFR GSGDTSNFDD YEEEDIRVSI TEKCGKEFCE F //