BioPAX pathway converted from "cAMP binds PKA tetramer" in the Reactome database.LEFT-TO-RIGHTcAMP binds PKA tetramerThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>PKA tetramerReactome DB_ID: 9829310cytosolGENE ONTOLOGYGO:0005829Converted from EntitySet in ReactomePRKACA,PRKACB,PRKACGPKA catalytic subunitReactome DB_ID: 9829308PrkacaPRKACAP27791Reactome DB_ID: 9829303UniProt:P27791 PrkacaPrkacaFUNCTION Phosphorylates a large number of substrates in the cytoplasm and the nucleus (By similarity). Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, SOX9 and VASP (By similarity). Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts (By similarity). Involved in chondrogenesis by mediating phosphorylation of SOX9 (By similarity). Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+). PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Negatively regulates tight junctions (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis (By similarity). Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation (By similarity). May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) (PubMed:20844122). Phosphorylates APOBEC3G and AICDA. Phosphorylates HSF1; this phosphorylation promotes HSF1 nuclear localization and transcriptional activity upon heat shock (By similarity).ACTIVITY REGULATION Allosterically activated by various compounds, including ATP. Activated by cAMP; the nucleotide acts as a dynamic and allosteric activator by coupling the two lobes of apo PKA, enhancing the enzyme dynamics synchronously and priming it for catalysis.SUBUNIT A number of inactive tetrameric holoenzymes are produced by the combination of homo- or heterodimers of the different regulatory subunits associated with two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. The cAMP-dependent protein kinase catalytic subunit binds PJA2. Both isoforms 1 and 2 forms activate cAMP-sensitive PKAI and PKAII holoenzymes by interacting with regulatory subunit (R) of PKA, PRKAR1A/PKR1 and PRKAR2A/PKR2, respectively. Interacts with NFKB1, NFKB2 and NFKBIA in platelets; these interactions are disrupted by thrombin and collagen. Binds to ABL1 in spermatozoa and with CDC25B in oocytes (By similarity). Interacts with APOBEC3G and AICDA (By similarity). Interacts with RAB13; downstream effector of RAB13 involved in tight junction assembly. Found in a complex at least composed of MROH2B, PRKACA isoform 2 and TCP11 (By similarity). Interacts with MROH2B (By similarity). Interacts with HSF1 (By similarity). Isoform 2 interacts with TCP11 (By similarity).TISSUE SPECIFICITY Ubiquitously expressed. Isoform 2 is round spermatid specific.DEVELOPMENTAL STAGE In spermatids, isoform 1 is expressed until spermatids become elutriated, whereafter isoform 2 is expressed.PTM Asn-3 is deaminated to Asp in more than 25% of the proteins, giving rise to 2 major isoelectric variants, called CB and CA respectively (0.4 pH unit change). Deamidation proceeds via the so-called beta-aspartyl shift mechanism and yields either 'D-Asp-2' (major) or 'D-isoAsp-2' (minor), in addition to L-isomers. Deamidation occurs after the addition of myristate. The Asn-3 form reaches a significantly larger nuclear/cytoplasmic ratio than the 'Asp-2' form.PTM Autophosphorylated. Phosphorylation is enhanced by vitamin K(2). Phosphorylated on threonine and serine residues. Phosphorylation on Thr-198 is required for full activity (By similarity).PTM Phosphorylated at Tyr-331 by activated receptor tyrosine kinases EGFR and PDGFR; this increases catalytic efficiency.SIMILARITY Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily.Rattus norvegicusNCBI Taxonomy10116UniProtP277912EQUAL351EQUALReactome Database ID Release 759829303Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9829303ReactomeR-RNO-578441Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-57844.1Reactomehttp://www.reactome.orgPrkacbPRKACBP68182Reactome DB_ID: 9829306UniProt:P68182 PrkacbPrkacbPkacbFUNCTION Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs. PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates GPKOW which regulates its ability to bind RNA.ACTIVITY REGULATION Activated by cAMP.SUBUNIT A number of inactive tetrameric holoenzymes are produced by the combination of homo- or heterodimers of the different regulatory subunits associated with two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. The cAMP-dependent protein kinase catalytic subunit binds PJA2. Interacts with GPKOW.PTM Asn-3 is deaminated to Asp in more than 25% of the proteins, giving rise to 2 major isoelectric variants, called CB and CA respectively (0.4 pH unit change). Deamidation proceeds via the so-called beta-aspartyl shift mechanism and yields either 'D-Asp-2' (major) or 'D-isoAsp-2' (minor), in addition to L-isomers. Deamidation occurs after the addition of myristate. The Asn-3 form reaches a significantly larger nuclear/cytoplasmic ratio than the 'Asp-2' form.SIMILARITY Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily.UniProtP681822EQUAL351EQUALReactome Database ID Release 759829306Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9829306ReactomeR-RNO-578461Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-57846.1Reactome Database ID Release 759829308Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9829308ReactomeR-RNO-1119201Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-111920.12Converted from EntitySet in ReactomePKA regulatory subunitReactome DB_ID: 9829300P09456Prkar1aPRKAR1AReactome DB_ID: 9829291UniProt:P09456 Prkar1aPrkar1aFUNCTION Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.SUBUNIT The inactive holoenzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP releases the two active catalytic monomers and the regulatory dimer. PRKAR1A also interacts with RFC2; the complex may be involved in cell survival. Interacts with AKAP4. Interacts with RARA; the interaction occurs in the presence of cAMP or FSH and regulates RARA transcriptional activity. Interacts with the phosphorylated form of PJA2. Interacts with CBFA2T3. Interacts with PRKX; regulates this cAMP-dependent protein kinase (By similarity). Interacts with smAKAP; this interaction may target PRKAR1A to the plasma membrane. Interacts with AICDA (By similarity).PTM The pseudophosphorylation site binds to the substrate-binding region of the catalytic chain, resulting in the inhibition of its activity.MISCELLANEOUS Two types of regulatory chains are found: type I, which predominates in skeletal muscle, and type II, which predominates in cardiac muscle.SIMILARITY Belongs to the cAMP-dependent kinase regulatory chain family.UniProtP094561EQUAL381EQUALReactome Database ID Release 759829291Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9829291ReactomeR-RNO-578361Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-57836.1Prkar1bcAMP-dependent protein kinase type I-beta regulatory subunitKAP1_RATPrkar1bReactome DB_ID: 446976UniProt:P81377 Prkar1bPrkar1bFUNCTION Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.SUBUNIT The inactive holoenzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP releases the two active catalytic monomers and the regulatory dimer. Interacts with PRKX; regulates this cAMP-dependent protein kinase (By similarity). Interacts with smAKAP; this interaction may target PRKAR1B to the plasma membrane (By similarity).TISSUE SPECIFICITY Abundant in brain and testis. No expression in lung, heart, liver, spleen, kidney and skeletal muscle.PTM The pseudophosphorylation site binds to the substrate-binding region of the catalytic chain, resulting in the inhibition of its activity.SIMILARITY Belongs to the cAMP-dependent kinase regulatory chain family.UniProtP813772EQUAL381EQUALReactome Database ID Release 75446976Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=446976ReactomeR-RNO-4469761Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-446976.1P12368Prkar2aPRKAR2AReactome DB_ID: 9829295UniProt:P12368 Prkar2aPrkar2aFUNCTION Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase.SUBUNIT The inactive form of the enzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP produces two active catalytic monomers and a regulatory dimer that binds four cAMP molecules. Interacts with AKAP4 and CBFA2T3 (By similarity). Interacts with the phosphorylated form of PJA2 (By similarity). Interacts with MYRIP; his interaction may link PKA to components of the exocytosis machinery, thus facilitating exocytosis, including insulin release. Forms a complex composed of PRKAR2A, GSK3B and GSKIP through GSKIP interaction; facilitates PKA-induced phosphorylation and regulates GSK3B activity (By similarity). Interacts with ADCY8; inhibits adenylate cyclase activity through PKA phosphorylation (By similarity).TISSUE SPECIFICITY Four types of regulatory chains are found: I-alpha, I-beta, II-alpha, and II-beta. Their expression varies among tissues and is in some cases constitutive and in others inducible.PTM Phosphorylated by the activated catalytic chain.SIMILARITY Belongs to the cAMP-dependent kinase regulatory chain family.UniProtP123682EQUAL404EQUALReactome Database ID Release 759829295Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9829295ReactomeR-RNO-578401Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-57840.1P12369Prkar2bPRKAR2BReactome DB_ID: 9829298UniProt:P12369 Prkar2bPrkar2bFUNCTION Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase.SUBUNIT The inactive form of the enzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP produces two active catalytic monomers and a regulatory dimer that binds four cAMP molecules. Interacts with the phosphorylated form of PJA2 (By similarity). Forms a complex composed of PRKAR2B, GSK3B and GSKIP through GSKIP interaction; facilitates PKA-induced phosphorylation and regulates GSK3B activity (By similarity).TISSUE SPECIFICITY Four types of regulatory chains are found: I-alpha, I-beta, II-alpha, and II-beta. Their expression varies among tissues and is in some cases constitutive and in others inducible. Brain. Present in a few pyramidal neurons and mostly in mossy fibers. Colocalizes with PJA2 in dentate granule cells and at postsynaptic sites of primary hippocampal neurons.PTM Phosphorylated by the activated catalytic chain.SIMILARITY Belongs to the cAMP-dependent kinase regulatory chain family.UniProtP123692EQUAL418EQUALReactome Database ID Release 759829298Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9829298ReactomeR-RNO-578421Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-57842.1Reactome Database ID Release 759829300Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9829300ReactomeR-RNO-1119211Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-111921.12Reactome Database ID Release 759829310Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9829310ReactomeR-RNO-1119221Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-111922.1cAMPCyclic adenylic acid3',5'-cyclic AMPCyclic AMPAdenosine 3',5'-phosphateReactome DB_ID: 303893',5'-cyclic AMP [ChEBI:17489]3',5'-cyclic AMPChEBICHEBI:17489Reactome Database ID Release 7530389Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=30389ReactomeR-ALL-303893Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-30389.3COMPOUNDC00575additional informationMIMI:03614PKA tetramer:4xcAMPReactome DB_ID: 982931214Reactome Database ID Release 759829312Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9829312ReactomeR-RNO-89517291Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-8951729.1Reactome Database ID Release 759921396Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9921396ReactomeR-RNO-89517271Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-8951727.1Protein kinase A (PKA) regulatory subunit isoforms differ in their tissue specificity and functional characteristics. The isoform activated in response to glucagon signaling is not known. <br><br>PKA kinase is a tetramer of two regulatory and two catalytic subunits. The regulatory subunits block the activity of the catalytic subunits. <br><br>cAMP binds the regulatory subunits, which leads to dissociation of the tetramer into two active dimers made up of a regulatory and a catalytic subunit.16407073Pubmed2006Dynamic binding of PKA regulatory subunit RI alphaGullingsrud, JKim, CTaylor, SSMcCammon, JAStructure 14:141-9inferred from electronic annotationEVIDENCE CODEECO:0000203