PRKAR1A
Summary: cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase, which transduces the signal through phosphorylation of different target proteins. The inactive kinase holoenzyme is a tetramer composed of two regulatory and 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. Four different regulatory subunits and three catalytic subunits have been identified in humans. This gene encodes one of the regulatory subunits. This protein was found to be a tissue-specific extinguisher that down-regulates the expression of seven liver genes in hepatoma x fibroblast hybrids. Mutations in this gene cause Carney complex (CNC). This gene can fuse to the RET protooncogene by gene rearrangement and form the thyroid tumor-specific chimeric oncogene known as PTC2. A nonconventional nuclear localization sequence (NLS) has been found for this protein which suggests a role in DNA replication via the protein serving as a nuclear transport protein for the second subunit of the Replication Factor C (RFC40). Several alternatively spliced transcript variants encoding two different isoforms have been observed. [provided by RefSeq, Jan 2013].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| protein kinase cAMP-dependent type I regulatory subunit alpha | MIM:188830 | Ensembl:ENSG00000108946 | HGNC:HGNC:9388 | PA33754 | 17q24.2 |
GO terms in PRKAR1A
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| MF | IDA | GO:0004862 | cAMP-dependent protein kinase inhibitor activity |
| MF | IPI | GO:0005515 | protein binding |
| MF | IDA | GO:0008603 | cAMP-dependent protein kinase regulator activity |
| MF | IPI | GO:0019904 | protein domain specific binding |
| MF | IEA | GO:0030552 | cAMP binding |
| MF | IDA | GO:0031625 | ubiquitin protein ligase binding |
| MF | IPI | GO:0034236 | protein kinase A catalytic subunit binding |
| MF | IBA | GO:0047555 | 3',5'-cyclic-GMP phosphodiesterase activity |
| CC | IDA | GO:0001772 | immunological synapse |
| CC | IDA | GO:0005737 | cytoplasm |
| CC | IBA | GO:0005829 | cytosol |
| CC | TAS | GO:0005829 | cytosol |
| CC | IDA | GO:0005930 | axoneme |
| CC | IEA | GO:0005952 | cAMP-dependent protein kinase complex |
| CC | HDA | GO:0016020 | membrane |
| CC | IDA | GO:0031588 | nucleotide-activated protein kinase complex |
| CC | IEA | GO:0031594 | neuromuscular junction |
| CC | IDA | GO:0032991 | protein-containing complex |
| CC | IDA | GO:0044853 | plasma membrane raft |
| CC | TAS | GO:0097546 | ciliary base |
| BP | IEA | GO:0001707 | mesoderm formation |
| BP | TAS | GO:0003091 | renal water homeostasis |
| BP | TAS | GO:0006357 | regulation of transcription by RNA polymerase II |
| BP | IEA | GO:0007143 | female meiotic nuclear division |
| BP | TAS | GO:0007596 | blood coagulation |
| BP | IBA | GO:0019934 | cGMP-mediated signaling |
| BP | TAS | GO:0034199 | activation of protein kinase A activity |
| BP | TAS | GO:0035556 | intracellular signal transduction |
| BP | IEA | GO:0045214 | sarcomere organization |
| BP | IEA | GO:0045835 | negative regulation of meiotic nuclear division |
| BP | IMP | GO:0046007 | negative regulation of activated T cell proliferation |
| BP | IEA | GO:0060038 | cardiac muscle cell proliferation |
| BP | TAS | GO:0071377 | cellular response to glucagon stimulus |
| BP | IDA | GO:2000480 | negative regulation of cAMP-dependent protein kinase activity |
Gene expression in normal tissue: PRKAR1A
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in PRKAR1A
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| netpath | Pathway_EGFR1 | EGFR1 |
| pid | integrin_a4b1_pathway | Alpha4 beta1 integrin signaling events |
| kegg | hsa04910 | Insulin signaling pathway - Homo sapiens (human) |
| wikipathways | WP2012 | miRs in Muscle Cell Differentiation |
| wikipathways | WP2857 | Mesodermal Commitment Pathway |
| wikipathways | WP289 | Myometrial Relaxation and Contraction Pathways |
| wikipathways | WP35 | G Protein Signaling Pathways |
| wikipathways | WP3965 | Lipid Metabolism Pathway |
| wikipathways | WP4010 | Liver steatosis AOP |
| wikipathways | WP536 | Calcium Regulation in the Cardiac Cell |
| wikipathways | WP706 | Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways |
| smpdb | SMP00296 | Acebutolol Action Pathway |
| smpdb | SMP00297 | Alprenolol Action Pathway |
| smpdb | SMP00298 | Atenolol Action Pathway |
| smpdb | SMP00299 | Betaxolol Action Pathway |
| smpdb | SMP00300 | Bisoprolol Action Pathway |
| smpdb | SMP00301 | Esmolol Action Pathway |
| smpdb | SMP00302 | Metoprolol Action Pathway |
| smpdb | SMP00303 | Nadolol Action Pathway |
| smpdb | SMP00304 | Oxprenolol Action Pathway |
| smpdb | SMP00305 | Penbutolol Action Pathway |
| smpdb | SMP00306 | Pindolol Action Pathway |
| smpdb | SMP00307 | Propranolol Action Pathway |
| smpdb | SMP00323 | Quinidine Action Pathway |
| smpdb | SMP00324 | Procainamide (Antiarrhythmic) Action Pathway |
| smpdb | SMP00325 | Disopyramide Action Pathway |
| smpdb | SMP00326 | Fosphenytoin (Antiarrhythmic) Action Pathway |
| smpdb | SMP00327 | Phenytoin (Antiarrhythmic) Action Pathway |
| smpdb | SMP00328 | Lidocaine (Antiarrhythmic) Action Pathway |
| smpdb | SMP00329 | Mexiletine Action Pathway |
| smpdb | SMP00330 | Tocainide Action Pathway |
| smpdb | SMP00331 | Flecainide Action Pathway |
| smpdb | SMP00332 | Ibutilide Action Pathway |
| smpdb | SMP00359 | Diltiazem Action Pathway |
| smpdb | SMP00366 | Nebivolol Action Pathway |
| smpdb | SMP00367 | Carvedilol Action Pathway |
| smpdb | SMP00368 | Labetalol Action Pathway |
| smpdb | SMP00375 | Verapamil Action Pathway |
| smpdb | SMP00376 | Amlodipine Action Pathway |
| smpdb | SMP00377 | Felodipine Action Pathway |
| smpdb | SMP00378 | Isradipine Action Pathway |
| smpdb | SMP00379 | Nifedipine Action Pathway |
| smpdb | SMP00380 | Nimodipine Action Pathway |
| smpdb | SMP00381 | Nisoldipine Action Pathway |
| smpdb | SMP00382 | Nitrendipine Action Pathway |
| smpdb | SMP00588 | Muscle/Heart Contraction |
| smpdb | SMP00657 | Bopindolol Action Pathway |
| smpdb | SMP00658 | Carteolol Action Pathway |
| smpdb | SMP00659 | Timolol Action Pathway |
| smpdb | SMP00660 | Sotalol Action Pathway |
| smpdb | SMP00661 | Epinephrine Action Pathway |
| smpdb | SMP00662 | Dobutamine Action Pathway |
| smpdb | SMP00663 | Isoprenaline Action Pathway |
| smpdb | SMP00664 | Arbutamine Action Pathway |
| smpdb | SMP00665 | Amiodarone Action Pathway |
| smpdb | SMP00666 | Levobunolol Action Pathway |
| smpdb | SMP00667 | Metipranolol Action Pathway |
| smpdb | SMP00668 | Bevantolol Action Pathway |
| smpdb | SMP00669 | Practolol Action Pathway |
| smpdb | SMP00670 | Bupranolol Action Pathway |
| reactome | R-HSA-109582 | Hemostasis |
| reactome | R-HSA-111885 | Opioid Signalling |
| reactome | R-HSA-111931 | PKA-mediated phosphorylation of CREB |
| reactome | R-HSA-111933 | Calmodulin induced events |
| reactome | R-HSA-111996 | Ca-dependent events |
| reactome | R-HSA-111997 | CaM pathway |
| reactome | R-HSA-112040 | G-protein mediated events |
| reactome | R-HSA-112043 | PLC beta mediated events |
| reactome | R-HSA-1430728 | Metabolism |
| reactome | R-HSA-1430728 | Metabolism |
| reactome | R-HSA-1489509 | DAG and IP3 signaling |
| reactome | R-HSA-162582 | Signal Transduction |
| reactome | R-HSA-163359 | Glucagon signaling in metabolic regulation |
| reactome | R-HSA-163615 | PKA activation |
| reactome | R-HSA-163685 | Integration of energy metabolism |
| reactome | R-HSA-163685 | Integration of energy metabolism |
| reactome | R-HSA-164378 | PKA activation in glucagon signalling |
| reactome | R-HSA-180024 | DARPP-32 events |
| reactome | R-HSA-372790 | Signaling by GPCR |
| reactome | R-HSA-381676 | Glucagon-like Peptide-1 (GLP1) regulates insulin secretion |
| reactome | R-HSA-382551 | Transport of small molecules |
| reactome | R-HSA-388396 | GPCR downstream signalling |
| reactome | R-HSA-418594 | G alpha (i) signalling events |
| reactome | R-HSA-422356 | Regulation of insulin secretion |
| reactome | R-HSA-432040 | Vasopressin regulates renal water homeostasis via Aquaporins |
| reactome | R-HSA-445717 | Aquaporin-mediated transport |
| reactome | R-HSA-5358351 | Signaling by Hedgehog |
| reactome | R-HSA-5610787 | Hedgehog 'off' state |
| reactome | R-HSA-9006925 | Intracellular signaling by second messengers |
| reactome | R-HSA-983231 | Factors involved in megakaryocyte development and platelet production |
| biocarta | agpcrpathway | attenuation of gpcr signaling |
| biocarta | badpathway | regulation of bad phosphorylation |
| biocarta | carm1pathway | transcription regulation by methyltransferase of carm1 |
| biocarta | cftrpathway | cystic fibrosis transmembrane conductance regulator (cftr) and beta 2 adrenergic receptor (b2ar) pathway |
| biocarta | chrebppathway | chrebp regulation by carbohydrates and camp |
| biocarta | ck1pathway | regulation of ck1/cdk5 by type 1 glutamate receptors |
| biocarta | crebpathway | transcription factor creb and its extracellular signals |
| biocarta | cskpathway | activation of csk by camp-dependent protein kinase inhibits signaling through the t cell receptor |
| biocarta | dreampathway | repression of pain sensation by the transcriptional regulator dream |
| biocarta | gata3pathway | gata3 participate in activating the th2 cytokine genes expression |
| biocarta | gpcrpathway | signaling pathway from g-protein families |
| biocarta | gspathway | activation of camp-dependent protein kinase pka |
| biocarta | mcalpainpathway | mcalpain and friends in cell motility |
| biocarta | mprpathway | how progesterone initiates the oocyte maturation |
| biocarta | no1pathway | actions of nitric oxide in the heart |
| biocarta | nos1pathway | nitric oxide signaling pathway |
| biocarta | plcepathway | phospholipase c-epsilon pathway |
| biocarta | pparapathway | mechanism of gene regulation by peroxisome proliferators via ppara |
| biocarta | stathminpathway | stathmin and breast cancer resistance to antimicrotubule agents |
Gene-Drug: Aster Plot
| Drug ID | Drug Name | Model Num. |
|---|---|---|
| iGMDRD513 | BML-259 | 3 |
| iGMDRD32 | Metformin | 1 |
| iGMDRD781 | Sirolimus | 3 |
| iGMDRD187 | BRD9876 | 2 |
| iGMDRD150 | RITA | 3 |
| iGMDRD61 | Kinetin riboside | 3 |
| iGMDRD100 | Zebularine | 3 |
| iGMDRD446 | LY 2183240 | 2 |
| iGMDRD341 | Triacsin c | 5 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in PRKAR1A
CLASSFICATION
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