======= PRKAR1A =======
== Gene Information ==
* **Official Symbol**: PRKAR1A
* **Official Name**: protein kinase cAMP-dependent type I regulatory subunit alpha
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5573|5573]]
* **UniProt**: [[https://www.uniprot.org/uniprot/P10644|P10644]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=PRKAR1A&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PRKAR1A|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/188830|Open OMIM]]
== Function Summary ==
* **Entrez 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].
* **UniProt Summary**: Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. {ECO:0000269|PubMed:16491121, ECO:0000269|PubMed:20215566, ECO:0000269|PubMed:26405036}.
|cNMP binding|
|RIIa|
|cAMP-dependent protein kinase regulator activity|
|negative regulation of cAMP-dependent protein kinase activity|
|cAMP-dependent protein kinase inhibitor activity|
|negative regulation of meiotic nuclear division|
|negative regulation of activated T cell proliferation|
|protein kinase A catalytic subunit binding|
|cAMP-dependent protein kinase complex|
|nucleotide-activated protein kinase complex|
|cardiac muscle cell proliferation|
|striated muscle cell proliferation|
|regulation of cAMP-dependent protein kinase activity|
|3,5-cyclic-GMP phosphodiesterase activity|
|negative regulation of meiotic cell cycle|
|muscle cell proliferation|
|activation of protein kinase A activity|
|cAMP binding|
|cGMP-mediated signaling|
|cellular response to glucagon stimulus|
|cardiac muscle tissue growth|
|heart growth|
|plasma membrane raft|
|regulation of meiotic nuclear division|
|female meiotic nuclear division|
|ciliary base|
|renal water homeostasis|
|regulation of activated T cell proliferation|
|immunological synapse|
|response to glucagon|
|sarcomere organization|
|negative regulation of nuclear division|
|regulation of meiotic cell cycle|
|negative regulation of reproductive process|
|negative regulation of T cell proliferation|
|myofibril assembly|
|multicellular organismal water homeostasis|
|mesoderm formation|
|mesoderm morphogenesis|
|water homeostasis|
|negative regulation of lymphocyte proliferation|
|negative regulation of mononuclear cell proliferation|
|neuromuscular junction|
|negative regulation of leukocyte proliferation|
|organ growth|
|cellular component assembly involved in morphogenesis|
|axoneme|
|renal system process|
|negative regulation of T cell activation|
|formation of primary germ layer|
|actomyosin structure organization|
|negative regulation of leukocyte cell-cell adhesion|
|mesoderm development|
|female gamete generation|
|negative regulation of protein serine/threonine kinase activity|
|striated muscle cell development|
|negative regulation of lymphocyte activation|
|muscle cell development|
|meiotic nuclear division|
|regulation of T cell proliferation|
|gastrulation|
|regulation of reproductive process|
|cardiac muscle tissue development|
|meiotic cell cycle process|
|cyclic-nucleotide-mediated signaling|
|negative regulation of cell-cell adhesion|
|negative regulation of leukocyte activation|
|regulation of nuclear division|
|negative regulation of cell activation|
|striated muscle cell differentiation|
|regulation of lymphocyte proliferation|
|regulation of mononuclear cell proliferation|
|regulation of leukocyte proliferation|
|meiotic cell cycle|
|negative regulation of protein kinase activity|
|protein domain specific binding|
|muscle cell differentiation|
|negative regulation of kinase activity|
|cellular response to peptide hormone stimulus|
|negative regulation of cell adhesion|
|negative regulation of transferase activity|
|striated muscle tissue development|
|nuclear division|
|ubiquitin protein ligase binding|
|blood coagulation|
|coagulation|
|regulation of leukocyte cell-cell adhesion|
|muscle tissue development|
|hemostasis|
|organelle fission|
|regulation of T cell activation|
|multicellular organismal homeostasis|
|negative regulation of cell cycle process|
|cellular response to peptide|
|activation of protein kinase activity|
|second-messenger-mediated signaling|
|glutamatergic synapse|
|cellular process involved in reproduction in multicellular organism|
|negative regulation of organelle organization|
|developmental growth|
|response to peptide hormone|
|growth|
|regulation of cell-cell adhesion|
|negative regulation of protein phosphorylation|
|negative regulation of immune system process|
|negative regulation of phosphorylation|
|supramolecular fiber organization|
|response to peptide|
|muscle structure development|
|wound healing|
|actin cytoskeleton organization|
|regulation of body fluid levels|
|regulation of lymphocyte activation|
|regulation of protein serine/threonine kinase activity|
|heart development|
|positive regulation of protein kinase activity|
|cell population proliferation|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|tissue morphogenesis|
|embryonic morphogenesis|
|actin filament-based process|
|response to wounding|
|negative regulation of cell cycle|
|positive regulation of kinase activity|
|negative regulation of protein modification process|
|protein-containing complex|
|cellular response to organonitrogen compound|
|regulation of leukocyte activation|
|cellular response to hormone stimulus|
|regulation of cell activation|
|positive regulation of transferase activity|
|cellular response to nitrogen compound|
|negative regulation of cell population proliferation|
|regulation of cell adhesion|
|gamete generation|
|negative regulation of cellular component organization|
|regulation of cell cycle process|
|organelle assembly|
|negative regulation of catalytic activity|
|regulation of protein kinase activity|
|cellular component morphogenesis|
|multicellular organismal reproductive process|
|sexual reproduction|
|multicellular organism reproduction|
|circulatory system development|
|regulation of kinase activity|
|anatomical structure formation involved in morphogenesis|
|response to hormone|
|embryo development|
|regulation of transferase activity|
|multi-organism reproductive process|
|cell cycle process|
|response to organonitrogen compound|
|positive regulation of protein phosphorylation|
|negative regulation of cellular protein metabolic process|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|response to nitrogen compound|
|negative regulation of protein metabolic process|
|cytoskeleton organization|
|chemical homeostasis|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|negative regulation of molecular function|
|regulation of cell cycle|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|regulation of organelle organization|
|cell cycle|
|reproductive process|
|reproduction|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|response to endogenous stimulus|
|response to oxygen-containing compound|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|homeostatic process|
|cell development|
|regulation of immune system process|
|intracellular signal transduction|
|positive regulation of protein metabolic process|
|tissue development|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of protein modification process|
|system process|
|membrane|
\\
=== CRISPR Data ===
^Screen^Score^
|[[:results:exp502|Milciclib 2μM R08 exp502]]|-3.24|
|[[:results:exp216|Erlotinib 10μM R05 exp216]]|-2.26|
|[[:results:exp274|Citral 50μM R06 exp274]]|-2.02|
|[[:results:exp535|Trimetrexate 0.03μM R08 exp535]]|-1.97|
|[[:results:exp357|Dorsomorphin 5μM R07 exp357]]|-1.91|
|[[:results:exp120|Dimethyl-Sulfoxide 1pc R03 exp120]]|-1.9|
|[[:results:exp229|Dimethyloxaloylglycine 100μM R05 exp229]]|-1.86|
|[[:results:exp70|INK128 0.2μM R02 exp70]]|-1.84|
|[[:results:exp189|Temozolomide 200μM R04 exp189]]|-1.81|
|[[:results:exp447|Amiloride 100μM R08 exp447]]|-1.8|
|[[:results:exp210|LB-100 2μM R05 exp210]]|-1.71|
|[[:results:exp379|MSC2530818 10μM R07 exp379]]|1.76|
|[[:results:exp417|Tubastatin-A 2.5μM R07 exp417]]|1.76|
|[[:results:exp530|Thioridazine 5μM R08 exp530]]|1.81|
|[[:results:exp228|Demecolcine 0.03μM R05 exp228]]|1.86|
|[[:results:exp454|Bafilomycin-A1 0.009μM R08 exp454]]|1.87|
|[[:results:exp482|Fas-L 44ng/ml R08 exp482]]|1.87|
|[[:results:exp460|BML-284 0.09μM R08 exp460]]|2.02|
|[[:results:exp34|Rotenone 20μM R00 exp34]]|2.04|
|[[:results:exp215|Colchicine 0.009μM R05 exp215]]|2.45|
|[[:results:exp335|Aminopterin 0.005μM R07 exp335]]|2.64|
|[[:results:exp97|BI-6727 0.0125μM R03 exp97]]|2.8|
|[[:results:exp106|UM131593 0.2μM R03 exp106]]|4.77|
^Gene^Correlation^
|[[:human genes:p:pde7a|PDE7A]]|0.507|
|[[:human genes:t:tmem161b|TMEM161B]]|0.472|
|[[:human genes:t:tle4|TLE4]]|0.456|
|[[:human genes:a:aip|AIP]]|0.45|
|[[:human genes:c:cmip|CMIP]]|0.444|
|[[:human genes:m:mtch1|MTCH1]]|0.443|
|[[:human genes:a:aff1|AFF1]]|0.434|
|[[:human genes:s:stk11|STK11]]|0.434|
|[[:human genes:s:scaf8|SCAF8]]|0.431|
|[[:human genes:c:celf1|CELF1]]|0.428|
|[[:human genes:m:mllt1|MLLT1]]|0.428|
|[[:human genes:o:otud5|OTUD5]]|0.426|
|[[:human genes:d:dot1l|DOT1L]]|0.425|
|[[:human genes:d:dek|DEK]]|0.423|
|[[:human genes:m:med13l|MED13L]]|0.422|
|[[:human genes:c:ccdc101|CCDC101]]|0.415|
|[[:human genes:h:hdac8|HDAC8]]|0.413|
|[[:human genes:a:atat1|ATAT1]]|0.412|
|[[:human genes:c:cbx3|CBX3]]|0.406|
|[[:human genes:t:tada2b|TADA2B]]|0.402|
Global Fraction of Cell Lines Where Essential: 4/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|1/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|1/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|1/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 4284
* **Expression level (log2 read counts)**: 6.89
{{:chemogenomics:nalm6 dist.png?nolink |}}