PRKACA [The Human Chemical-Genetic Interaction Map Project]

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======= PRKACA =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: PRKACA
  * **<color #00a2e8>Official Name</color>**: protein kinase cAMP-activated catalytic subunit alpha
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5566|5566]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P17612|P17612]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=PRKACA&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PRKACA|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/601639|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes one of the catalytic subunits of protein kinase A, which exists as a tetrameric holoenzyme with two regulatory subunits and two catalytic subunits, in its inactive form. 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. cAMP-dependent phosphorylation of proteins by protein kinase A is important to many cellular processes, including differentiation, proliferation, and apoptosis. Constitutive activation of this gene caused either by somatic mutations, or genomic duplications of regions that include this gene, have been associated with hyperplasias and adenomas of the adrenal cortex and are linked to corticotropin-independent Cushing's syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. Tissue-specific isoforms that differ at the N-terminus have been described, and these isoforms may differ in the post-translational modifications that occur at the N-terminus of some isoforms. [provided by RefSeq, Jan 2015]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Phosphorylates a large number of substrates in the cytoplasm and the nucleus. 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 CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA and VASP. RORA is activated by phosphorylation. Required for glucose- mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. 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. Prevents the antiproliferative and anti-invasive effects of alpha- difluoromethylornithine in breast cancer cells when activated. 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. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT). Phosphorylates APOBEC3G and AICDA. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. Phosphorylates HSF1; this phosphorylation promotes HSF1 nuclear localization and transcriptional activity upon heat shock (PubMed:21085490). {ECO:0000269|PubMed:15642694, ECO:0000269|PubMed:15905176, ECO:0000269|PubMed:16387847, ECO:0000269|PubMed:17333334, ECO:0000269|PubMed:17565987, ECO:0000269|PubMed:17693412, ECO:0000269|PubMed:18836454, ECO:0000269|PubMed:19949837, ECO:0000269|PubMed:20356841, ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:21514275, ECO:0000269|PubMed:21812984}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Pkinase Tyr|
|Pkinase|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning|
|regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning|
|cellular response to parathyroid hormone stimulus|
|cAMP-dependent protein kinase activity|
|response to parathyroid hormone|
|high-density lipoprotein particle assembly|
|protein kinase A signaling|
|cAMP-dependent protein kinase complex|
|cellular response to epinephrine stimulus|
|cell communication by electrical coupling involved in cardiac conduction|
|response to epinephrine|
|activation of protein kinase A activity|
|cell communication by electrical coupling|
|regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion|
|positive regulation of protein export from nucleus|
|protein kinase A regulatory subunit binding|
|regulation of bicellular tight junction assembly|
|calcium-mediated signaling using intracellular calcium source|
|calcium channel complex|
|regulation of cardiac muscle contraction by calcium ion signaling|
|regulation of ryanodine-sensitive calcium-release channel activity|
|cellular response to glucagon stimulus|
|plasma lipoprotein particle assembly|
|negative regulation of embryonic development|
|sperm capacitation|
|regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum|
|protein serine/threonine/tyrosine kinase activity|
|plasma membrane raft|
|negative regulation of smoothened signaling pathway|
|protein-lipid complex assembly|
|ciliary base|
|renal water homeostasis|
|response to glucagon|
|regulation of protein export from nucleus|
|cell communication involved in cardiac conduction|
|sperm flagellum|
|plasma lipoprotein particle organization|
|protein-lipid complex subunit organization|
|intercellular bridge|
|manganese ion binding|
|positive regulation of nucleocytoplasmic transport|
|regulation of protein processing|
|mesoderm formation|
|multicellular organismal water homeostasis|
|regulation of protein maturation|
|regulation of cardiac conduction|
|mesoderm morphogenesis|
|cellular response to glucose stimulus|
|cellular response to heat|
|cellular response to hexose stimulus|
|regulation of plasma lipoprotein particle levels|
|cellular response to monosaccharide stimulus|
|water homeostasis|
|regulation of cardiac muscle contraction|
|regulation of smoothened signaling pathway|
|neuromuscular junction|
|regulation of release of sequestered calcium ion into cytosol|
|positive regulation of cell cycle arrest|
|cellular response to carbohydrate stimulus|
|peptidyl-threonine phosphorylation|
|acrosomal vesicle|
|regulation of calcium ion transmembrane transporter activity|
|cellular glucose homeostasis|
|regulation of cell junction assembly|
|neural tube closure|
|peptidyl-threonine modification|
|regulation of striated muscle contraction|
|tube closure|
|cardiac conduction|
|ciliary basal body-plasma membrane docking|
|regulation of heart rate|
|regulation of calcium-mediated signaling|
|primary neural tube formation|
|regulation of calcium ion transport into cytosol|
|cellular response to monoamine stimulus|
|cellular response to catecholamine stimulus|
|axoneme|
|regulation of nucleocytoplasmic transport|
|response to monoamine|
|neural tube formation|
|response to catecholamine|
|regulation of cell cycle arrest|
|response to heat|
|renal system process|
|formation of primary germ layer|
|regulation of osteoblast differentiation|
|stimulatory C-type lectin receptor signaling pathway|
|innate immune response activating cell surface receptor signaling pathway|
|embryonic epithelial tube formation|
|mesoderm development|
|regulation of sequestering of calcium ion|
|regulation of embryonic development|
|G2/M transition of mitotic cell cycle|
|epithelial tube formation|
|cell cycle G2/M phase transition|
|multicellular organismal signaling|
|response to glucose|
|response to hexose|
|morphogenesis of embryonic epithelium|
|calcium-mediated signaling|
|regulation of calcium ion transmembrane transport|
|tube formation|
|dendritic spine|
|response to monosaccharide|
|spermatid development|
|positive regulation of intracellular protein transport|
|spermatid differentiation|
|cell maturation|
|gastrulation|
|neural tube development|
|regulation of muscle contraction|
|organelle localization by membrane tethering|
|response to carbohydrate|
|regulation of cation channel activity|
|regulation of macroautophagy|
|peptidyl-serine phosphorylation|
|response to temperature stimulus|
|membrane docking|
|regulation of proteasomal protein catabolic process|
|glucose homeostasis|
|carbohydrate homeostasis|
|regulation of ossification|
|protein autophosphorylation|
|regulation of G2/M transition of mitotic cell cycle|
|peptidyl-serine modification|
|positive regulation of intracellular transport|
|regulation of cell cycle G2/M phase transition|
|magnesium ion binding|
|regulation of proteolysis involved in cellular protein catabolic process|
|regulation of protein binding|
|regulation of intracellular protein transport|
|innate immune response-activating signal transduction|
|regulation of muscle system process|
|protein kinase activity|
|developmental maturation|
|regulation of heart contraction|
|protein domain specific binding|
|regulation of cellular protein catabolic process|
|regulation of calcium ion transport|
|germ cell development|
|activation of innate immune response|
|regulation of ion transmembrane transporter activity|
|regulation of transmembrane transporter activity|
|cellular response to peptide hormone stimulus|
|mitotic cell cycle phase transition|
|regulation of transporter activity|
|cell cycle phase transition|
|positive regulation of cell cycle process|
|regulation of blood circulation|
|blood coagulation|
|ubiquitin protein ligase binding|
|coagulation|
|hemostasis|
|epithelial tube morphogenesis|
|negative regulation of nervous system development|
|multicellular organismal homeostasis|
|positive regulation of cellular protein localization|
|cellular response to peptide|
|regulation of cytosolic calcium ion concentration|
|activation of protein kinase activity|
|regulation of autophagy|
|regulation of cation transmembrane transport|
|second-messenger-mediated signaling|
|positive regulation of innate immune response|
|cilium assembly|
|regulation of intracellular transport|
|cellular process involved in reproduction in multicellular organism|
|positive regulation of response to biotic stimulus|
|protein serine/threonine kinase activity|
|cilium organization|
|positive regulation of cell cycle|
|regulation of binding|
|regulation of protein catabolic process|
|regulation of metal ion transport|
|extracellular structure organization|
|response to peptide hormone|
|nuclear speck|
|regulation of mitotic cell cycle phase transition|
|positive regulation of protein transport|
|morphogenesis of an epithelium|
|cellular calcium ion homeostasis|
|modulation of chemical synaptic transmission|
|regulation of trans-synaptic signaling|
|plasma membrane bounded cell projection assembly|
|regulation of cell cycle phase transition|
|calcium ion homeostasis|
|immune response-activating cell surface receptor signaling pathway|
|regulation of innate immune response|
|cell projection assembly|
|positive regulation of establishment of protein localization|
|protein kinase binding|
|cellular divalent inorganic cation homeostasis|
|response to peptide|
|positive regulation of defense response|
|mRNA processing|
|regulation of ion transmembrane transport|
|wound healing|
|immune response-regulating cell surface receptor signaling pathway|
|divalent inorganic cation homeostasis|
|centrosome|
|regulation of body fluid levels|
|positive regulation of multi-organism process|
|regulation of response to biotic stimulus|
|positive regulation of protein kinase activity|
|regulation of cellular protein localization|
|cellular response to organic cyclic compound|
|spermatogenesis|
|cellular metal ion homeostasis|
|immune response-activating signal transduction|
|regulation of transmembrane transport|
|male gamete generation|
|tissue morphogenesis|
|embryonic morphogenesis|
|response to wounding|
|positive regulation of kinase activity|
|organelle localization|
|regulation of system process|
|immune response-regulating signaling pathway|
|mitotic cell cycle process|
|cellular response to organonitrogen compound|
|positive regulation of response to external stimulus|
|cellular response to hormone stimulus|
|metal ion homeostasis|
|activation of immune response|
|regulation of mitotic cell cycle|
|chordate embryonic development|
|cellular cation homeostasis|
|cellular ion homeostasis|
|embryo development ending in birth or egg hatching|
|tube morphogenesis|
|positive regulation of transferase activity|
|cellular response to nitrogen compound|
|developmental process involved in reproduction|
|cytokine-mediated signaling pathway|
|mitotic cell cycle|
|gamete generation|
|mRNA metabolic process|
|perinuclear region of cytoplasm|
|regulation of ion transport|
|regulation of protein transport|
|cation homeostasis|
|inorganic ion homeostasis|
|regulation of proteolysis|
|regulation of peptide transport|
|cellular chemical homeostasis|
|regulation of establishment of protein localization|
|regulation of cell cycle process|
|organelle assembly|
|regulation of defense response|
|regulation of multi-organism process|
|ion homeostasis|
|regulation of protein kinase activity|
|multicellular organismal reproductive process|
|sexual reproduction|
|regulation of cellular catabolic process|
|multicellular organism reproduction|
|tube development|
|positive regulation of immune response|
|regulation of kinase activity|
|RNA processing|
|peptidyl-amino acid modification|
|anatomical structure formation involved in morphogenesis|
|cellular homeostasis|
|response to hormone|
|regulation of cellular localization|
|response to organic cyclic compound|
|regulation of nervous system development|
|negative regulation of developmental process|
|regulation of cellular component biogenesis|
|protein phosphorylation|
|regulation of transferase activity|
|embryo development|
|positive regulation of transport|
|regulation of catabolic process|
|multi-organism reproductive process|
|cell cycle process|
|response to organonitrogen compound|
|cellular response to cytokine stimulus|
|positive regulation of protein phosphorylation|
|regulation of protein localization|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|response to nitrogen compound|
|regulation of response to external stimulus|
|response to cytokine|
|chemical homeostasis|
|epithelium development|
|plasma membrane bounded cell projection organization|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|regulation of immune response|
|positive regulation of immune system process|
|response to abiotic stimulus|
|cell projection organization|
|regulation of cell cycle|
|negative regulation of multicellular organismal process|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|mitochondrion|
|negative regulation of signal transduction|
|phosphorylation|
|cell cycle|
|negative regulation of cell communication|
|negative regulation of signaling|
|reproductive process|
|reproduction|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|response to endogenous stimulus|
|regulation of response to stress|
|ATP binding|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|negative regulation of response to stimulus|
|homeostatic process|
|cell development|
|regulation of immune system process|
|RNA metabolic process|
|intracellular signal transduction|
|cellular response to stress|
|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 cell differentiation|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|protein-containing complex subunit organization|
|regulation of transport|
|system process|
|membrane|
|gene expression|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp514|Phorbol-12-myristate-13-acetate 0.57μM R08 exp514]]|-3.15|
|[[:results:exp302|35°C R06 exp302]]|-2.7|
|[[:results:exp461|BS-181 20μM R08 exp461]]|-2.43|
|[[:results:exp415|Trichostatin-A 0.06μM R07 exp415]]|-2.38|
|[[:results:exp365|I-BRD9 4μM R07 exp365]]|-2.33|
|[[:results:exp162|BI-D1870 2μM R04 exp162]]|-2.19|
|[[:results:exp440|Aphidicolin 0.4μM R08 exp440]]|1.77|
|[[:results:exp466|Cannabidiol 20μM R08 exp466]]|1.81|
|[[:results:exp307|Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307]]|1.87|
|[[:results:exp535|Trimetrexate 0.03μM R08 exp535]]|1.89|
|[[:results:exp211|AICAR 240μM R05 exp211]]|2.05|
|[[:results:exp135|MS023 7μM R03 exp135]]|2.09|
|[[:results:exp82|Torin1 0.08μM R02 exp82]]|2.18|
|[[:results:exp216|Erlotinib 10μM R05 exp216]]|2.32|
|[[:results:exp282|Fluvastatin 2.2μM R06 exp282]]|2.32|
|[[:results:exp234|Ethanol 0.01 R05 exp234]]|2.36|
|[[:results:exp518|RK-33 8μM R08 exp518]]|2.44|
|[[:results:exp134|MS023 2μM R03 exp134]]|2.59|
|[[:results:exp502|Milciclib 2μM R08 exp502]]|2.69|
|[[:results:exp72|LB-100 4.1μM R02 exp72]]|2.85|
|[[:results:exp489|Hippuristanol 0.12μM R08 exp489 no dilution day6]]|3.13|
|[[:results:exp488|Hippuristanol 0.12μM R08 exp488]]|3.64|
|[[:results:exp524|Staurosporine 0.02μM R08 exp524]]|4.08|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:g:gnas|GNAS]]|0.69|
|[[:human genes:a:ankmy2|ANKMY2]]|0.45|
|[[:human genes:n:ncor1|NCOR1]]|0.419|
|[[:human genes:m:midn|MIDN]]|0.41|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|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|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 4774
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 5.33 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='PRKACA Expression in NALM6 Cells: 5.33'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>