PRKAA2 [The Human Chemical-Genetic Interaction Map Project]

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======= PRKAA2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: PRKAA2
  * **<color #00a2e8>Official Name</color>**: protein kinase AMP-activated catalytic subunit alpha 2
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5563|5563]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P54646|P54646]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=PRKAA2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PRKAA2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/600497|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. Involved in insulin receptor/INSR internalization (PubMed:25687571). AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1. AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1. Plays an important role in the differential regulation of pro-autophagy (composed of PIK3C3, BECN1, PIK3R4 and UVRAG or ATG14) and non-autophagy (composed of PIK3C3, BECN1 and PIK3R4) complexes, in response to glucose starvation. Can inhibit the non-autophagy complex by phosphorylating PIK3C3 and can activate the pro-autophagy complex by phosphorylating BECN1 (By similarity). {ECO:0000250|UniProtKB:Q8BRK8, ECO:0000269|PubMed:11518699, ECO:0000269|PubMed:11554766, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15866171, ECO:0000269|PubMed:17486097, ECO:0000269|PubMed:17711846, ECO:0000269|PubMed:18184930, ECO:0000269|PubMed:20074060, ECO:0000269|PubMed:20160076, ECO:0000269|PubMed:21205641, ECO:0000269|PubMed:25687571, ECO:0000269|PubMed:7959015}.

<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'>
|[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity|
|[acetyl-CoA carboxylase] kinase activity|
|histone serine kinase activity|
|regulation of stress granule assembly|
|negative regulation of tubulin deacetylation|
|AMP-activated protein kinase activity|
|regulation of tubulin deacetylation|
|histone-serine phosphorylation|
|carnitine shuttle|
|nucleotide-activated protein kinase complex|
|fatty acid homeostasis|
|fatty acid transmembrane transport|
|cellular response to prostaglandin E stimulus|
|cellular response to prostaglandin stimulus|
|positive regulation of glycolytic process|
|response to prostaglandin E|
|response to muscle activity|
|protein serine/threonine/tyrosine kinase activity|
|histone phosphorylation|
|response to prostaglandin|
|positive regulation of peptidyl-lysine acetylation|
|energy homeostasis|
|intracellular lipid transport|
|positive regulation of protein acetylation|
|cholesterol biosynthetic process|
|cellular response to glucose starvation|
|secondary alcohol biosynthetic process|
|regulation of protein deacetylation|
|positive regulation of purine nucleotide metabolic process|
|regulation of fatty acid biosynthetic process|
|positive regulation of ATP metabolic process|
|positive regulation of nucleotide metabolic process|
|sterol biosynthetic process|
|negative regulation of TOR signaling|
|cellular response to fatty acid|
|anion homeostasis|
|long-chain fatty acid transport|
|regulation of peptidyl-lysine acetylation|
|response to activity|
|cytoplasmic stress granule|
|positive regulation of macroautophagy|
|cellular response to glucose stimulus|
|regulation of protein acetylation|
|cellular response to hexose stimulus|
|cellular response to monosaccharide stimulus|
|fatty acid transport|
|positive regulation of carbohydrate metabolic process|
|regulation of glycolytic process|
|cellular response to carbohydrate stimulus|
|cellular response to calcium ion|
|cellular response to alcohol|
|response to fatty acid|
|regulation of fatty acid metabolic process|
|cellular glucose homeostasis|
|regulation of carbohydrate catabolic process|
|cellular response to ketone|
|mitochondrial transmembrane transport|
|regulation of TOR signaling|
|alcohol biosynthetic process|
|regulation of circadian rhythm|
|regulation of purine nucleotide metabolic process|
|cholesterol metabolic process|
|regulation of nucleotide metabolic process|
|fatty acid biosynthetic process|
|positive regulation of autophagy|
|regulation of ATP metabolic process|
|steroid biosynthetic process|
|organic acid transmembrane transport|
|carboxylic acid transmembrane transport|
|secondary alcohol metabolic process|
|lipid homeostasis|
|sterol metabolic process|
|monocarboxylic acid transport|
|response to glucose|
|positive regulation of small molecule metabolic process|
|response to hexose|
|cell cycle arrest|
|response to monosaccharide|
|response to calcium ion|
|cellular response to starvation|
|regulation of generation of precursor metabolites and energy|
|macroautophagy|
|regulation of cellular ketone metabolic process|
|response to carbohydrate|
|regulation of macroautophagy|
|peptidyl-serine phosphorylation|
|regulation of signal transduction by p53 class mediator|
|glucose homeostasis|
|monocarboxylic acid biosynthetic process|
|organic hydroxy compound biosynthetic process|
|carbohydrate homeostasis|
|regulation of lipid biosynthetic process|
|regulation of microtubule cytoskeleton organization|
|cellular response to metal ion|
|response to starvation|
|response to ketone|
|peptidyl-serine modification|
|regulation of carbohydrate metabolic process|
|cellular response to acid chemical|
|mitochondrial transport|
|cellular response to inorganic substance|
|regulation of organelle assembly|
|regulation of microtubule-based process|
|response to alcohol|
|cellular response to nutrient levels|
|protein kinase activity|
|cellular response to oxidative stress|
|steroid metabolic process|
|autophagy|
|process utilizing autophagic mechanism|
|cellular response to extracellular stimulus|
|anion transmembrane transport|
|rhythmic process|
|carboxylic acid transport|
|organic acid transport|
|axon|
|lipid transport|
|carboxylic acid biosynthetic process|
|organic acid biosynthetic process|
|alcohol metabolic process|
|lipid localization|
|fatty acid metabolic process|
|multicellular organismal homeostasis|
|positive regulation of cellular protein localization|
|regulation of autophagy|
|cellular response to external stimulus|
|response to acid chemical|
|Wnt signaling pathway|
|cell-cell signaling by wnt|
|protein serine/threonine kinase activity|
|positive regulation of cellular catabolic process|
|histone modification|
|response to metal ion|
|neuronal cell body|
|covalent chromatin modification|
|response to oxidative stress|
|chromatin binding|
|regulation of lipid metabolic process|
|nuclear speck|
|cellular response to drug|
|dendrite|
|cell surface receptor signaling pathway involved in cell-cell signaling|
|regulation of small molecule metabolic process|
|positive regulation of catabolic process|
|regulation of protein complex assembly|
|organic hydroxy compound metabolic process|
|organic anion transport|
|response to nutrient levels|
|negative regulation of intracellular signal transduction|
|cellular response to lipid|
|monocarboxylic acid metabolic process|
|response to extracellular stimulus|
|response to inorganic substance|
|regulation of cellular protein localization|
|regulation of cytoskeleton organization|
|negative regulation of cell cycle|
|lipid biosynthetic process|
|anion transport|
|small molecule biosynthetic process|
|negative regulation of protein modification process|
|cellular response to hormone stimulus|
|chromatin organization|
|cellular chemical homeostasis|
|ion homeostasis|
|regulation of cellular catabolic process|
|response to lipid|
|peptidyl-amino acid modification|
|negative regulation of apoptotic process|
|cellular homeostasis|
|negative regulation of programmed cell death|
|response to hormone|
|carboxylic acid metabolic process|
|regulation of cellular localization|
|ion transmembrane transport|
|cellular lipid metabolic process|
|regulation of cellular component biogenesis|
|protein phosphorylation|
|Golgi apparatus|
|regulation of catabolic process|
|negative regulation of cell death|
|cell cycle process|
|oxoacid metabolic process|
|response to drug|
|organic acid metabolic process|
|regulation of protein localization|
|negative regulation of cellular protein metabolic process|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|chromosome organization|
|negative regulation of protein metabolic process|
|chemical homeostasis|
|cell-cell signaling|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|regulation of cell cycle|
|lipid metabolic process|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|negative regulation of signal transduction|
|transmembrane transport|
|phosphorylation|
|regulation of organelle organization|
|organic cyclic compound biosynthetic process|
|cell cycle|
|negative regulation of cell communication|
|negative regulation of signaling|
|ion transport|
|response to endogenous stimulus|
|ATP binding|
|intracellular transport|
|regulation of apoptotic process|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|negative regulation of response to stimulus|
|homeostatic process|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|negative regulation of gene expression|
|small molecule metabolic process|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|cellular catabolic process|
|regulation of intracellular signal transduction|
|establishment of localization in cell|
|regulation of protein modification process|
|positive regulation of nucleobase-containing compound metabolic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' 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:exp116|AICAR 240μM R03 exp116]]|1.83|
|[[:results:exp97|BI-6727 0.0125μM R03 exp97]]|1.85|
|[[:results:exp126|GSK461364A 0.1μM R03 exp126]]|2.02|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/25|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/14|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 18004
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 1.02 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='PRKAA2 Expression in NALM6 Cells: 1.02'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>