AKT2 [The Human Chemical-Genetic Interaction Map Project]

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======= AKT2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: AKT2
  * **<color #00a2e8>Official Name</color>**: AKT serine/threonine kinase 2
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=208|208]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P31751|P31751]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=AKT2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20AKT2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/164731|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene is a putative oncogene encoding a protein belonging to a subfamily of serine/threonine kinases containing SH2-like (Src homology 2-like) domains. The gene was shown to be amplified and overexpressed in 2 of 8 ovarian carcinoma cell lines and 2 of 15 primary ovarian tumors. Overexpression contributes to the malignant phenotype of a subset of human ductal pancreatic cancers. The encoded protein is a general protein kinase capable of phophorylating several known proteins. [provided by RefSeq, Jul 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  AKT2 is one of 3 closely related serine/threonine- protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)- response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I). AKT mediates the antiapoptotic effects of IGF-I. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development.

<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'>
|PH|
|Pkinase|
|Pkinase Tyr|
|Pkinase C|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|cellular response to high light intensity|
|retinal rod cell apoptotic process|
|response to high light intensity|
|cellular response to light intensity|
|retinal cell apoptotic process|
|negative regulation of long-chain fatty acid import across plasma membrane|
|negative regulation of long-chain fatty acid import into cell|
|regulation of long-chain fatty acid import across plasma membrane|
|regulation of long-chain fatty acid import into cell|
|peripheral nervous system myelin maintenance|
|negative regulation of fatty acid transport|
|positive regulation of vesicle fusion|
|positive regulation of mitochondrial membrane potential|
|positive regulation of fatty acid beta-oxidation|
|response to light intensity|
|negative regulation of anion transmembrane transport|
|myelin maintenance|
|positive regulation of membrane potential|
|positive regulation of fatty acid oxidation|
|positive regulation of glycogen biosynthetic process|
|mammary gland epithelial cell differentiation|
|regulation of fatty acid beta-oxidation|
|positive regulation of glycogen metabolic process|
|glycogen biosynthetic process|
|glucan biosynthetic process|
|negative regulation of organic acid transport|
|positive regulation of lipid catabolic process|
|negative regulation of lipid transport|
|peripheral nervous system axon ensheathment|
|myelination in peripheral nervous system|
|regulation of fatty acid transport|
|regulation of anion transmembrane transport|
|negative regulation of anion transport|
|regulation of glucan biosynthetic process|
|Schwann cell development|
|regulation of glycogen biosynthetic process|
|regulation of fatty acid oxidation|
|regulation of vesicle fusion|
|positive regulation of protein targeting to membrane|
|positive regulation of fatty acid metabolic process|
|Schwann cell differentiation|
|regulation of glycogen metabolic process|
|regulation of protein targeting to membrane|
|positive regulation of glucose import|
|regulation of polysaccharide biosynthetic process|
|positive regulation of glucose metabolic process|
|negative regulation of lipid localization|
|regulation of polysaccharide metabolic process|
|positive regulation of glucose transmembrane transport|
|polysaccharide biosynthetic process|
|neuron apoptotic process|
|cellular polysaccharide biosynthetic process|
|intracellular protein transmembrane transport|
|glycogen metabolic process|
|glucan metabolic process|
|cellular glucan metabolic process|
|neuron death|
|regulation of lipid catabolic process|
|regulation of glucose import|
|mammary gland epithelium development|
|regulation of organic acid transport|
|positive regulation of cellular carbohydrate metabolic process|
|cellular carbohydrate biosynthetic process|
|protein transmembrane transport|
|energy reserve metabolic process|
|regulation of mitochondrial membrane potential|
|regulation of glucose transmembrane transport|
|peripheral nervous system development|
|carbohydrate transport|
|cellular polysaccharide metabolic process|
|positive regulation of carbohydrate metabolic process|
|regulation of protein targeting|
|polysaccharide metabolic process|
|regulation of fatty acid metabolic process|
|insulin receptor signaling pathway|
|plasma membrane organization|
|regulation of carbohydrate biosynthetic process|
|regulation of anion transport|
|negative regulation of ion transmembrane transport|
|ruffle membrane|
|activation of GTPase activity|
|myelination|
|fat cell differentiation|
|regulation of cell cycle arrest|
|glial cell development|
|axon ensheathment|
|ensheathment of neurons|
|regulation of lipid transport|
|cellular response to light stimulus|
|regulation of glucose metabolic process|
|glucose metabolic process|
|negative regulation of transmembrane transport|
|positive regulation of protein localization to membrane|
|carbohydrate biosynthetic process|
|mammary gland development|
|cell cortex|
|positive regulation of small molecule metabolic process|
|regulation of lipid localization|
|regulation of cellular carbohydrate metabolic process|
|positive regulation of lipid metabolic process|
|negative regulation of ion transport|
|positive regulation of intracellular protein transport|
|hexose metabolic process|
|regulation of generation of precursor metabolites and energy|
|cellular response to insulin stimulus|
|glial cell differentiation|
|cellular carbohydrate metabolic process|
|regulation of cellular ketone metabolic process|
|peptidyl-serine phosphorylation|
|cellular response to radiation|
|protein localization to plasma membrane|
|regulation of protein localization to membrane|
|peptidyl-serine modification|
|monosaccharide metabolic process|
|positive regulation of transmembrane transport|
|regulation of carbohydrate metabolic process|
|positive regulation of intracellular transport|
|gliogenesis|
|response to insulin|
|protein localization to cell periphery|
|regulation of intracellular protein transport|
|energy derivation by oxidation of organic compounds|
|early endosome|
|cellular response to peptide hormone stimulus|
|response to light stimulus|
|cellular response to abiotic stimulus|
|cellular response to environmental stimulus|
|positive regulation of cellular protein localization|
|cellular response to peptide|
|regulation of intracellular transport|
|regulation of translation|
|protein serine/threonine kinase activity|
|positive regulation of cellular catabolic process|
|response to peptide hormone|
|regulation of lipid metabolic process|
|regulation of cellular amide metabolic process|
|gland development|
|positive regulation of GTPase activity|
|endomembrane system organization|
|generation of precursor metabolites and energy|
|positive regulation of protein transport|
|regulation of small molecule metabolic process|
|regulation of membrane potential|
|positive regulation of catabolic process|
|response to radiation|
|positive regulation of establishment of protein localization|
|response to peptide|
|carbohydrate metabolic process|
|regulation of ion transmembrane transport|
|protein localization to membrane|
|regulation of GTPase activity|
|negative regulation of transport|
|positive regulation of cell migration|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|positive regulation of cell motility|
|posttranscriptional regulation of gene expression|
|positive regulation of cellular component movement|
|regulation of cellular protein localization|
|regulation of vesicle-mediated transport|
|positive regulation of locomotion|
|regulation of transmembrane transport|
|protein-containing complex|
|cellular response to organonitrogen compound|
|cellular response to hormone stimulus|
|positive regulation of organelle organization|
|cellular response to nitrogen compound|
|epithelial cell differentiation|
|intracellular membrane-bounded organelle|
|regulation of ion transport|
|regulation of protein transport|
|enzyme linked receptor protein signaling pathway|
|regulation of peptide transport|
|regulation of establishment of protein localization|
|regulation of cell cycle process|
|positive regulation of hydrolase activity|
|regulation of cellular catabolic process|
|regulation of cell migration|
|membrane organization|
|peptidyl-amino acid modification|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|response to hormone|
|regulation of cell motility|
|positive regulation of cell population proliferation|
|regulation of cellular localization|
|apoptotic process|
|oxidation-reduction process|
|protein phosphorylation|
|regulation of locomotion|
|positive regulation of transport|
|intracellular protein transport|
|regulation of cellular component movement|
|regulation of catabolic process|
|negative regulation of cell death|
|response to organonitrogen compound|
|positive regulation of protein phosphorylation|
|regulation of protein localization|
|programmed cell death|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|response to nitrogen compound|
|cell death|
|epithelium development|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|response to abiotic stimulus|
|regulation of cell cycle|
|positive regulation of cellular component organization|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|regulation of hydrolase activity|
|transmembrane transport|
|phosphorylation|
|regulation of organelle organization|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|response to endogenous stimulus|
|ATP binding|
|protein transport|
|intracellular transport|
|peptide transport|
|regulation of apoptotic process|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|amide transport|
|cellular protein localization|
|regulation of phosphorylation|
|cellular macromolecule localization|
|positive regulation of cellular protein metabolic process|
|establishment of protein localization|
|regulation of cell population proliferation|
|neurogenesis|
|cell development|
|regulation of cell death|
|intracellular signal transduction|
|positive regulation of protein metabolic process|
|cellular macromolecule biosynthetic process|
|small molecule metabolic process|
|tissue development|
|macromolecule biosynthetic process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|establishment of localization in cell|
|nitrogen compound transport|
|regulation of protein modification process|
|regulation of transport|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of biosynthetic process|
</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:exp190|Vincristine 0.0005μM R04 exp190]]|1.7|
|[[:results:exp275|Citral 75μM R06 exp275]]|1.71|
|[[:results:exp78|Pterostilbene 16μM R02 exp78]]|1.74|
|[[:results:exp264|Arsenate 40μM R06 exp264]]|1.77|
|[[:results:exp299|Talazoparib 0.006μM R06 exp299]]|1.83|
|[[:results:exp135|MS023 7μM R03 exp135]]|1.85|
|[[:results:exp330|5-Azacytidine 2μM R07 exp330]]|1.89|
|[[:results:exp355|Dinaciclib 0.007μM R07 exp355]]|1.91|
|[[:results:exp512|Olaparib 4μM R08 exp512]]|1.91|
|[[:results:exp440|Aphidicolin 0.4μM R08 exp440]]|1.92|
|[[:results:exp334|All-trans-Retinoic-Acid 40μM R07 exp334]]|1.95|
|[[:results:exp349|Cytochalasin-B 5μM R07 exp349]]|1.95|
|[[:results:exp291|LLY-284 2.6μM R06 exp291]]|1.98|
|[[:results:exp489|Hippuristanol 0.12μM R08 exp489 no dilution day6]]|2.01|
|[[:results:exp488|Hippuristanol 0.12μM R08 exp488]]|2.09|
|[[:results:exp259|6-Thio-2-deoxyguanosine 2μM R06 exp259]]|2.11|
|[[:results:exp500|LY2090314 0.003μM R08 exp500 no dilution day6]]|2.11|
|[[:results:exp534|Trientine 500μM R08 exp534]]|2.12|
|[[:results:exp234|Ethanol 0.01 R05 exp234]]|2.15|
|[[:results:exp456|Benzoate 20000μM R08 exp456]]|2.25|
|[[:results:exp499|LY2090314 0.003μM R08 exp499]]|2.25|
|[[:results:exp211|AICAR 240μM R05 exp211]]|2.3|
|[[:results:exp520|Rucaparib 6.5μM R08 exp520]]|2.42|
|[[:results:exp256|HMS-I1 10μM R06 exp256]]|2.48|
|[[:results:exp535|Trimetrexate 0.03μM R08 exp535]]|2.61|
|[[:results:exp21|MLN-4924 0.2μM R00 exp21]]|2.69|
|[[:results:exp102|Nifuroxazide 5μM R03 exp102]]|2.77|
|[[:results:exp497|Lead acetate 2000μM R08 exp497]]|2.92|
|[[:results:exp498|Lead acetate 2000μM R08 exp498 no dilution day6]]|2.94|
|[[:results:exp116|AICAR 240μM R03 exp116]]|3.38|
|[[:results:exp525|Sulforaphane 9μM R08 exp525]]|3.49|
|[[:results:exp134|MS023 2μM R03 exp134]]|3.9|
|[[:results:exp526|Sulforaphane 9μM R08 exp526 no dilution day6]]|4.3|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:m:mapkap1|MAPKAP1]]|0.749|
|[[:human genes:r:rictor|RICTOR]]|0.741|
|[[:human genes:p:pik3cd|PIK3CD]]|0.675|
|[[:human genes:c:cd19|CD19]]|0.668|
|[[:human genes:m:mlst8|MLST8]]|0.645|
|[[:human genes:c:cd81|CD81]]|0.625|
|[[:human genes:p:pdpk1|PDPK1]]|0.614|
|[[:human genes:r:rhoh|RHOH]]|0.601|
|[[:human genes:s:syk|SYK]]|0.583|
|[[:human genes:i:igll1|IGLL1]]|0.525|
|[[:human genes:a:akt1|AKT1]]|0.468|
|[[:human genes:b:bcl2l11|BCL2L11]]|0.446|
|[[:human genes:p:prrc2c|PRRC2C]]|0.434|
|[[:human genes:e:ergic1|ERGIC1]]|0.431|
|[[:human genes:p:pim3|PIM3]]|0.418|
|[[:human genes:c:cd79a|CD79A]]|0.404|
|[[:human genes:c:cd79b|CD79B]]|0.403|
|[[:human genes:w:wdr37|WDR37]]|0.402|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 1/739
^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|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>**: 2512
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.26 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='AKT2 Expression in NALM6 Cells: 7.26'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>