A eukaryotic translation initiation factor 2-alpha kinase 3 that is encoded in the genome of human. [PRO:CNx, UniProtKB:Q9NZJ5]
EC 2.7.11.1;
PRKR-like endoplasmic reticulum kinase;
Pancreatic eIF2-alpha kinase;
HsPEK
| Timeframe | Studies on this Protein(%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 0 (0.00) | 29.6817 |
| 2010's | 6 (100.00) | 24.3611 |
| 2020's | 0 (0.00) | 2.80 |
| Drug | Taxonomy | Measurement | Average (mM) | Bioassay(s) | Publication(s) |
|---|---|---|---|---|---|
| entrectinib | Homo sapiens (human) | IC50 | 10.0000 | 1 | 1 |
| nms p937 | Homo sapiens (human) | IC50 | 10.0000 | 1 | 1 |
| nms-p118 | Homo sapiens (human) | IC50 | 10.0000 | 1 | 1 |
| gsk2656157 | Homo sapiens (human) | IC50 | 0.0154 | 2 | 2 |
| 7-methyl-5-(1-((3-(trifluoromethyl)phenyl)acetyl)-2,3-dihydro-1h-indol-5-yl)-7h-pyrrolo(2,3-d)pyrimidin-4-amine | Homo sapiens (human) | IC50 | 0.0152 | 4 | 4 |
| nms-e973 | Homo sapiens (human) | IC50 | 0.0100 | 1 | 1 |
This protein enables 10 target(s):
| Target | Category | Definition |
|---|---|---|
| protein kinase activity | molecular function | Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction: a protein + ATP = a phosphoprotein + ADP. [PMID:25399640] |
| protein serine/threonine kinase activity | molecular function | Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate. [GOC:bf, MetaCyc:PROTEIN-KINASE-RXN, PMID:2956925] |
| eukaryotic translation initiation factor 2alpha kinase activity | molecular function | Catalysis of the reaction: ATP + [eukaryotic translation initiation factor 2 alpha subunit] = ADP + [eukaryotic translation initiation factor 2 alpha subunit] phosphate. [GOC:mah, InterPro:IPR015516] |
| protein binding | molecular function | Binding to a protein. [GOC:go_curators] |
| ATP binding | molecular function | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. [ISBN:0198506732] |
| enzyme binding | molecular function | Binding to an enzyme, a protein with catalytic activity. [GOC:jl] |
| protein phosphatase binding | molecular function | Binding to a protein phosphatase. [GOC:jl] |
| identical protein binding | molecular function | Binding to an identical protein or proteins. [GOC:jl] |
| Hsp90 protein binding | molecular function | Binding to Hsp90 proteins, any of a group of heat shock proteins around 90kDa in size. [GOC:ai] |
| protein serine kinase activity | molecular function | Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate. [RHEA:17989] |
This protein is located in 6 target(s):
| Target | Category | Definition |
|---|---|---|
| cytoplasm | cellular component | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. [ISBN:0198547684] |
| endoplasmic reticulum | cellular component | The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached). [ISBN:0198506732] |
| endoplasmic reticulum membrane | cellular component | The lipid bilayer surrounding the endoplasmic reticulum. [GOC:mah] |
| cytosol | cellular component | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. [GOC:hjd, GOC:jl] |
| membrane | cellular component | A lipid bilayer along with all the proteins and protein complexes embedded in it and attached to it. [GOC:dos, GOC:mah, ISBN:0815316194] |
| perinuclear region of cytoplasm | cellular component | Cytoplasm situated near, or occurring around, the nucleus. [GOC:jid] |
This protein is active in 2 target(s):
| Target | Category | Definition |
|---|---|---|
| cytoplasm | cellular component | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. [ISBN:0198547684] |
| nucleus | cellular component | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. [GOC:go_curators] |
This protein is involved in 34 target(s):
| Target | Category | Definition |
|---|---|---|
| skeletal system development | biological process | The process whose specific outcome is the progression of the skeleton over time, from its formation to the mature structure. The skeleton is the bony framework of the body in vertebrates (endoskeleton) or the hard outer envelope of insects (exoskeleton or dermoskeleton). [GOC:dph, GOC:jid, GOC:tb] |
| ossification | biological process | The formation of bone or of a bony substance, or the conversion of fibrous tissue or of cartilage into bone or a bony substance. [GOC:mtg_mpo, PMID:17572649] |
| angiogenesis | biological process | Blood vessel formation when new vessels emerge from the proliferation of pre-existing blood vessels. [ISBN:0878932453] |
| chondrocyte development | biological process | The process whose specific outcome is the progression of a chondrocyte over time, from its commitment to its mature state. Chondrocyte development does not include the steps involved in committing a chondroblast to a chondrocyte fate. [GOC:dph] |
| protein phosphorylation | biological process | The process of introducing a phosphate group on to a protein. [GOC:hb] |
| activation of cysteine-type endopeptidase activity involved in apoptotic process | biological process | Any process that initiates the activity of the inactive enzyme cysteine-type endopeptidase in the context of an apoptotic process. [GOC:al, GOC:dph, GOC:jl, GOC:mtg_apoptosis, GOC:tb, PMID:14744432, PMID:18328827, Wikipedia:Caspase] |
| ER overload response | biological process | The series of molecular signals initiated by the accumulation of normal or misfolded proteins in the endoplasmic reticulum and leading to activation of transcription by NF-kappaB. [PMID:10390516] |
| endoplasmic reticulum organization | biological process | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of the endoplasmic reticulum. [GOC:dph, GOC:jl, GOC:mah] |
| positive regulation of vascular endothelial growth factor production | biological process | Any process that increases or activates the frequency, rate, or extent of production of vascular endothelial growth factor. [GOC:BHF, GOC:rl] |
| positive regulation of gene expression | biological process | Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA). [GOC:txnOH-2018] |
| regulation of translational initiation by eIF2 alpha phosphorylation | biological process | Any process that modulates the frequency, rate or extent of translation initiation in response to stress by the phosphorylation of eIF2 alpha. [GOC:BHF, GOC:dph, GOC:hjd, GOC:tb] |
| negative regulation of translation | biological process | Any process that stops, prevents, or reduces the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of proteins by the translation of mRNA or circRNA. [GOC:isa_complete] |
| peptidyl-serine phosphorylation | biological process | The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine. [RESID:AA0037] |
| calcium-mediated signaling | biological process | Any intracellular signal transduction in which the signal is passed on within the cell via calcium ions. [GOC:signaling] |
| bone mineralization | biological process | The deposition of hydroxyapatite, a form of calcium phosphate with the formula Ca10(PO4)6(OH)2, in bone tissue. [GOC:mah, PMID:22936354] |
| endoplasmic reticulum unfolded protein response | biological process | The series of molecular signals generated as a consequence of the presence of unfolded proteins in the endoplasmic reticulum (ER) or other ER-related stress; results in changes in the regulation of transcription and translation. [GOC:mah, PMID:12042763] |
| endocrine pancreas development | biological process | The process whose specific outcome is the progression of the endocrine pancreas over time, from its formation to the mature structure. The endocrine pancreas is made up of islet cells that produce insulin, glucagon and somatostatin. [GOC:cvs] |
| negative regulation of myelination | biological process | Any process that stops, prevents, or reduces the frequency, rate or extent of the formation of a myelin sheath around nerve axons. [GOC:mah] |
| negative regulation of translation in response to stress | biological process | Any process that stops, prevents or reduces the rate of translation as a result of a stimulus indicating the organism is under stress. [GOC:mah] |
| negative regulation of translational initiation in response to stress | biological process | Any process that stops, prevents or reduces the rate of translation initiation as a result of a stimulus indicating the organism is under stress. [GOC:mah] |
| cellular response to amino acid starvation | biological process | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of deprivation of amino acids. [GOC:ecd] |
| response to endoplasmic reticulum stress | biological process | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stress acting at the endoplasmic reticulum. ER stress usually results from the accumulation of unfolded or misfolded proteins in the ER lumen. [GOC:cjm, GOC:mah] |
| eiF2alpha phosphorylation in response to endoplasmic reticulum stress | biological process | The addition of a phosphate group on to the translation initiation factor eIF2alpha, as a result of endoplasmic reticulum stress. [GOC:bf, GOC:PARL, PMID:14676213, PMID:16835242] |
| PERK-mediated unfolded protein response | biological process | The series of molecular signals mediated by the endoplasmic reticulum membrane stress sensor PERK (PKR-like ER kinase). Begins with activation of PERK in response to endoplasmic reticulum (ER) stress and ends with regulation of a downstream cellular process, e.g. transcription. The main substrate of PERK is the translation initiation factor eIF2alpha. Serine-phosphorylation of eIF2alpha by PERK inactivates eIF2alpha and inhibits general protein translation. In addition, eIF2alpha phosphorylation preferentially increases the translation of selective mRNAs such as ATF4 (activating transcription factor 4), which up regulates a subset of UPR genes required to restore folding capacity. [GOC:bf, GOC:PARL, PMID:22013210, PMID:27629041] |
| cellular response to glucose starvation | biological process | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of deprivation of glucose. [GOC:jl] |
| positive regulation of transcription by RNA polymerase I | biological process | Any process that activates or increases the frequency, rate or extent of transcription mediated by RNA polymerase I. [GOC:go_curators, GOC:txnOH] |
| negative regulation of translational initiation | biological process | Any process that stops, prevents, or reduces the frequency, rate or extent of translational initiation. [GOC:go_curators] |
| protein autophosphorylation | biological process | The phosphorylation by a protein of one or more of its own amino acid residues (cis-autophosphorylation), or residues on an identical protein (trans-autophosphorylation). [ISBN:0198506732] |
| insulin-like growth factor receptor signaling pathway | biological process | The series of molecular signals initiated by a ligand binding to an insulin-like growth factor receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:ceb] |
| regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation | biological process | Any process that modulates the rate, frequency, or extent of eIF2 alpha phosphorylation as a cellular response to endoplasmic reticulum stress. [GOC:dph, GOC:tb] |
| cellular response to cold | biological process | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cold stimulus, a temperature stimulus below the optimal temperature for that organism. [GOC:jp] |
| positive regulation of protein localization to nucleus | biological process | Any process that activates or increases the frequency, rate or extent of protein localization to nucleus. [GOC:TermGenie] |
| regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway | biological process | Any process that modulates the frequency, rate or extent of an endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway. [GOC:BHF, GOC:mtg_apoptosis, GOC:rl, GOC:TermGenie, PMID:20160352] |
| response to manganese-induced endoplasmic reticulum stress | biological process | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of endoplasmic reticulum stress caused by a manganese stimulus. [GOC:bf, GOC:PARL, PMID:23934647] |