Property Summary

NCBI Gene PubMed Count 52
PubMed Score 262.05
PubTator Score 86.88

Knowledge Summary

Patent (7,596)

Expression

  Differential Expression (8)

Disease log2 FC p
Rheumatoid Arthritis 1.100 4.6e-02
osteosarcoma -1.779 6.8e-07
cystic fibrosis -1.290 1.6e-04
atypical teratoid / rhabdoid tumor 1.100 1.7e-04
glioblastoma 1.200 2.5e-04
subependymal giant cell astrocytoma 1.509 5.4e-03
ovarian cancer 2.400 6.0e-06
ileal Crohn's disease -1.345 4.3e-02

 GO Component (2)

MLP Assay (1)

AID Type Active / Inconclusive / Inactive Description
1982 other 0 / 0 / 0 Kinase inhibition selectivity assay for compound SID-48409448

Gene RIF (30)

PMID Text
26647830 IDO, through GCN2 kinase activation, downregulates the levels of TCRcomplex tchain and cMyc, resulting in the suppression of Tcell proliferation and a reduction in the levels of LDHA and GLS2
26543160 Upon deprivation of various amino acids, activated GCN2 up-regulates ATF4 to induce expression of the stress response protein Sestrin2, which is required to sustain repression of mTORC1 by blocking its lysosomal localization
26541523 EIF2AK4 mutation was associated with pulmonary veno-occlusive disease. PVOD patients who were not significantly exposed to trichloroethylene were more likely to harbour EIF2AK4 mutations.
26147366 IDO through GCN2 kinase activation inhibits CD4(+) T-cell proliferation and down-regulates key enzymes that directly or indirectly promote FA synthesis, a prerequisite for CD4(+) T-cell proliferation and differentiation into effector cell lineages.
26082174 Targeting ALDH18A1 activated the serine/threonine protein kinase GCN2 (general control nonderepressible 2) to inhibit protein synthesis in melanoma.
25759478 GCN2 activation and phosphorylation of eIF2alpha in response to mTORC1 inhibition are necessary for autophagy.
25589675 GCN2 can exert its proapoptotic function in cancer cell death by posttranslational mechanisms.
25512148 Data show that sequenced eukaryotic translation initiation factor 2 alpha kinase 4 protein (EIF2AK4) with a homozygous mutation in all five families: c.3344C>T(p.P1115L).
25329545 p58IPK is a general inhibitor of the eIF2alpha kinases in that it also interacts with GCN2. Thus forced overexpression of cytoplasmic p58 delays eIF2alpha phosphorylation, suppresses GCN2 phosphorylation and prolongs protein synthesis
25142489 This study is the first to examine the perceptual response to CPET in patients with PVOD who were carriers of EIF2AK4 mutations compared with PAH patients matched for resting haemodynamics and pulmonary function
24827717 Association of EIF2AKE with body mass index in Chinese has been confirmed and is suggested to be 'ethnic specific'.
24292273 EIF2AK4 mutations cause pulmonary veno-occlusive disease.
24256275 REVIEW: roles of GCN2
24135949 Mutations in EIF2AK4 are likely to cause autosomal-recessive pulmonary capillary hemangiomatosis in familial and some nonfamilial cases.
23908598 Data indicate that suppressing GCN2 and activating transcription factor 4 (ATF4), expression decreased Amino acid deprivation (AAD)-induced VEGF expression.
23417324 GCN2 has a role as an early mediator in the cellular response to HIV-1 infection
23417324 HIV-1 PR directly cleaves GCN2 at amino acid residues 560-561, which leads to inactivate GCN2 activity
23417324 Knockdown of GCN2 by siRNA enhances HIV-1 infectivity in HeLa P4 cells
23216249 In this review, GCN2 senses the absence of one or more amino acids by virtue of direct binding to cognate tRNAs.
23110064 GCN2 leading to inhibition of viral RNA translation, and that HIV-1 protease cleaves GCN2 to overcome its antiviral effect.
23110064 HIV-1 PR directly cleaves GCN2 at amino acid residues 560-561, which leads to inactivate GCN2 activity
22896630 The activation of autophagy in response to interferon (IFN)-gamma is promoted by tryptophan depletion and relies, at least in part, on the activation of GCN2-eIF2alpha kinase in kidney epithelial cells.
22435535 Changes in translational control of mitochondrial proteins are signaled by the activation of AMPK (AMP-activated protein kinase) and GCN2, leading also to the activation of autophagy.
21203563 the GCN2/eIF2alpha/ATF4 pathway is essential for the induction of the TRB3 gene transcription
21113813 The results suggest that GCN2 pathways can mediate the limiting effects of Gln deprivation on protein synthesis according to its severity.
20551969 GCN2 and its downstream target, the transcriptional activator ATF4, is critical for proliferation and survival of tumour cells after starvation for amino acids or glucose and is essential for growth in vivo in a xenograft model.
20473272 The authors conclude that the GCN2-eIF2alpha-ATF4 pathway is critical for maintaining metabolic homeostasis in tumour cells, making it a novel and attractive target for anti-tumour approaches.
20168091 Data show that impairment of autophagy stimulates PS1 expression and gamma-secretase activity through GCN2.
19586904 UV-induced eIF2alpha phosphorylation by activation of both PERK and GCN2 via oxidative stress and l-arginine starvation signaling pathways.
18287093 MEK functions to enhance GCN2-dependent eIF2alpha phosphorylation rather than suppressing dephosphorylation

AA Sequence

MAGGRGAPGRGRDEPPESYPQRQDHELQALEAIYGADFQDLRPDACGPVKEPPEINLVLYPQGLTGEEVY      1 - 70
VKVDLRVKCPPTYPDVVPEIELKNAKGLSNESVNLLKSRLEELAKKHCGEVMIFELAYHVQSFLSEHNKP     71 - 140
PPKSFHEEMLERRAQEEQQRLLEAKRKEEQEQREILHEIQRRKEEIKEEKKRKEMAKQERLEIASLSNQD    141 - 210
HTSKKDPGGHRTAAILHGGSPDFVGNGKHRANSSGRSRRERQYSVCNSEDSPGSCEILYFNMGSPDQLMV    211 - 280
HKGKCIGSDEQLGKLVYNALETATGGFVLLYEWVLQWQKKMGPFLTSQEKEKIDKCKKQIQGTETEFNSL    281 - 350
VKLSHPNVVRYLAMNLKEQDDSIVVDILVEHISGVSLAAHLSHSGPIPVHQLRRYTAQLLSGLDYLHSNS    351 - 420
VVHKVLSASNVLVDAEGTVKITDYSISKRLADICKEDVFEQTRVRFSDNALPYKTGKKGDVWRLGLLLLS    421 - 490
LSQGQECGEYPVTIPSDLPADFQDFLKKCVCLDDKERWSPQQLLKHSFINPQPKMPLVEQSPEDSEGQDY    491 - 560
VETVIPSNRLPSAAFFSETQRQFSRYFIEFEELQLLGKGAFGAVIKVQNKLDGCCYAVKRIPINPASRQF    561 - 630
RRIKGEVTLLSRLHHENIVRYYNAWIERHERPAGPGTPPPDSGPLAKDDRAARGQPASDTDGLDSVEAAA    631 - 700
PPPILSSSVEWSTSGERSASARFPATGPGSSDDEDDDEDEHGGVFSQSFLPASDSESDIIFDNEDENSKS    701 - 770
QNQDEDCNEKNGCHESEPSVTTEAVHYLYIQMEYCEKSTLRDTIDQGLYRDTVRLWRLFREILDGLAYIH    771 - 840
EKGMIHRDLKPVNIFLDSDDHVKIGDFGLATDHLAFSADSKQDDQTGDLIKSDPSGHLTGMVGTALYVSP    841 - 910
EVQGSTKSAYNQKVDLFSLGIIFFEMSYHPMVTASERIFVLNQLRDPTSPKFPEDFDDGEHAKQKSVISW    911 - 980
LLNHDPAKRPTATELLKSELLPPPQMEESELHEVLHHTLTNVDGKAYRTMMAQIFSQRISPAIDYTYDSD    981 - 1050
ILKGNFSIRTAKMQQHVCETIIRIFKRHGAVQLCTPLLLPRNRQIYEHNEAALFMDHSGMLVMLPFDLRI   1051 - 1120
PFARYVARNNILNLKRYCIERVFRPRKLDRFHPKELLECAFDIVTSTTNSFLPTAEIIYTIYEIIQEFPA   1121 - 1190
LQERNYSIYLNHTMLLKAILLHCGIPEDKLSQVYIILYDAVTEKLTRREVEAKFCNLSLSSNSLCRLYKF   1191 - 1260
IEQKGDLQDLMPTINSLIKQKTGIAQLVKYGLKDLEEVVGLLKKLGIKLQVLINLGLVYKVQQHNGIIFQ   1261 - 1330
FVAFIKRRQRAVPEILAAGGRYDLLIPQFRGPQALGPVPTAIGVSIAIDKISAAVLNMEESVTISSCDLL   1331 - 1400
VVSVGQMSMSRAINLTQKLWTAGITAEIMYDWSQSQEELQEYCRHHEITYVALVSDKEGSHVKVKSFEKE   1401 - 1470
RQTEKRVLETELVDHVLQKLRTKVTDERNGREASDNLAVQNLKGSFSNASGLFEIHGATVVPIVSVLAPE   1471 - 1540
KLSASTRRRYETQVQTRLQTSLANLHQKSSEIEILAVDLPKETILQFLSLEWDADEQAFNTTVKQLLSRL   1541 - 1610
PKQRYLKLVCDEIYNIKVEKKVSVLFLYSYRDDYYRILF                                  1611 - 1649
//

Text Mined References (63)

PMID Year Title
26647830 2016 Indoleamine 2,3?dioxygenase downregulates T?cell receptor complex ??chain and c?Myc, and reduces proliferation, lactate dehydrogenase levels and mitochondrial glutaminase in human T?cells.
26543160 2015 GCN2 sustains mTORC1 suppression upon amino acid deprivation by inducing Sestrin2.
26541523 2015 Occupational exposure to organic solvents: a risk factor for pulmonary veno-occlusive disease.
26147366 2015 Indoleamine 2,3-dioxygenase depletes tryptophan, activates general control non-derepressible 2 kinase and down-regulates key enzymes involved in fatty acid synthesis in primary human CD4+ T cells.
26102367 2015 Translational Upregulation of an Individual p21Cip1 Transcript Variant by GCN2 Regulates Cell Proliferation and Survival under Nutrient Stress.
26082174 2015 Disruption of Proline Synthesis in Melanoma Inhibits Protein Production Mediated by the GCN2 Pathway.
25759478 2015 Phosphorylation of eIF2? triggered by mTORC1 inhibition and PP6C activation is required for autophagy and is aberrant in PP6C-mutated melanoma.
25589675 2015 Involvement of general control nonderepressible kinase 2 in cancer cell apoptosis by posttranslational mechanisms.
25512148 2015 A founder EIF2AK4 mutation causes an aggressive form of pulmonary arterial hypertension in Iberian Gypsies.
25329545 2015 p58IPK is an inhibitor of the eIF2? kinase GCN2 and its localization and expression underpin protein synthesis and ER processing capacity.
25142489 2014 Mechanisms of exertional dyspnoea in pulmonary veno-occlusive disease with EIF2AK4 mutations.
24827717 2014 Genome wide association study: searching for genes underlying body mass index in the Chinese.
24751813 2014 Genome-wide association study supports the role of the immunological system and of the neurodevelopmental processes in response to haloperidol treatment.
24310610 2014 Vaccine activation of the nutrient sensor GCN2 in dendritic cells enhances antigen presentation.
24292273 2014 EIF2AK4 mutations cause pulmonary veno-occlusive disease, a recessive form of pulmonary hypertension.
24256275 2013 GCN2, an old dog with new tricks.
24135949 2014 EIF2AK4 mutations in pulmonary capillary hemangiomatosis.
24019515 2013 General control nonderepressible 2 (GCN2) kinase protects oligodendrocytes and white matter during branched-chain amino acid deficiency in mice.
23908598 2013 Amino acid deprivation promotes tumor angiogenesis through the GCN2/ATF4 pathway.
23417324 2013 Activation of GCN2 upon HIV-1 infection and inhibition of translation.
23354059 2013 The eIF2? kinases: their structures and functions.
23216249 2013 Amino acid sensing in dietary-restriction-mediated longevity: roles of signal-transducing kinases GCN2 and TOR.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23129244 2012 New functions of protein kinase Gcn2 in yeast and mammals.
23110064 2012 GCN2 has inhibitory effect on human immunodeficiency virus-1 protein synthesis and is cleaved upon viral infection.
22969067 2012 Genetic variants near PDGFRA are associated with corneal curvature in Australians.
22896630 2012 Tryptophan depletion and the kinase GCN2 mediate IFN-?-induced autophagy.
22435535 2012 AMPK and GCN2-ATF4 signal the repression of mitochondria in colon cancer cells.
22327514 2012 Common variants near TARDBP and EGR2 are associated with susceptibility to Ewing sarcoma.
22301437 2013 Nucleofection induces transient eIF2? phosphorylation by GCN2 and PERK.
21406692 2011 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21269460 2011 Initial characterization of the human central proteome.
21203563 2010 Amino acid availability controls TRB3 transcription in liver through the GCN2/eIF2?/ATF4 pathway.
21113813 2012 Effects of essential amino acids or glutamine deprivation on intestinal permeability and protein synthesis in HCT-8 cells: involvement of GCN2 and mTOR pathways.
21076179 2010 HDAC pharmacological inhibition promotes cell death through the eIF2? kinases PKR and GCN2.
20551969 2010 How do tumours adapt to nutrient stress?
20473272 2010 The GCN2-ATF4 pathway is critical for tumour cell survival and proliferation in response to nutrient deprivation.
20168091 2010 Autophagy impairment stimulates PS1 expression and gamma-secretase activity.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
19608861 2009 Lysine acetylation targets protein complexes and co-regulates major cellular functions.
19586904 2009 The role of nitric-oxide synthase in the regulation of UVB light-induced phosphorylation of the alpha subunit of eukaryotic initiation factor 2.
19369195 2009 Large-scale proteomics analysis of the human kinome.
19029902 2009 Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans.
18691976 2008 Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18287093 2008 MEK signaling is required for phosphorylation of eIF2alpha following amino acid limitation of HepG2 human hepatoma cells.
17974005 2007 The full-ORF clone resource of the German cDNA Consortium.
17344846 2007 Patterns of somatic mutation in human cancer genomes.
17276353 2007 The GCN2 eIF2alpha kinase regulates fatty-acid homeostasis in the liver during deprivation of an essential amino acid.
17202131 2007 Conserved intermolecular salt bridge required for activation of protein kinases PKR, GCN2, and PERK.
17192257 2007 Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry.
17081983 2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
16601681 2006 Antiviral effect of the mammalian translation initiation factor 2alpha kinase GCN2 against RNA viruses.
16572171 2006 Analysis of the DNA sequence and duplication history of human chromosome 15.
16121183 2005 Translational control of hippocampal synaptic plasticity and memory by the eIF2alpha kinase GCN2.
15761153 2005 High-throughput mapping of a dynamic signaling network in mammalian cells.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14671302 2003 Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12215525 2002 The GCN2 eIF2alpha kinase is required for adaptation to amino acid deprivation in mice.
10718198 2000 Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro.
10504407 1999 Characterization of a mammalian homolog of the GCN2 eukaryotic initiation factor 2alpha kinase.