Property Summary

NCBI Gene PubMed Count 52
Grant Count 109
R01 Count 73
Funding $11,089,870.28
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 0.046
osteosarcoma -1.779 0.000
cystic fibrosis -1.290 0.000
atypical teratoid / rhabdoid tumor 1.100 0.000
glioblastoma 1.200 0.000
subependymal giant cell astrocytoma 1.509 0.005
ovarian cancer 2.400 0.000
ileal Crohn's disease -1.345 0.043

Synonym

Accession Q9P2K8 C9JEC4 Q69YL7 Q6DC97 Q96GN6 Q9H5K1 Q9NSQ3 Q9NSZ5 Q9UJ56
Symbols GCN2
PVOD2

Gene

  TechDev Info (1)

Gary Johnson Kinome profile via MIB/MS Technology

 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 (31)

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
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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.
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