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Browse EIF2AK3

Summary
SymbolEIF2AK3
Nameeukaryotic translation initiation factor 2-alpha kinase 3
Aliases PEK; PERK; PRKR-like endoplasmic reticulum kinase; pancreatic EIF2-alpha kinase; HsPEK
Chromosomal Location2p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Endoplasmic reticulum membrane; Single-pass type I membrane protein.
Domain PF00069 Protein kinase domain
Function

Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) on 'Ser-52' during the unfolded protein response (UPR) and in response to low amino acid availability. Converts phosphorylated eIF-2-alpha/EIF2S1 either in a global protein synthesis inhibitor, leading to a reduced overall utilization of amino acids, or to a translation initiation activator of specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion. Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1). Involved in control of mitochondrial morphology and function.

> Gene Ontology
 
Biological Process GO:0001501 skeletal system development
GO:0001503 ossification
GO:0001525 angiogenesis
GO:0001819 positive regulation of cytokine production
GO:0002062 chondrocyte differentiation
GO:0002063 chondrocyte development
GO:0002790 peptide secretion
GO:0006356 regulation of transcription from RNA polymerase I promoter
GO:0006360 transcription from RNA polymerase I promoter
GO:0006413 translational initiation
GO:0006417 regulation of translation
GO:0006446 regulation of translational initiation
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006983 ER overload response
GO:0006984 ER-nucleus signaling pathway
GO:0006986 response to unfolded protein
GO:0007029 endoplasmic reticulum organization
GO:0007272 ensheathment of neurons
GO:0008366 axon ensheathment
GO:0009266 response to temperature stimulus
GO:0009267 cellular response to starvation
GO:0009306 protein secretion
GO:0009409 response to cold
GO:0009914 hormone transport
GO:0009991 response to extracellular stimulus
GO:0010035 response to inorganic substance
GO:0010038 response to metal ion
GO:0010042 response to manganese ion
GO:0010573 vascular endothelial growth factor production
GO:0010574 regulation of vascular endothelial growth factor production
GO:0010575 positive regulation of vascular endothelial growth factor production
GO:0010608 posttranscriptional regulation of gene expression
GO:0010817 regulation of hormone levels
GO:0010950 positive regulation of endopeptidase activity
GO:0010952 positive regulation of peptidase activity
GO:0010998 regulation of translational initiation by eIF2 alpha phosphorylation
GO:0015833 peptide transport
GO:0017148 negative regulation of translation
GO:0018105 peptidyl-serine phosphorylation
GO:0018209 peptidyl-serine modification
GO:0019722 calcium-mediated signaling
GO:0019932 second-messenger-mediated signaling
GO:0023061 signal release
GO:0030072 peptide hormone secretion
GO:0030073 insulin secretion
GO:0030282 bone mineralization
GO:0030968 endoplasmic reticulum unfolded protein response
GO:0031016 pancreas development
GO:0031018 endocrine pancreas development
GO:0031214 biomineral tissue development
GO:0031641 regulation of myelination
GO:0031642 negative regulation of myelination
GO:0031644 regulation of neurological system process
GO:0031645 negative regulation of neurological system process
GO:0031667 response to nutrient levels
GO:0031668 cellular response to extracellular stimulus
GO:0031669 cellular response to nutrient levels
GO:0032055 negative regulation of translation in response to stress
GO:0032057 negative regulation of translational initiation in response to stress
GO:0034198 cellular response to amino acid starvation
GO:0034248 regulation of cellular amide metabolic process
GO:0034249 negative regulation of cellular amide metabolic process
GO:0034504 protein localization to nucleus
GO:0034620 cellular response to unfolded protein
GO:0034976 response to endoplasmic reticulum stress
GO:0035270 endocrine system development
GO:0035966 response to topologically incorrect protein
GO:0035967 cellular response to topologically incorrect protein
GO:0036490 regulation of translation in response to endoplasmic reticulum stress
GO:0036491 regulation of translation initiation in response to endoplasmic reticulum stress
GO:0036492 eiF2alpha phosphorylation in response to endoplasmic reticulum stress
GO:0036499 PERK-mediated unfolded protein response
GO:0042149 cellular response to glucose starvation
GO:0042552 myelination
GO:0042594 response to starvation
GO:0042886 amide transport
GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043281 regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043555 regulation of translation in response to stress
GO:0043558 regulation of translational initiation in response to stress
GO:0044057 regulation of system process
GO:0045862 positive regulation of proteolysis
GO:0045943 positive regulation of transcription from RNA polymerase I promoter
GO:0045947 negative regulation of translational initiation
GO:0046777 protein autophosphorylation
GO:0046879 hormone secretion
GO:0048009 insulin-like growth factor receptor signaling pathway
GO:0048514 blood vessel morphogenesis
GO:0051216 cartilage development
GO:0051259 protein oligomerization
GO:0051260 protein homooligomerization
GO:0051961 negative regulation of nervous system development
GO:0052547 regulation of peptidase activity
GO:0052548 regulation of endopeptidase activity
GO:0060734 regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation
GO:0061448 connective tissue development
GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
GO:0070417 cellular response to cold
GO:0071216 cellular response to biotic stimulus
GO:0071241 cellular response to inorganic substance
GO:0071248 cellular response to metal ion
GO:0071287 cellular response to manganese ion
GO:0071496 cellular response to external stimulus
GO:0097193 intrinsic apoptotic signaling pathway
GO:1900180 regulation of protein localization to nucleus
GO:1900182 positive regulation of protein localization to nucleus
GO:1902235 regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
GO:1903829 positive regulation of cellular protein localization
GO:1990267 response to transition metal nanoparticle
GO:1990737 response to manganese-induced endoplasmic reticulum stress
GO:2000116 regulation of cysteine-type endopeptidase activity
GO:2001056 positive regulation of cysteine-type endopeptidase activity
GO:2001233 regulation of apoptotic signaling pathway
GO:2001242 regulation of intrinsic apoptotic signaling pathway
Molecular Function GO:0004674 protein serine/threonine kinase activity
GO:0004694 eukaryotic translation initiation factor 2alpha kinase activity
GO:0019902 phosphatase binding
GO:0019903 protein phosphatase binding
GO:0031072 heat shock protein binding
GO:0051879 Hsp90 protein binding
Cellular Component GO:0030176 integral component of endoplasmic reticulum membrane
GO:0031227 intrinsic component of endoplasmic reticulum membrane
> KEGG and Reactome Pathway
 
KEGG hsa04140 Regulation of autophagy
hsa04141 Protein processing in endoplasmic reticulum
hsa04210 Apoptosis
Reactome R-HSA-392499: Metabolism of proteins
R-HSA-381042: PERK regulates gene expression
R-HSA-381119: Unfolded Protein Response (UPR)
Summary
SymbolEIF2AK3
Nameeukaryotic translation initiation factor 2-alpha kinase 3
Aliases PEK; PERK; PRKR-like endoplasmic reticulum kinase; pancreatic EIF2-alpha kinase; HsPEK
Chromosomal Location2p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between EIF2AK3 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 

There is no record.
Summary
SymbolEIF2AK3
Nameeukaryotic translation initiation factor 2-alpha kinase 3
Aliases PEK; PERK; PRKR-like endoplasmic reticulum kinase; pancreatic EIF2-alpha kinase; HsPEK
Chromosomal Location2p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of EIF2AK3 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell logFC: -2.20; FDR: 0.04630 Resistant to T cell-mediated killing
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen Total # shRNA with >= 4-fold: 5 Resistant to T-cell proliferation
Summary
SymbolEIF2AK3
Nameeukaryotic translation initiation factor 2-alpha kinase 3
Aliases PEK; PERK; PRKR-like endoplasmic reticulum kinase; pancreatic EIF2-alpha kinase; HsPEK
Chromosomal Location2p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of EIF2AK3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.0960.683
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.2870.837
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.0460.964
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.2120.378
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.3180.883
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.080.976
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.0760.835
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.0630.967
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.2240.896
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 48-0.2490.806
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.1670.912
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0520.459
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of EIF2AK3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 141705.9-5.91
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 41407.1-7.11
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27737.41.460.177
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.41.75.70.231
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21179.509.50.492
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolEIF2AK3
Nameeukaryotic translation initiation factor 2-alpha kinase 3
Aliases PEK; PERK; PRKR-like endoplasmic reticulum kinase; pancreatic EIF2-alpha kinase; HsPEK
Chromosomal Location2p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of EIF2AK3. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolEIF2AK3
Nameeukaryotic translation initiation factor 2-alpha kinase 3
Aliases PEK; PERK; PRKR-like endoplasmic reticulum kinase; pancreatic EIF2-alpha kinase; HsPEK
Chromosomal Location2p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of EIF2AK3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by EIF2AK3.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolEIF2AK3
Nameeukaryotic translation initiation factor 2-alpha kinase 3
Aliases PEK; PERK; PRKR-like endoplasmic reticulum kinase; pancreatic EIF2-alpha kinase; HsPEK
Chromosomal Location2p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of EIF2AK3. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolEIF2AK3
Nameeukaryotic translation initiation factor 2-alpha kinase 3
Aliases PEK; PERK; PRKR-like endoplasmic reticulum kinase; pancreatic EIF2-alpha kinase; HsPEK
Chromosomal Location2p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of EIF2AK3 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolEIF2AK3
Nameeukaryotic translation initiation factor 2-alpha kinase 3
Aliases PEK; PERK; PRKR-like endoplasmic reticulum kinase; pancreatic EIF2-alpha kinase; HsPEK
Chromosomal Location2p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between EIF2AK3 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolEIF2AK3
Nameeukaryotic translation initiation factor 2-alpha kinase 3
Aliases PEK; PERK; PRKR-like endoplasmic reticulum kinase; pancreatic EIF2-alpha kinase; HsPEK
Chromosomal Location2p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting EIF2AK3 collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.