TISIDB

Summary
Symbol	EIF2AK3
Name	eukaryotic translation initiation factor 2-alpha kinase 3
Aliases	PEK; PERK; PRKR-like endoplasmic reticulum kinase; pancreatic EIF2-alpha kinase; HsPEK
Chromosomal Location	2p12
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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
Symbol	EIF2AK3
Name	eukaryotic translation initiation factor 2-alpha kinase 3
Aliases	PEK; PERK; PRKR-like endoplasmic reticulum kinase; pancreatic EIF2-alpha kinase; HsPEK
Chromosomal Location	2p12
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 [ TOP ]
There is no record.

Summary
Symbol	EIF2AK3
Name	eukaryotic translation initiation factor 2-alpha kinase 3
Aliases	PEK; PERK; PRKR-like endoplasmic reticulum kinase; pancreatic EIF2-alpha kinase; HsPEK
Chromosomal Location	2p12
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

[ TOP ]

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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	logFC: -2.20; FDR: 0.04630	Resistant to T cell-mediated killing
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	Total # shRNA with >= 4-fold: 5	Resistant to T-cell proliferation

Summary
Symbol	EIF2AK3
Name	eukaryotic translation initiation factor 2-alpha kinase 3
Aliases	PEK; PERK; PRKR-like endoplasmic reticulum kinase; pancreatic EIF2-alpha kinase; HsPEK
Chromosomal Location	2p12
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

[ TOP ]

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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.096	0.683
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.287	0.837
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.046	0.964
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.212	0.378
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.318	0.883
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.08	0.976
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.076	0.835
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.063	0.967
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.224	0.896
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.249	0.806
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.167	0.912
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.052	0.459

> Mutation difference between responders and non-responders

[ TOP ]

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
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	5.9	-5.9	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	7.1	-7.1	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	1.4	6	0.177
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	1.7	5.7	0.231
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	0	9.5	0.492
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	EIF2AK3
Name	eukaryotic translation initiation factor 2-alpha kinase 3
Aliases	PEK; PERK; PRKR-like endoplasmic reticulum kinase; pancreatic EIF2-alpha kinase; HsPEK
Chromosomal Location	2p12
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 [ TOP ]

Summary
Symbol	EIF2AK3
Name	eukaryotic translation initiation factor 2-alpha kinase 3
Aliases	PEK; PERK; PRKR-like endoplasmic reticulum kinase; pancreatic EIF2-alpha kinase; HsPEK
Chromosomal Location	2p12
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	EIF2AK3
Name	eukaryotic translation initiation factor 2-alpha kinase 3
Aliases	PEK; PERK; PRKR-like endoplasmic reticulum kinase; pancreatic EIF2-alpha kinase; HsPEK
Chromosomal Location	2p12
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	EIF2AK3
Name	eukaryotic translation initiation factor 2-alpha kinase 3
Aliases	PEK; PERK; PRKR-like endoplasmic reticulum kinase; pancreatic EIF2-alpha kinase; HsPEK
Chromosomal Location	2p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of EIF2AK3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	EIF2AK3
Name	eukaryotic translation initiation factor 2-alpha kinase 3
Aliases	PEK; PERK; PRKR-like endoplasmic reticulum kinase; pancreatic EIF2-alpha kinase; HsPEK
Chromosomal Location	2p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between EIF2AK3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	EIF2AK3
Name	eukaryotic translation initiation factor 2-alpha kinase 3
Aliases	PEK; PERK; PRKR-like endoplasmic reticulum kinase; pancreatic EIF2-alpha kinase; HsPEK
Chromosomal Location	2p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting EIF2AK3 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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