Tchem eIF-2-alpha kinase GCN2

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(Microbial infection) Plays a role in modulating the adaptive immune response to yellow fever virus infection; promotes dendritic cells to initiate autophagy and antigene presentation to both CD4(+) and CD8(+) T-cells under amino acid starvation (PubMed:24310610).

This gene encodes a member of a family of kinases that phosphorylate the alpha subunit of eukaryotic translation initiation factor-2 (EIF2), resulting in the downregulaton of protein synthesis. The encoded protein responds to amino acid deprivation by binding uncharged transfer RNAs. It may also be activated by glucose deprivation and viral infection. Mutations in this gene have been found in individuals suffering from autosomal recessive pulmonary venoocclusive-disease-2. [provided by RefSeq, Mar 2014]

Comments

Property Summary

Ligand Count	8
NCBI Gene PubMed Count	60
PubMed Score	276.54

PubTator Score	86.88

Knowledge Summary

Patent (7,596)

TINX Plot

Disease (7)

Disease	Target Count	Z-score	Confidence
Amino Acid Metabolism, Inborn Errors	13	0.0	0.0
Hair Diseases	3	0.0	0.0
Hypertension, Pulmonary	37	0.0	0.0
Immune System Diseases	4	0.0	0.0
Muscular Diseases	27	0.0	0.0
Pulmonary Veno-Occlusive Disease	2	0.0	0.0

Disease	Target Count
Familial primary pulmonary hypertension	11
Myopathy	185
PULMONARY VENOOCCLUSIVE DISEASE 2, AUTOSOMAL RECESSIVE	1
Pulmonary Veno-Occlusive Disease (disorder)	2
Pulmonary capillary hemangiomatosis	2

Disease	Target Count	P-value
osteosarcoma	7950	6.8e-07
ovarian cancer	8520	9.6e-05
cystic fibrosis	1696	1.6e-04
atypical teratoid / rhabdoid tumor	5112	1.7e-04
glioblastoma	5792	2.5e-04
subependymal giant cell astrocytoma	2287	5.4e-03
ileal Crohn's disease	9	4.3e-02
Rheumatoid arthritis	1191	4.6e-02

Disease	Target Count	Z-score	Confidence
Carcinoma	11493	0.0	1.1
Liver cancer	604	0.0	0.6

Disease	Target Count	Z-score	Confidence
Globe disease	67	0.0	0.9

Disease	Target Count	Z-score	Confidence
Pulmonary venoocclusive disease	3	6.972	3.5
Primary pulmonary hypertension	14	0.0	5.0

Disease	Target Count
Familial pulmonary capillary hemangiomatosis	1
Pulmonary Venoocclusive Disease 1, Autosomal Dominant	2
Pulmonary hypertension	85

Differential Expression (8)

Disease	log2 FC	p
atypical teratoid / rhabdoid tumor	1.100	1.7e-04
cystic fibrosis	-1.290	1.6e-04
glioblastoma	1.200	2.5e-04
ileal Crohn's disease	-1.345	4.3e-02
osteosarcoma	-1.779	6.8e-07
ovarian cancer	-1.300	9.6e-05
Rheumatoid arthritis	1.100	4.6e-02
subependymal giant cell astrocytoma	1.509	5.4e-03

Cells - Transformed fibroblasts 17,577

Cells - EBV-transformed lymphocytes 18,186

Pituitary 18,147

Nerve - Tibial 18,007

Adipose - Subcutaneous 18,110

Ovary 17,971

Thyroid 18,024

Uterus 17,618

Adipose - Visceral (Omentum) 17,937

Breast - Mammary Tissue 18,103

Prostate 18,213

Brain - Cerebellar Hemisphere 18,015

Artery - Coronary 17,949

Brain - Cerebellum 17,983

Artery - Tibial 17,631

Vagina 17,834

Spleen 17,614

Colon - Sigmoid 18,089

Artery - Aorta 17,896

Lung 18,057

Minor Salivary Gland 18,005

Brain - Nucleus accumbens (basal ganglia... 18,024

Esophagus - Gastroesophageal Junction 18,000

Skin - Sun Exposed (Lower leg) 17,968

Brain - Cortex 18,039

Brain - Frontal Cortex (BA9) 18,069

Stomach 17,879

Skin - Not Sun Exposed (Suprapubic) 18,081

Esophagus - Muscularis 18,017

Colon - Transverse 17,825

Brain - Hypothalamus 18,169

Small Intestine - Terminal Ileum 17,954

Esophagus - Mucosa 18,076

Brain - Caudate (basal ganglia) 18,001

Testis 18,518

Brain - Anterior cingulate cortex (BA24) 17,989

Brain - Spinal cord (cervical c-1) 17,973

Adrenal Gland 18,071

Heart - Atrial Appendage 17,896

Brain - Substantia nigra 17,981

Brain - Hippocampus 18,011

Brain - Amygdala 18,006

Muscle - Skeletal 17,778

Brain - Putamen (basal ganglia) 17,863

Liver 18,071

Kidney - Cortex 17,329

Pancreas 18,123

Heart - Left Ventricle 18,006

Whole Blood 17,439

Adult Testis 10,836

Adult Ovary 10,192

Adult Frontal Cortex 9,048

Fetal Ovary 9,118

Adult Pancreas 9,168

Fetal Brain 7,866

Fetal Testis 7,955

Fetal Heart 9,228

Monocytes 7,422

Adult Gallbladder 7,612

Adult Retina 10,115

CD8 Cells 9,840

Fetal Liver 8,402

CD4 Cells 7,773

Adult Adrenal 8,475

B Cells 9,086

Adult Urinary Bladder 7,592

NK Cells 8,475

Adult Spinal Cord 7,594

Adult Prostate 8,952

Adrenal gland

Brain

Frontal lobe

Gall bladder

Heart

Liver

B-lymphocyte

Monocyte

Natural killer cell

Ovary

Pancreas

Placenta 6,083

Prostate gland

Retina

Spinal cord

Testis

Urinary bladder

BTO:0004410

BTO:0005453

adipose tissue 15,837

adrenal gland 15,963

appendix 16,247

bone marrow 14,571

breast 16,063

cerebral cortex 16,630

cervix, uterine 15,871

colon 15,959

duodenum 15,975

endometrium 16,349

epididymis 15,863

esophagus 15,898

fallopian tube 16,245

gallbladder 16,333

heart muscle 14,972

kidney 15,917

liver 14,587

lung 16,312

lymph node 15,833

ovary 15,408

pancreas 14,070

parathyroid gland 14,769

placenta 15,937

prostate 16,460

rectum 15,705

salivary gland 14,981

seminal vesicle 15,918

skeletal muscle 14,011

skin 16,206

small intestine 16,154

smooth muscle 15,857

spleen 15,972

stomach 16,099

testis 17,936

thyroid gland 15,959

tonsil 15,400

urinary bladder 15,814

Liver and Pancreas 16,750

Digestive Tract 17,369

Urinary Tract 16,678

Endocrine System 18,159

Blood and immune system 16,909

Respiratory system 16,393

Female tissues 17,400

Male tissues 17,142

Skin and soft tissues 17,230

Nervous System 16,725

Cardiovascular System 15,192

Brain 7,346

Cervical carcinoma cell 4,944

Erythroleukemia cell 4,300

Melanoma cell line 364

Muscle 725

Testis 3,897

Uterus 1,493

See source...

Embryonic fibroblast 88

See source...

Synonym

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

Gene

EIF2AK4

PANTHER Protein Class (4)

transferase 625

kinase 362

protein kinase 257

non-receptor serine/threonine protein ki... 162

Ortholog (14)

Species	Source	Disease
Chimp 14,136	OMA EggNOG
Mouse 16,567	Inparanoid OMA EggNOG
Rat 15,112	Inparanoid OMA EggNOG
Dog 15,069	Inparanoid OMA EggNOG
Horse 14,249	Inparanoid OMA EggNOG
Cow 15,316	Inparanoid OMA EggNOG
Opossum 12,223	Inparanoid EggNOG
Platypus 5,699	OMA EggNOG
Chicken 7,823	Inparanoid OMA
Anole lizard 10,585	Inparanoid OMA EggNOG
Xenopus 10,463	OMA EggNOG
C. elegans 3,178	Inparanoid OMA
Fruitfly 3,048	Inparanoid EggNOG
S.cerevisiae 1,798	Inparanoid OMA EggNOG

UniProt Keyword (28)

Complete proteome 20,231

Polymorphism 12,194

Reference proteome 20,231

Repeat 4,916

Alternative splicing 10,528

Cytoplasm 4,952

Disease mutation 2,804

Phosphoprotein 8,216

Acetylation 3,409

Cell cycle 647

See all...

GO Function (4)

ATP binding 1,477

protein serine-threonine kinase activity 360

tRNA binding 52

eukaryotic translation initiation factor... 4

GO Component (2)

polysome 39

cytosolic ribosome 8

GO Process (30)

cellular response to UV 50

cellular response to amino acid starvati... 42

protein autophosphorylation 168

protein phosphorylation 334

defense response to virus 181

negative regulation of translational ini... 14

neuron projection extension 18

cell cycle arrest 142

regulation of translational initiation 25

DNA damage checkpoint 30

See all...

Compartment GO Term (26)

Cell 16,178

Cell part 16,177

Cytoplasm 10,983

Cytoplasmic part 9,247

Cytosol 6,686

Cytosolic part 407

Cytosolic ribosome 120

Endomembrane system 4,237

Endoplasmic reticulum 2,001

Eukaryotic translation initiation factor... 41

Eukaryotic translation initiation factor... 19

Intracellular 14,108

Intracellular non-membrane-bounded organ... 3,975

Intracellular organelle 12,025

Intracellular part 13,972

See all...

MGI Phenotype (11)

growth-size-body region phenotype 4,157

homeostasis-metabolism phenotype 4,747

cellular phenotype 3,637

nervous system phenotype 3,447

hematopoietic system phenotype 3,383

reproductive system phenotype 1,999

mortality-aging 5,018

liver-biliary system phenotype 1,300

immune system phenotype 3,461

behavior-neurological phenotype 3,401

See all...

GWAS Trait (9)

Mean corpuscular hemoglobin 238

Red cell distribution width 182

Body mass index 379

Reticulocyte fraction of red cells 163

High light scatter reticulocyte percenta... 153

Endometrial cancer 11

Corneal curvature 12

Response to haloperidol in psychosis 3

Endometrial endometrioid carcinoma 4

HCA RNA Cell Line (56)

A-431 16,131

A549 15,174

AF22 16,160

AN3-CA 15,648

ASC TERT1 14,842

BEWO 16,726

BJ 15,448

BJ hTERT+ 15,353

BJ hTERT+ SV40 Large T+ 15,609

BJ hTERT+ SV40 Large T+ RasG12V 15,493

See all...

Pathway (7)

Epstein-Barr virus infection 280

Measles 133

Influenza A 182

Herpes simplex infection 262

Protein processing in endoplasmic reticu... 164

Autophagy - animal 128

Hepatitis C 130

Ligand (8)

CHEMBL386051
pKd 7.59

CHEMBL388978
pKd 7.80

CHEMBL3407850
pIC50 7.92

CHEMBL3407851
pIC50 8.00

CHEMBL3407849
pIC50 8.30

CHEMBL603469
pKd 8.39

CHEMBL475251
pKd 8.48

compound A127 [WO2013110309]
pIC50 6.52

Gene RIF (38)

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 (71)

Summary
Details

	PMID	Year	Title

Tchem eIF-2-alpha kinase GCN2 Add to cart View Collections Empty Collection

Property Summary

Knowledge Summary

Patent (7,596)

TINX Plot

Disease (7)

Expression

Differential Expression (8)

Synonym

Gene

PANTHER Protein Class (4)

Ortholog (14)

UniProt Keyword (28)

GO Function (4)

GO Component (2)

GO Process (30)

Compartment GO Term (26)

MGI Phenotype (11)

GWAS Trait (9)

HCA RNA Cell Line (56)

Pathway (7)

Ligand (8)

Gene RIF (38)

AA Sequence

Text Mined References (71)

Tchem eIF-2-alpha kinase GCN2

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