EIF2AK3 - eukaryotic translation initiation factor 2 alpha kinase 3 Gene

Homo sapiens

Also known as PEK; WRS; PERK

Gene ID: 9451 | Gene type: protein coding

About EIF2AK3

Cytogenetic location: 2p11.2 Genomic coordinates (GRCh38): 2:88,556,741-88,628,145 (from NCBI)

This gene has 24 transcripts (splice variants), 197 orthologues, 8 paralogues and is associated with 3 phenotypes. Ubiquitous expression in thyroid (RPKM 13.4), stomach (RPKM 10.9) and 25 other tissues.

Summary

The protein encoded by this gene phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2, leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. This protein is thought to modulate mitochondrial function. It is a type I membrane protein located in the endoplasmic reticulum (ER), where it is induced by ER stress caused by malfolded proteins. Mutations in this gene are associated with Wolcott-Rallison syndrome. [provided by RefSeq, Sep 2015]

EIF2AK3 Products(5)

mRNA	Protein	Name
XM_047446428.1	XP_047302384.1	eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1
XM_047446429.1	XP_047302385.1	eukaryotic translation initiation factor 2-alpha kinase 3 isoform X2
NM_004836.7	NP_004827.4	eukaryotic translation initiation factor 2-alpha kinase 3 isoform 1 precursor
XM_047446430.1	XP_047302386.1	eukaryotic translation initiation factor 2-alpha kinase 3 isoform X3
NM_001313915.2	NP_001300844.1	eukaryotic translation initiation factor 2-alpha kinase 3 isoform 2

Gene Ontology

Molecular Function
Biological Process

Molecular Function GO Annotation	Evidence	Reference	Source
enables enzyme binding	IPI IPI: Inferred from physical interaction	23103912	GOA
enables eukaryotic translation initiation factor 2alpha kinase activity	IDA IDA: Inferred from direct assay	10026192	GOA
enables eukaryotic translation initiation factor 2alpha kinase activity	IMP IMP: Inferred from mutant phenotype	12086964	GOA
enables identical protein binding	IPI IPI: Inferred from physical interaction	11907036	GOA
enables protein binding	IPI IPI: Inferred from physical interaction	11907036	GOA
enables protein phosphatase binding	IPI IPI: Inferred from physical interaction	22169477	GOA

Biological Process GO Annotation	Evidence	Reference	Source
involved in ER overload response	IDA IDA: Inferred from direct assay	10677345	GOA
involved in angiogenesis	IMP IMP: Inferred from mutant phenotype	22915762	GOA
involved in cellular response to amino acid starvation	IMP IMP: Inferred from mutant phenotype	25329545	GOA
involved in cellular response to cold	IMP IMP: Inferred from mutant phenotype	25329545	GOA
involved in cellular response to glucose starvation	IMP IMP: Inferred from mutant phenotype	22915762	GOA
involved in eiF2alpha phosphorylation in response to endoplasmic reticulum stress	IMP IMP: Inferred from mutant phenotype	25329545	GOA
involved in endocrine pancreas development	IMP IMP: Inferred from mutant phenotype	12086964	GOA
involved in endoplasmic reticulum unfolded protein response	IDA IDA: Inferred from direct assay	10677345	GOA
involved in ossification	IMP IMP: Inferred from mutant phenotype	12086964	GOA
involved in positive regulation of gene expression	IMP IMP: Inferred from mutant phenotype	22915762	GOA
involved in positive regulation of transcription by RNA polymerase I	IMP IMP: Inferred from mutant phenotype	22915762	GOA
involved in positive regulation of vascular endothelial growth factor production	IMP IMP: Inferred from mutant phenotype	22915762	GOA
involved in protein autophosphorylation	IDA IDA: Inferred from direct assay	10026192	GOA
involved in protein autophosphorylation	IMP IMP: Inferred from mutant phenotype	12086964	GOA
involved in regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	IMP IMP: Inferred from mutant phenotype	23000344	GOA
involved in response to endoplasmic reticulum stress	IMP IMP: Inferred from mutant phenotype	19061639	GOA

EXP: Inferred from Experiment IDA: Inferred from direct assay IPI: Inferred from physical interaction IMP: Inferred from mutant phenotype IGI: Inferred from genetic interaction IEP: Inferred from expression pattern

EIF2AK3 Protein Structure

Pkinase

0
200
400
600
800
1000
1116 a.a.

Protein Preferred Names

Protein Names

eukaryotic translation initiation factor 2-alpha kinase 3

PKR-like ER kinase	PRKR-like endoplasmic reticulum kinase
pancreatic EIF2-alpha kinase	pancreatic eIF-2alpha kinase

EIF2AK3 Protein-protein interaction Information

Type Cross Intra	Protein Name	Protein ID	Interactor	Interactor Species	Interactor ID	Detection Method	Reference
Intra	EIF2AK3	Q9NZJ5	HSPA5	Homo sapiens	P11021	Anti Bait CoIP	27238082
Intra	EIF2AK3	Q9NZJ5	HSPA5	Homo sapiens	P11021	Anti Bait CoIP	11907036

Cross: Cross-species interaction Intra: Intraspecies interaction

Related Diseases

Diseases

Alias

Type 2 Diabetes Mellitus

Insulin Resistance	NIDDM
Diabetes Mellitus, Non-Insulin-Dependent	Type 2 Diabetes
T2D	Noninsulin-Dependent Diabetes Mellitus
Diabetes Mellitus, Type Ii	Maturity-Onset Diabetes
Insulin Resistance, Severe, Digenic	Diabetes Mellitus, Type 2
Diabetes Mellitus, Noninsulin-Dependent	Diabetes Mellitus, Noninsulin-Dependent, Association With
Diabetes Mellitus, Noninsulin-Dependent, Late Onset	Hypertension, Insulin Resistance-Related, Susceptibility To
Insulin Resistance, Susceptibility To	Non-Insulin-Dependent Diabetes Mellitus
Type Ii Diabetes Mellitus	Adult-Onset Diabetes Mellitus
Maturity-Onset Diabetes Mellitus	Diabetes Mellitus Type 2
Type Ii Diabetes	Type 2 Diabetes Mellitus, Susceptibility To
Diabetes, Type 2	Diabetes Mellitus, Noninsulin-Dependent, Susceptibility To
Diabetes Mellitus, Non-Insulin-Dependent, Susceptibility To	Diabetes Mellitus, Type 2, Susceptibility To
Diabetes Mellitus, Noninsulin-Dependent, 2	Diabetes Mellitus, Type Ii, Susceptibility To
Hypertension, Insulin Resistance-Related	Adult-Onset Diabetes
Aodm	Diabetes Mellitus, Adult-Onset
Diabetes Mellitus Type Ii	Diabetes Mellitus Type 2, Susceptibility To
Diabetes, Type Ii, Susceptibility To	Diabetes Type 2
Diabetes Mellitus	Adult Onset Diabetes
Maturity Onset Diabetes	Nonketotic Diabetes
Non-Insulin Dependent Diabetes Mellitus	T2dm - [Type 2 Diabetes Mellitus]
Niddm - [Non Insulin Dependent Diabetes Mellitus]	Dm2
Dm Type Ii	Diabetic Type 2
Insulin Requiring Type 2 Diabetes	Noninsulin Dependent Diabetes
Non-Insulin-Dependent Diabetes Mellitus Without Complications	Diabetes Due To Insulin Secretory Defect
Diabetes Mellitus Due To Insulin Secretory Defect	Non-Insulin-Dependent Diabetes Of The Young
Senile Diabetes	Nonketotic Hyperglycaemia
Stable Diabetes

Leukoencephalopathy With Vanishing White Matter

Cree Leukoencephalopathy	Vanishing White Matter Disease
Ovarioleukodystrophy	Vanishing White Matter Leukodystrophy
Childhood Ataxia With Central Nervous System Hypomyelinization	Cach
Cach Syndrome	Myelinosis Centralis Diffusa
VWM	Cle
Childhood Ataxia With Central Nervous System Hypomyelination	Childhood Ataxia With Diffuse Central Nervous System Hypomyelination
Cach/Vwm	Cach/Vwm Syndrome
Childhood Ataxia With Central Nervous System Hypomyelination/Vanishing White Matter	Cree Leukoencehalopathy
Late Infantile Cach Syndrome	Juvenile Or Adult Cach Syndrome
Congenital Or Early Infantile Cach Syndrome	Leukodystrophy With Vanishing White Matter

Glioblastoma

Glioblastoma Multiforme	Gbm
Adult Glioblastoma Multiforme	Grade Iv Adult Astrocytic Tumor
Primary Glioblastoma Multiforme	Spongioblastoma Multiforme
Adult Glioblastoma	Primary Glioblastoma

Retinitis Pigmentosa

RP	Rod-Cone Dystrophy
Autosomal Recessive Retinitis Pigmentosa	Non-Syndromic Retinitis Pigmentosa
Pericentral Pigmentary Retinopathy	Pigmentary Retinopathy
Tapetoretinal Degeneration	Rcd
Retinitis Pigmentosa Autosomal Recessive	ARRP
Retinitis Pigmentosa, Autosomal Recessive	Retinitis Pigmentosa 1

Retinal Degeneration

Degeneration Of Retina

Epiphyseal Dysplasia, Multiple, With Early-Onset Diabetes Mellitus

Wolcott-Rallison Syndrome	Med-Iddm Syndrome
Iddm-Med Syndrome	Wolcott Rallison Syndrome
WRS	Epiphyseal Dysplasia Multiple With Early-Onset Diabetes Mellitus
Early-Onset Diabetes Mellitus With Multiple Epiphyseal Dysplasia	Multiple Epiphyseal Dysplasia With Early-Onset Diabetes Mellitus

Permanent Neonatal Diabetes Mellitus

Pndm	Permanent Diabetes Mellitus Of Infancy
Pdmi	Neonatal Diabetes Mellitus, Permanent

Menkes Disease

Menkes Syndrome	Copper Transport Disease
MNK	Kinky Hair Disease
Steely Hair Disease	Menkes Kinky-Hair Syndrome
Mk	Steely Hair Syndrome
Menkea Syndrome	Md
Menkes Kinky Hair Syndrome	Hypocupremia, Congenital
Kinky Hair Syndrome	X-Linked Copper Deficiency
Menkes Kinky Hair Disease

Osteoporosis

Postmenopausal Osteoporosis	Osteoporosis, Postmenopausal
Bone Mineral Density Quantitative Trait Locus	Bmnd
Osteoporosis, Involutional	Osteoporosis, Susceptibility To
Osteoporosis, Postmenopausal, Susceptibility	Bone Mineral Density Variation Qtl, Osteoporosis
OSTEOP	Involutional Osteoporosis
Senile Osteoporosis	Osteoporosis Postmenopausal
Bone Mineral Density, Quantitative Trait Locus	Osteoporosis, Senile
Idiopathic Osteoporosis	Bone Rarefaction Nos
Type 1 Osteoporosis

Retinitis Pigmentosa 58

RP58	Retinitis Pigmentosa, Type 58

Ovarian Cancer

Ovarian Carcinoma	Ovarian Neoplasm
Malignant Tumour Of Ovary	Epithelial Ovarian Cancer
Neoplasm Of Ovary	Ovarian Neoplasms
Ovarian Cancers	Malignant Neoplasm Of Ovary
Primary Malignant Neoplasm Of Ovary	Ovarian Cancer, Somatic
Malignant Ovarian Tumor	Ovary Neoplasm
Primary Ovarian Cancer	Tumor Of The Ovary
Cancer Of The Ovary	Malignant Neoplasm Of The Ovary
Malignant Tumor Of The Ovary	Ovarian Malignant Tumor
OC	Ovarian Carcinomas
Cancer, Ovarian	Cancer Of Ovary
Ovary Cancer	Ca Ovary

Diabetes Mellitus

Diabetes

Melanoma

Malignant Melanoma	Cutaneous Melanoma
Naevocarcinoma	Malignant Melanomas

Autosomal Dominant Intellectual Developmental Disorder 8

Autosomal Dominant Non-Syndromic Intellectual Disability 8	Mental Retardation, Autosomal Dominant 8
Autosomal Dominant Mental Retardation 8	Mrd8

Colorectal Cancer

Colon Cancer	Colorectal Carcinoma
Colon Carcinoma	Colorectal Cancer, Susceptibility To
Carcinoma Of Colon	CRC
Colorectal Cancer With Chromosomal Instability, Somatic	Colon Cancer, Somatic
Colon Cancer, Susceptibility To	Colonic Neoplasms
Colorectal Neoplasms	Colorectal Cancer, Somatic
Colon Cancer, Advanced, Somatic	Colonic Carcinoma
Colorectal Carcinomas	Colon Cancers
Colorectal Cancers	Cancer, Colorectal, Somatic
Cancer, Colon	Cancer, Colorectal, Susceptibility To
Colorectal Neoplasm	Colonic Neoplasm
Malignant Tumor Of Colon

Maturity-Onset Diabetes Of The Young

MODY	Maturity Onset Diabetes Mellitus In Young
Mason-Type Diabetes	Mason Type Diabetes
Maturity Onset Diabetes Of The Young	Mody Syndrome
Diabetes Of The Young, Maturity-Onset

Osteochondrodysplasia

Chondrodystrophy	Skeletal Dysplasia
Congenital Anomaly Of Cartilage	Osteochondrodysplasias
Cartilage Development Disorder	Osteochondrodysplasia Syndrome
Dysplasia, Skeletal	Mucopolysaccharidosis Iv

Lung Cancer

Lung Carcinoma	Non-Small Cell Lung Carcinoma
Lung Cancer, Protection Against	Lung Cancer, Susceptibility To
Adenocarcinoma Of Lung, Somatic	Nonsmall Cell Lung Cancer
Adenocarcinoma Of Lung, Response To Tyrosine Kinase Inhibitor In	Lung Neoplasm
Carcinoma Of Lung	Lung Non-Small Cell Carcinoma
Non-Small Cell Lung Cancer	Nsclc
Lung Neoplasms	Malignant Neoplasm Of Lung
Alveolar Cell Carcinoma	Nonsmall Cell Lung Cancer, Somatic
Nonsmall Cell Lung Cancer, Response To Tyrosine Kinase Inhibitor In	Nonsmall Cell Lung Cancer, Susceptibility To
Lung Cancer, Somatic	Lung Cancer, Resistance To
Cancer Of Lung	Cancer Of Bronchus
Cancer Of The Lung	Lung Malignancies
Lung Malignant Tumors	Malignant Lung Tumor
Malignant Tumor Of Lung	Pulmonary Cancer
Pulmonary Carcinoma	Pulmonary Neoplasms
Respiratory Carcinoma	LNCR
Adenocarcinoma Of Lung	Neoplasm Of Lung
Cancer Lung	Carcinoma Non-Small Cell Lung
Carcinoma, Non-Small-Cell Lung	Lung Cancers
Lung Carcinomas	Cancer, Lung
Cancer, Lung, Non-Small Cell	Primary Malignant Neoplasm Of Lung
Bronchioloalveolar Adenocarcinoma

Deafness, Autosomal Dominant 44

DFNA44	Autosomal Dominant Nonsyndromic Deafness 44
Autosomal Dominant Deafness 44	Deafness, Autosomal Dominant, 44
Deafness, Autosomal Dominant, Type 44

Acute Salpingo-Oophoritis

Acute Salpingitis And Oophoritis

Nervous System Disease

Abnormality Of The Nervous System	Nervous System Diseases
Nervous System Disorder

Glioblastoma Classical Subtype

Multiple Epiphyseal Dysplasia

Med	Polyepiphyseal Dysplasia
Edm	Epiphyseal Dysplasia, Multiple, 1
Epiphyseal Dysplasia, Multiple, 2	Epiphyseal Dysplasia, Multiple, 3
Epiphyseal Dysplasia, Multiple, 4	Epiphyseal Dysplasia, Multiple, 5
Epiphyseal Dysplasia, Multiple	Edm1
Edm2	Edm3
Edm4	Edm5
Epiphyseal Dysplasia, Fairbank Type	Epiphyseal Dysplasia, Ribbing Type
Multiple Epiphyseal Dysplasia, Autosomal Dominant	Multiple Epiphyseal Dysplasia, Autosomal Recessive
Rmed	Dysplasia, Epiphyseal, Multiple
Osteochondrodysplasias

Wolfram Syndrome

Didmoad Syndrome	Didmoad
Diabetes Insipidus And Mellitus With Optic Atrophy And Deafness	Wfs
Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, And Deafness	Didmoadud
Diabetes Insipidus-Diabetes Mellitus-Optic Atrophy-Deafness Syndrome	Diabetes Insipidus-Diabetes Mellitus-Optic Atrophy-Hearing Loss Syndrome

Amyotrophic Lateral Sclerosis 1

Amyotrophic Lateral Sclerosis	ALS
Lou Gehrig Disease	Amyotrophic Lateral Sclerosis Type 1
Charcot Disease	ALS1
Amyotrophic Lateral Sclerosis, Susceptibility To	Fals
Lou Gehrig'S Disease	Mnd
Motor Neuron Disease	Familial Amyotrophic Lateral Sclerosis
Amyotrophic Lateral Sclerosis 1, Familial	Amyotrophic Lateral Sclerosis 1, Autosomal Dominant
Motor Neuron Disease, Bulbar	Motor Neurone Disease
Amyotrophic Lateral Sclerosis With Dementia	Dementia With Amyotrophic Lateral Sclerosis
Motor Neuron Disease, Amyotrophic Lateral Sclerosis	Sclerosis, Lateral, Amyotrophic
Sclerosis, Lateral, Amyotrophic, Type 1	Amyotrophic Sclerosis
Als - [Amyotrophic Lateral Sclerosis]	Wasting Palsy
Amyotrophic Paralysis	Amyotrophy Lateral Sclerosis
Wasting Paralysis	Spinal Progressive Amyotrophy
Progressive Atrophic Paralysis

Neonatal Diabetes

Neonatal Diabetes Mellitus	Diabetes Mellitus Syndrome In Newborn Infant
Ndm

Peripheral Nervous System Disease

Peripheral Neuropathy	Peripheral Nerve Disease
Peripheral Nerve Disorders	Neuropathy, Peripheral
Peripheral Neuropathy Due To Vitamin Pyridoxine Hyperalimentation

Rasopathy

Ras/Mitogen-Activated Protein Kinase Syndrome

Mesothelioma, Malignant

Malignant Mesothelioma	Pleural Mesothelioma
MESOM	Mesothelioma, Somatic
Advanced Malignant Mesothelioma	Asbestos-Related Malignant Mesothelioma
Diffuse Malignant Mesothelioma	Malignant Tumor Of Mesothelium
Malignant Mesothelioma, Susceptibility To	Mesothelioma Diffuse Malignant
Mesothelioma	Malignant Pleural Mesothelioma

Diseases	Alias
Waldenstroem'S Macroglobulinemia	Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma

Related Agents

Pre-clinical Phase

Bioactive Molecules (4)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-119240	CCT020312	Activator	99.05%	Unkown
HY-RS04244	EIF2AK3 Human Pre-designed siRNA Set A	Pre-designed Sets	/	Unkown
HY-RS04245	Eif2ak3 Mouse Pre-designed siRNA Set A	Pre-designed Sets	/	Unkown
HY-RS04246	Eif2ak3 Rat Pre-designed siRNA Set A	Pre-designed Sets	/	Unkown

Orthologs Information

Species	Symbol	Source	ID
Macaca mulatta	EIF2AK3	VGNC	VGNC:72181
Bos taurus	EIF2AK3	VGNC	VGNC:28382
Felis catus	EIF2AK3	VGNC	VGNC:61771
Canis familiaris	EIF2AK3	VGNC	VGNC:40258
Mus musculus	EIF2AK3	MGD	MGI:1341830
Rattus norvegicus	EIF2AK3	RGD	RGD:70884

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