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Aliases for EIF2AK3 Gene

Aliases for EIF2AK3 Gene

  • Eukaryotic Translation Initiation Factor 2-Alpha Kinase 3 2 3
  • PERK 3 4 6
  • PEK 3 4 6
  • PRKR-Like Endoplasmic Reticulum Kinase 3 4
  • Pancreatic EIF2-Alpha Kinase 3 4
  • EC 2.7.11.1 4 64
  • HsPEK 3 4
  • WRS 3 6
  • Eukaryotic Translation Initiation Factor 2 Alpha Kinase 3 3

External Ids for EIF2AK3 Gene

Summaries for EIF2AK3 Gene

Entrez Gene Summary for EIF2AK3 Gene

  • The protein encoded by this gene phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (EIF2), leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. 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, Jan 2010]

GeneCards Summary for EIF2AK3 Gene

EIF2AK3 (Eukaryotic Translation Initiation Factor 2-Alpha Kinase 3) is a Protein Coding gene. Diseases associated with EIF2AK3 include wolcott-rallison syndrome and brain ischemia. Among its related pathways are Apoptotic Pathways in Synovial Fibroblasts and Nanog in Mammalian ESC Pluripotency. GO annotations related to this gene include identical protein binding and protein kinase activity. An important paralog of this gene is EIF2AK4.

UniProtKB/Swiss-Prot for EIF2AK3 Gene

  • Phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (EIF2), leading to its inactivation and thus to a rapid reduction of translational initiation and repression of global protein synthesis. 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 (By similarity).

Gene Wiki entry for EIF2AK3 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for EIF2AK3 Gene

Genomics for EIF2AK3 Gene

Genomic Location for EIF2AK3 Gene

Start:
88,556,741 bp from pter
End:
88,627,576 bp from pter
Size:
70,836 bases
Orientation:
Minus strand

Genomic View for EIF2AK3 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for EIF2AK3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for EIF2AK3 Gene

Regulatory Elements for EIF2AK3 Gene

Proteins for EIF2AK3 Gene

  • Protein details for EIF2AK3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NZJ5-E2AK3_HUMAN
    Recommended name:
    Eukaryotic translation initiation factor 2-alpha kinase 3
    Protein Accession:
    Q9NZJ5
    Secondary Accessions:
    • A0AVH1
    • A0AVH2
    • B2RCU9
    • O95846
    • Q53QY0
    • Q53SB1

    Protein attributes for EIF2AK3 Gene

    Size:
    1116 amino acids
    Molecular mass:
    125216 Da
    Quaternary structure:
    • Forms dimers with HSPA5/BIP in resting cells. Oligomerizes in ER-stressed cells. Interacts with DNAJC3 and MFN2 (By similarity).

    Three dimensional structures from OCA and Proteopedia for EIF2AK3 Gene

neXtProt entry for EIF2AK3 Gene

Proteomics data for EIF2AK3 Gene at MOPED

Selected DME Specific Peptides for EIF2AK3 Gene

Post-translational modifications for EIF2AK3 Gene

  • ADP-ribosylated by PARP16 upon ER stress, which increases kinase activity
  • N-glycosylated.
  • Oligomerization of the N-terminal ER luminal domain by ER stress promotes PERK trans-autophosphorylation of the C-terminal cytoplasmic kinase domain at multiple residues including Thr-982 on the kinase activation loop (By similarity). Autophosphorylated. Phosphorylated at Tyr-619 following endoplasmic reticulum stress, leading to activate its tyrosine-protein kinase activity. Dephosphorylated by PTPN1/TP1B, leading to inactivate its enzyme activity.
  • Modification sites at PhosphoSitePlus
  • Glycosylation at Asn258

Other Protein References for EIF2AK3 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for EIF2AK3 Gene

UniProtKB/Swiss-Prot:

E2AK3_HUMAN
Domain:
  • The lumenal domain senses perturbations in protein folding in the ER, probably through reversible interaction with HSPA5/BIP.:
    • Q9NZJ5
  • Contains 1 protein kinase domain.:
    • Q9NZJ5
Family:
  • Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.:
    • Q9NZJ5
genes like me logo Genes that share domains with EIF2AK3: view

Function for EIF2AK3 Gene

Molecular function for EIF2AK3 Gene

GENATLAS Biochemistry: elongation initiation factor 2-alpha kinase 3,mainly expressed in pancreas,colocolizing with somatostatin in islet delta-cells,putatively involved in regulating protein synthesis
UniProtKB/Swiss-Prot CatalyticActivity: ATP + a protein = ADP + a phosphoprotein
UniProtKB/Swiss-Prot EnzymeRegulation: Perturbation in protein folding in the endoplasmic reticulum (ER) promotes reversible dissociation from HSPA5/BIP and oligomerization, resulting in transautophosphorylation and kinase activity induction.
UniProtKB/Swiss-Prot Function: Phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (EIF2), leading to its inactivation and thus to a rapid reduction of translational initiation and repression of global protein synthesis. 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 (By similarity).
UniProtKB/Swiss-Prot Induction: By endoplasmic reticulum stress

Enzyme Numbers (IUBMB) for EIF2AK3 Gene

Gene Ontology (GO) - Molecular Function for EIF2AK3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity TAS 10026192
GO:0004674 protein serine/threonine kinase activity TAS --
GO:0004694 eukaryotic translation initiation factor 2alpha kinase activity IMP 12086964
GO:0004713 protein tyrosine kinase activity --
GO:0005515 protein binding IPI 11907036
genes like me logo Genes that share ontologies with EIF2AK3: view
genes like me logo Genes that share phenotypes with EIF2AK3: view

Animal Models for EIF2AK3 Gene

MGI Knock Outs for EIF2AK3:

miRNA for EIF2AK3 Gene

No data available for Transcription Factor Targeting and HOMER Transcription for EIF2AK3 Gene

Localization for EIF2AK3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for EIF2AK3 Gene

Endoplasmic reticulum membrane; Single-pass type I membrane protein.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for EIF2AK3 Gene COMPARTMENTS Subcellular localization image for EIF2AK3 gene
Compartment Confidence
endoplasmic reticulum 5
cytosol 2
extracellular 2
mitochondrion 2
nucleus 2
plasma membrane 2
cytoskeleton 1
golgi apparatus 1
vacuole 1

Gene Ontology (GO) - Cellular Components for EIF2AK3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005623 cell --
GO:0005737 cytoplasm ISS --
GO:0005783 endoplasmic reticulum TAS 12086964
GO:0005789 endoplasmic reticulum membrane TAS --
GO:0016020 membrane IDA 19946888
genes like me logo Genes that share ontologies with EIF2AK3: view

Pathways for EIF2AK3 Gene

genes like me logo Genes that share pathways with EIF2AK3: view

Pathways by source for EIF2AK3 Gene

1 GeneGo (Thomson Reuters Life Sciences Research) pathway for EIF2AK3 Gene
2 Qiagen pathways for EIF2AK3 Gene
1 Cell Signaling Technology pathway for EIF2AK3 Gene

Gene Ontology (GO) - Biological Process for EIF2AK3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001501 skeletal system development ISS --
GO:0001503 ossification IMP 12086964
GO:0001525 angiogenesis IMP 22915762
GO:0002063 chondrocyte development ISS --
GO:0006412 translation IEA --
genes like me logo Genes that share ontologies with EIF2AK3: view

Compounds for EIF2AK3 Gene

(2) HMDB Compounds for EIF2AK3 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0

(23) Novoseek inferred chemical compound relationships for EIF2AK3 Gene

Compound -log(P) Hits PubMed IDs
pd 98,059 53.9 4
thapsigargin 52.7 4
ly294002 44.2 1
inositol 30.2 6
tyrosine 20 3
genes like me logo Genes that share compounds with EIF2AK3: view

Transcripts for EIF2AK3 Gene

Unigene Clusters for EIF2AK3 Gene

Eukaryotic translation initiation factor 2-alpha kinase 3:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for EIF2AK3 Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4a · 4b · 4c ^ 5 ^ 6 ^ 7a · 7b ^ 8 ^ 9a · 9b ^ 10a · 10b ^ 11 ^ 12a · 12b ^ 13a · 13b · 13c ^ 14 ^ 15a · 15b ^ 16 ^
SP1: -
SP2: -
SP3:
SP4: -
SP5:
SP6: -
SP7:
SP8:
SP9:

ExUns: 17 ^ 18 ^ 19 ^ 20
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:

Relevant External Links for EIF2AK3 Gene

GeneLoc Exon Structure for
EIF2AK3
ECgene alternative splicing isoforms for
EIF2AK3

Expression for EIF2AK3 Gene

mRNA expression in normal human tissues for EIF2AK3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for EIF2AK3 Gene

SOURCE GeneReport for Unigene cluster for EIF2AK3 Gene Hs.591589

mRNA Expression by UniProt/SwissProt for EIF2AK3 Gene

Q9NZJ5-E2AK3_HUMAN
Tissue specificity: Ubiquitous. A high level expression is seen in secretory tissues
genes like me logo Genes that share expressions with EIF2AK3: view

Orthologs for EIF2AK3 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for EIF2AK3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia EIF2AK3 36
  • 99.55 (n)
  • 99.46 (a)
EIF2AK3 37
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia EIF2AK3 36
  • 86.95 (n)
  • 89.53 (a)
EIF2AK3 37
  • 89 (a)
OneToOne
dog
(Canis familiaris)
Mammalia EIF2AK3 36
  • 90.21 (n)
  • 91.73 (a)
EIF2AK3 37
  • 92 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Eif2ak3 36
  • 82.76 (n)
  • 87.83 (a)
Eif2ak3 16
Eif2ak3 37
  • 88 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia EIF2AK3 37
  • 82 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia EIF2AK3 37
  • 83 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Eif2ak3 36
  • 83.3 (n)
  • 87.99 (a)
chicken
(Gallus gallus)
Aves EIF2AK3 36
  • 77.03 (n)
  • 81.93 (a)
EIF2AK3 37
  • 78 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia EIF2AK3 37
  • 77 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia eif2ak3 36
  • 69.18 (n)
  • 71.9 (a)
Str.7282 36
zebrafish
(Danio rerio)
Actinopterygii eif2ak3 36
  • 62.25 (n)
  • 64.56 (a)
eif2ak3 37
  • 58 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP013266 36
  • 45.73 (n)
  • 39.34 (a)
fruit fly
(Drosophila melanogaster)
Insecta PEK 37
  • 31 (a)
OneToOne
PEK 38
  • 31 (a)
worm
(Caenorhabditis elegans)
Secernentea pek-1 37
  • 24 (a)
OneToMany
Y38E10A.8 37
  • 33 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes GCN2 37
  • 10 (a)
OneToMany
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.13424 36
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 32 (a)
OneToOne
Species with no ortholog for EIF2AK3:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for EIF2AK3 Gene

ENSEMBL:
Gene Tree for EIF2AK3 (if available)
TreeFam:
Gene Tree for EIF2AK3 (if available)

Paralogs for EIF2AK3 Gene

Paralogs for EIF2AK3 Gene

Selected SIMAP similar genes for EIF2AK3 Gene using alignment to 3 proteins:

genes like me logo Genes that share paralogs with EIF2AK3: view

Variants for EIF2AK3 Gene

Sequence variations from dbSNP and Humsavar for EIF2AK3 Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type MAF
rs13045 Likely benign, - 88,595,605(-) GGACC(A/G)AGACC reference, missense, upstream-variant-2KB
rs867014 -- 88,620,189(+) CACAT(A/C)AAGCC intron-variant
rs867529 Likely benign, - 88,613,755(+) CCAAG(C/G)AACCG reference, missense
rs960147 -- 88,605,143(+) AACTT(C/T)TAAGG intron-variant
rs968798 -- 88,607,573(+) TAAAT(A/G)TAATT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for EIF2AK3 Gene

Variant ID Type Subtype PubMed ID
dgv61n16 CNV Deletion 17901297
nsv470476 CNV Gain 18288195
nsv507022 CNV Insertion 20534489
nsv874582 CNV Gain 21882294

Relevant External Links for EIF2AK3 Gene

HapMap Linkage Disequilibrium report
EIF2AK3
Human Gene Mutation Database (HGMD)
EIF2AK3
Locus Specific Mutation Databases (LSDB)
EIF2AK3

Disorders for EIF2AK3 Gene

(1) OMIM Diseases for EIF2AK3 Gene (604032)

UniProtKB/Swiss-Prot

E2AK3_HUMAN
  • Wolcott-Rallison syndrome (WRS) [MIM:226980]: A rare autosomal recessive disorder, characterized by permanent neonatal or early infancy insulin-dependent diabetes and, at a later age, epiphyseal dysplasia, osteoporosis, growth retardation and other multisystem manifestations, such as hepatic and renal dysfunctions, mental retardation and cardiovascular abnormalities. {ECO:0000269 PubMed:10932183}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(2) University of Copenhagen DISEASES for EIF2AK3 Gene

(18) Novoseek inferred disease relationships for EIF2AK3 Gene

Disease -log(P) Hits PubMed IDs
wolcott-rallison syndrome 92.6 10
tumors 36.3 25
cancer 30.4 7
melanoma 25.6 5
breast cancer 24.1 2

Relevant External Links for EIF2AK3

Genetic Association Database (GAD)
EIF2AK3
Human Genome Epidemiology (HuGE) Navigator
EIF2AK3
genes like me logo Genes that share disorders with EIF2AK3: view

Publications for EIF2AK3 Gene

  1. Characterization of a mutant pancreatic eIF-2alpha kinase, PEK, and co-localization with somatostatin in islet delta cells. (PMID: 10026192) Shi Y. … Yang N.N. (J. Biol. Chem. 1999) 2 3 4 23
  2. Pancreatic eukaryotic initiation factor-2alpha kinase (PEK) homologues in humans, Drosophila melanogaster and Caenorhabditis elegans that mediate translational control in response to endoplasmic reticulum stress. (PMID: 10677345) Sood R. … Wek R.C. (Biochem. J. 2000) 3 4 23
  3. EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome. (PMID: 10932183) Delepine M. … Julier C. (Nat. Genet. 2000) 3 4 23
  4. Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2alpha. (PMID: 12370288) Koumenis C. … Wouters B.G. (Mol. Cell. Biol. 2002) 3 23
  5. The EIF2AK3 gene region and type I diabetes in subjects from South India. (PMID: 15483661) Allotey R.A. … Hitman G.A. (Genes Immun. 2004) 3 23

Products for EIF2AK3 Gene

Sources for EIF2AK3 Gene

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