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EIF2AK3 Gene

protein-coding   GIFtS: 69
GCID: GC02M088857

Eukaryotic Translation Initiation Factor 2-Alpha Kinase...

  See EIF2AK3-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Eukaryotic Translation Initiation Factor 2-Alpha Kinase 31 2     EC 2.7.11.13 8
PEK2 3 5     WRS2 5
PERK2 3 5     Eukaryotic Translation Initiation Factor 2 Alpha Kinase 32
Pancreatic EIF2-Alpha Kinase2 3     hsPEK2
PRKR-Like Endoplasmic Reticulum Kinase2 3     HsPEK3

External Ids:    HGNC: 32551   Entrez Gene: 94512   Ensembl: ENSG000001720717   OMIM: 6040325   UniProtKB: Q9NZJ53   

Export aliases for EIF2AK3 gene to outside databases

Previous GC identifers: GC02M088410 GC02M089149 GC02M088741 GC02M088758 GC02M088695 GC02M088637 GC02M087778


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 epiphyseal dysplasia multiple with early-onset diabetes mellitus, and brain ischemia. GO annotations related to this gene include protein kinase activity and identical protein binding. An important paralog of this gene is EIF2AK1.

UniProtKB/Swiss-Prot: E2AK3_HUMAN, Q9NZJ5
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) (By similarity)

Gene Wiki entry for EIF2AK3 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000002.11  NT_022184.16  NC_018913.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the EIF2AK3 gene promoter:
         AP-1   ATF-2   NF-kappaB   CBF-A   STAT3   c-Jun   NF-kappaB1   NF-Y   CBF(2)   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidEIF2AK3 promoter sequence
   Search Chromatin IP Primers for EIF2AK3

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat EIF2AK3


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2p12   Ensembl cytogenetic band:  2p11.2   HGNC cytogenetic band: 2p12

EIF2AK3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
EIF2AK3 gene location

GeneLoc information about chromosome 2         GeneLoc Exon Structure

GeneLoc location for GC02M088857:  view genomic region     (about GC identifiers)

Start:
88,856,259 bp from pter      End:
88,927,094 bp from pter
Size:
70,836 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: E2AK3_HUMAN, Q9NZJ5 (See protein sequence)
Recommended Name: Eukaryotic translation initiation factor 2-alpha kinase 3 precursor  
Size: 1116 amino acids; 125216 Da
Subunit: Forms dimers with HSPA5/BIP in resting cells. Oligomerizes in ER-stressed cells. Interacts with DNAJC3
(By similarity)
2 PDB 3D structures from and Proteopedia for EIF2AK3:
4G31 (3D)        4G34 (3D)    
Secondary accessions: A0AVH1 A0AVH2 B2RCU9 O95846 Q53QY0 Q53SB1

Explore the universe of human proteins at neXtProt for EIF2AK3: NX_Q9NZJ5

Explore proteomics data for EIF2AK3 at MOPED

Post-translational modifications: 

  • 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
    activity1
  • N-glycosylated (By similarity)1
  • ADP-ribosylated by PARP16 upon ER stress, which increases kinase activity1
  • Glycosylation2 at Asn258
  • Modification sites at PhosphoSitePlus
  • 2 DME Specific Peptides for EIF2AK3 (Q9NZJ5)
     IVRYFNAW  KVYLYIQMQLCRKE 


    See EIF2AK3 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_004827.4  
    ENSEMBL proteins: 
     ENSP00000408325   ENSP00000307235   ENSP00000412076  
    Reactome Protein details: Q9NZJ5

    EIF2AK3 Human Recombinant Protein Products:

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    Novus Biologicals EIF2AK3 Protein
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    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp.

     
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    antibodies-online proteins for EIF2AK3 (2 products) 

     
    antibodies-online peptides for EIF2AK3

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    antibodies-online kits for EIF2AK3 (18 products) 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    IUPHAR Guide to PHARMACOLOGY protein family classification: eukaryotic translation initiation factor 2-alpha kinase 3
    PEK subfamily

    Selected InterPro protein domains (see all 6):
     IPR017441 Protein_kinase_ATP_BS
     IPR011009 Kinase-like_dom
     IPR008271 Ser/Thr_kinase_AS
     IPR000719 Prot_kinase_dom
     IPR027295 Quinonprotein_ADH-like_fam

    Graphical View of Domain Structure for InterPro Entry Q9NZJ5

    ProtoNet protein and cluster: Q9NZJ5

    UniProtKB/Swiss-Prot: E2AK3_HUMAN, Q9NZJ5
    Domain: The lumenal domain senses perturbations in protein folding in the ER, probably through reversible
    interaction with HSPA5/BIP (By similarity)
    Similarity: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily
    Similarity: Contains 1 protein kinase domain


    Find genes that share domains with EIF2AK3           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: E2AK3_HUMAN, Q9NZJ5
    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) (By similarity)
    Catalytic activity: ATP + a protein = ADP + a phosphoprotein
    Enzyme regulation: Perturbation in protein folding in the endoplasmic reticulum (ER) promotes reversible
    dissociation from HSPA5/BIP and oligomerization, resulting in transautophosphorylation and kinase activity
    induction (By similarity)
    Induction: By endoplasmic reticulum stress

         Genatlas biochemistry entry for EIF2AK3:
    elongation initiation factor 2-alpha kinase 3,mainly expressed in pancreas,colocolizing with somatostatin in islet
    delta-cells,putatively involved in regulating protein synthesis

         Enzyme Number (IUBMB): EC 2.7.11.11 2

         Gene Ontology (GO): Selected molecular function terms (see all 10):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004672protein kinase activity TAS10026192
    GO:0004674protein serine/threonine kinase activity TAS--
    GO:0004694eukaryotic translation initiation factor 2alpha kinase activity IMP12086964
    GO:0004713protein tyrosine kinase activity ----
    GO:0005515protein binding IPI11907036
         
    Find genes that share ontologies with EIF2AK3           About GenesLikeMe


    Phenotypes:
         12 MGI mutant phenotypes (inferred from 4 alleles(MGI details for Eif2ak3):
     behavior/neurological  cellular  digestive/alimentary  endocrine/exocrine gland  growth/size/body 
     homeostasis/metabolism  immune system  limbs/digits/tail  mortality/aging  nervous system 
     no phenotypic analysis  skeleton 

    Find genes that share phenotypes with EIF2AK3           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for EIF2AK3: Eif2ak3tm1Dron Eif2ak3tm1Drc

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for EIF2AK3
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       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for EIF2AK3

    miRNA
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    miRTarBase miRNAs that target EIF2AK3:
    hsa-mir-26b-5p (MIRT030259), hsa-mir-335-5p (MIRT019050), hsa-mir-192-5p (MIRT026817), hsa-mir-215-5p (MIRT024874)

    Block miRNA regulation of human, mouse, rat EIF2AK3 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate EIF2AK3 (see all 16):
    hsa-miR-548k hsa-miR-488 hsa-miR-340 hsa-miR-218 hsa-miR-548c-3p hsa-miR-2113 hsa-miR-3163 hsa-miR-224
    SwitchGear 3'UTR luciferase reporter plasmidEIF2AK3 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat EIF2AK3

    Gene Editing
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for EIF2AK3


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    E2AK3_HUMAN, Q9NZJ5: Endoplasmic reticulum membrane; Single-pass type I membrane protein
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    endoplasmic reticulum5
    cytosol2
    extracellular2
    mitochondrion2
    nucleus2
    plasma membrane2
    cytoskeleton1
    golgi apparatus1
    vacuole1

    Gene Ontology (GO): 5 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005623cell ----
    GO:0005737cytoplasm ISS--
    GO:0005783endoplasmic reticulum TAS12086964
    GO:0005789endoplasmic reticulum membrane TAS--
    GO:0016021integral component of membrane IEA--

    Find genes that share ontologies with EIF2AK3           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for EIF2AK3 About   (see all 14)  
    See pathways by source

    SuperPathContained pathways About
    1Alzheimer's disease
    Alzheimers Disease0.44
    Alzheimer's disease0.44
    2Influenza A
    Influenza A0.34
    Herpes simplex infection0.33
    Measles0.34
    3PERK regulated gene expression
    PERK regulated gene expression0.90
    4Nanog in Mammalian ESC Pluripotency
    GSK3 Signaling0.61
    5Unfolded Protein Response
    Unfolded Protein Response0.61


    Find genes that share SuperPaths with EIF2AK3           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    2 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for EIF2AK3
        GSK3 Signaling
    eIF2 Pathway

    1 Cell Signaling Technology (CST) Pathway for EIF2AK3
        Translational Control

    1 GeneGo (Thomson Reuters) Pathway for EIF2AK3
        Translation Regulation of EIF2 activity

    2 BioSystems Pathways for EIF2AK3
        Translation Factors
    Alzheimers Disease

    1 Reactome Pathway for EIF2AK3
        PERK regulates gene expression


    Selected Kegg Pathways  (Kegg details for EIF2AK3) (see all 8):
        Protein processing in endoplasmic reticulum
    Non-alcoholic fatty liver disease (NAFLD)
    Alzheimer's disease
    Hepatitis C
    Measles

        Pathway & Disease-focused RT2 Profiler PCR Arrays including EIF2AK3: 
              Neurotoxicity in human mouse rat
              Autophagy in human mouse rat
              Apoptosis 384HT in human mouse rat
              Unfolded Protein Response in human mouse rat
              Molecular Toxicology PathwayFinder 384HT in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for EIF2AK3

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for EIF2AK3 (Q9NZJ51, 3 ENSP000003072354) via UniProtKB, MINT, STRING, and/or I2D (see all 47)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    HSPA5P110213, ENSP000003241734I2D: score=3 STRING: ENSP00000324173
    NFE2L2Q162363, ENSP000003802524I2D: score=3 STRING: ENSP00000380252
    EIF2S1P051983, ENSP000002563834I2D: score=1 STRING: ENSP00000256383
    NFE2L1Q144943, ENSP000003551904I2D: score=1 STRING: ENSP00000355190
    DNAJC3Q132173, ENSP000003659914I2D: score=2 STRING: ENSP00000365991
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 32):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001501skeletal system development ISS--
    GO:0001503ossification IMP12086964
    GO:0002063chondrocyte development ISS--
    GO:0006412translation IEA--
    GO:0006468protein phosphorylation ISS--

    Find genes that share ontologies with EIF2AK3           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for EIF2AK3 (E2AK3)

    2 HMDB Compounds for EIF2AK3    About this table
    CompoundSynonyms CAS #PubMed Ids
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--

    Selected Novoseek inferred chemical compound relationships for EIF2AK3 gene (see all 23)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    pd 98,059 53.9 8 18455446 (1), 19087521 (1), 18989579 (1), 20056088 (1)
    thapsigargin 52.7 6 19428936 (1), 20022965 (1), 17525289 (1), 17941056 (1)
    ly294002 44.2 1 18383822 (1)
    inositol 30.2 6 17349291 (1), 17178827 (1), 16205645 (1), 15799970 (1) (see all 6)
    tyrosine 20 3 17998206 (3)
    rapamycin 17.6 2 18768473 (1)
    vitamin-e 17.4 1 18468636 (1)
    s-nitroso-n-acetylpenicillamine 15.6 5 15605392 (1), 16029920 (1)
    tamoxifen 13.7 7 15753463 (2), 17011908 (2), 12425799 (1), 18468636 (1)
    nitric oxide 12.8 16 16029920 (3), 20170287 (2), 16141331 (2), 15677503 (1) (see all 9)



    Find genes that share compounds with EIF2AK3           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for EIF2AK3 gene: 
    NM_004836.5  

    Unigene Cluster for EIF2AK3:

    Eukaryotic translation initiation factor 2-alpha kinase 3
    Hs.591589  [show with all ESTs]
    Unigene Representative Sequence: NM_004836
    6 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000419748 ENST00000303236(uc002stc.4) ENST00000415570 ENST00000470706
    ENST00000478003 ENST00000477083
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    hsa-miR-548k hsa-miR-488 hsa-miR-340 hsa-miR-218 hsa-miR-548c-3p hsa-miR-2113 hsa-miR-3163 hsa-miR-224
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      QuantiFast Probe-based Assays in human, mouse, rat EIF2AK3

    Additional mRNA sequence: 

    AF110146.1 AF193339.1 AK128659.1 AK308312.1 AK315287.1 BC126354.1 BC126356.1 CR749382.1 

    11 DOTS entries:

    DT.121033331  DT.101982874  DT.100815553  DT.121033339  DT.97783687  DT.114894  DT.86857088  DT.102830891 
    DT.121033357  DT.121033371  DT.91967352 

    Selected AceView cDNA sequences (see all 142):

    F07171 AA215520 CA440854 AI589666 AI382902 AV714829 AA768127 BG698166 
    BM666209 AI524196 BF055061 BU739521 BE672887 AA744670 AA766941 AI650734 
    AI337430 CB215469 AI686701 AA552360 BX112252 AA806924 BG291342 BM785962 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for EIF2AK3 (see all 9)    About this scheme

    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:                                                                                                                                                            

    ExUns: 17 ^ 18 ^ 19 ^ 20
    SP1:                        
    SP2:                        
    SP3:                        
    SP4:                        
    SP5:                        


    ECgene alternative splicing isoforms for EIF2AK3

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    EIF2AK3 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TTTTTATTTT
    EIF2AK3 Expression
    About this image


    EIF2AK3 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 5) fully expand
     
     Brain (Nervous System)    fully expand to see all 4 entries
             Cerebral Cortex
     
     Skeletal Muscle (Muscoskeletal System)    fully expand to see all 2 entries
             Muscle Progenitor Cells Mandibular Arch Muscles
     
     Trophoblast (Extraembryonic Tissues)
             Trophoblast Cells Trophoblast
     
     Testis (Reproductive System)
             Leydig Cells Testis Interstitium
     
     Blood (Hematopoietic System)
             Mature B-Cells Peripheral Blood
    EIF2AK3 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    EIF2AK3 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.591589

    UniProtKB/Swiss-Prot: E2AK3_HUMAN, Q9NZJ5
    Tissue specificity: Ubiquitous. A high level expression is seen in secretory tissues

        Pathway & Disease-focused RT2 Profiler PCR Arrays including EIF2AK3: 
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              Molecular Toxicology PathwayFinder 384HT in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals and fungi.

    Orthologs for EIF2AK3 gene from Selected species (see all 18)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Eif2ak31 , 5 eukaryotic translation initiation factor 2 alpha kinase more1, 5 82.76(n)1
    87.83(a)1
      6 (32.09 cM)5
    136661  NM_010121.21  NP_034251.21 
     708445155 
    chicken
    (Gallus gallus)
    Aves EIF2AK31 eukaryotic translation initiation factor 2-alpha kinase more 77.03(n)
    81.93(a)
      422930  XM_420868.4  XP_420868.2 
    lizard
    (Anolis carolinensis)
    Reptilia EIF2AK36
    eukaryotic translation initiation factor 2-alpha k...
    77(a)
    1 ↔ 1
    6(59670350-59711857)
    African clawed frog
    (Xenopus laevis)
    Amphibia BJ620132.12   -- 74.65(n)    BJ620132.1 
    zebrafish
    (Danio rerio)
    Actinopterygii BM777428.12   -- 72.78(n)    BM777428.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta PEK3 protein amino acid phosphorylation
    protein kinase
    31(a)   83A4   --
    worm
    (Caenorhabditis elegans)
    Secernentea Y38E10A.86
    pek-16
    Protein PEK-1 (pek-1) mRNA, complete cds
    33(a)
    24(a)
    1 ↔ many
    1 ↔ many
    II(12607200-12608788) WBGene00012586
    X(11410181-11414811) WBGene00003970
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes GCN26
    Protein kinase, phosphorylates the alpha-subunit o...
    10(a)
    1 → many
    IV(1025070-1030049) YDR283C


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for EIF2AK3 gene
    EIF2AK12  EIF2AK42  EIF2AK22  
    5 SIMAP similar genes for EIF2AK3 using alignment to 3 protein entries:     E2AK3_HUMAN (see all proteins):
    DKFZp781H1925    MAPK8    STK11    CAMK1    NUAK1

    Find genes that share paralogs with EIF2AK3           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for EIF2AK3 (see all 1198)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 2 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0114084
    Wolcott-Rallison syndrome (WRS)4--see VAR_0114082 R Q mis40--------
    rs1825755831,2
    --88638807(+) AGATTG/TTGTCT 1 -- ds50010--------
    rs1463384421,2
    --88638839(+) CCCAGA/CCTGCC 1 -- ds50010--------
    rs1389987461,2
    C--88638856(+) CTCGAC/TGTGGC 1 -- ds50010--------
    rs1854589711,2
    --88638879(+) CACCTC/TGGTAT 1 -- ds50010--------
    rs1493297031,2
    --88638925(+) AGAGCG/TCTCCC 1 -- ds50010--------
    rs1445761591,2
    --88639028(+) GGCCTA/GCCAAG 1 -- ds50010--------
    rs130181711,2
    C,F,H--88639044(+) GGGAAA/GTGATG 1 -- ds500116Minor allele frequency- G:0.21NS EA NA 2220
    rs339574021,2
    C,F--88639180(-) TGACTC/GTTATT 1 -- ds50016Minor allele frequency- G:0.25NA WA EA 364
    rs1895904671,2
    --88639278(+) ACCAAC/TCCAAA 1 -- ut310--------

    HapMap Linkage Disequilibrium report for EIF2AK3 (88856259 - 88927094 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 4 variations for EIF2AK3:    About this table    
    Variant IDTypeSubtypePubMed ID
    dgv61n16CNV Deletion17901297
    nsv507022CNV Insertion20534489
    nsv874582CNV Gain21882294
    nsv470476CNV Gain18288195

    Human Gene Mutation Database (HGMD): EIF2AK3
    Locus Specific Mutation Databases (LSDB): EIF2AK3

    Site Specific Mutation Identification with PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 604032   
    OMIM disorders: 226980  
    UniProtKB/Swiss-Prot: E2AK3_HUMAN, Q9NZJ5
  • 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. Note=The disease is caused by mutations affecting the gene
    represented in this entry

  • 2 diseases for EIF2AK3:    
    About MalaCards
    epiphyseal dysplasia multiple with early-onset diabetes mellitus    brain ischemia

    2 diseases from the University of Copenhagen DISEASES database for EIF2AK3:
    Cancer     Myopia

    Find genes that share disorders with EIF2AK3           About GenesLikeMe

    Selected Novoseek inferred disease relationships for EIF2AK3 gene (see all 18)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    wolcott-rallison syndrome 92.6 14 16813601 (2), 12475790 (1), 16972080 (1), 18704764 (1) (see all 9)
    tumors 36.3 33 18451152 (2), 15483017 (2), 16009947 (2), 16452230 (2) (see all 19)
    cancer 30.4 12 19396842 (2), 16983702 (1), 18193422 (1), 16792545 (1) (see all 6)
    melanoma 25.6 5 16254105 (4), 18794803 (1)
    breast cancer 24.1 2 14613031 (1), 20371724 (1)
    brain ischemia 23.5 1 11823711 (1)
    ovarian carcinoma 21 2 16191507 (2)
    solid tumor 18.6 1 16494928 (1)
    malignant mesothelioma 12.1 1 16517979 (1)
    leukemia 10.5 1 17548474 (1)

    Genetic Association Database (GAD): EIF2AK3
    Human Genome Epidemiology (HuGE) Navigator: EIF2AK3 (5 documents)

    Export disorders for EIF2AK3 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for EIF2AK3 gene, integrated from 10 sources (see all 322):
    (articles sorted by number of sources associating them with EIF2AK3)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Characterization of a mutant pancreatic eIF-2alpha kinase, PEK, and co-localization with somatostatin in islet delta cells. (PubMed id 10026192)1, 2, 3, 9 Shi Y....Yang N.N. (J. Biol. Chem. 1999)
    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. (PubMed id 10677345)1, 2, 9 Sood R.... Wek R.C. (Biochem. J. 2000)
    3. EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome. (PubMed id 10932183)1, 2, 9 Delepine M....Julier C. (Nat. Genet. 2000)
    4. PARP16 is a tail-anchored endoplasmic reticulum protein required for the PERK-and IRE1alpha-mediated unfolded protein response. (PubMed id 23103912)1, 2 Jwa M. and Chang P. (Nat. Cell Biol. 2012)
    5. H2s-induced sulfhydration of the phosphatase PTP1B and its role in the endoplasmic reticulum stress response. (PubMed id 22169477)1, 2 Krishnan N.... Tonks N.K. (Sci. Signal. 2011)
    6. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. (PubMed id 21685912)1, 4 HAPglinger G.U....Schellenberg G.D. (Nat. Genet. 2011)
    7. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PubMed id 20379614)1, 4 Rose J.E....Uhl G.R. (Mol. Med. 2010)
    8. Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study. (PubMed id 20800603)1, 4 Flachsbart F....Nebel A. (Mutat. Res. 2010)
    9. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PubMed id 20628086)1, 4 Bailey S.D....Anand S. (Diabetes Care 2010)
    10. Hundreds of variants clustered in genomic loci and biological pathways affect human height. (PubMed id 20881960)1, 4 Lango Allen H....Hirschhorn J.N. (Nature 2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 9451 HGNC: 3255 AceView: EIF2AK3 Ensembl:ENSG00000172071 euGenes: HUgn9451
    ECgene: EIF2AK3 Kegg: 9451 H-InvDB: EIF2AK3

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for EIF2AK3 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for EIF2AK3 Genetics and Cytogenetics in Oncology and Haematology
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=EIF2AK3[genesymbol]

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for EIF2AK3 gene:
    Search GeneIP for patents involving EIF2AK3

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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