EIF2AK3: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''Eukaryotic translation initiation factor 2-alpha kinase 3''', also known as '''protein kinase R (PKR)-like endoplasmic reticulum kinase''' ('''PERK'''), is an [[enzyme]] that in humans is encoded by the ''EIF2AK3'' [[gene]].<ref name="pmid9819435">{{cite journal | vauthors = Shi Y, Vattem KM, Sood R, An J, Liang J, Stramm L, Wek RC | title = Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control | journal = Mol. Cell. Biol. | volume = 18 | issue = 12 | pages = 7499–509  | date = Dec 1998 | pmid = 9819435 | pmc = 109330 | doi = 10.1128/MCB.18.12.7499 }}</ref><ref name="pmid9930704">{{cite journal | vauthors = Harding HP, Zhang Y, Ron D | title = Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase | journal = Nature | volume = 397 | issue = 6716 | pages = 271–4  | date = Jan 21, 1999 | pmid = 9930704 | pmc =  | doi =  10.1038/16729}}</ref><ref name="pmid10575235">{{cite journal | vauthors = Hayes SE, Conner LJ, Stramm LE, Shi Y | title = Assignment of pancreatic eIF-2alpha kinase (EIF2AK3) to human chromosome band 2p12 by radiation hybrid mapping and in situ hybridization | journal = Cytogenet. Cell Genet. | volume = 86 | issue = 3-4 | pages = 327–8 | year = 1999 | pmid = 10575235 | pmc = | doi = 10.1159/000015328 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: EIF2AK3 eukaryotic translation initiation factor 2-alpha kinase 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9451| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Eukaryotic translation initiation factor 2-alpha kinase 3
| HGNCid = 3255
| Symbol = EIF2AK3
| AltSymbols =; WRS; DKFZp781H1925; PEK; PERK
| OMIM = 604032
| ECnumber = 
| Homologene = 3557
| MGIid = 1341830
| GeneAtlas_image1 = PBB_GE_EIF2AK3_218696_at_tn.png
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0004694 |text = eukaryotic translation initiation factor 2alpha kinase activity}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0016740 |text = transferase activity}} {{GNF_GO|id=GO:0042802 |text = identical protein binding}}
| Component = {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0005783 |text = endoplasmic reticulum}} {{GNF_GO|id=GO:0005789 |text = endoplasmic reticulum membrane}} {{GNF_GO|id=GO:0016020 |text = membrane}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}}
| Process = {{GNF_GO|id=GO:0002063 |text = chondrocyte development}} {{GNF_GO|id=GO:0006919 |text = caspase activation}} {{GNF_GO|id=GO:0006926 |text = virus-infected cell apoptosis}} {{GNF_GO|id=GO:0006983 |text = ER overload response}} {{GNF_GO|id=GO:0007029 |text = endoplasmic reticulum organization and biogenesis}} {{GNF_GO|id=GO:0017148 |text = negative regulation of protein biosynthetic process}} {{GNF_GO|id=GO:0019722 |text = calcium-mediated signaling}} {{GNF_GO|id=GO:0030073 |text = insulin secretion}} {{GNF_GO|id=GO:0030282 |text = bone mineralization}} {{GNF_GO|id=GO:0030968 |text = unfolded protein response}} {{GNF_GO|id=GO:0031018 |text = endocrine pancreas development}} {{GNF_GO|id=GO:0031642 |text = negative regulation of myelination}} {{GNF_GO|id=GO:0032057 |text = negative regulation of translation initiation in response to stress}} {{GNF_GO|id=GO:0032092 |text = positive regulation of protein binding}} {{GNF_GO|id=GO:0046777 |text = protein amino acid autophosphorylation}} {{GNF_GO|id=GO:0048009 |text = insulin-like growth factor receptor signaling pathway}} {{GNF_GO|id=GO:0051260 |text = protein homooligomerization}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 9451
    | Hs_Ensembl = ENSG00000172071
    | Hs_RefseqProtein = NP_004827
    | Hs_RefseqmRNA = NM_004836
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 2
    | Hs_GenLoc_start = 88637376
    | Hs_GenLoc_end = 88707907
    | Hs_Uniprot = Q9NZJ5
    | Mm_EntrezGene = 13666
    | Mm_Ensembl = ENSMUSG00000031668
    | Mm_RefseqmRNA = XM_988416
    | Mm_RefseqProtein = XP_993510
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 6
    | Mm_GenLoc_start = 70774094
    | Mm_GenLoc_end = 70834818
    | Mm_Uniprot = Q7TQC8
  }}
}}
'''Eukaryotic translation initiation factor 2-alpha kinase 3''', also known as '''EIF2AK3''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: EIF2AK3 eukaryotic translation initiation factor 2-alpha kinase 3| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9451| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
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 [[proteopathy|malfolded proteins]].<ref name="pmid9930704" />
{{PBB_Summary
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| summary_text =
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==References==
== Clinical significance ==
{{reflist|2}}
 
==Further reading==
Patients with mutations in this gene develop [[Wolcott-Rallison syndrome]].<ref name="pmid18500571">{{cite journal | vauthors = Søvik O, Njølstad PR, Jellum E, Molven A | title = Wolcott-Rallison syndrome with 3-hydroxydicarboxylic aciduria and lethal outcome | journal = J. Inherit. Metab. Dis. | volume = 31 Suppl 2 | issue =  | pages = S293-7  | date = May 2008 | pmid = 18500571 | doi = 10.1007/s10545-008-0866-1 }}</ref>
 
== Interactions ==
 
EIF2AK3 has been shown to [[Protein-protein interaction|interact]] with [[DNAJC3]]<ref name="pmid12446838">{{cite journal | vauthors = Yan W, Frank CL, Korth MJ, Sopher BL, Novoa I, Ron D, Katze MG | title = Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPK | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 99 | issue = 25 | pages = 15920–5  | date = December 2002 | pmid = 12446838 | pmc = 138540 | doi = 10.1073/pnas.252341799 }}</ref> and [[NFE2L2]].<ref name="pmid14517290">{{cite journal | vauthors = Cullinan SB, Zhang D, Hannink M, Arvisais E, Kaufman RJ, Diehl JA | title = Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival | journal = Mol. Cell. Biol. | volume = 23 | issue = 20 | pages = 7198–209  | date = October 2003 | pmid = 14517290 | pmc = 230321 | doi = 10.1128/MCB.23.20.7198-7209.2003 }}</ref>
 
==Inhibitors==
* [[GSK2606414]]
* 3-Fluoro-GSK2606414
 
== References ==
{{reflist}}
{{Clear}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Mellor H, Proud CG | title = A synthetic peptide substrate for initiation factor-2 kinases | journal = Biochem. Biophys. Res. Commun. | volume = 178 | issue = 2 | pages = 430–7 | year = 1991 | pmid = 1677563 | doi = 10.1016/0006-291X(91)90125-Q }}
| citations =
* {{cite journal | vauthors = Dever TE, Chen JJ, Barber GN, Cigan AM, Feng L, Donahue TF, London IM, Katze MG, Hinnebusch AG | title = Mammalian eukaryotic initiation factor 2 alpha kinases functionally substitute for GCN2 protein kinase in the GCN4 translational control mechanism of yeast | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 90 | issue = 10 | pages = 4616–20 | year = 1993 | pmid = 8099443 | pmc = 46563 | doi = 10.1073/pnas.90.10.4616 }}
*{{cite journal | author=Mellor H, Proud CG |title=A synthetic peptide substrate for initiation factor-2 kinases. |journal=Biochem. Biophys. Res. Commun. |volume=178 |issue= 2 |pages= 430-7 |year= 1991 |pmid= 1677563 |doi= }}
* {{cite journal | vauthors = Shi Y, Vattem KM, Sood R, An J, Liang J, Stramm L, Wek RC | title = Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control | journal = Mol. Cell. Biol. | volume = 18 | issue = 12 | pages = 7499–509 | year = 1998 | pmid = 9819435 | pmc = 109330 | doi =  10.1128/MCB.18.12.7499}}
*{{cite journal | author=Dever TE, Chen JJ, Barber GN, ''et al.'' |title=Mammalian eukaryotic initiation factor 2 alpha kinases functionally substitute for GCN2 protein kinase in the GCN4 translational control mechanism of yeast. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=90 |issue= 10 |pages= 4616-20 |year= 1993 |pmid= 8099443 |doi= }}
* {{cite journal | vauthors = Sood R, Porter AC, Ma K, Quilliam LA, Wek RC | title = 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 | journal = Biochem. J. | volume = 346 | issue = 2 | pages = 281–93 | year = 2000 | pmid = 10677345 | pmc = 1220852 | doi = 10.1042/0264-6021:3460281 }}
*{{cite journal | author=Shi Y, Vattem KM, Sood R, ''et al.'' |title=Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control. |journal=Mol. Cell. Biol. |volume=18 |issue= 12 |pages= 7499-509 |year= 1998 |pmid= 9819435 |doi=  }}
* {{cite journal | vauthors = Delépine M, Nicolino M, Barrett T, Golamaully M, Lathrop GM, Julier C | title = EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome | journal = Nat. Genet. | volume = 25 | issue = 4 | pages = 406–9 | year = 2000 | pmid = 10932183 | doi = 10.1038/78085 }}
*{{cite journal | author=Shi Y, An J, Liang J, ''et al.'' |title=Characterization of a mutant pancreatic eIF-2alpha kinase, PEK, and co-localization with somatostatin in islet delta cells. |journal=J. Biol. Chem. |volume=274 |issue= 9 |pages= 5723-30 |year= 1999 |pmid= 10026192 |doi= }}
* {{cite journal | vauthors = Saelens X, Kalai M, Vandenabeele P | title = Translation inhibition in apoptosis: caspase-dependent PKR activation and eIF2-alpha phosphorylation | journal = J. Biol. Chem. | volume = 276 | issue = 45 | pages = 41620–8 | year = 2001 | pmid = 11555640 | doi = 10.1074/jbc.M103674200 }}
*{{cite journal | author=Hayes SE, Conner LJ, Stramm LE, Shi Y |title=Assignment of pancreatic eIF-2alpha kinase (EIF2AK3) to human chromosome band 2p12 by radiation hybrid mapping and in situ hybridization. |journal=Cytogenet. Cell Genet. |volume=86 |issue= 3-4 |pages= 327-8 |year= 2000 |pmid= 10575235 |doi= }}
* {{cite journal | vauthors = Ma K, Vattem KM, Wek RC | title = Dimerization and release of molecular chaperone inhibition facilitate activation of eukaryotic initiation factor-2 kinase in response to endoplasmic reticulum stress | journal = J. Biol. Chem. | volume = 277 | issue = 21 | pages = 18728–35 | year = 2002 | pmid = 11907036 | doi = 10.1074/jbc.M200903200 }}
*{{cite journal | author=Sood R, Porter AC, Ma K, ''et al.'' |title=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. |journal=Biochem. J. |volume=346 Pt 2 |issue= |pages= 281-93 |year= 2000 |pmid= 10677345 |doi= }}
* {{cite journal | vauthors = Okada T, Yoshida H, Akazawa R, Negishi M, Mori K | title = Distinct roles of activating transcription factor 6 (ATF6) and double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK) in transcription during the mammalian unfolded protein response | journal = Biochem. J. | volume = 366 | issue = Pt 2 | pages = 585–94 | year = 2002 | pmid = 12014989 | pmc = 1222788 | doi = 10.1042/BJ20020391 }}
*{{cite journal | author=Delépine M, Nicolino M, Barrett T, ''et al.'' |title=EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome. |journal=Nat. Genet. |volume=25 |issue= 4 |pages= 406-9 |year= 2000 |pmid= 10932183 |doi= 10.1038/78085 }}
* {{cite journal | vauthors = Biason-Lauber A, Lang-Muritano M, Vaccaro T, Schoenle EJ | title = Loss of kinase activity in a patient with Wolcott-Rallison syndrome caused by a novel mutation in the EIF2AK3 gene | journal = Diabetes | volume = 51 | issue = 7 | pages = 2301–5 | year = 2002 | pmid = 12086964 | doi = 10.2337/diabetes.51.7.2301 }}
*{{cite journal | author=Saelens X, Kalai M, Vandenabeele P |title=Translation inhibition in apoptosis: caspase-dependent PKR activation and eIF2-alpha phosphorylation. |journal=J. Biol. Chem. |volume=276 |issue= 45 |pages= 41620-8 |year= 2001 |pmid= 11555640 |doi= 10.1074/jbc.M103674200 }}
* {{cite journal | vauthors = Koumenis C, Naczki C, Koritzinsky M, Rastani S, Diehl A, Sonenberg N, Koromilas A, Wouters BG | title = Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2alpha | journal = Mol. Cell. Biol. | volume = 22 | issue = 21 | pages = 7405–16 | year = 2002 | pmid = 12370288 | pmc = 135664 | doi = 10.1128/MCB.22.21.7405-7416.2002 }}
*{{cite journal | author=Ma K, Vattem KM, Wek RC |title=Dimerization and release of molecular chaperone inhibition facilitate activation of eukaryotic initiation factor-2 kinase in response to endoplasmic reticulum stress. |journal=J. Biol. Chem. |volume=277 |issue= 21 |pages= 18728-35 |year= 2002 |pmid= 11907036 |doi= 10.1074/jbc.M200903200 }}
* {{cite journal | vauthors = Marcu MG, Doyle M, Bertolotti A, Ron D, Hendershot L, Neckers L | title = Heat shock protein 90 modulates the unfolded protein response by stabilizing IRE1alpha | journal = Mol. Cell. Biol. | volume = 22 | issue = 24 | pages = 8506–13 | year = 2002 | pmid = 12446770 | pmc = 139892 | doi = 10.1128/MCB.22.24.8506-8513.2002 }}
*{{cite journal | author=Okada T, Yoshida H, Akazawa R, ''et al.'' |title=Distinct roles of activating transcription factor 6 (ATF6) and double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK) in transcription during the mammalian unfolded protein response. |journal=Biochem. J. |volume=366 |issue= Pt 2 |pages= 585-94 |year= 2002 |pmid= 12014989 |doi= 10.1042/BJ20020391 }}
* {{cite journal | vauthors = Yan W, Frank CL, Korth MJ, Sopher BL, Novoa I, Ron D, Katze MG | title = Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPK | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 99 | issue = 25 | pages = 15920–5 | year = 2002 | pmid = 12446838 | pmc = 138540 | doi = 10.1073/pnas.252341799 }}
*{{cite journal | author=Biason-Lauber A, Lang-Muritano M, Vaccaro T, Schoenle EJ |title=Loss of kinase activity in a patient with Wolcott-Rallison syndrome caused by a novel mutation in the EIF2AK3 gene. |journal=Diabetes |volume=51 |issue= 7 |pages= 2301-5 |year= 2002 |pmid= 12086964 |doi= }}
* {{cite journal | vauthors = Pavio N, Romano PR, Graczyk TM, Feinstone SM, Taylor DR | title = Protein synthesis and endoplasmic reticulum stress can be modulated by the hepatitis C virus envelope protein E2 through the eukaryotic initiation factor 2alpha kinase PERK | journal = J. Virol. | volume = 77 | issue = 6 | pages = 3578–85 | year = 2003 | pmid = 12610133 | pmc = 149509 | doi = 10.1128/JVI.77.6.3578-3585.2003 }}
*{{cite journal | author=Koumenis C, Naczki C, Koritzinsky M, ''et al.'' |title=Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2alpha. |journal=Mol. Cell. Biol. |volume=22 |issue= 21 |pages= 7405-16 |year= 2002 |pmid= 12370288 |doi= }}
* {{cite journal | vauthors = Cullinan SB, Zhang D, Hannink M, Arvisais E, Kaufman RJ, Diehl JA | title = Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival | journal = Mol. Cell. Biol. | volume = 23 | issue = 20 | pages = 7198–209 | year = 2003 | pmid = 14517290 | pmc = 230321 | doi = 10.1128/MCB.23.20.7198-7209.2003 }}
*{{cite journal | author=Marcu MG, Doyle M, Bertolotti A, ''et al.'' |title=Heat shock protein 90 modulates the unfolded protein response by stabilizing IRE1alpha. |journal=Mol. Cell. Biol. |volume=22 |issue= 24 |pages= 8506-13 |year= 2003 |pmid= 12446770 |doi= }}
* {{cite journal | vauthors = Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, Li Y, Xu C, Fang R, Guegler K, Rao MS, Mandalam R, Lebkowski J, Stanton LW | title = Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation | journal = Nat. Biotechnol. | volume = 22 | issue = 6 | pages = 707–16 | year = 2004 | pmid = 15146197 | doi = 10.1038/nbt971 }}
*{{cite journal | author=Yan W, Frank CL, Korth MJ, ''et al.'' |title=Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPK. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 25 |pages= 15920-5 |year= 2003 |pmid= 12446838 |doi= 10.1073/pnas.252341799 }}
* {{cite journal | vauthors = Senée V, Vattem KM, Delépine M, Rainbow LA, Haton C, Lecoq A, Shaw NJ, Robert JJ, Rooman R, Diatloff-Zito C, Michaud JL, Bin-Abbas B, Taha D, Zabel B, Franceschini P, Topaloglu AK, Lathrop GM, Barrett TG, Nicolino M, Wek RC, Julier C | title = Wolcott-Rallison Syndrome: clinical, genetic, and functional study of EIF2AK3 mutations and suggestion of genetic heterogeneity | journal = Diabetes | volume = 53 | issue = 7 | pages = 1876–83 | year = 2004 | pmid = 15220213 | doi = 10.2337/diabetes.53.7.1876 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Allotey RA, Mohan V, McDermott MF, Deepa R, Premalatha G, Hassan Z, Cassell PG, North BV, Vaxillaire M, Mein CA, Swan DC, O'Grady E, Ramachandran A, Snehalatha C, Sinnot PJ, Hemmatpour SK, Froguel P, Hitman GA | title = The EIF2AK3 gene region and type I diabetes in subjects from South India | journal = Genes Immun. | volume = 5 | issue = 8 | pages = 648–52 | year = 2004 | pmid = 15483661 | doi = 10.1038/sj.gene.6364139 }}
*{{cite journal | author=Pavio N, Romano PR, Graczyk TM, ''et al.'' |title=Protein synthesis and endoplasmic reticulum stress can be modulated by the hepatitis C virus envelope protein E2 through the eukaryotic initiation factor 2alpha kinase PERK. |journal=J. Virol. |volume=77 |issue= 6 |pages= 3578-85 |year= 2003 |pmid= 12610133 |doi= }}
*{{cite journal | author=Cullinan SB, Zhang D, Hannink M, ''et al.'' |title=Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival. |journal=Mol. Cell. Biol. |volume=23 |issue= 20 |pages= 7198-209 |year= 2003 |pmid= 14517290 |doi=  }}
*{{cite journal  | author=Brandenberger R, Wei H, Zhang S, ''et al.'' |title=Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. |journal=Nat. Biotechnol. |volume=22 |issue= 6 |pages= 707-16 |year= 2005 |pmid= 15146197 |doi= 10.1038/nbt971 }}
*{{cite journal  | author=Senée V, Vattem KM, Delépine M, ''et al.'' |title=Wolcott-Rallison Syndrome: clinical, genetic, and functional study of EIF2AK3 mutations and suggestion of genetic heterogeneity. |journal=Diabetes |volume=53 |issue= 7 |pages= 1876-83 |year= 2004 |pmid= 15220213 |doi=  }}
*{{cite journal  | author=Allotey RA, Mohan V, McDermott MF, ''et al.'' |title=The EIF2AK3 gene region and type I diabetes in subjects from South India. |journal=Genes Immun. |volume=5 |issue= 8 |pages= 648-52 |year= 2005 |pmid= 15483661 |doi= 10.1038/sj.gene.6364139 }}
}}
{{refend}}
{{refend}}


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Latest revision as of 00:23, 31 August 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Wikidata
View/Edit Human

Eukaryotic translation initiation factor 2-alpha kinase 3, also known as protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), is an enzyme that in humans is encoded by the EIF2AK3 gene.[1][2][3][4]

Function

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.[2]

Clinical significance

Patients with mutations in this gene develop Wolcott-Rallison syndrome.[5]

Interactions

EIF2AK3 has been shown to interact with DNAJC3[6] and NFE2L2.[7]

Inhibitors

References

  1. ↑ Shi Y, Vattem KM, Sood R, An J, Liang J, Stramm L, Wek RC (Dec 1998). "Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control". Mol. Cell. Biol. 18 (12): 7499–509. doi:10.1128/MCB.18.12.7499. PMC 109330. PMID 9819435.
  2. ↑ 2.0 2.1 Harding HP, Zhang Y, Ron D (Jan 21, 1999). "Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase". Nature. 397 (6716): 271–4. doi:10.1038/16729. PMID 9930704.
  3. ↑ Hayes SE, Conner LJ, Stramm LE, Shi Y (1999). "Assignment of pancreatic eIF-2alpha kinase (EIF2AK3) to human chromosome band 2p12 by radiation hybrid mapping and in situ hybridization". Cytogenet. Cell Genet. 86 (3–4): 327–8. doi:10.1159/000015328. PMID 10575235.
  4. ↑ "Entrez Gene: EIF2AK3 eukaryotic translation initiation factor 2-alpha kinase 3".
  5. ↑ Søvik O, Njølstad PR, Jellum E, Molven A (May 2008). "Wolcott-Rallison syndrome with 3-hydroxydicarboxylic aciduria and lethal outcome". J. Inherit. Metab. Dis. 31 Suppl 2: S293–7. doi:10.1007/s10545-008-0866-1. PMID 18500571.
  6. ↑ Yan W, Frank CL, Korth MJ, Sopher BL, Novoa I, Ron D, Katze MG (December 2002). "Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPK". Proc. Natl. Acad. Sci. U.S.A. 99 (25): 15920–5. doi:10.1073/pnas.252341799. PMC 138540. PMID 12446838.
  7. ↑ Cullinan SB, Zhang D, Hannink M, Arvisais E, Kaufman RJ, Diehl JA (October 2003). "Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival". Mol. Cell. Biol. 23 (20): 7198–209. doi:10.1128/MCB.23.20.7198-7209.2003. PMC 230321. PMID 14517290.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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