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Gene Review

EIF2AK3  -  eukaryotic translation initiation factor 2...

Homo sapiens

Synonyms: Eukaryotic translation initiation factor 2-alpha kinase 3, HsPEK, PEK, PERK, PRKR-like endoplasmic reticulum kinase, ...
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Disease relevance of EIF2AK3

  • Using recombinant PEK produced in Escherichia coli or Sf-9 insect cells, we demonstrate that PEK is autophosphorylated on both serine and threonine residues and that the recombinant enzyme can specifically phosphorylate eIF-2alpha on serine-51 [1].
  • Pancreata of Perk(-/-) mice are morphologically and functionally normal at birth, but the islets of Langerhans progressively degenerate, resulting in loss of insulin-secreting beta cells and development of diabetes mellitus, followed later by loss of glucagon-secreting alpha cells [2].
  • RCGP WRS may give the most reliable prevalence figures for musculoskeletal and other chronic diseases [3].

High impact information on EIF2AK3

  • Here, we show that tumors derived from K-Ras-transformed Perk(-/-) mouse embryonic fibroblasts (MEFs) are smaller and exhibit less angiogenesis than tumors with an intact ISR [4].
  • This analysis revealed that a subset of proangiogenic transcripts is preferentially translated in a Perk-dependent manner; these transcripts include VCIP, an adhesion molecule that promotes cellular adhesion, integrin binding, and capillary morphogenesis [4].
  • Northern blot analyses indicate that PEK mRNA is expressed in all tissues examined, with highest levels in pancreas cells [1].
  • The addition of recombinant PEK to reticulocyte lysates caused a dose-dependent inhibition of translation [1].
  • In addition to a catalytic domain with sequence and structural features conserved among eIF-2alpha kinases, PEK contains a distinctive amino-terminal region 550 residues in length [1].

Biological context of EIF2AK3


Anatomical context of EIF2AK3


Associations of EIF2AK3 with chemical compounds

  • Sequencing analysis of her EIF2AK3 gene revealed the presence of a homozygous T to C exchange in exon 13 leading to the missense serine 877 proline mutation [6].
  • We describe the characterization of two regions in the ER luminal portion of the transmembrane PEK that carry out distinct functions in the regulation of this eIF2 kinase [8].
  • The international review board was set up as the scientific advisory body of the Swiss Complementary Medicine Evaluation Programme (PEK) in 2002 [12].
  • The use of bethanechol during RT for HNC cancer was associated with significantly higher WRS immediately after RT (p=0.03) in comparison to a similar cohort of patients who had not received bethanechol [13].

Regulatory relationships of EIF2AK3

  • We show that human PEK is regulated by different mechanisms than PKR or HRI [10].

Other interactions of EIF2AK3

  • ER luminal sequences flanking the transmembrane domain are required for GRP78 interaction, and deletion of this portion of PEK led to its activation even in the absence of ER stress [8].
  • Permanent diabetes of non autoimmune origin can present up to 6 months from birth in individuals with KCNJ11 and EIF2AK3 mutations [14].

Analytical, diagnostic and therapeutic context of EIF2AK3

  • We have identified a novel mutation in EIF2AK3, and prenatal diagnosis may now be offered to affected families [15].
  • Results of the Prospective Evaluation of Radial Keratotomy (PERK) Study 4 years after surgery for myopia. Perk Study Group [16].
  • These observations were corroborated by a microarray analysis of polysome-bound RNA in aerobic and hypoxic Perk(+/+) and Perk(-/-) MEFs [4].
  • Within the framework of the Swiss governmental Program of Evaluation of Complementary Medicine (PEK) we assessed the prevalence, use, perceived effectiveness and appreciation of complementary medicine (CAM) in Switzerland, according to published surveys [17].


  1. Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control. Shi, Y., Vattem, K.M., Sood, R., An, J., Liang, J., Stramm, L., Wek, R.C. Mol. Cell. Biol. (1998) [Pubmed]
  2. The PERK eukaryotic initiation factor 2 alpha kinase is required for the development of the skeletal system, postnatal growth, and the function and viability of the pancreas. Zhang, P., McGrath, B., Li, S., Frank, A., Zambito, F., Reinert, J., Gannon, M., Ma, K., McNaughton, K., Cavener, D.R. Mol. Cell. Biol. (2002) [Pubmed]
  3. Measuring disease prevalence: a comparison of musculoskeletal disease using four general practice consultation databases. Jordan, K., Clarke, A.M., Symmons, D.P., Fleming, D., Porcheret, M., Kadam, U.T., Croft, P. The British journal of general practice : the journal of the Royal College of General Practitioners (2007) [Pubmed]
  4. Perk-dependent translational regulation promotes tumor cell adaptation and angiogenesis in response to hypoxic stress. Blais, J.D., Addison, C.L., Edge, R., Falls, T., Zhao, H., Wary, K., Koumenis, C., Harding, H.P., Ron, D., Holcik, M., Bell, J.C. Mol. Cell. Biol. (2006) [Pubmed]
  5. Wolcott-Rallison Syndrome: clinical, genetic, and functional study of EIF2AK3 mutations and suggestion of genetic heterogeneity. Senée, V., Vattem, K.M., Delépine, M., Rainbow, L.A., Haton, C., Lecoq, A., Shaw, N.J., Robert, J.J., Rooman, R., Diatloff-Zito, C., Michaud, J.L., Bin-Abbas, B., Taha, D., Zabel, B., Franceschini, P., Topaloglu, A.K., Lathrop, G.M., Barrett, T.G., Nicolino, M., Wek, R.C., Julier, C. Diabetes (2004) [Pubmed]
  6. Loss of kinase activity in a patient with Wolcott-Rallison syndrome caused by a novel mutation in the EIF2AK3 gene. Biason-Lauber, A., Lang-Muritano, M., Vaccaro, T., Schoenle, E.J. Diabetes (2002) [Pubmed]
  7. Assignment of pancreatic eIF-2alpha kinase (EIF2AK3) to human chromosome band 2p12 by radiation hybrid mapping and in situ hybridization. Hayes, S.E., Conner, L.J., Stramm, L.E., Shi, Y. Cytogenet. Cell Genet. (1999) [Pubmed]
  8. Dimerization and release of molecular chaperone inhibition facilitate activation of eukaryotic initiation factor-2 kinase in response to endoplasmic reticulum stress. Ma, K., Vattem, K.M., Wek, R.C. J. Biol. Chem. (2002) [Pubmed]
  9. PERK EIF2AK3 control of pancreatic beta cell differentiation and proliferation is required for postnatal glucose homeostasis. Zhang, W., Feng, D., Li, Y., Iida, K., McGrath, B., Cavener, D.R. Cell metabolism (2006) [Pubmed]
  10. Characterization of a mutant pancreatic eIF-2alpha kinase, PEK, and co-localization with somatostatin in islet delta cells. Shi, Y., An, J., Liang, J., Hayes, S.E., Sandusky, G.E., Stramm, L.E., Yang, N.N. J. Biol. Chem. (1999) [Pubmed]
  11. The perineorectal reflex The perineorectal reflex in health and obstructed defecation. Gosselink, M.J., Schouten, W.R. Dis. Colon Rectum (2002) [Pubmed]
  12. Summary consensus statement of the Review Board of the Swiss Complementary Medicine Evaluation Programme, (Programme Evaluation Komplementärmedizin, PEK) regarding the PEK process and products. Walach, H., Linde, K., Eichenberger, R., Stalder, H., Børlum Kristensen, F., Kleijnen, J. Homeopathy : the journal of the Faculty of Homeopathy. (2006) [Pubmed]
  13. A randomized phase III prospective trial of bethanechol to prevent radiotherapy-induced salivary gland damage in patients with head and neck cancer. Jham, B.C., Teixeira, I.V., Aboud, C.G., Carvalho, A.L., Coelho, M.d.e. .M., Freire, A.R. Oral Oncol. (2007) [Pubmed]
  14. KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes. Massa, O., Iafusco, D., D'Amato, E., Gloyn, A.L., Hattersley, A.T., Pasquino, B., Tonini, G., Dammacco, F., Zanette, G., Meschi, F., Porzio, O., Bottazzo, G., Crinó, A., Lorini, R., Cerutti, F., Vanelli, M., Barbetti, F. Hum. Mutat. (2005) [Pubmed]
  15. Wolcott-Rallison syndrome: a clinical and genetic study of three children, novel mutation in EIF2AK3 and a review of the literature. Iyer, S., Korada, M., Rainbow, L., Kirk, J., Brown, R.M., Shaw, N., Barrett, T.G. Acta Paediatr. (2004) [Pubmed]
  16. Results of the Prospective Evaluation of Radial Keratotomy (PERK) Study 4 years after surgery for myopia. Perk Study Group. Waring, G.O., Lynn, M.J., Fielding, B., Asbell, P.A., Balyeat, H.D., Cohen, E.A., Culbertson, W., Doughman, D.J., Fecko, P., McDonald, M.B. JAMA (1990) [Pubmed]
  17. Use of complementary medicine in Switzerland. Wolf, U., Maxion-Bergemann, S., Bornhoft, G., Matthiessen, P.F., Wolf, M. Forschende Komplementärmedizin (2006) (2006) [Pubmed]
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