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{
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"name": {
"name": "The Luminal domain, a dimerization domain, of the Serine/Threonine protein kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3",
"short": "Luminal_EIF2AK3"
},
"description": [
{
"text": "<p>The Luminal domain is a dimerization domain present in eukaryotic translation Initiation Factor 2-Alpha Kinase 3 (EIF2AK3), also called PKR-like Endoplasmic Reticulum Kinase (PERK). EIF2AK3 is a serine/threonine protein kinase (STK) and a type I transmembrane protein that is localized in the endoplasmic reticulum (ER). As a EIF2AK, it phosphorylates the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis: General Control Non-derepressible-2 (GCN2), protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PERK. PERK contains a luminal domain bound with the chaperone BiP under unstressed conditions and a cytoplasmic catalytic kinase domain. In response to the accumulation of misfolded or unfolded proteins in the ER, PERK is activated through the release of BiP, allowing it to dimerize through its luminal domain and autophosphorylate. It functions as the central regulator of translational control during the Unfolded Protein Response (UPR) pathway. In addition to the eIF-2 alpha subunit, PERK also phosphorylates Nrf2, a leucine zipper transcription factor which regulates cellular redox status and promotes cell survival during the UPR. [[cite:PUB00125141], [cite:PUB00125142], [cite:PUB00125143], [cite:PUB00125144], [cite:PUB00125145], [cite:PUB00125146], [cite:PUB00125147], [cite:PUB00125148], [cite:PUB00125149], [cite:PUB00125150], [cite:PUB00125151], [cite:PUB00125152], [cite:PUB00125153], [cite:PUB00125154], [cite:PUB00125155], [cite:PUB00125156], [cite:PUB00125157], [cite:PUB00125158]]</p>",
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"PUB00125141": {
"PMID": 11907036,
"ISBN": null,
"volume": "277",
"issue": "21",
"year": 2002,
"title": "Dimerization and release of molecular chaperone inhibition facilitate activation of eukaryotic initiation factor-2 kinase in response to endoplasmic reticulum stress.",
"URL": null,
"raw_pages": "18728-35",
"medline_journal": "J Biol Chem",
"ISO_journal": "J Biol Chem",
"authors": [
"Ma K",
"Vattem KM",
"Wek RC."
],
"DOI_URL": null
},
"PUB00125157": {
"PMID": 17377498,
"ISBN": null,
"volume": "6",
"issue": "7",
"year": 2007,
"title": "Switch between apoptosis and autophagy: radiation-induced endoplasmic reticulum stress?",
"URL": null,
"raw_pages": "793-8",
"medline_journal": "Cell Cycle",
"ISO_journal": "Cell Cycle",
"authors": [
"Moretti L",
"Cha YI",
"Niermann KJ",
"Lu B."
],
"DOI_URL": null
},
"PUB00125148": {
"PMID": 17141632,
"ISBN": null,
"volume": "4",
"issue": "6",
"year": 2006,
"title": "PERK EIF2AK3 control of pancreatic beta cell differentiation and proliferation is required for postnatal glucose homeostasis.",
"URL": null,
"raw_pages": "491-7",
"medline_journal": "Cell Metab",
"ISO_journal": "Cell Metab",
"authors": [
"Zhang W",
"Feng D",
"Li Y",
"Iida K",
"McGrath B",
"Cavener DR."
],
"DOI_URL": null
},
"PUB00125152": {
"PMID": 18418049,
"ISBN": null,
"volume": "7",
"issue": "9",
"year": 2008,
"title": "PERK and PKR: old kinases learn new tricks.",
"URL": null,
"raw_pages": "1146-50",
"medline_journal": "Cell Cycle",
"ISO_journal": "Cell Cycle",
"authors": [
"Raven JF",
"Koromilas AE."
],
"DOI_URL": null
},
"PUB00125147": {
"PMID": 19732428,
"ISBN": null,
"volume": "10",
"issue": null,
"year": 2009,
"title": "Acute ablation of PERK results in ER dysfunctions followed by reduced insulin secretion and cell proliferation.",
"URL": null,
"raw_pages": "61",
"medline_journal": "BMC Cell Biol",
"ISO_journal": "BMC Cell Biol",
"authors": [
"Feng D",
"Wei J",
"Gupta S",
"McGrath BC",
"Cavener DR."
],
"DOI_URL": null
},
"PUB00125151": {
"PMID": 15384883,
"ISBN": null,
"volume": "93",
"issue": "9",
"year": 2004,
"title": "Wolcott-Rallison syndrome: a clinical and genetic study of three children, novel mutation in EIF2AK3 and a review of the literature.",
"URL": null,
"raw_pages": "1195-201",
"medline_journal": "Acta Paediatr",
"ISO_journal": "Acta Paediatr",
"authors": [
"Iyer S",
"Korada M",
"Rainbow L",
"Kirk J",
"Brown RM",
"Shaw N",
"Barrett TG."
],
"DOI_URL": null
},
"PUB00125144": {
"PMID": 20850340,
"ISBN": null,
"volume": "21",
"issue": "12",
"year": 2010,
"title": "PERK in beta cell biology and insulin biogenesis.",
"URL": null,
"raw_pages": "714-21",
"medline_journal": "Trends Endocrinol Metab",
"ISO_journal": "Trends Endocrinol Metab",
"authors": [
"Cavener DR",
"Gupta S",
"McGrath BC."
],
"DOI_URL": null
},
"PUB00125149": {
"PMID": 16813601,
"ISBN": null,
"volume": "70",
"issue": "1",
"year": 2006,
"title": "A novel mutation in the EIF2AK3 gene with variable expressivity in two patients with Wolcott-Rallison syndrome.",
"URL": null,
"raw_pages": "34-8",
"medline_journal": "Clin Genet",
"ISO_journal": "Clin Genet",
"authors": [
"Durocher F",
"Faure R",
"Labrie Y",
"Pelletier L",
"Bouchard I",
"Laframboise R."
],
"DOI_URL": null
},
"PUB00125153": {
"PMID": 16861899,
"ISBN": null,
"volume": "5",
"issue": "7",
"year": 2006,
"title": "The PERK/eIF2alpha/ATF4 module of the UPR in hypoxia resistance and tumor growth.",
"URL": null,
"raw_pages": "723-8",
"medline_journal": "Cancer Biol Ther",
"ISO_journal": "Cancer Biol Ther",
"authors": [
"Fels DR",
"Koumenis C."
],
"DOI_URL": null
},
"PUB00125155": {
"PMID": 16290097,
"ISBN": null,
"volume": "38",
"issue": "3",
"year": 2006,
"title": "Coordination of ER and oxidative stress signaling: the PERK/Nrf2 signaling pathway.",
"URL": null,
"raw_pages": "317-32",
"medline_journal": "Int J Biochem Cell Biol",
"ISO_journal": "Int J Biochem Cell Biol",
"authors": [
"Cullinan SB",
"Diehl JA."
],
"DOI_URL": null
},
"PUB00125146": {
"PMID": 20202148,
"ISBN": null,
"volume": "11",
"issue": "4",
"year": 2010,
"title": "Wolcott-Rallison syndrome due to the same mutation (W522X) in EIF2AK3 in two unrelated families and review of the literature.",
"URL": null,
"raw_pages": "279-85",
"medline_journal": "Pediatr Diabetes",
"ISO_journal": "Pediatr Diabetes",
"authors": [
"Ozbek MN",
"Senee V",
"Aydemir S",
"Kotan LD",
"Mungan NO",
"Yuksel B",
"Julier C",
"Topaloglu AK."
],
"DOI_URL": null
},
"PUB00125156": {
"PMID": 17883326,
"ISBN": null,
"volume": "9",
"issue": "12",
"year": 2007,
"title": "ERADicate ER stress or die trying.",
"URL": null,
"raw_pages": "2373-87",
"medline_journal": "Antioxid Redox Signal",
"ISO_journal": "Antioxid Redox Signal",
"authors": [
"Kincaid MM",
"Cooper AA."
],
"DOI_URL": null
},
"PUB00125158": {
"PMID": 16472113,
"ISBN": null,
"volume": "6",
"issue": "1",
"year": 2006,
"title": "ER stress, hypoxia tolerance and tumor progression.",
"URL": null,
"raw_pages": "55-69",
"medline_journal": "Curr Mol Med",
"ISO_journal": "Curr Mol Med",
"authors": [
"Koumenis C."
],
"DOI_URL": null
},
"PUB00125145": {
"PMID": 20530744,
"ISBN": null,
"volume": "59",
"issue": "8",
"year": 2010,
"title": "PERK (EIF2AK3) regulates proinsulin trafficking and quality control in the secretory pathway.",
"URL": null,
"raw_pages": "1937-47",
"medline_journal": "Diabetes",
"ISO_journal": "Diabetes",
"authors": [
"Gupta S",
"McGrath B",
"Cavener DR."
],
"DOI_URL": null
},
"PUB00125150": {
"PMID": 15483661,
"ISBN": null,
"volume": "5",
"issue": "8",
"year": 2004,
"title": "The EIF2AK3 gene region and type I diabetes in subjects from South India.",
"URL": null,
"raw_pages": "648-52",
"medline_journal": "Genes Immun",
"ISO_journal": "Genes Immun",
"authors": [
"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."
],
"DOI_URL": null
},
"PUB00125142": {
"PMID": 17760508,
"ISBN": null,
"volume": "9",
"issue": "12",
"year": 2007,
"title": "Translational control and the unfolded protein response.",
"URL": null,
"raw_pages": "2357-71",
"medline_journal": "Antioxid Redox Signal",
"ISO_journal": "Antioxid Redox Signal",
"authors": [
"Wek RC",
"Cavener DR."
],
"DOI_URL": null
},
"PUB00125154": {
"PMID": 16472110,
"ISBN": null,
"volume": "6",
"issue": "1",
"year": 2006,
"title": "Divergent roles of IRE1alpha and PERK in the unfolded protein response.",
"URL": null,
"raw_pages": "5-36",
"medline_journal": "Curr Mol Med",
"ISO_journal": "Curr Mol Med",
"authors": [
"Schroder M",
"Kaufman RJ."
],
"DOI_URL": null
},
"PUB00125143": {
"PMID": 16246168,
"ISBN": null,
"volume": "34",
"issue": "Pt 1",
"year": 2006,
"title": "Coping with stress: eIF2 kinases and translational control.",
"URL": null,
"raw_pages": "7-11",
"medline_journal": "Biochem Soc Trans",
"ISO_journal": "Biochem Soc Trans",
"authors": [
"Wek RC",
"Jiang HY",
"Anthony TG."
],
"DOI_URL": null
}
},
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},
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"taxa": 2213
},
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}
}
