The Luminal domain, a dimerization domain, of Inositol-requiring protein 1-like proteins; The Luminal domain is a dimerization domain present in Inositol-requiring protein 1 (IRE1), eukaryotic translation Initiation Factor 2-Alpha Kinase 3 (EIF2AK3), and similar proteins. IRE1 and EIF2AK3 are serine/threonine protein kinases (STKs) and are type I transmembrane proteins that are localized in the endoplasmic reticulum (ER). They are kinase receptors that are activated through the release of BiP, a chaperone bound to their luminal domains under unstressed conditions. This results in dimerization through their luminal domains, allowing trans-autophosphorylation of their kinase domains and activation. They play roles in the signaling of the unfolded protein response (UPR), which is activated when protein misfolding is detected in the ER in order to decrease the synthesis of new proteins and increase the capacity of the ER to cope with the stress. IRE1, also called Endoplasmic reticulum (ER)-to-nucleus signaling protein (or ERN), contains an endoribonuclease domain in its cytoplasmic side and acts as an ER stress sensor. It is the oldest and most conserved component of the UPR in eukaryotes. Its activation results in the cleavage of its mRNA substrate, HAC1 in yeast and Xbp1 in metazoans, promoting a splicing event that enables translation into a transcription factor which activates the UPR. EIF2AK3, also called PKR-like Endoplasmic Reticulum Kinase (PERK), phosphorylates the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. It functions as the central regulator of translational control during the UPR pathway. In addition to the eIF-2 alpha subunit, EIF2AK3 also phosphorylates Nrf2, a leucine zipper transcription factor which regulates cellular redox status and promotes cell survival during the UPR.

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gi 927028879 100 SLVIISTLDGRIAALDAENDGKKQWDLD 127
Cdd:cd09768    1 SLIIVSTLDGKLTALDIENSGKKVWSLD 28

The Luminal domain, a dimerization domain, of the Serine/Threonine protein kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3; 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.

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gi 927028879 100 SLVIISTLDGRIAALDAENDGKKQWDLD 127
Cdd:cd09768    1 SLIIVSTLDGKLTALDIENSGKKVWSLD 28

The Luminal domain, a dimerization domain, of the Serine/Threonine protein kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3; 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.

                         10        20
                 ....*....|....*....|....*...
gi 927028879 100 SLVIISTLDGRIAALDAENDGKKQWDLD 127
Cdd:cd09768    1 SLIIVSTLDGKLTALDIENSGKKVWSLD 28