EIF2AK3 Proteins

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 Neonatal Diabetes Mellitus. Among its related pathways are Autophagy - animal and Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and transferase activity, transferring phosphorus-containing groups. An important paralog of this gene is EIF2AK4.

CUSABIO has five systems (E. coli, In vitro E.coli, Yeast, Insect Baculovirus, Mammalian) from prokaryotic to eukaryotic to express the recombinant protein, and a very strict QC system so that the quality can be guaranteed. And the following EIF2AK3 proteins are produced under the system.
EIF2AK3 proteins produced by CUSABIO are featured with high purity, low endotoxin, multi-Sources & tags, animal-free, etc. And you will have many choices on sizes from μg to mg. In addition, EIF2AK3 custom service is also available for research with more specific needs.

EIF2AK3 Proteins Catalog

EIF2AK3 Proteins for Homo sapiens (Human)

EIF2AK3 Proteins for Mus musculus (Mouse)

EIF2AK3 Proteins for Rattus norvegicus (Rat)

EIF2AK3 Background

Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3), also known as PERK (protein kinase R (PKR)-like endoplasmic reticulum kinase) [1], is one of the eIF2α kinases (EIF2AKs), a family of four distinct serine-threonine kinases [2]. PERK is an endoplasmic reticulum (ER) transmembrane protein. Its N-terminal region is important for dimerization, regulation, and association with ER chaperone, including immunoglobulin binding protein (BiP) and HspA5 [3]. While its C-terminal region is cytosolic and contains Kinase Domains (KDs) with autophosphorylation sites [3]. Under normal physiological conditions, Bip binds to IRE-1, activating transcription factor-6α (ATF6α), and PERK, rendering them inactive. Following the accumulation of misfolded/unfolded proteins within the ER, Bip dissociates from the three ER sensor proteins, thereby leading to their activation and subsequent induction of the unfolded protein response (UPR) [4][13]. Upon induction of the UPR, PERK autoactivates by homodimerization and autophosphorylation [5][6]. Activated PERK phosphorylates the alpha subunit of the eukaryotic initiation factor 2 (eIF2α) which blocks "cap-dependent" protein synthesis but results in the preferential translation of ATF4, a transcription factor that upregulates the proapoptotic transcription factor CHOP (CAAT/enhancer-binding protein homologous protein) and genes required to restore normal ER function [7]. So transient PERK activation is protective. However, chronic ER stress and sustained PERK activation can be detrimental to cell health. Unresolved UPR and protracted ER stresses cause sustained activation of eIF2α phosphorylation and CHOP induction, resulting in ER stress-triggered apoptosis involving the induction of BH3 domain-only proteins BIK and BIM [8][9] as well as the death receptor DR5 [10] and the activation of the intrinsic pathway of apoptosis including the caspase-9/caspase-3/caspase-7 caspase cascade [11]. Many diseases are related to PERK over-activation, suggesting that small molecule PERK inhibitors may provide new opportunities for treating cancer and neurodegenerative diseases [12].

[1] Shi Y, Vattem KM, Sood R, et al. Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control [J]. Mol. Cell. Biol. 1998, 18 (12): 7499–509.
[2] Donnelly N, Gorman AM, et al. The eIF2alpha kinases: their structures and functions [J]. Cell Mol Life Sci 2013, 70: 3493–3511.
[3] Harding HP, Zhang Y, et al. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase [J]. Nature 1999, 397: 271–274.
[4] Jager R, Bertrand MJ, et al. The unfolded protein response at the crossroads of cellular life and death during endoplasmic reticulum stress [J]. Biol Cell 2012, 104:259–270.
[5] Ma K, Vattem KM, et al. Dimerization and release of molecular chaperone inhibition facilitate activation of eukaryotic initiation factor-2 kinase in response to endoplasmic reticulum stress. J Biol Chem 2002, 277: 18728–18735.
[6] Bertolotti A, Zhang Y, et al. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response [J]. Nat Cell Biol 2000, 2: 326–332.
[7] David Ron, Peter Walter. Signal Integration in the Endoplasmic Reticulum Unfolded Protein Response [J]. Nat Rev Mol Cell Biol, 2007, 8 (7), 519-29.
[8] Lin J.H., Li H., et al. IRE1 signaling affects cell fate during the unfolded protein response [J]. Science. 2007, 318:944–949.
[9] Hamsa Puthalakath, Lorraine A O'Reilly, et al. ER Stress Triggers Apoptosis by Activating BH3-only Protein Bim [J]. Cell, 2007, 129 (7), 1337-49.
[10] Hirohito Yamaguchi and Hong-Gang Wang. CHOP Is Involved in Endoplasmic Reticulum Stress-induced Apoptosis by Enhancing DR5 Expression in Human Carcinoma Cells [J]. The Journal of Biological Chemistry 2004, 279, 45495-45502.
[11] Ali Masud, Alexander Mohapatra, et al. Endoplasmic Reticulum Stress-induced Death ofMouse Embryonic Fibroblasts Requires the Intrinsic Pathway of Apoptosis [J]. THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 2007, 282, NO. 19, pp. 14132–14139.
[12] Jeffrey M Axten Protein Kinase R(PKR)-like Endoplasmic Reticulum Kinase (PERK) Inhibitors: A Patent Review (2010-2015) [J]. Expert Opin Ther Pat, 2007, 27 (1), 37-48.
[13] Szegezdi E, Logue SE, et al. Mediators of endoplasmic reticulum stress-induced apoptosis [J]. EMBO Rep 2006, 7: 880–885.


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