ERN1
Serine/threonine-protein kinase/endoribonuclease IRE1 is an enzyme that in humans is encoded by the ERN1 gene.[1][2]
The protein encoded by this gene is the ER to nucleus signalling 1 protein, a human homologue of the yeast Ire1 gene product. This protein possesses intrinsic kinase activity and an endoribonuclease activity and it is important in altering gene expression as a response to endoplasmic reticulum-based stress signals. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene.[2]
Interactions
ERN1 has been shown to interact with Heat shock protein 90kDa alpha (cytosolic), member A1.[3]
References
Further reading
- Katayama T, Imaizumi K, Sato N et al. (2000). "Presenilin-1 mutations downregulate the signalling pathway of the unfolded-protein response". Nat. Cell Biol. 1 (8): 479–85. doi:10.1038/70265. PMID 10587643.
- Urano F, Wang X, Bertolotti A et al. (2000). "Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1". Science 287 (5453): 664–6. doi:10.1126/science.287.5453.664. PMID 10650002.
- Dias Neto E, Correa RG, Verjovski-Almeida S et al. (2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3491–6. doi:10.1073/pnas.97.7.3491. PMC 16267. PMID 10737800. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=16267.
- Iwawaki T, Hosoda A, Okuda T et al. (2001). "Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress". Nat. Cell Biol. 3 (2): 158–64. doi:10.1038/35055065. PMID 11175748.
- Yoneda T, Imaizumi K, Oono K et al. (2001). "Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress". J. Biol. Chem. 276 (17): 13935–40. doi:10.1074/jbc.M010677200. PMID 11278723.
- Lee K, Tirasophon W, Shen X et al. (2002). "IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response". Genes Dev. 16 (4): 452–66. doi:10.1101/gad.964702. PMC 155339. PMID 11850408. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=155339.
- Liu CY, Wong HN, Schauerte JA, Kaufman RJ (2002). "The protein kinase/endoribonuclease IRE1alpha that signals the unfolded protein response has a luminal N-terminal ligand-independent dimerization domain". J. Biol. Chem. 277 (21): 18346–56. doi:10.1074/jbc.M112454200. PMID 11897784.
- Nishitoh H, Matsuzawa A, Tobiume K et al. (2002). "ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats". Genes Dev. 16 (11): 1345–55. doi:10.1101/gad.992302. PMC 186318. PMID 12050113. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=186318.
- Marcu MG, Doyle M, Bertolotti A et al. (2003). "Heat Shock Protein 90 Modulates the Unfolded Protein Response by Stabilizing IRE1α". Mol. Cell. Biol. 22 (24): 8506–13. doi:10.1128/MCB.22.24.8506-8513.2002. PMC 139892. PMID 12446770. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139892.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Liu CY, Xu Z, Kaufman RJ (2003). "Structure and intermolecular interactions of the luminal dimerization domain of human IRE1alpha". J. Biol. Chem. 278 (20): 17680–7. doi:10.1074/jbc.M300418200. PMID 12637535.
- Kaneko M, Niinuma Y, Nomura Y (2004). "Activation signal of nuclear factor-kappa B in response to endoplasmic reticulum stress is transduced via IRE1 and tumor necrosis factor receptor-associated factor 2". Biol. Pharm. Bull. 26 (7): 931–5. doi:10.1248/bpb.26.931. PMID 12843613.
- Ota T, Suzuki Y, Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Shang J, Lehrman MA (2004). "Discordance of UPR signaling by ATF6 and Ire1p-XBP1 with levels of target transcripts". Biochem. Biophys. Res. Commun. 317 (2): 390–6. doi:10.1016/j.bbrc.2004.03.058. PMID 15063770.
- Oono K, Yoneda T, Manabe T et al. (2004). "JAB1 participates in unfolded protein responses by association and dissociation with IRE1". Neurochem. Int. 45 (5): 765–72. doi:10.1016/j.neuint.2004.01.003. PMID 15234121.
- Huang ZM, Tan T, Yoshida H et al. (2005). "Activation of Hepatitis B Virus S Promoter by a Cell Type-Restricted IRE1-Dependent Pathway Induced by Endoplasmic Reticulum Stress". Mol. Cell. Biol. 25 (17): 7522–33. doi:10.1128/MCB.25.17.7522-7533.2005. PMC 1190304. PMID 16107700. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1190304.
- Kimura K, Wakamatsu A, Suzuki Y et al. (2006). "Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1356129.
- Hetz C, Bernasconi P, Fisher J et al. (2006). "Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha". Science 312 (5773): 572–6. doi:10.1126/science.1123480. PMID 16645094.
- Oikawa D, Tokuda M, Iwawaki T (2007). "Site-specific cleavage of CD59 mRNA by endoplasmic reticulum-localized ribonuclease, IRE1". Biochem. Biophys. Res. Commun. 360 (1): 122–7. doi:10.1016/j.bbrc.2007.06.020. PMID 17585877.
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PDB gallery
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2hz6: The crystal structure of human IRE1-alpha luminal domain
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