IRE1/YHR079C Summary Help

Standard Name IRE1 1
Systematic Name YHR079C
Alias ERN1
Feature Type ORF, Verified
Description Serine-threonine kinase and endoribonuclease; transmembrane protein that mediates the unfolded protein response (UPR) by regulating Hac1p synthesis through HAC1 mRNA splicing; role in homeostatic adaptation to ER stress; Kar2p binds inactive Ire1p and releases from it upon ER stress (2, 3, 4, 5, 6 and see Summary Paragraph)
Name Description Inositol REquiring 1
Chromosomal Location
ChrVIII:261591 to 258244 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All IRE1 GO evidence and references
  View Computational GO annotations for IRE1
Molecular Function
Manually curated
High-throughput
Biological Process
Manually curated
High-throughput
Cellular Component
Manually curated
Regulators 1 genes
Resources
Classical genetics
activation
null
Large-scale survey
null
overexpression
Resources
579 total interaction(s) for 333 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 4
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 12
  • Biochemical Activity: 82
  • Co-crystal Structure: 1
  • FRET: 1
  • PCA: 1
  • Protein-RNA: 2
  • Reconstituted Complex: 7
  • Two-hybrid: 4

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Rescue: 17
  • Negative Genetic: 314
  • Phenotypic Enhancement: 4
  • Phenotypic Suppression: 5
  • Positive Genetic: 40
  • Synthetic Growth Defect: 48
  • Synthetic Lethality: 29
  • Synthetic Rescue: 5

Resources
Expression Summary
histogram
Resources
Length (a.a.) 1,115
Molecular Weight (Da) 126,974
Isoelectric Point (pI) 6.55
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrVIII:261591 to 258244 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..3348 261591..258244 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000001121
SUMMARY PARAGRAPH for IRE1

IRE1 encodes a transmembrane protein that is involved in the unfolded protein response (7,8, 9). Heat stress, drug treatment, mutations in secretory proteins, or overexpression of wild type secretory proteins can cause unfolded proteins to accumulate in the endoplasmic reticulum (ER), triggering the unfolded protein response (UPR). Increased transcription of genes encoding soluble ER resident proteins, including chaperones, is a key feature of the UPR (see reference 9 for a review of the UPR). IRE1 is not essential under normal growth conditions, but is essential under conditions that trigger the UPR (7, 8). ire1 mutants are also inositol auxotrophs (1).

The N-terminal region of Ire1p, which contains an ER targeting sequence, senses the extent of misfolded proteins in the ER through interaction with Kar2p (4). The C-terminal half of Ire1p contains both protein kinase and site-specific endoribonuclease activities (7, 8, 2). Between these 2 halves of the protein is a functional nuclear localization sequence that is recognized by yeast importins (10). Activation of Ire1p involves release from Kar2p, oligomerization and trans-autophoshorylation, and induction of Ire1p's ribonuclease activity (11, 3, 2). The Ire1p ribonuclease performs the cleavage step in the unconventional splicing of mRNA encoding Hac1p, the transcription factor that activates gene expression in the UPR (2, 12, 9). Transcription of UPR target genes also involves the SAGA histone acetyltransferase complex; Ire1p interacts physically with SAGA components Gcn5p and Spt20p (13, 14, 9). The protein phosphatase Dcr2p is involved in downregulation of the UPR and dephosphorylates Ire1p in vitro (15). Phosphatase Ptc2p has also been shown to downregulate the UPR by dephosphorylating Ire1p (16).

The UPR in mammalian cells involves homologs of Ire1p; examples include the mouse ern1 and ern2 and human ERN1 and ERN2 gene products (17, 18, 9). The ribonuclease domain of Ire1p is similar to that of mammaliam RNase L (e.g human RNASEL) (9).

Last updated: 2007-05-14 Contact SGD

References cited on this page View Complete Literature Guide for IRE1
1) Nikawa J and Yamashita S  (1992) IRE1 encodes a putative protein kinase containing a membrane-spanning domain and is required for inositol phototrophy in Saccharomyces cerevisiae. Mol Microbiol 6(11):1441-6
2) Sidrauski C and Walter P  (1997) The transmembrane kinase Ire1p is a site-specific endonuclease that initiates mRNA splicing in the unfolded protein response. Cell 90(6):1031-9
3) Welihinda AA and Kaufman RJ  (1996) The unfolded protein response pathway in Saccharomyces cerevisiae. Oligomerization and trans-phosphorylation of Ire1p (Ern1p) are required for kinase activation. J Biol Chem 271(30):18181-7
4) Okamura K, et al.  (2000) Dissociation of Kar2p/BiP from an ER sensory molecule, Ire1p, triggers the unfolded protein response in yeast. Biochem Biophys Res Commun 279(2):445-50
5) Rubio C, et al.  (2011) Homeostatic adaptation to endoplasmic reticulum stress depends on Ire1 kinase activity. J Cell Biol 193(1):171-84
6) Thibault G, et al.  (2012) The membrane stress response buffers lethal effects of lipid disequilibrium by reprogramming the protein homeostasis network. Mol Cell 48(1):16-27
7) Cox JS, et al.  (1993) Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase. Cell 73(6):1197-206
8) Mori K, et al.  (1993) A transmembrane protein with a cdc2+/CDC28-related kinase activity is required for signaling from the ER to the nucleus. Cell 74(4):743-56
9) Kaufman RJ  (1999) Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev 13(10):1211-33
10) Goffin L, et al.  (2006) The unfolded protein response transducer Ire1p contains a nuclear localization sequence recognized by multiple beta importins. Mol Biol Cell 17(12):5309-23
11) Shamu CE and Walter P  (1996) Oligomerization and phosphorylation of the Ire1p kinase during intracellular signaling from the endoplasmic reticulum to the nucleus. EMBO J 15(12):3028-39
12) Gonzalez TN, et al.  (1999) Mechanism of non-spliceosomal mRNA splicing in the unfolded protein response pathway. EMBO J 18(11):3119-32
13) Welihinda AA, et al.  (1997) Gene induction in response to unfolded protein in the endoplasmic reticulum is mediated through Ire1p kinase interaction with a transcriptional coactivator complex containing Ada5p. Proc Natl Acad Sci U S A 94(9):4289-94
14) Welihinda AA, et al.  (2000) The transcriptional co-activator ADA5 is required for HAC1 mRNA processing in vivo. J Biol Chem 275(5):3377-81
15) Guo J and Polymenis M  (2006) Dcr2 targets Ire1 and downregulates the unfolded protein response in Saccharomyces cerevisiae. EMBO Rep 7(11):1124-7
16) Welihinda AA, et al.  (1998) Protein serine/threonine phosphatase Ptc2p negatively regulates the unfolded-protein response by dephosphorylating Ire1p kinase. Mol Cell Biol 18(4):1967-77
17) Tirasophon W, et al.  (1998) A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells. Genes Dev 12(12):1812-24
18) Wang XZ, et al.  (1998) Cloning of mammalian Ire1 reveals diversity in the ER stress responses. EMBO J 17(19):5708-17