IRE1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0051082 unfolded protein binding	IEA GO_REF:0000118	MODIFY	Summary: IRE1 senses unfolded-protein stress; the obsolete binding term requires a sensor-appropriate replacement. Reason: Live QuickGO verifies GO:0051082 is obsolete, but its historical definition was simply binding to an unfolded protein. The prior assertion that sensors cannot have this binding activity was wrong: yeast Ire1 directly binds unfolded proteins (PMID:21852455). Trichoderma IRE1 functional rescue and UPR activation support detection of unfolded-protein stress. Replace the obsolete MF with GO:0002235 detection of unfolded protein, explicitly a BP describing stimulus-to-signal conversion; do not replace it with a folding chaperone or holdase activity. Target direct ligand binding is not established by the accessible primary abstract. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN001017826 SUPPORTS TRANSFER Fungal IRE1 relationship and functional complementation support conserved sensing. Direct yeast ligand binding does not establish target binding kinetics. The annotation needs term-scope migration, not a claim of absent sensor binding. Proposed replacements: detection of unfolded protein Supporting Evidence: PMID:15480788 The data presented demonstrates that the T. reesei genes can complement Saccharomyces cerevisiae mutants that are deficient in the corresponding homologues. PMID:21852455 Peptide binding caused Ire1 cLD oligomerization in vitro
GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	IEA GO_REF:0000118	MARK AS OVER ANNOTATED	Summary: Mark mammalian ER-stress apoptosis signaling as over-propagation to fungal IRE1. Reason: The focused fungal IRE1 report found no evidence that Trichoderma IRE1 drives the mammalian IRE1-TRAF2-ASK1/JNK apoptotic arm. The direct target paper supports adaptive UPR signaling through kinase autophosphorylation and HAC1 processing, while the apoptotic branch derives from mammalian SF17 IRE1 experiments and is not placed on the fungal SF6 branch that contains G0RBE3 and the TreeGrafter Sclerotinia leaf. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN001017826 SOURCE STALE OR MISSING Verified Sclerotinia sclerotiorum A7EHN1/SS1G_04823 fungal leaf. Current mammalian PTN000359344 IBD is not in its ancestor chain and the focused report places the apoptosis evidence on the mammalian SF17 subfamily rather than fungal SF6 IRE1. Supporting Evidence: file:HYPJE/IRE1/IRE1-hypotheses/fungal-stress-death-and-signaling-complex/openscientist.md has never been demonstrated for the fungal protein PMID:15480788 The T. reesei IREI protein has intrinsic kinase activity, as revealed by an in vitro autophosphorylation assay.
GO:1990604 IRE1-TRAF2-ASK1 complex	IEA GO_REF:0000118	REMOVE	Summary: Remove IRE1-TRAF2-ASK1 complex membership from fungal IRE1. Reason: The focused report confirms that GO:1990604 requires an IRE1, TRAF2 and ASK1 complex, but Trichoderma encodes neither TRAF2 nor ASK1/MAP3K5; ASK1 was also absent across the Fungi kingdom query. The mammalian complex evidence sits on human/rat metazoan systems and the mammalian PTHR13954:SF17 subfamily, not the fungal SF6 IRE1 lineage. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH WRONG ORTHOLOG OR PARALOG LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN001017826 SOURCE STALE OR MISSING Verified Sclerotinia sclerotiorum A7EHN1/SS1G_04823 fungal leaf. Current mammalian PTN000359344 complex IBD is not in its ancestor chain and the focused report places the direct complex evidence on mammalian IRE1 rather than fungal SF6 IRE1. Supporting Evidence: file:HYPJE/IRE1/IRE1-hypotheses/fungal-stress-death-and-signaling-complex/openscientist.md 0 proteins matching TRAF2 / "TNF receptor-associated factor" and 0 proteins** matching ASK1
GO:0000166 nucleotide binding	IEA GO_REF:0000043	MODIFY	Summary: IEA annotation for nucleotide binding from UniProt keyword mapping. IRE1 binds ATP/ADP in its kinase domain. The protein has ATP-binding keyword in UniProt. Reason: Correct but very broad. ATP binding is the informative child term for the kinase nucleotide-binding site. Proposed replacements: ATP binding Supporting Evidence: PMID:15480788 The T. reesei IREI protein has intrinsic kinase activity, as revealed by an in vitro autophosphorylation assay.
GO:0004521 RNA endonuclease activity	IEA GO_REF:0000120	ACCEPT	Summary: Combined IEA annotation for RNA endonuclease activity based on ARBA, InterPro, and PANTHER. IRE1 has a KEN endoribonuclease domain (residues 1108-1240) that cleaves HAC1 mRNA. Consistent with IGI evidence (PMID:15480788). Reason: Correct. IRE1 is a site-specific endonuclease. The KEN domain is conserved across IRE1 orthologs and complementation of S. cerevisiae ire1 mutants confirms functional conservation including mRNA splicing (PMID:15480788). Supporting Evidence: PMID:15480788 Splicing of the mRNA encoding the transcription factor HAC1 is also observed. PMID:15480788 The data presented demonstrates that the T. reesei genes can complement Saccharomyces cerevisiae mutants that are deficient in the corresponding homologues.
GO:0004540 RNA nuclease activity	IEA GO_REF:0000002	MODIFY	Summary: IEA annotation for RNA nuclease activity from InterPro (KEN domain). Broader parent of RNA endonuclease activity. Reason: Correct but less specific than GO:0004521 RNA endonuclease activity, which captures the conserved HAC1-cleaving RNase activity. Proposed replacements: RNA endonuclease activity Supporting Evidence: PMID:15480788 Splicing of the mRNA encoding the transcription factor HAC1 is also observed. PMID:15480788 The data presented demonstrates that the T. reesei genes can complement Saccharomyces cerevisiae mutants that are deficient in the corresponding homologues.
GO:0004672 protein kinase activity	IEA GO_REF:0000002	MODIFY	Summary: IEA annotation for protein kinase activity from InterPro. Broader parent of protein serine/threonine kinase activity. Reason: Correct but less specific than GO:0004674 protein serine/threonine kinase activity, which captures the autophosphorylation chemistry demonstrated directly for T. reesei IRE1. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: PMID:15480788 The T. reesei IREI protein has intrinsic kinase activity, as revealed by an in vitro autophosphorylation assay.
GO:0004674 protein serine/threonine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Combined IEA annotation for protein Ser/Thr kinase activity based on InterPro, EC number, UniProt keyword, and PANTHER. Consistent with IDA evidence (PMID:15480788). Reason: Correct. IRE1 has intrinsic kinase activity demonstrated by in vitro autophosphorylation assay (PMID:15480788). Consistent with IDA evidence. Supporting Evidence: PMID:15480788 The T. reesei IREI protein has intrinsic kinase activity, as revealed by an in vitro autophosphorylation assay.
GO:0005524 ATP binding	IEA GO_REF:0000120	ACCEPT	Summary: Combined IEA annotation for ATP binding. IRE1 binds ATP in its kinase domain. Based on InterPro and UniProt keyword mapping. Reason: Correct. ATP binding is essential for kinase activity. IRE1 autophosphorylation requires ATP (PMID:15480788). Supporting Evidence: PMID:15480788 The T. reesei IREI protein has intrinsic kinase activity, as revealed by an in vitro autophosphorylation assay.
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation for ER membrane from UniProt subcellular location mapping. IRE1 is a type I transmembrane protein with a single transmembrane helix (residues 586-606) spanning the ER membrane. Reason: Correct. IRE1 is a type I ER transmembrane protein with lumenal and cytoplasmic domains. Confirmed by topology and transmembrane helix prediction in UniProt. Supporting Evidence: file:HYPJE/IRE1/IRE1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane file:HYPJE/IRE1/IRE1-deep-research-falcon.md A single transmembrane segment is predicted at codons 584–606
GO:0006397 mRNA processing	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation for mRNA processing from InterPro (KEN domain). IRE1 endoribonuclease domain processes HAC1 mRNA through unconventional splicing. Overexpression of T. reesei ire1 leads to HAC1 mRNA splicing (PMID:15480788). Reason: Correct. IRE1 endoribonuclease activity directly processes HAC1 pre-mRNA. Confirmed by observation of HAC1 mRNA splicing upon ire1 overexpression (PMID:15480788). Supporting Evidence: PMID:15480788 Splicing of the mRNA encoding the transcription factor HAC1 is also observed. PMID:15480788 The data presented demonstrates that the T. reesei genes can complement Saccharomyces cerevisiae mutants that are deficient in the corresponding homologues.
GO:0016301 kinase activity	IEA GO_REF:0000043	MODIFY	Summary: IEA annotation for kinase activity from UniProt keyword mapping. Broader parent of protein kinase activity. Reason: Correct but very broad; the specific Ser/Thr protein kinase term is already supported by direct IRE1 evidence. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: PMID:15480788 The T. reesei IREI protein has intrinsic kinase activity, as revealed by an in vitro autophosphorylation assay.
GO:0016740 transferase activity	IEA GO_REF:0000043	MODIFY	Summary: IEA annotation for transferase activity from UniProt keyword mapping. Very broad parent of kinase activity. Reason: Correct but extremely broad; the specific Ser/Thr protein kinase term should be used for IRE1's phosphotransferase activity. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: PMID:15480788 The T. reesei IREI protein has intrinsic kinase activity, as revealed by an in vitro autophosphorylation assay.
GO:0016787 hydrolase activity	IEA GO_REF:0000043	MODIFY	Summary: IEA annotation for hydrolase activity from UniProt keyword mapping. Broad parent of RNA nuclease activity. Reason: Correct but extremely broad; the relevant hydrolytic activity is RNA endonuclease activity. Proposed replacements: RNA endonuclease activity Supporting Evidence: PMID:15480788 Splicing of the mRNA encoding the transcription factor HAC1 is also observed. PMID:15480788 The data presented demonstrates that the T. reesei genes can complement Saccharomyces cerevisiae mutants that are deficient in the corresponding homologues.
GO:0030968 endoplasmic reticulum unfolded protein response	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation for ER UPR from InterPro. IRE1 is the primary sensor and effector of the UPR in T. reesei. Overexpression upregulates UPR target genes bip1 and pdi1 (PMID:15480788). Reason: Correct. This is the core biological process of IRE1. Confirmed by functional studies showing UPR target gene upregulation (PMID:15480788). Supporting Evidence: PMID:15480788 The data presented demonstrates that the T. reesei genes can complement Saccharomyces cerevisiae mutants that are deficient in the corresponding homologues. PMID:15480788 Splicing of the mRNA encoding the transcription factor HAC1 is also observed.
GO:0036498 IRE1-mediated unfolded protein response	IEA GO_REF:0000120	ACCEPT	Summary: Combined IEA annotation for IRE1-mediated UPR based on ARBA and PANTHER. This is the core biological process of IRE1. Consistent with IGI evidence (PMID:15480788). Reason: Correct. This is the defining biological process for IRE1. T. reesei IRE1 complements S. cerevisiae ire1 mutants, confirming functional conservation of the IRE1-mediated UPR pathway (PMID:15480788). Supporting Evidence: PMID:15480788 The data presented demonstrates that the T. reesei genes can complement Saccharomyces cerevisiae mutants that are deficient in the corresponding homologues. PMID:15480788 Splicing of the mRNA encoding the transcription factor HAC1 is also observed.
GO:0046872 metal ion binding	IEA GO_REF:0000043	MODIFY	Summary: IEA annotation for metal ion binding from UniProt keyword (Magnesium). IRE1 kinase domain requires Mg2+ as a cofactor, with binding residues at positions 936 and 953 (by similarity to S. cerevisiae IRE1). Reason: Metal binding is inferred from the conserved IRE1 protein-kinase active site and the UniProt annotation transferred from yeast P32361. Magnesium ion binding is the informative child term for this conserved kinase cofactor. Proposed replacements: magnesium ion binding
GO:0004521 RNA endonuclease activity	IGI PMID:15480788 The ire1 and ptc2 genes involved in the unfolded protein res...	ACCEPT	Summary: IGI annotation for RNA endonuclease activity based on complementation of S. cerevisiae ire1 mutants with T. reesei ire1 (with/from P32361). The complementation demonstrates that T. reesei IRE1 can substitute for yeast IRE1 endonuclease function in HAC1 mRNA splicing (PMID:15480788). Reason: Core molecular function of IRE1. Demonstrated by complementation of yeast ire1 mutant and observation of HAC1 mRNA splicing upon ire1 overexpression (PMID:15480788). The KEN domain (residues 1108-1240) is the catalytic domain. Supporting Evidence: PMID:15480788 Splicing of the mRNA encoding the transcription factor HAC1 is also observed. PMID:15480788 The data presented demonstrates that the T. reesei genes can complement Saccharomyces cerevisiae mutants that are deficient in the corresponding homologues.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:15480788 The ire1 and ptc2 genes involved in the unfolded protein res...	ACCEPT	Summary: IDA annotation for protein Ser/Thr kinase activity from Valkonen et al. (2004). The T. reesei IRE1 protein has intrinsic kinase activity demonstrated by in vitro autophosphorylation assay (PMID:15480788). Reason: Core molecular function of IRE1. Directly demonstrated by in vitro autophosphorylation assay (PMID:15480788). UniProt annotates autophosphorylation mainly on serine residues. Supporting Evidence: PMID:15480788 The T. reesei IREI protein has intrinsic kinase activity, as revealed by an in vitro autophosphorylation assay.
GO:0036498 IRE1-mediated unfolded protein response	IGI PMID:15480788 The ire1 and ptc2 genes involved in the unfolded protein res...	ACCEPT	Summary: IGI annotation for IRE1-mediated UPR based on complementation of S. cerevisiae ire1 mutant (with/from P32361) and overexpression studies showing upregulation of UPR target genes and HAC1 mRNA splicing (PMID:15480788). Reason: Core biological process of IRE1. Demonstrated by complementation of yeast ire1 mutant and functional studies showing UPR pathway activation (PMID:15480788). Supporting Evidence: PMID:15480788 The data presented demonstrates that the T. reesei genes can complement Saccharomyces cerevisiae mutants that are deficient in the corresponding homologues. PMID:15480788 Splicing of the mRNA encoding the transcription factor HAC1 is also observed.
GO:0051082 unfolded protein binding	IGI PMID:15480788 The ire1 and ptc2 genes involved in the unfolded protein res...	MODIFY	Summary: IRE1 senses unfolded-protein stress; the obsolete binding term requires a sensor-appropriate replacement. Reason: Live QuickGO verifies GO:0051082 is obsolete, but its historical definition was simply binding to an unfolded protein. The prior assertion that sensors cannot have this binding activity was wrong: yeast Ire1 directly binds unfolded proteins (PMID:21852455). Trichoderma IRE1 functional rescue and UPR activation support detection of unfolded-protein stress. Replace the obsolete MF with GO:0002235 detection of unfolded protein, explicitly a BP describing stimulus-to-signal conversion; do not replace it with a folding chaperone or holdase activity. Target direct ligand binding is not established by the accessible primary abstract. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: UniProtKB:P32361 SUPPORTS TRANSFER Fungal IRE1 relationship and functional complementation support conserved sensing. Direct yeast ligand binding does not establish target binding kinetics. The annotation needs term-scope migration, not a claim of absent sensor binding. Proposed replacements: detection of unfolded protein Supporting Evidence: PMID:15480788 The data presented demonstrates that the T. reesei genes can complement Saccharomyces cerevisiae mutants that are deficient in the corresponding homologues. PMID:21852455 Peptide binding caused Ire1 cLD oligomerization in vitro
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based IEA (protein kinase domain and kinase ATP-binding signature) for ATP binding. IRE1 carries a canonical protein kinase domain with conserved ATP-binding residues, and its demonstrated autophosphorylation requires ATP. Reason: ATP binding is intrinsic to the protein kinase activity directly demonstrated for T. reesei IRE1 by in vitro autophosphorylation. This row replaces the retired combined-IEA ATP binding row with the same assertion from the InterPro pipeline. Supporting Evidence: PMID:15480788 The T. reesei IREI protein has intrinsic kinase activity, as revealed by an in vitro autophosphorylation assay.
GO:0005789 endoplasmic reticulum membrane	ISS GO_REF:0000024	ACCEPT	Summary: ISS transfer of ER membrane localization from S. cerevisiae Ire1 (P32361). IRE1 is a type I ER transmembrane sensor with a lumenal sensing domain and cytosolic kinase/RNase domains; the T. reesei protein has a signal peptide and a single transmembrane segment. Reason: Consistent with the conserved IRE1 architecture, the predicted topology of G0RBE3 and the UniProt subcellular-location annotation; duplicates the accepted IEA ER membrane row with a curator-judged sequence-similarity transfer. Supporting Evidence: file:HYPJE/IRE1/IRE1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane file:HYPJE/IRE1/IRE1-deep-research-falcon.md A single transmembrane segment is predicted at codons 584–606
GO:0106310 protein serine kinase activity	ISS GO_REF:0000024	ACCEPT	Summary: ISS transfer from S. cerevisiae Ire1 of protein serine kinase activity. IRE1 is a Ser/Thr kinase whose activation involves trans-autophosphorylation, and UniProt records autophosphorylation mainly on serine residues. T. reesei IRE1 autophosphorylation has been shown directly in vitro. Reason: Protein serine kinase activity (GO:0106310) is a valid, more specific facet of the directly demonstrated protein serine/threonine kinase activity (IDA, PMID:15480788), and the serine preference of IRE1 autophosphorylation is transferred from the yeast ortholog. The broader GO:0004674 remains the core function term. Supporting Evidence: PMID:15480788 The T. reesei IREI protein has intrinsic kinase activity, as revealed by an in vitro autophosphorylation assay. file:HYPJE/IRE1/IRE1-uniprot.txt Autophosphorylated mainly on serine residues

Gene Description

Existing Annotations Review

Core Functions

Protein serine/threonine kinase that undergoes autophosphorylation upon ER stress-induced activation, contributing to activation of the endoribonuclease domain for HAC1 mRNA splicing and UPR signaling.

RNA endonuclease that cleaves HAC1 pre-mRNA to initiate unconventional mRNA splicing, producing mature HAC1 mRNA encoding the UPR transcription factor.

References

Deep Research

Falcon

OpenScientist

📚 Additional Documentation

Notes

📄 View Raw YAML