Optineurin (OPTN) is a ubiquitously expressed, predominantly cytoplasmic coiled-coil adaptor protein that functions as a selective autophagy receptor. It carries two functional cargo-recognition modules: an LC3-interacting region (LIR motif, residues 176-181, with the critical Phe178) that binds ATG8-family modifiers (MAP1LC3A/B, GABARAP, GABARAPL1, GABARAPL2), and a UBAN (ubiquitin binding in ABIN and NEMO) motif (residues 474-479, with the essential Asp474/Phe475) that binds linear (M1) and K63-linked polyubiquitin chains. By simultaneously engaging ubiquitinated cargo and ATG8 proteins on the nascent autophagosomal membrane, OPTN bridges cargo to the autophagy machinery. Its C-terminus contains a CCHC NOA-type zinc finger (residues 547-577) that coordinates Zn2+. OPTN partners with and is activated by the kinase TBK1, which phosphorylates OPTN at Ser177 adjacent to the LIR, markedly increasing LC3 binding affinity and thereby driving cargo-selective autophagy. Through this mechanism OPTN mediates antibacterial xenophagy of ubiquitin-coated cytosolic bacteria (e.g. Salmonella) and PINK1/Parkin-dependent mitophagy of damaged mitochondria, acting alongside the related receptors SQSTM1/p62 and CALCOCO2/NDP52. As a NEMO-related protein, OPTN also regulates innate immune and inflammatory signaling: it negatively regulates canonical NF-kB signaling (competing for polyubiquitin within the TNFR1 complex) and dampens virus-triggered IFN-beta induction, while recruiting and activating TBK1 at the Golgi after RNA-virus sensing. Independently, OPTN links myosin VI and GTP-Rab8 to the Golgi complex, contributing to Golgi ribbon organization, post-Golgi exocytosis, and Rab8/TBC1D17-dependent endocytic recycling (e.g. of the transferrin receptor). OPTN mutations cause primary open-angle glaucoma (GLC1E; e.g. E50K), normal-pressure glaucoma, and amyotrophic lateral sclerosis with or without frontotemporal dementia (ALS12; e.g. the UBAN mutant E478G and the truncation Q398X), linking impaired selective autophagy and vesicular trafficking to neurodegeneration.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0043122 regulation of canonical NF-kappaB signal transduction | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic inference that OPTN regulates canonical NF-kB signaling, consistent with its NEMO-related architecture and its competition with NEMO/IKBKG for polyubiquitin within the TNFR1 complex. Reason: OPTN is a NEMO-related protein that negatively regulates NF-kB signaling (e.g. by binding polyubiquitinated RIPK1 and recruiting CYLD to the TNFR1 complex), but this regulatory role is secondary to its core selective-autophagy-receptor function. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt NEMO-related protein |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic inference of cytoplasmic activity, consistent with OPTN's predominantly cytoplasmic/perinuclear localization where it acts as an autophagy receptor and trafficking adaptor. Reason: Correct but generic compartment; the specific cytosol/Golgi/autophagosome localizations are more informative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, perinuclear region. Golgi apparatus |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic inference of nuclear activity. OPTN can be phosphorylated by PLK1 and translocate to the nucleus (Reactome), and was first identified as a TFIIIA-interacting protein, but the dominant functional pool is cytoplasmic. Reason: A nuclear pool is reported but minor relative to the cytoplasmic autophagy-receptor and trafficking functions; retained as non-core. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Transcription factor IIIA-interacting protein |
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic inference of Golgi localization, strongly corroborated by experimental data showing OPTN at the Golgi where it links myosin VI/Rab8 and supports Golgi organization. Reason: Experimentally supported localization tied to the secondary Golgi-maintenance/trafficking role rather than the core autophagy-receptor function. Supporting Evidence: PMID:15837803 Both proteins colocalize at the Golgi complex and in vesicles at the plasma membrane |
| GO:0070530 K63-linked polyubiquitin modification-dependent protein binding | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that OPTN binds K63-linked polyubiquitin via its UBAN domain - a core molecular activity underlying cargo recognition in selective autophagy and ubiquitin-dependent signaling. Reason: Core molecular function; the UBAN motif binds K63-linked (and linear) polyubiquitin, enabling recognition of ubiquitin-coated cargo (mitochondria, bacteria) and signaling complexes. Supporting Evidence: PMID:21617041 OPTN bound to ubiquitin chains and autophagy modifiers ATG8/LC3/GABARAP proteins but not to mono-ubiquitin |
| GO:0034067 protein localization to Golgi apparatus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic inference that OPTN contributes to protein localization to the Golgi, consistent with the IMP evidence that OPTN anchors myosin VI at the Golgi. Reason: Secondary Golgi-trafficking role; redundant with the IMP annotation from PMID:15837803. Supporting Evidence: PMID:15837803 depletion of optineurin causes a marked reduction in the amount of myosin VI associated with the Golgi complex |
| GO:0090161 Golgi ribbon formation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic inference of a role in Golgi ribbon formation, corroborated by IDA/IMP evidence that OPTN depletion fragments the Golgi. Reason: Secondary Golgi-maintenance role; redundant with the experimental annotations from PMID:15837803. Supporting Evidence: PMID:15837803 optineurin links myosin VI to the Golgi complex and plays a central role in Golgi ribbon formation and exocytosis |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA machine-learning assignment of cytoplasmic localization, consistent with the IBA/experimental evidence. Reason: Correct but generic; redundant with the more specific cytosol/Golgi/autophagosome localizations. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, perinuclear region |
| GO:0005776 autophagosome | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic transfer of autophagosome localization from the UniProt subcellular location; OPTN localizes to LC3-positive autophagic vesicles upon autophagy induction, where it functions as an autophagy receptor. Reason: Core localization for the autophagy-receptor function; OPTN clusters into LC3-positive cytoplasmic vesicles upon autophagy induction. Supporting Evidence: PMID:21617041 OPTN localized in LC3-positive vesicles upon induction of autophagy |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic transfer of Golgi localization from the UniProt subcellular location, corroborated by multiple experimental studies. Reason: Experimentally supported but tied to the secondary Golgi/trafficking role; redundant with the IDA annotations. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Cytoplasm, perinuclear region. Golgi apparatus |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic transfer of cytoplasmic vesicle localization from the UniProt subcellular location; OPTN associates with vesicular structures (including autophagic and post-Golgi vesicles). Reason: Correct but generic vesicle term; the specific autophagosome and recycling-endosome localizations are more informative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Cytoplasmic vesicle, autophagosome. Cytoplasmic vesicle |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Electronic assignment of perinuclear cytoplasmic localization, consistent with OPTN's perinuclear/Golgi-associated distribution. Reason: Correct cytoplasmic sub-compartment but secondary; reflects the perinuclear/Golgi-associated pool. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Found in the perinuclear region and associates with the Golgi apparatus |
| GO:0055037 recycling endosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic transfer of recycling-endosome localization; UBAN-dependent recruitment of OPTN to recycling endosomes is required for transferrin-receptor trafficking. Reason: Experimentally supported (UBAN-dependent) localization tied to the secondary endocytic-recycling role; redundant with the EXP annotation. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Ubiquitin-binding motif (UBAN) ... is essential for subcellular localization to recycling endosomes |
| GO:0070530 K63-linked polyubiquitin modification-dependent protein binding | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (InterPro/orthology) assignment of K63-linked polyubiquitin binding via the UBAN domain - a core OPTN molecular activity. Reason: Core molecular function; redundant with the IBA annotation and supported by direct experimental ubiquitin-chain binding. Supporting Evidence: PMID:21617041 OPTN bound to ubiquitin chains and autophagy modifiers ATG8/LC3/GABARAP proteins but not to mono-ubiquitin |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | KEEP AS NON CORE | Summary: High-throughput proteome-scale interaction. Bare protein binding is uninformative. Reason: Records real interactions but bare protein binding is uninformative per curation guidelines. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt IntAct=EBI-748974 |
| GO:0005515 protein binding | IPI PMID:17500595 Huntingtin interacting proteins are genetic modifiers of neu... | KEEP AS NON CORE | Summary: Interaction with huntingtin (HTT) from a study of huntingtin-interacting proteins as genetic modifiers of neurodegeneration. Bare protein binding is uninformative. Reason: Records the real OPTN-HTT interaction (relevant to trafficking) but bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; P42858: HTT; NbExp=13; IntAct=EBI-748974, EBI-466029 |
| GO:0005515 protein binding | IPI PMID:18307994 Enhanced binding of TBK1 by an optineurin mutant that causes... | KEEP AS NON CORE | Summary: Interaction with TBK1, specifically enhanced binding by the glaucoma-associated OPTN mutant. The real interactor (TBK1) is functionally central, but bare protein binding is uninformative. Reason: Documents the functionally important OPTN-TBK1 interaction (and its disease-relevant enhancement) but bare protein binding is uninformative; the TBK1 partnership is captured in core functions and other annotations. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; Q9UHD2: TBK1; NbExp=17; IntAct=EBI-748974, EBI-356402 |
| GO:0005515 protein binding | IPI PMID:19805065 Cargo binding induces dimerization of myosin VI. | KEEP AS NON CORE | Summary: Interaction with myosin VI (MYO6) from a study of cargo-induced myosin VI dimerization. Bare protein binding is uninformative. Reason: Records the real OPTN-MYO6 interaction (relevant to Golgi/trafficking) but bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; Q29122: MYO6; Xeno; NbExp=3 |
| GO:0005515 protein binding | IPI PMID:20195357 A comprehensive resource of interacting protein regions for ... | KEEP AS NON CORE | Summary: Interacting-protein-regions resource for transcription-factor networks (ZMAT2). Bare protein binding is uninformative. Reason: High-throughput interaction; bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; Q96NC0: ZMAT2; NbExp=4 |
| GO:0005515 protein binding | IPI PMID:20388642 Overexpression of optineurin E50K disrupts Rab8 interaction ... | KEEP AS NON CORE | Summary: Interaction with RAB8A, in the context of the glaucoma E50K mutant disrupting Rab8 interaction. Bare protein binding is uninformative. Reason: Records the real OPTN-RAB8A interaction (relevant to trafficking/glaucoma) but bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; P61006: RAB8A; NbExp=4; IntAct=EBI-748974, EBI-722293 |
| GO:0005515 protein binding | IPI PMID:21516116 Next-generation sequencing to generate interactome datasets. | KEEP AS NON CORE | Summary: Next-generation interactome dataset. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt IntAct=EBI-748974 |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | KEEP AS NON CORE | Summary: Innate-immunity protein interaction network (type I interferon). Bare protein binding is uninformative. Reason: High-throughput interactome (relevant to OPTN's IFN role) but bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt IntAct=EBI-748974 |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | KEEP AS NON CORE | Summary: Human liver protein interaction network (TNIP1). Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; Q15025: TNIP1; NbExp=23 |
| GO:0005515 protein binding | IPI PMID:22854040 Optineurin mediates a negative regulation of Rab8 by the GTP... | KEEP AS NON CORE | Summary: Interaction with TBC1D17 (and RAB8A) from the study showing OPTN bridges Rab8 to its GAP. Bare protein binding is uninformative. Reason: Records the real OPTN-TBC1D17 interaction (relevant to Rab8 regulation) but bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; Q9HA65: TBC1D17; NbExp=7 |
| GO:0005515 protein binding | IPI PMID:23275563 Development and application of a DNA microarray-based yeast ... | KEEP AS NON CORE | Summary: DNA microarray-based yeast two-hybrid interaction. Bare protein binding is uninformative. Reason: High-throughput interaction; bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt IntAct=EBI-748974 |
| GO:0005515 protein binding | IPI PMID:23414517 A human skeletal muscle interactome centered on proteins inv... | KEEP AS NON CORE | Summary: Skeletal-muscle (LGMD) interactome. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt IntAct=EBI-748974 |
| GO:0005515 protein binding | IPI PMID:23956131 Interaction between optineurin and the bZIP transcription fa... | KEEP AS NON CORE | Summary: Interaction with the bZIP transcription factor NRL. Bare protein binding is uninformative. Reason: Records the real OPTN-NRL interaction but bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; P54845-1: NRL; NbExp=6 |
| GO:0005515 protein binding | IPI PMID:24136289 Identification and comparative analysis of hepatitis C virus... | KEEP AS NON CORE | Summary: Hepatitis C virus host-cell interactome. Bare protein binding is uninformative. Reason: High-throughput host-virus interactome; bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt IntAct=EBI-748974 |
| GO:0005515 protein binding | IPI PMID:25026213 Ubiquitylation of autophagy receptor Optineurin by HACE1 act... | KEEP AS NON CORE | Summary: Interaction with the E3 ligase HACE1, which ubiquitinates OPTN to activate selective autophagy for tumor suppression. Bare protein binding is uninformative. Reason: Records the functionally important OPTN-HACE1 interaction (regulates OPTN's autophagy activity) but bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; Q8IYU2: HACE1; NbExp=15 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Proteome-scale interactome map. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt IntAct=EBI-748974 |
| GO:0005515 protein binding | IPI PMID:25803835 Haploinsufficiency of TBK1 causes familial ALS and fronto-te... | KEEP AS NON CORE | Summary: Interaction with TBK1 from the study identifying TBK1 haploinsufficiency in ALS/FTD. Bare protein binding is uninformative. Reason: Records the functionally central OPTN-TBK1 interaction but bare protein binding is uninformative; captured more specifically by the adaptor-activity annotation from the same paper. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; Q9UHD2: TBK1; NbExp=17 |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | KEEP AS NON CORE | Summary: Macromolecular interaction perturbations in genetic disorders. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt IntAct=EBI-748974 |
| GO:0005515 protein binding | IPI PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by ... | KEEP AS NON CORE | Summary: Alternative-splicing interactome expansion. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt IntAct=EBI-748974 |
| GO:0005515 protein binding | IPI PMID:27086836 The TBK1-binding domain of optineurin promotes type I interf... | KEEP AS NON CORE | Summary: Interaction with TBK1 via OPTN's TBK1-binding domain, which promotes type I interferon responses. Bare protein binding is uninformative. Reason: Records the functionally central OPTN-TBK1 interaction but bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; Q9UHD2: TBK1; NbExp=17 |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | KEEP AS NON CORE | Summary: Interactome-perturbation framework for damaging missense mutations. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt IntAct=EBI-748974 |
| GO:0005515 protein binding | IPI PMID:30561431 A protein-protein interaction map of the TNF-induced NF-ΞΊB s... | KEEP AS NON CORE | Summary: TNF-induced NF-kB signal-transduction interaction map (TNIP1). Bare protein binding is uninformative. Reason: High-throughput interactome (relevant to OPTN's NF-kB role) but bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; Q15025: TNIP1; NbExp=23 |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: Disruption of protein interactions by genetic variants. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt IntAct=EBI-748974 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Binary protein interactome reference map. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt IntAct=EBI-748974 |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | KEEP AS NON CORE | Summary: Kinase interaction network (TBK1). Bare protein binding is uninformative. Reason: High-throughput kinase interactome (TBK1) but bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; Q9UHD2: TBK1; NbExp=17 |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Large neurodegeneration interactome screen contributing many OPTN interactors. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt IntAct=EBI-748974 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Cell-specific interactome remodeling (TNIP1). Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; Q15025: TNIP1; NbExp=23 |
| GO:0005515 protein binding | IPI PMID:34524948 Global Proximity Interactome of the Human Macroautophagy Pat... | KEEP AS NON CORE | Summary: Proximity interactome of the human macroautophagy pathway (TBK1). Bare protein binding is uninformative. Reason: High-throughput proximity interactome (relevant to autophagy) but bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; Q9UHD2: TBK1; NbExp=17 |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Multimodal cell-map interactome (TNIP1). Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; Q15025: TNIP1; NbExp=23 |
| GO:0042802 identical protein binding | IPI PMID:23414517 A human skeletal muscle interactome centered on proteins inv... | KEEP AS NON CORE | Summary: OPTN self-association (homo-oligomerization), supported by the strong OPTN-OPTN IntAct interaction. Reason: OPTN genuinely self-associates (coiled-coil-mediated oligomerization), but identical protein binding is an uninformative molecular-function term that does not capture a specific activity. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; Q96CV9: OPTN; NbExp=16; IntAct=EBI-748974, EBI-748974 |
| GO:0042802 identical protein binding | IPI PMID:24983867 Oligomerization of optineurin and its oxidative stress- or E... | KEEP AS NON CORE | Summary: OPTN oligomerization and oxidative-stress/E50K-driven covalent cross-linking. Self-association is real but identical protein binding is uninformative. Reason: Documents real OPTN self-association (and its aberrant cross-linking by the E50K glaucoma mutant) but identical protein binding is uninformative as a molecular function. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Self-associates (PubMed:23669351) |
| GO:0042802 identical protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: OPTN-OPTN self-association from a proteome-scale interactome. Identical protein binding is uninformative. Reason: Real self-association but uninformative term. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; Q96CV9: OPTN; NbExp=16 |
| GO:0042802 identical protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | KEEP AS NON CORE | Summary: OPTN self-association from an interaction-perturbation study. Identical protein binding is uninformative. Reason: Real self-association but uninformative term. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; Q96CV9: OPTN; NbExp=16 |
| GO:0042802 identical protein binding | IPI PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by ... | KEEP AS NON CORE | Summary: OPTN self-association from an alternative-splicing interactome. Identical protein binding is uninformative. Reason: Real self-association but uninformative term. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; Q96CV9: OPTN; NbExp=16 |
| GO:0042802 identical protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: OPTN self-association from the binary interactome reference map. Identical protein binding is uninformative. Reason: Real self-association but uninformative term. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; Q96CV9: OPTN; NbExp=16 |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas immunofluorescence evidence for cytosolic localization, consistent with OPTN's predominantly cytoplasmic distribution. Reason: Correct and well-supported cytosolic localization where OPTN performs its autophagy-receptor and trafficking-adaptor functions. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, perinuclear region |
| GO:0005794 Golgi apparatus | EXP PMID:10807909 Phorbol esters and cytokines regulate the expression of the ... | KEEP AS NON CORE | Summary: Experimental evidence (NEMO-related protein study) that OPTN localizes to the Golgi apparatus. Reason: Experimentally supported Golgi localization tied to the secondary Golgi/trafficking role. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Golgi apparatus {ECO:0000269|PubMed:10807909 |
| GO:0005794 Golgi apparatus | EXP PMID:20085643 Regulation of endocytic trafficking of transferrin receptor ... | KEEP AS NON CORE | Summary: Experimental Golgi localization from the transferrin-receptor trafficking study. Reason: Experimentally supported but redundant Golgi localization; tied to the secondary trafficking role. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Golgi apparatus {ECO:0000269|PubMed:20085643 |
| GO:0005794 Golgi apparatus | EXP PMID:20174559 Optineurin negatively regulates the induction of IFNbeta in ... | KEEP AS NON CORE | Summary: Experimental Golgi localization from the IFN-beta negative-regulation study; OPTN/TBK1 complex localizes to the Golgi region. Reason: Experimentally supported but redundant Golgi localization. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Golgi apparatus {ECO:0000269|PubMed:20174559 |
| GO:0005794 Golgi apparatus | EXP PMID:27538435 The Golgi apparatus acts as a platform for TBK1 activation a... | KEEP AS NON CORE | Summary: Experimental Golgi localization from the study showing the Golgi acts as a platform for OPTN-mediated TBK1 activation after viral RNA sensing. Reason: Experimentally supported Golgi localization; here mechanistically linked to TBK1 activation but still a secondary compartment relative to the autophagy-receptor core. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Golgi apparatus {ECO:0000269|PubMed:27538435 |
| GO:0055037 recycling endosome | EXP PMID:20085643 Regulation of endocytic trafficking of transferrin receptor ... | KEEP AS NON CORE | Summary: Experimental evidence that OPTN localizes (UBAN-dependently) to recycling endosomes, required for transferrin-receptor trafficking. Reason: Experimentally supported localization tied to the secondary endocytic-recycling role. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Ubiquitin-binding motif (UBAN) ... is essential for subcellular localization to recycling endosomes |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9824892 | ACCEPT | Summary: Reactome cytosol localization for the mitophagy reaction (MAP1LC3B binds phospho-OPTN bound to Ub-mitochondria). Consistent with the cytosolic site of action. Reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization. Supporting Evidence: PMID:25294927 Optineurin then induces autophagosome formation around damaged mitochondria via its LC3 interaction region (LIR) domain |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9824897 | ACCEPT | Summary: Reactome cytosol localization for the mitophagy reaction (phospho-TBK1 phosphorylates OPTN). Consistent with the cytosolic site of action. Reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization. Supporting Evidence: PMID:21617041 The protein kinase TANK binding kinase 1 (TBK1) phosphorylated optineurin on serine-177 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9840807 | ACCEPT | Summary: Reactome cytosol localization for the reaction OPTN binds ATG9A. Consistent with the cytosolic site of action. Reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, perinuclear region |
| GO:0005515 protein binding | IPI PMID:17646400 Functional dissection of Rab GTPases involved in primary cil... | KEEP AS NON CORE | Summary: Interaction with RAB8A from a study dissecting Rab GTPases in primary cilium formation. Bare protein binding is uninformative. Reason: Records the real OPTN-RAB8A interaction but bare protein binding is uninformative. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Q96CV9; P61006: RAB8A; NbExp=4 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9793680 | ACCEPT | Summary: Reactome cytosol localization for OPTN binding polyUb-RIPK1 within the TNFR1 complex. Consistent with the cytosolic site of action in NF-kB regulation. Reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt NEMO-related protein |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9823816 | ACCEPT | Summary: Reactome cytosol localization for OPTN binding CASP8. Consistent with the cytosolic site of action. Reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, perinuclear region |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9823934 | ACCEPT | Summary: Reactome cytosol localization for OPTN binding TBK1 within the activated TLR4 complex. Consistent with the cytosolic site of action. Reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, perinuclear region |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9824874 | ACCEPT | Summary: Reactome cytosol localization for OPTN recruiting CYLD to the TNFR1 complex. Consistent with the cytosolic site of action in NF-kB regulation. Reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Interacts with CYLD (PubMed:32185393) |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9824888 | ACCEPT | Summary: Reactome cytosol localization for OPTN/TBK1 binding ubiquitinated mitochondrial outer-membrane proteins (mitophagy). Consistent with the cytosolic site of action. Reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization. Supporting Evidence: PMID:25294927 allowing optineurin to stably associate with ubiquitinated mitochondria via its ubiquitin binding domain |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9824894 | ACCEPT | Summary: Reactome cytosol localization for TBK1 phosphorylation within the TBK1:OPTN:Ub-mitochondria complex. Consistent with the cytosolic site of action. Reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization. Supporting Evidence: PMID:25294927 optineurin as an autophagy receptor in parkin-mediated mitophagy |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9828209 | ACCEPT | Summary: Reactome cytosol localization for OPTN binding TBK1 within the activated TLR3 complex. Consistent with the cytosolic site of action. Reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, perinuclear region |
| GO:0005794 Golgi apparatus | IDA PMID:27534431 A novel amyotrophic lateral sclerosis mutation in OPTN induc... | KEEP AS NON CORE | Summary: Direct evidence that OPTN localizes to the Golgi/perinuclear region (ALS V295F mutant study). Reason: Experimentally supported Golgi localization tied to the secondary Golgi/trafficking role. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Found in the perinuclear region and associates with the Golgi apparatus (PubMed:27534431) |
| GO:0034620 cellular response to unfolded protein | IMP PMID:27534431 A novel amyotrophic lateral sclerosis mutation in OPTN induc... | KEEP AS NON CORE | Summary: Mutant-phenotype evidence that the ALS-associated OPTN V295F variant increases susceptibility to ER stress and Golgi fragmentation; interpreted as OPTN involvement in the response to unfolded protein. Reason: Experimentally derived (IMP) but based on a disease-mutant readout (ER-stress susceptibility) rather than a clearly established normal OPTN function; retained as non-core, deferring to the curator rather than removing. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt increased susceptibility to endoplasmic reticulum (ER) stress |
| GO:0090161 Golgi ribbon formation | IMP PMID:27534431 A novel amyotrophic lateral sclerosis mutation in OPTN induc... | KEEP AS NON CORE | Summary: Mutant-phenotype evidence that the ALS V295F variant decreases Golgi ribbon formation, supporting OPTN involvement in Golgi ribbon formation. Reason: Experimentally supported secondary Golgi-maintenance role; redundant with the IDA annotation from PMID:15837803. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt decreased Golgi ribbon formation |
| GO:0010508 positive regulation of autophagy | IDA PMID:21617041 Phosphorylation of the autophagy receptor optineurin restric... | ACCEPT | Summary: Direct evidence that OPTN promotes selective autophagy; it is recruited to and clusters with LC3 to drive autophagic clearance of cargo. Reason: Core biological process; OPTN is a selective autophagy receptor that positively drives cargo-selective autophagy (here demonstrated for cytosolic Salmonella). Supporting Evidence: PMID:21617041 phosphorylation of an autophagy receptor, optineurin, promoted selective autophagy of ubiquitin-coated cytosolic Salmonella enterica |
| GO:1904417 positive regulation of xenophagy | IMP PMID:21617041 Phosphorylation of the autophagy receptor optineurin restric... | ACCEPT | Summary: Mutant-phenotype evidence that OPTN (and its UBAN/LIR domains) is required to restrict cytosolic Salmonella by autophagy; OPTN depletion increases bacterial proliferation. Reason: Core biological process; OPTN positively regulates xenophagy of ubiquitin-coated cytosolic bacteria, requiring both ubiquitin and LC3 binding. Supporting Evidence: PMID:21617041 silencing of optineurin or TBK1 impaired Salmonella autophagy, resulting in increased intracellular bacterial proliferation |
| GO:0055038 recycling endosome membrane | TAS Reactome:R-HSA-8854182 | KEEP AS NON CORE | Summary: Reactome localization to the recycling-endosome membrane for the reaction TBC1D17 binds OPTN:RAB8A. Reason: Correct membrane compartment tied to the secondary Rab8/TBC1D17 endocytic-recycling role. Supporting Evidence: PMID:22854040 Optineurin mediates a negative regulation of Rab8 by the GTPase-activating protein TBC1D17 |
| GO:0061734 type 2 mitophagy | IMP PMID:25294927 Optineurin is an autophagy receptor for damaged mitochondria... | ACCEPT | Summary: Mutant-phenotype evidence that OPTN is an autophagy receptor for damaged mitochondria in PINK1/Parkin-mediated mitophagy; OPTN depletion inhibits LC3 recruitment and mitochondrial degradation, not rescued by the UBAN mutant E478G or a LIR mutant. Reason: Core biological process; GO:0061734 (type 2 mitophagy) is precisely the Parkin/depolarization-initiated mitophagy in which OPTN functions as the cargo receptor bridging ubiquitinated mitochondria to LC3. Supporting Evidence: PMID:25294927 our study establishes an important role for optineurin as an autophagy receptor in parkin-mediated mitophagy |
| GO:0005515 protein binding | IPI PMID:21617041 Phosphorylation of the autophagy receptor optineurin restric... | KEEP AS NON CORE | Summary: Interactions with ATG8-family proteins (MAP1LC3A/B, GABARAP, GABARAPL1/2) from the Salmonella autophagy study. Bare protein binding is uninformative but the interactors are central to the LIR-mediated receptor function. Reason: Records the functionally central OPTN-LC3/GABARAP interactions but bare protein binding is uninformative; the LIR/ATG8-binding activity is captured in core functions. Supporting Evidence: PMID:21617041 The specific interactions between OPTN and LC3/GABARAP proteins were verified by pull-down assays |
| GO:0030674 protein-macromolecule adaptor activity | IPI PMID:25803835 Haploinsufficiency of TBK1 causes familial ALS and fronto-te... | ACCEPT | Summary: OPTN functions as an adaptor that bridges TBK1 (and, more broadly, ubiquitinated cargo to ATG8 proteins); interaction with TBK1 underpins this adaptor activity. Reason: Core molecular function; OPTN is an adaptor/scaffold that physically bridges its binding partners (ubiquitinated cargo, LC3/GABARAP, TBK1), the molecular basis of its autophagy-receptor and signaling-scaffold roles. More informative than bare protein binding. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Interacts with TBK1; this interaction leads to the Golgi localization of TBK1 and its subsequent activation |
| GO:0001920 negative regulation of receptor recycling | IMP PMID:22854040 Optineurin mediates a negative regulation of Rab8 by the GTP... | KEEP AS NON CORE | Summary: Mutant-phenotype evidence that OPTN, by bridging Rab8 to the GAP TBC1D17, negatively regulates Rab8-mediated endocytic recycling (e.g. of the transferrin receptor). Reason: Experimentally supported but secondary trafficking-regulatory role distinct from the core autophagy-receptor function. Supporting Evidence: PMID:22854040 Optineurin mediates a negative regulation of Rab8 by the GTPase-activating protein TBC1D17 |
| GO:0031593 polyubiquitin modification-dependent protein binding | IDA PMID:21617041 Phosphorylation of the autophagy receptor optineurin restric... | ACCEPT | Summary: Direct evidence that OPTN binds polyubiquitin chains (but not mono-ubiquitin) via its UBAN domain - a core molecular function for cargo recognition. Reason: Core molecular function; OPTN's UBAN domain binds polyubiquitin chains, enabling recognition of ubiquitin-coated cargo. Complements the more specific K63-linkage annotation. Supporting Evidence: PMID:21617041 OPTN bound to ubiquitin chains and autophagy modifiers ATG8/LC3/GABARAP proteins but not to mono-ubiquitin |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:21617041 Phosphorylation of the autophagy receptor optineurin restric... | ACCEPT | Summary: Mutant-phenotype evidence that OPTN mediates autophagic defense against cytosolic Gram-negative Salmonella; loss of OPTN increases bacterial proliferation. Reason: Core biological process; OPTN-mediated xenophagy is a cell-autonomous defense against cytosolic Gram-negative bacteria. Supporting Evidence: PMID:21617041 OPTN appears to function in innate immunity against cytosolic bacteria by linking the TBK1 signaling pathway to autophagic elimination of cytosolic pathogens |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-2562526 | KEEP AS NON CORE | Summary: Reactome Golgi-membrane localization for the reaction PLK1 phosphorylates OPTN. Reason: Correct membrane compartment from a Reactome pathway annotation; tied to the secondary Golgi/cell-cycle context. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Cytoplasm, perinuclear region. Golgi apparatus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2562594 | KEEP AS NON CORE | Summary: Reactome nucleoplasm localization for the reaction phosphorylated OPTN translocates to the nucleus (PLK1-phosphorylated pool). Reason: A minor PLK1-phosphorylated nuclear pool; secondary to the dominant cytoplasmic functions. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Transcription factor IIIA-interacting protein |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2562526 | ACCEPT | Summary: Reactome cytosol localization for the reaction PLK1 phosphorylates OPTN. Consistent with the cytosolic site of action. Reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, perinuclear region |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2562594 | ACCEPT | Summary: Reactome cytosol localization for the reaction phosphorylated OPTN translocates to the nucleus. Consistent with the cytosolic starting compartment. Reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, perinuclear region |
| GO:0005515 protein binding | IPI PMID:15837803 Optineurin links myosin VI to the Golgi complex and is invol... | KEEP AS NON CORE | Summary: Interactions with myosin VI (MYO6) and RAB8 from the Golgi/exocytosis study. Bare protein binding is uninformative. Reason: Records the functionally important OPTN-MYO6 and OPTN-RAB8 interactions but bare protein binding is uninformative. Supporting Evidence: PMID:15837803 we identified optineurin as a binding partner for myosin VI at the Golgi complex |
| GO:0005515 protein binding | IPI PMID:20174559 Optineurin negatively regulates the induction of IFNbeta in ... | KEEP AS NON CORE | Summary: Interactions with TBK1 and TRAF3 from the IFN-beta negative-regulation study. Bare protein binding is uninformative. Reason: Records the functionally important OPTN-TBK1 and OPTN-TRAF3 interactions but bare protein binding is uninformative. Supporting Evidence: PMID:20174559 Immunoprecipitation and immunofluorescence studies identified optineurin in a protein complex containing the antiviral protein kinase TBK1 and the ubiquitin ligase TRAF3 |
| GO:0005802 trans-Golgi network | IDA PMID:20174559 Optineurin negatively regulates the induction of IFNbeta in ... | KEEP AS NON CORE | Summary: Direct evidence that OPTN localizes to the trans-Golgi network. Reason: Experimentally supported localization tied to the secondary Golgi/trafficking and TBK1-scaffolding roles. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt Golgi apparatus, trans-Golgi network |
| GO:0090161 Golgi ribbon formation | IDA PMID:15837803 Optineurin links myosin VI to the Golgi complex and is invol... | KEEP AS NON CORE | Summary: Direct evidence that OPTN is required for Golgi ribbon formation; its depletion fragments the Golgi. Reason: Experimentally supported secondary Golgi-maintenance role distinct from the core autophagy-receptor function. Supporting Evidence: PMID:15837803 the Golgi is fragmented and exocytosis of vesicular stomatitis virus G-protein to the plasma membrane is dramatically reduced |
| GO:0005737 cytoplasm | TAS PMID:9488477 Interaction of an adenovirus E3 14.7-kilodalton protein with... | KEEP AS NON CORE | Summary: Author-statement cytoplasmic localization from the original FIP-2/E3-14.7K study. Reason: Correct but generic compartment; redundant with the more specific cytosol/Golgi localizations. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, perinuclear region |
| GO:0007165 signal transduction | TAS PMID:9488477 Interaction of an adenovirus E3 14.7-kilodalton protein with... | KEEP AS NON CORE | Summary: Author-statement (original FIP-2 study) of a role in signal transduction, reflecting OPTN's role in TNF/NF-kB and innate immune signaling. Reason: Very generic process term; OPTN does participate in signaling (NF-kB, IFN, TBK1), but this is captured better by the specific NF-kB-regulation annotation, and is secondary to the autophagy-receptor core. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt E3-14.7K-interacting protein |
| GO:0008219 cell death | TAS PMID:9488477 Interaction of an adenovirus E3 14.7-kilodalton protein with... | KEEP AS NON CORE | Summary: Author-statement (original FIP-2 study) linking OPTN to cell death; FIP-2 was identified by its ability to reverse E3-14.7K protection against TNF-induced cytolysis. Reason: Generic process term reflecting OPTN's modulation of TNF cytotoxicity; secondary to the autophagy-receptor core function. Supporting Evidence: file:human/OPTN/OPTN-uniprot.txt E3-14.7K-interacting protein {ECO:0000303|PubMed:9488477} |
| GO:0043001 Golgi to plasma membrane protein transport | IMP PMID:15837803 Optineurin links myosin VI to the Golgi complex and is invol... | KEEP AS NON CORE | Summary: Mutant-phenotype (RNAi) evidence that OPTN is required for post-Golgi exocytic transport; its depletion dramatically reduces VSV-G transport to the cell surface. Reason: Experimentally supported secondary exocytosis/trafficking role distinct from the autophagy-receptor core. Supporting Evidence: PMID:15837803 exocytosis of vesicular stomatitis virus G-protein to the plasma membrane is dramatically reduced |
| GO:0005794 Golgi apparatus | IDA PMID:15837803 Optineurin links myosin VI to the Golgi complex and is invol... | KEEP AS NON CORE | Summary: Direct evidence that OPTN localizes to the Golgi complex, where it colocalizes with myosin VI and Rab8. Reason: Experimentally supported Golgi localization tied to the secondary Golgi/trafficking role. Supporting Evidence: PMID:15837803 Both proteins colocalize at the Golgi complex and in vesicles at the plasma membrane |
| GO:0007030 Golgi organization | IMP PMID:15837803 Optineurin links myosin VI to the Golgi complex and is invol... | KEEP AS NON CORE | Summary: Mutant-phenotype (RNAi) evidence that OPTN is required for Golgi organization; its depletion fragments the Golgi. Reason: Experimentally supported secondary Golgi-maintenance role distinct from the autophagy-receptor core. Supporting Evidence: PMID:15837803 the Golgi is fragmented |
| GO:0034067 protein localization to Golgi apparatus | IMP PMID:15837803 Optineurin links myosin VI to the Golgi complex and is invol... | KEEP AS NON CORE | Summary: Mutant-phenotype (RNAi) evidence that OPTN is required to localize myosin VI to the Golgi; its depletion removes myosin VI from the Golgi. Reason: Experimentally supported secondary Golgi-trafficking role; OPTN anchors myosin VI at the Golgi. Supporting Evidence: PMID:15837803 depletion of optineurin causes a marked reduction in the amount of myosin VI associated with the Golgi complex |
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Download this section (compressed HTML)Q: How is OPTN's selective-autophagy-receptor activity partitioned among its different cargoes (mitochondria, cytosolic bacteria, protein aggregates) and signaling roles, and what determines cargo specificity given that OPTN, NDP52, and p62 occupy distinct subdomains on the same ubiquitinated targets?
Q: To what extent do the ALS- and glaucoma-causing OPTN mutations act through loss of selective autophagy (UBAN mutants such as E478G), gain of aberrant interactions (E50K enhancing TBK1 binding and driving insolubility), or disruption of Golgi/vesicular trafficking, and are these mechanistically separable?
Experiment: Domain-resolved reconstitution and cellular rescue of OPTN-dependent mitophagy and xenophagy using LIR (F178A), UBAN (D474N/E478G), and TBK1-phosphosite (S177A/S177D) variants, with quantitative imaging of LC3/cargo recruitment, to dissect the contribution of each module to cargo-selective autophagy.
Experiment: Quantitative proximity-labeling (BioID/APEX) and ubiquitin-linkage profiling of OPTN under basal, mitophagy-inducing, bacterial-infection, and TNF/NF-kB-stimulating conditions to map how OPTN's interactome and ubiquitin-chain preferences switch it between autophagy-receptor and signaling-scaffold roles.
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