id: Q96CV9
gene_symbol: OPTN
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  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.
alternative_products:
- name: '1'
  id: Q96CV9-1
- name: '2'
  id: Q96CV9-2
  sequence_note: VSP_013262
- name: '3'
  id: Q96CV9-3
  sequence_note: VSP_013261
existing_annotations:
- term:
    id: GO:0043122
    label: regulation of canonical NF-kappaB signal transduction
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: NEMO-related protein
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic inference of cytoplasmic activity, consistent with OPTN's predominantly cytoplasmic/perinuclear localization where it acts as an autophagy receptor and trafficking adaptor.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic compartment; the specific cytosol/Golgi/autophagosome localizations are more informative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, perinuclear region. Golgi apparatus'
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: A nuclear pool is reported but minor relative to the cytoplasmic autophagy-receptor and trafficking functions; retained as non-core.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: Transcription factor IIIA-interacting protein
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported localization tied to the secondary Golgi-maintenance/trafficking role rather than the core autophagy-receptor function.
    supported_by:
    - reference_id: PMID:15837803
      supporting_text: Both proteins colocalize at the Golgi complex and in vesicles at the plasma membrane
- term:
    id: GO:0070530
    label: K63-linked polyubiquitin modification-dependent protein binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Core molecular function; the UBAN motif binds K63-linked (and linear) polyubiquitin, enabling recognition of ubiquitin-coated cargo (mitochondria, bacteria) and signaling complexes.
    supported_by:
    - reference_id: PMID:21617041
      supporting_text: OPTN bound to ubiquitin chains and autophagy modifiers ATG8/LC3/GABARAP proteins but not to mono-ubiquitin
- term:
    id: GO:0034067
    label: protein localization to Golgi apparatus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Secondary Golgi-trafficking role; redundant with the IMP annotation from PMID:15837803.
    supported_by:
    - reference_id: PMID:15837803
      supporting_text: depletion of optineurin causes a marked reduction in the amount of myosin VI associated with the Golgi complex
- term:
    id: GO:0090161
    label: Golgi ribbon formation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic inference of a role in Golgi ribbon formation, corroborated by IDA/IMP evidence that OPTN depletion fragments the Golgi.
    action: KEEP_AS_NON_CORE
    reason: Secondary Golgi-maintenance role; redundant with the experimental annotations from PMID:15837803.
    supported_by:
    - reference_id: PMID:15837803
      supporting_text: optineurin links myosin VI to the Golgi complex and plays a central role in Golgi ribbon formation and exocytosis
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: ARBA machine-learning assignment of cytoplasmic localization, consistent with the IBA/experimental evidence.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; redundant with the more specific cytosol/Golgi/autophagosome localizations.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, perinuclear region'
- term:
    id: GO:0005776
    label: autophagosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    reason: Core localization for the autophagy-receptor function; OPTN clusters into LC3-positive cytoplasmic vesicles upon autophagy induction.
    supported_by:
    - reference_id: PMID:21617041
      supporting_text: OPTN localized in LC3-positive vesicles upon induction of autophagy
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic transfer of Golgi localization from the UniProt subcellular location, corroborated by multiple experimental studies.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported but tied to the secondary Golgi/trafficking role; redundant with the IDA annotations.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: Cytoplasm, perinuclear region. Golgi apparatus
- term:
    id: GO:0031410
    label: cytoplasmic vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic transfer of cytoplasmic vesicle localization from the UniProt subcellular location; OPTN associates with vesicular structures (including autophagic and post-Golgi vesicles).
    action: KEEP_AS_NON_CORE
    reason: Correct but generic vesicle term; the specific autophagosome and recycling-endosome localizations are more informative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: Cytoplasmic vesicle, autophagosome. Cytoplasmic vesicle
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Electronic assignment of perinuclear cytoplasmic localization, consistent with OPTN's perinuclear/Golgi-associated distribution.
    action: KEEP_AS_NON_CORE
    reason: Correct cytoplasmic sub-compartment but secondary; reflects the perinuclear/Golgi-associated pool.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: Found in the perinuclear region and associates with the Golgi apparatus
- term:
    id: GO:0055037
    label: recycling endosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic transfer of recycling-endosome localization; UBAN-dependent recruitment of OPTN to recycling endosomes is required for transferrin-receptor trafficking.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported (UBAN-dependent) localization tied to the secondary endocytic-recycling role; redundant with the EXP annotation.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: Ubiquitin-binding motif (UBAN) ... is essential for subcellular localization to recycling endosomes
- term:
    id: GO:0070530
    label: K63-linked polyubiquitin modification-dependent protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic (InterPro/orthology) assignment of K63-linked polyubiquitin binding via the UBAN domain - a core OPTN molecular activity.
    action: ACCEPT
    reason: Core molecular function; redundant with the IBA annotation and supported by direct experimental ubiquitin-chain binding.
    supported_by:
    - reference_id: PMID:21617041
      supporting_text: OPTN bound to ubiquitin chains and autophagy modifiers ATG8/LC3/GABARAP proteins but not to mono-ubiquitin
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16189514
  qualifier: enables
  review:
    summary: High-throughput proteome-scale interaction. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records real interactions but bare protein binding is uninformative per curation guidelines.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'IntAct=EBI-748974'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17500595
  qualifier: enables
  review:
    summary: Interaction with huntingtin (HTT) from a study of huntingtin-interacting proteins as genetic modifiers of neurodegeneration. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the real OPTN-HTT interaction (relevant to trafficking) but bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; P42858: HTT; NbExp=13; IntAct=EBI-748974, EBI-466029'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18307994
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; Q9UHD2: TBK1; NbExp=17; IntAct=EBI-748974, EBI-356402'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19805065
  qualifier: enables
  review:
    summary: Interaction with myosin VI (MYO6) from a study of cargo-induced myosin VI dimerization. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the real OPTN-MYO6 interaction (relevant to Golgi/trafficking) but bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; Q29122: MYO6; Xeno; NbExp=3'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20195357
  qualifier: enables
  review:
    summary: Interacting-protein-regions resource for transcription-factor networks (ZMAT2). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interaction; bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; Q96NC0: ZMAT2; NbExp=4'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20388642
  qualifier: enables
  review:
    summary: Interaction with RAB8A, in the context of the glaucoma E50K mutant disrupting Rab8 interaction. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the real OPTN-RAB8A interaction (relevant to trafficking/glaucoma) but bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; P61006: RAB8A; NbExp=4; IntAct=EBI-748974, EBI-722293'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21516116
  qualifier: enables
  review:
    summary: Next-generation interactome dataset. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'IntAct=EBI-748974'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21903422
  qualifier: enables
  review:
    summary: Innate-immunity protein interaction network (type I interferon). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome (relevant to OPTN's IFN role) but bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'IntAct=EBI-748974'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21988832
  qualifier: enables
  review:
    summary: Human liver protein interaction network (TNIP1). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; Q15025: TNIP1; NbExp=23'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22854040
  qualifier: enables
  review:
    summary: Interaction with TBC1D17 (and RAB8A) from the study showing OPTN bridges Rab8 to its GAP. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the real OPTN-TBC1D17 interaction (relevant to Rab8 regulation) but bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; Q9HA65: TBC1D17; NbExp=7'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23275563
  qualifier: enables
  review:
    summary: DNA microarray-based yeast two-hybrid interaction. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interaction; bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'IntAct=EBI-748974'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23414517
  qualifier: enables
  review:
    summary: Skeletal-muscle (LGMD) interactome. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'IntAct=EBI-748974'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23956131
  qualifier: enables
  review:
    summary: Interaction with the bZIP transcription factor NRL. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the real OPTN-NRL interaction but bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; P54845-1: NRL; NbExp=6'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24136289
  qualifier: enables
  review:
    summary: Hepatitis C virus host-cell interactome. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput host-virus interactome; bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'IntAct=EBI-748974'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25026213
  qualifier: enables
  review:
    summary: Interaction with the E3 ligase HACE1, which ubiquitinates OPTN to activate selective autophagy for tumor suppression. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the functionally important OPTN-HACE1 interaction (regulates OPTN's autophagy activity) but bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; Q8IYU2: HACE1; NbExp=15'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Proteome-scale interactome map. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'IntAct=EBI-748974'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25803835
  qualifier: enables
  review:
    summary: Interaction with TBK1 from the study identifying TBK1 haploinsufficiency in ALS/FTD. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; Q9UHD2: TBK1; NbExp=17'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25910212
  qualifier: enables
  review:
    summary: Macromolecular interaction perturbations in genetic disorders. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'IntAct=EBI-748974'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26871637
  qualifier: enables
  review:
    summary: Alternative-splicing interactome expansion. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'IntAct=EBI-748974'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27086836
  qualifier: enables
  review:
    summary: Interaction with TBK1 via OPTN's TBK1-binding domain, which promotes type I interferon responses. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the functionally central OPTN-TBK1 interaction but bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; Q9UHD2: TBK1; NbExp=17'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29892012
  qualifier: enables
  review:
    summary: Interactome-perturbation framework for damaging missense mutations. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'IntAct=EBI-748974'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30561431
  qualifier: enables
  review:
    summary: TNF-induced NF-kB signal-transduction interaction map (TNIP1). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome (relevant to OPTN's NF-kB role) but bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; Q15025: TNIP1; NbExp=23'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: Disruption of protein interactions by genetic variants. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'IntAct=EBI-748974'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Binary protein interactome reference map. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'IntAct=EBI-748974'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32707033
  qualifier: enables
  review:
    summary: Kinase interaction network (TBK1). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput kinase interactome (TBK1) but bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; Q9UHD2: TBK1; NbExp=17'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: Large neurodegeneration interactome screen contributing many OPTN interactors. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'IntAct=EBI-748974'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Cell-specific interactome remodeling (TNIP1). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; Q15025: TNIP1; NbExp=23'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:34524948
  qualifier: enables
  review:
    summary: Proximity interactome of the human macroautophagy pathway (TBK1). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput proximity interactome (relevant to autophagy) but bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; Q9UHD2: TBK1; NbExp=17'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Multimodal cell-map interactome (TNIP1). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; Q15025: TNIP1; NbExp=23'
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:23414517
  qualifier: enables
  review:
    summary: OPTN self-association (homo-oligomerization), supported by the strong OPTN-OPTN IntAct interaction.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; Q96CV9: OPTN; NbExp=16; IntAct=EBI-748974, EBI-748974'
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:24983867
  qualifier: enables
  review:
    summary: OPTN oligomerization and oxidative-stress/E50K-driven covalent cross-linking. Self-association is real but identical protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: Self-associates (PubMed:23669351)
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: OPTN-OPTN self-association from a proteome-scale interactome. Identical protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real self-association but uninformative term.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; Q96CV9: OPTN; NbExp=16'
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:25910212
  qualifier: enables
  review:
    summary: OPTN self-association from an interaction-perturbation study. Identical protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real self-association but uninformative term.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; Q96CV9: OPTN; NbExp=16'
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:26871637
  qualifier: enables
  review:
    summary: OPTN self-association from an alternative-splicing interactome. Identical protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real self-association but uninformative term.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; Q96CV9: OPTN; NbExp=16'
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: OPTN self-association from the binary interactome reference map. Identical protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real self-association but uninformative term.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; Q96CV9: OPTN; NbExp=16'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Human Protein Atlas immunofluorescence evidence for cytosolic localization, consistent with OPTN's predominantly cytoplasmic distribution.
    action: ACCEPT
    reason: Correct and well-supported cytosolic localization where OPTN performs its autophagy-receptor and trafficking-adaptor functions.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, perinuclear region'
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: EXP
  original_reference_id: PMID:10807909
  qualifier: located_in
  review:
    summary: Experimental evidence (NEMO-related protein study) that OPTN localizes to the Golgi apparatus.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported Golgi localization tied to the secondary Golgi/trafficking role.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: Golgi apparatus {ECO:0000269|PubMed:10807909
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: EXP
  original_reference_id: PMID:20085643
  qualifier: located_in
  review:
    summary: Experimental Golgi localization from the transferrin-receptor trafficking study.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported but redundant Golgi localization; tied to the secondary trafficking role.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: Golgi apparatus {ECO:0000269|PubMed:20085643
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: EXP
  original_reference_id: PMID:20174559
  qualifier: located_in
  review:
    summary: Experimental Golgi localization from the IFN-beta negative-regulation study; OPTN/TBK1 complex localizes to the Golgi region.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported but redundant Golgi localization.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: Golgi apparatus {ECO:0000269|PubMed:20174559
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: EXP
  original_reference_id: PMID:27538435
  qualifier: located_in
  review:
    summary: Experimental Golgi localization from the study showing the Golgi acts as a platform for OPTN-mediated TBK1 activation after viral RNA sensing.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported Golgi localization; here mechanistically linked to TBK1 activation but still a secondary compartment relative to the autophagy-receptor core.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: Golgi apparatus {ECO:0000269|PubMed:27538435
- term:
    id: GO:0055037
    label: recycling endosome
  evidence_type: EXP
  original_reference_id: PMID:20085643
  qualifier: located_in
  review:
    summary: Experimental evidence that OPTN localizes (UBAN-dependently) to recycling endosomes, required for transferrin-receptor trafficking.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported localization tied to the secondary endocytic-recycling role.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: Ubiquitin-binding motif (UBAN) ... is essential for subcellular localization to recycling endosomes
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9824892
  qualifier: located_in
  review:
    summary: Reactome cytosol localization for the mitophagy reaction (MAP1LC3B binds phospho-OPTN bound to Ub-mitochondria). Consistent with the cytosolic site of action.
    action: ACCEPT
    reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization.
    supported_by:
    - reference_id: PMID:25294927
      supporting_text: Optineurin then induces autophagosome formation around damaged mitochondria via its LC3 interaction region (LIR) domain
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9824897
  qualifier: located_in
  review:
    summary: Reactome cytosol localization for the mitophagy reaction (phospho-TBK1 phosphorylates OPTN). Consistent with the cytosolic site of action.
    action: ACCEPT
    reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization.
    supported_by:
    - reference_id: PMID:21617041
      supporting_text: The protein kinase TANK binding kinase 1 (TBK1) phosphorylated optineurin on serine-177
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9840807
  qualifier: located_in
  review:
    summary: Reactome cytosol localization for the reaction OPTN binds ATG9A. Consistent with the cytosolic site of action.
    action: ACCEPT
    reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, perinuclear region'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17646400
  qualifier: enables
  review:
    summary: Interaction with RAB8A from a study dissecting Rab GTPases in primary cilium formation. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the real OPTN-RAB8A interaction but bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'Q96CV9; P61006: RAB8A; NbExp=4'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9793680
  qualifier: located_in
  review:
    summary: Reactome cytosol localization for OPTN binding polyUb-RIPK1 within the TNFR1 complex. Consistent with the cytosolic site of action in NF-kB regulation.
    action: ACCEPT
    reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: NEMO-related protein
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9823816
  qualifier: located_in
  review:
    summary: Reactome cytosol localization for OPTN binding CASP8. Consistent with the cytosolic site of action.
    action: ACCEPT
    reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, perinuclear region'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9823934
  qualifier: located_in
  review:
    summary: Reactome cytosol localization for OPTN binding TBK1 within the activated TLR4 complex. Consistent with the cytosolic site of action.
    action: ACCEPT
    reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, perinuclear region'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9824874
  qualifier: located_in
  review:
    summary: Reactome cytosol localization for OPTN recruiting CYLD to the TNFR1 complex. Consistent with the cytosolic site of action in NF-kB regulation.
    action: ACCEPT
    reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: Interacts with CYLD (PubMed:32185393)
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9824888
  qualifier: located_in
  review:
    summary: Reactome cytosol localization for OPTN/TBK1 binding ubiquitinated mitochondrial outer-membrane proteins (mitophagy). Consistent with the cytosolic site of action.
    action: ACCEPT
    reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization.
    supported_by:
    - reference_id: PMID:25294927
      supporting_text: allowing optineurin to stably associate with ubiquitinated mitochondria via its ubiquitin binding domain
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9824894
  qualifier: located_in
  review:
    summary: Reactome cytosol localization for TBK1 phosphorylation within the TBK1:OPTN:Ub-mitochondria complex. Consistent with the cytosolic site of action.
    action: ACCEPT
    reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization.
    supported_by:
    - reference_id: PMID:25294927
      supporting_text: optineurin as an autophagy receptor in parkin-mediated mitophagy
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9828209
  qualifier: located_in
  review:
    summary: Reactome cytosol localization for OPTN binding TBK1 within the activated TLR3 complex. Consistent with the cytosolic site of action.
    action: ACCEPT
    reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, perinuclear region'
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IDA
  original_reference_id: PMID:27534431
  qualifier: located_in
  review:
    summary: Direct evidence that OPTN localizes to the Golgi/perinuclear region (ALS V295F mutant study).
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported Golgi localization tied to the secondary Golgi/trafficking role.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: Found in the perinuclear region and associates with the Golgi apparatus (PubMed:27534431)
- term:
    id: GO:0034620
    label: cellular response to unfolded protein
  evidence_type: IMP
  original_reference_id: PMID:27534431
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: increased susceptibility to endoplasmic reticulum (ER) stress
- term:
    id: GO:0090161
    label: Golgi ribbon formation
  evidence_type: IMP
  original_reference_id: PMID:27534431
  qualifier: involved_in
  review:
    summary: Mutant-phenotype evidence that the ALS V295F variant decreases Golgi ribbon formation, supporting OPTN involvement in Golgi ribbon formation.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported secondary Golgi-maintenance role; redundant with the IDA annotation from PMID:15837803.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: decreased Golgi ribbon formation
- term:
    id: GO:0010508
    label: positive regulation of autophagy
  evidence_type: IDA
  original_reference_id: PMID:21617041
  qualifier: involved_in
  review:
    summary: Direct evidence that OPTN promotes selective autophagy; it is recruited to and clusters with LC3 to drive autophagic clearance of cargo.
    action: ACCEPT
    reason: Core biological process; OPTN is a selective autophagy receptor that positively drives cargo-selective autophagy (here demonstrated for cytosolic Salmonella).
    supported_by:
    - reference_id: PMID:21617041
      supporting_text: phosphorylation of an autophagy receptor, optineurin, promoted selective autophagy of ubiquitin-coated cytosolic Salmonella enterica
- term:
    id: GO:1904417
    label: positive regulation of xenophagy
  evidence_type: IMP
  original_reference_id: PMID:21617041
  qualifier: involved_in
  review:
    summary: Mutant-phenotype evidence that OPTN (and its UBAN/LIR domains) is required to restrict cytosolic Salmonella by autophagy; OPTN depletion increases bacterial proliferation.
    action: ACCEPT
    reason: Core biological process; OPTN positively regulates xenophagy of ubiquitin-coated cytosolic bacteria, requiring both ubiquitin and LC3 binding.
    supported_by:
    - reference_id: PMID:21617041
      supporting_text: silencing of optineurin or TBK1 impaired Salmonella autophagy, resulting in increased intracellular bacterial proliferation
- term:
    id: GO:0055038
    label: recycling endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8854182
  qualifier: located_in
  review:
    summary: Reactome localization to the recycling-endosome membrane for the reaction TBC1D17 binds OPTN:RAB8A.
    action: KEEP_AS_NON_CORE
    reason: Correct membrane compartment tied to the secondary Rab8/TBC1D17 endocytic-recycling role.
    supported_by:
    - reference_id: PMID:22854040
      supporting_text: Optineurin mediates a negative regulation of Rab8 by the GTPase-activating protein TBC1D17
- term:
    id: GO:0061734
    label: type 2 mitophagy
  evidence_type: IMP
  original_reference_id: PMID:25294927
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:25294927
      supporting_text: our study establishes an important role for optineurin as an autophagy receptor in parkin-mediated mitophagy
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21617041
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:21617041
      supporting_text: The specific interactions between OPTN and LC3/GABARAP proteins were verified by pull-down assays
- term:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  evidence_type: IPI
  original_reference_id: PMID:25803835
  qualifier: enables
  review:
    summary: OPTN functions as an adaptor that bridges TBK1 (and, more broadly, ubiquitinated cargo to ATG8 proteins); interaction with TBK1 underpins this adaptor activity.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: Interacts with TBK1; this interaction leads to the Golgi localization of TBK1 and its subsequent activation
- term:
    id: GO:0001920
    label: negative regulation of receptor recycling
  evidence_type: IMP
  original_reference_id: PMID:22854040
  qualifier: involved_in
  review:
    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).
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported but secondary trafficking-regulatory role distinct from the core autophagy-receptor function.
    supported_by:
    - reference_id: PMID:22854040
      supporting_text: Optineurin mediates a negative regulation of Rab8 by the GTPase-activating protein TBC1D17
- term:
    id: GO:0031593
    label: polyubiquitin modification-dependent protein binding
  evidence_type: IDA
  original_reference_id: PMID:21617041
  qualifier: enables
  review:
    summary: Direct evidence that OPTN binds polyubiquitin chains (but not mono-ubiquitin) via its UBAN domain - a core molecular function for cargo recognition.
    action: ACCEPT
    reason: Core molecular function; OPTN's UBAN domain binds polyubiquitin chains, enabling recognition of ubiquitin-coated cargo. Complements the more specific K63-linkage annotation.
    supported_by:
    - reference_id: PMID:21617041
      supporting_text: OPTN bound to ubiquitin chains and autophagy modifiers ATG8/LC3/GABARAP proteins but not to mono-ubiquitin
- term:
    id: GO:0050829
    label: defense response to Gram-negative bacterium
  evidence_type: IMP
  original_reference_id: PMID:21617041
  qualifier: involved_in
  review:
    summary: Mutant-phenotype evidence that OPTN mediates autophagic defense against cytosolic Gram-negative Salmonella; loss of OPTN increases bacterial proliferation.
    action: ACCEPT
    reason: Core biological process; OPTN-mediated xenophagy is a cell-autonomous defense against cytosolic Gram-negative bacteria.
    supported_by:
    - reference_id: PMID:21617041
      supporting_text: OPTN appears to function in innate immunity against cytosolic bacteria by linking the TBK1 signaling pathway to autophagic elimination of cytosolic pathogens
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2562526
  qualifier: located_in
  review:
    summary: Reactome Golgi-membrane localization for the reaction PLK1 phosphorylates OPTN.
    action: KEEP_AS_NON_CORE
    reason: Correct membrane compartment from a Reactome pathway annotation; tied to the secondary Golgi/cell-cycle context.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: Cytoplasm, perinuclear region. Golgi apparatus
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2562594
  qualifier: located_in
  review:
    summary: Reactome nucleoplasm localization for the reaction phosphorylated OPTN translocates to the nucleus (PLK1-phosphorylated pool).
    action: KEEP_AS_NON_CORE
    reason: A minor PLK1-phosphorylated nuclear pool; secondary to the dominant cytoplasmic functions.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: Transcription factor IIIA-interacting protein
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2562526
  qualifier: located_in
  review:
    summary: Reactome cytosol localization for the reaction PLK1 phosphorylates OPTN. Consistent with the cytosolic site of action.
    action: ACCEPT
    reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, perinuclear region'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2562594
  qualifier: located_in
  review:
    summary: Reactome cytosol localization for the reaction phosphorylated OPTN translocates to the nucleus. Consistent with the cytosolic starting compartment.
    action: ACCEPT
    reason: Cytosol is the core site of OPTN action; this is a Reactome pathway-context annotation consistent with the direct (HPA IDA) cytosolic localization.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, perinuclear region'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15837803
  qualifier: enables
  review:
    summary: Interactions with myosin VI (MYO6) and RAB8 from the Golgi/exocytosis study. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the functionally important OPTN-MYO6 and OPTN-RAB8 interactions but bare protein binding is uninformative.
    supported_by:
    - reference_id: PMID:15837803
      supporting_text: we identified optineurin as a binding partner for myosin VI at the Golgi complex
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20174559
  qualifier: enables
  review:
    summary: Interactions with TBK1 and TRAF3 from the IFN-beta negative-regulation study. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the functionally important OPTN-TBK1 and OPTN-TRAF3 interactions but bare protein binding is uninformative.
    supported_by:
    - reference_id: PMID:20174559
      supporting_text: Immunoprecipitation and immunofluorescence studies identified optineurin in a protein complex containing the antiviral protein kinase TBK1 and the ubiquitin ligase TRAF3
- term:
    id: GO:0005802
    label: trans-Golgi network
  evidence_type: IDA
  original_reference_id: PMID:20174559
  qualifier: located_in
  review:
    summary: Direct evidence that OPTN localizes to the trans-Golgi network.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported localization tied to the secondary Golgi/trafficking and TBK1-scaffolding roles.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: Golgi apparatus, trans-Golgi network
- term:
    id: GO:0090161
    label: Golgi ribbon formation
  evidence_type: IDA
  original_reference_id: PMID:15837803
  qualifier: involved_in
  review:
    summary: Direct evidence that OPTN is required for Golgi ribbon formation; its depletion fragments the Golgi.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported secondary Golgi-maintenance role distinct from the core autophagy-receptor function.
    supported_by:
    - reference_id: PMID:15837803
      supporting_text: the Golgi is fragmented and exocytosis of vesicular stomatitis virus G-protein to the plasma membrane is dramatically reduced
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: TAS
  original_reference_id: PMID:9488477
  qualifier: located_in
  review:
    summary: Author-statement cytoplasmic localization from the original FIP-2/E3-14.7K study.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic compartment; redundant with the more specific cytosol/Golgi localizations.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, perinuclear region'
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: TAS
  original_reference_id: PMID:9488477
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: E3-14.7K-interacting protein
- term:
    id: GO:0008219
    label: cell death
  evidence_type: TAS
  original_reference_id: PMID:9488477
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Generic process term reflecting OPTN's modulation of TNF cytotoxicity; secondary to the autophagy-receptor core function.
    supported_by:
    - reference_id: file:human/OPTN/OPTN-uniprot.txt
      supporting_text: E3-14.7K-interacting protein {ECO:0000303|PubMed:9488477}
- term:
    id: GO:0043001
    label: Golgi to plasma membrane protein transport
  evidence_type: IMP
  original_reference_id: PMID:15837803
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported secondary exocytosis/trafficking role distinct from the autophagy-receptor core.
    supported_by:
    - reference_id: PMID:15837803
      supporting_text: exocytosis of vesicular stomatitis virus G-protein to the plasma membrane is dramatically reduced
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IDA
  original_reference_id: PMID:15837803
  qualifier: located_in
  review:
    summary: Direct evidence that OPTN localizes to the Golgi complex, where it colocalizes with myosin VI and Rab8.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported Golgi localization tied to the secondary Golgi/trafficking role.
    supported_by:
    - reference_id: PMID:15837803
      supporting_text: Both proteins colocalize at the Golgi complex and in vesicles at the plasma membrane
- term:
    id: GO:0007030
    label: Golgi organization
  evidence_type: IMP
  original_reference_id: PMID:15837803
  qualifier: involved_in
  review:
    summary: Mutant-phenotype (RNAi) evidence that OPTN is required for Golgi organization; its depletion fragments the Golgi.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported secondary Golgi-maintenance role distinct from the autophagy-receptor core.
    supported_by:
    - reference_id: PMID:15837803
      supporting_text: the Golgi is fragmented
- term:
    id: GO:0034067
    label: protein localization to Golgi apparatus
  evidence_type: IMP
  original_reference_id: PMID:15837803
  qualifier: involved_in
  review:
    summary: Mutant-phenotype (RNAi) evidence that OPTN is required to localize myosin VI to the Golgi; its depletion removes myosin VI from the Golgi.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported secondary Golgi-trafficking role; OPTN anchors myosin VI at the Golgi.
    supported_by:
    - reference_id: PMID:15837803
      supporting_text: depletion of optineurin causes a marked reduction in the amount of myosin VI associated with the Golgi complex
core_functions:
- description: Acts as a selective autophagy receptor by simultaneously binding polyubiquitin chains on cargo (via the UBAN motif) and ATG8/LC3/GABARAP-family modifiers on the autophagosomal membrane (via the LIR motif), thereby bridging ubiquitinated cargo to the nascent autophagosome; TBK1-mediated phosphorylation at Ser177 enhances LC3 binding.
  molecular_function:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0005776
    label: autophagosome
  supported_by:
  - reference_id: PMID:21617041
    supporting_text: OPTN is an autophagy receptor that binds and localizes with LC3/GABARAP via a phenylalanine-containing LIR motif and ubiquitin via its ubiquitin binding in ABIN and NEMO (UBAN) domains
  - reference_id: PMID:25294927
    supporting_text: Optineurin then induces autophagosome formation around damaged mitochondria via its LC3 interaction region (LIR) domain
  directly_involved_in:
  - id: GO:0010508
    label: positive regulation of autophagy
- description: Binds K63-linked and linear polyubiquitin chains via the UBAN domain, the molecular basis for recognizing ubiquitin-coated cargo (damaged mitochondria, cytosolic bacteria) and for engaging polyubiquitinated components of inflammatory/innate-immune signaling complexes.
  molecular_function:
    id: GO:0070530
    label: K63-linked polyubiquitin modification-dependent protein binding
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:21617041
    supporting_text: OPTN bound to ubiquitin chains and autophagy modifiers ATG8/LC3/GABARAP proteins but not to mono-ubiquitin
  - reference_id: PMID:25294927
    supporting_text: allowing optineurin to stably associate with ubiquitinated mitochondria via its ubiquitin binding domain
  directly_involved_in:
  - id: GO:0061734
    label: type 2 mitophagy
  - id: GO:1904417
    label: positive regulation of xenophagy
- description: Functions in antibacterial autophagy (xenophagy), serving as the cell-autonomous defense receptor that targets ubiquitin-coated cytosolic Gram-negative bacteria such as Salmonella for autophagic clearance, acting downstream of TBK1 and alongside SQSTM1/p62 and CALCOCO2/NDP52.
  molecular_function:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:21617041
    supporting_text: OPTN requires both Ub and LC3-binding domains to restrict bacterial growth in cells and can therefore be classified as a bona fide autophagy receptor for ubiquitinated bacteria
  directly_involved_in:
  - id: GO:1904417
    label: positive regulation of xenophagy
  - id: GO:0050829
    label: defense response to Gram-negative bacterium
- description: Serves as a receptor for PINK1/Parkin-dependent mitophagy, recognizing ubiquitinated outer-membrane proteins on depolarized/damaged mitochondria and recruiting LC3 to drive autophagosome formation around them; this function is disrupted by the ALS-linked UBAN mutant E478G.
  molecular_function:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:25294927
    supporting_text: our study establishes an important role for optineurin as an autophagy receptor in parkin-mediated mitophagy
  directly_involved_in:
  - id: GO:0061734
    label: type 2 mitophagy
proposed_new_terms: []
suggested_questions:
- question: 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?
- question: 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?
suggested_experiments:
- description: 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.
- description: 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.
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10807909
  title: Phorbol esters and cytokines regulate the expression of the NEMO-related
    protein, a molecule involved in a NF-kappa B-independent pathway.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Establishes OPTN as the NEMO-related protein (NRP), its Golgi localization, and cytokine-regulated expression. Supports the Golgi localization annotation.
- id: PMID:15837803
  title: Optineurin links myosin VI to the Golgi complex and is involved in Golgi
    organization and exocytosis.
  findings:
  - statement: OPTN binds myosin VI (and Rab8/huntingtin) at the Golgi; its depletion fragments the Golgi, removes myosin VI from the Golgi, and reduces VSV-G exocytosis, establishing roles in Golgi ribbon formation and exocytosis.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text available; foundational study for OPTN's secondary Golgi-maintenance/trafficking functions and its MYO6/Rab8 interactions.
- id: PMID:16189514
  title: Towards a proteome-scale map of the human protein-protein interaction network.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome; source of bare protein binding annotations.
- id: PMID:17500595
  title: Huntingtin interacting proteins are genetic modifiers of neurodegeneration.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Source of a bare protein binding (HTT) annotation.
- id: PMID:17646400
  title: Functional dissection of Rab GTPases involved in primary cilium formation.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Source of a bare protein binding (RAB8A) annotation.
- id: PMID:18307994
  title: Enhanced binding of TBK1 by an optineurin mutant that causes a familial form
    of primary open angle glaucoma.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Documents the disease-relevant OPTN-TBK1 interaction (E50K enhances binding); contributes a bare protein binding annotation.
- id: PMID:19805065
  title: Cargo binding induces dimerization of myosin VI.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Source of a bare protein binding (MYO6) annotation.
- id: PMID:20085643
  title: Regulation of endocytic trafficking of transferrin receptor by optineurin
    and its impairment by a glaucoma-associated mutant.
  findings:
  - statement: OPTN binds GTP-Rab8 and ubiquitinated TFRC via its UBAN domain and is required for transferrin-receptor endocytic recycling; the UBAN is essential for recycling-endosome localization. The E50K glaucoma mutant impairs this trafficking.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text available; establishes UBAN-dependent recycling-endosome localization and TFRC trafficking role.
- id: PMID:20174559
  title: Optineurin negatively regulates the induction of IFNbeta in response to RNA
    virus infection.
  findings:
  - statement: OPTN negatively regulates virus-triggered IFN-beta induction; it forms a complex with TBK1 and TRAF3 at the Golgi/TGN, and ubiquitin binding (via UBAN) is required for both correct localization and inhibitory function.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text available; basis for the TBK1/TRAF3 interactions, TGN localization, and the innate-immune (IFN) regulatory role.
- id: PMID:20195357
  title: A comprehensive resource of interacting protein regions for refining human
    transcription factor networks.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome; source of a bare protein binding annotation.
- id: PMID:20388642
  title: Overexpression of optineurin E50K disrupts Rab8 interaction and leads to
    a progressive retinal degeneration in mice.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Glaucoma E50K disrupts Rab8 interaction; contributes a bare protein binding (RAB8A) annotation.
- id: PMID:21516116
  title: Next-generation sequencing to generate interactome datasets.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome; source of a bare protein binding annotation.
- id: PMID:21617041
  title: Phosphorylation of the autophagy receptor optineurin restricts Salmonella
    growth.
  findings:
  - statement: OPTN is a bona fide selective autophagy receptor that binds polyubiquitin (UBAN) and LC3/GABARAP (LIR); TBK1 phosphorylates OPTN at Ser177, enhancing LC3 affinity and autophagic clearance of cytosolic Salmonella. Loss of OPTN or TBK1, or UBAN/LIR mutations, increases bacterial proliferation.
    reference_section_type: RESULTS
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text available; foundational study defining OPTN's core autophagy-receptor mechanism, LIR/UBAN domains, TBK1-S177 phosphorylation, and xenophagy/antibacterial defense.
- id: PMID:21903422
  title: Mapping a dynamic innate immunity protein interaction network regulating
    type I interferon production.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput innate-immunity interactome; source of a bare protein binding annotation.
- id: PMID:21988832
  title: Toward an understanding of the protein interaction network of the human liver.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome; source of a bare protein binding (TNIP1) annotation.
- id: PMID:22854040
  title: Optineurin mediates a negative regulation of Rab8 by the GTPase-activating
    protein TBC1D17.
  findings:
  - statement: OPTN bridges Rab8 to the GAP TBC1D17, negatively regulating Rab8-mediated endocytic recycling (including transferrin-receptor recycling).
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text available; basis for the negative regulation of receptor recycling and TBC1D17/Rab8 trafficking role.
- id: PMID:23275563
  title: Development and application of a DNA microarray-based yeast two-hybrid system.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput Y2H; source of a bare protein binding annotation.
- id: PMID:23414517
  title: 'A human skeletal muscle interactome centered on proteins involved in muscular
    dystrophies: LGMD interactome.'
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome; source of bare protein binding and identical protein binding (self-association) annotations.
- id: PMID:23956131
  title: Interaction between optineurin and the bZIP transcription factor NRL.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Source of a bare protein binding (NRL) annotation.
- id: PMID:24136289
  title: Identification and comparative analysis of hepatitis C virus-host cell protein
    interactions.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput host-virus interactome; source of a bare protein binding annotation.
- id: PMID:24983867
  title: 'Oligomerization of optineurin and its oxidative stress- or E50K mutation-driven
    covalent cross-linking: possible relationship with glaucoma pathology.'
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Documents OPTN self-association/oligomerization and aberrant E50K cross-linking; supports the identical protein binding annotation.
- id: PMID:25026213
  title: Ubiquitylation of autophagy receptor Optineurin by HACE1 activates selective
    autophagy for tumor suppression.
  findings:
  - statement: The E3 ligase HACE1 ubiquitinates OPTN to activate selective autophagy, contributing to tumor suppression; establishes the OPTN-HACE1 functional interaction.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Full text available; source of the OPTN-HACE1 (bare protein binding) annotation and a regulatory mechanism for OPTN's autophagy activity.
- id: PMID:25294927
  title: Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated
    mitophagy that is disrupted by an ALS-linked mutation.
  findings:
  - statement: OPTN is recruited (Parkin-dependently, via its UBAN domain) to ubiquitinated damaged mitochondria and recruits LC3 via its LIR to drive mitophagy; the ALS-linked UBAN mutant E478G fails to rescue, defining OPTN as a mitophagy receptor.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text available; foundational study for OPTN's role in PINK1/Parkin (type 2) mitophagy.
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome; source of bare protein binding and self-association annotations.
- id: PMID:25803835
  title: Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia.
  findings:
  - statement: TBK1 loss-of-function causes ALS/FTD; OPTN-TBK1 binding is a basis for the protein-macromolecule adaptor activity annotation.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Source of the OPTN protein-macromolecule adaptor activity (TBK1) annotation; links OPTN-TBK1 axis to ALS.
- id: PMID:25910212
  title: Widespread macromolecular interaction perturbations in human genetic disorders.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome; source of bare protein binding and self-association annotations.
- id: PMID:26871637
  title: Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome; source of bare protein binding and self-association annotations.
- id: PMID:27086836
  title: The TBK1-binding domain of optineurin promotes type I interferon responses.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Documents the OPTN TBK1-binding domain and its role in type I IFN responses; contributes a bare protein binding (TBK1) annotation.
- id: PMID:27534431
  title: A novel amyotrophic lateral sclerosis mutation in OPTN induces ER stress
    and Golgi fragmentation in vitro.
  findings:
  - statement: The ALS12 OPTN variant V295F increases Golgi fragmentation, decreases Golgi ribbon formation, and increases susceptibility to ER stress, without changing Golgi localization or expression level.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Full text available; basis for the Golgi-ribbon-formation, Golgi localization, and cellular-response-to-unfolded-protein (ER stress) annotations (mutant-phenotype readouts).
- id: PMID:27538435
  title: The Golgi apparatus acts as a platform for TBK1 activation after viral RNA
    sensing.
  findings:
  - statement: OPTN recruits TBK1 to the Golgi apparatus, promoting its trans-phosphorylation/activation after RLR or TLR3 stimulation, leading to IRF3 phosphorylation and IFN-beta production.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text available; mechanistic basis for OPTN-mediated Golgi recruitment/activation of TBK1 in innate immune signaling.
- id: PMID:29892012
  title: An interactome perturbation framework prioritizes damaging missense mutations
    for developmental disorders.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome; source of a bare protein binding annotation.
- id: PMID:30561431
  title: A protein-protein interaction map of the TNF-induced NF-κB signal transduction
    pathway.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput NF-kB pathway interactome (TNIP1); source of a bare protein binding annotation.
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the
    allele frequency spectrum in human populations.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome; source of a bare protein binding annotation.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Binary interactome reference map; source of bare protein binding and self-association annotations.
- id: PMID:32707033
  title: Kinase Interaction Network Expands Functional and Disease Roles of Human
    Kinases.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput kinase interactome (TBK1); source of a bare protein binding annotation.
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Large neurodegeneration interactome; source of many bare protein binding annotations.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Cell-specific interactome; source of a bare protein binding (TNIP1) annotation.
- id: PMID:34524948
  title: Global Proximity Interactome of the Human Macroautophagy Pathway.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Proximity interactome of macroautophagy (TBK1); source of a bare protein binding annotation.
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput cell-map interactome; source of a bare protein binding annotation.
- id: PMID:9488477
  title: Interaction of an adenovirus E3 14.7-kilodalton protein with a novel tumor
    necrosis factor alpha-inducible cellular protein containing leucine zipper domains.
  findings:
  - statement: OPTN (FIP-2) was identified as a TNF-alpha-inducible, leucine-zipper-containing protein that interacts with adenovirus E3-14.7K and modulates TNF-induced cytolysis; cytoplasmic localization.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Original identification of OPTN/FIP-2; basis for the generic cytoplasm, signal transduction, and cell death TAS annotations.
- id: Reactome:R-HSA-2562526
  title: PLK1 phosphorylates OPTN
  findings: []
- id: Reactome:R-HSA-2562594
  title: Phosphorylated OPTN translocates to the nucleus
  findings: []
- id: Reactome:R-HSA-8854182
  title: TBC1D17 binds OPTN:RAB8A
  findings: []
- id: Reactome:R-HSA-9793680
  title: OPTN binds polyUb-RIPK1 within the TNFR1 complex
  findings: []
- id: Reactome:R-HSA-9823816
  title: OPTN binds CASP8
  findings: []
- id: Reactome:R-HSA-9823934
  title: OPTN binds TBK1 within the activated TLR4 complex
  findings: []
- id: Reactome:R-HSA-9824874
  title: OPTN recruits CYLD to the TNFR1 complex
  findings: []
- id: Reactome:R-HSA-9824888
  title: OPTN, TBK1 bind ubiquitinated MOM proteins
  findings: []
- id: Reactome:R-HSA-9824892
  title: MAP1LC3B binds p-S-OPTN bound to Ub-mitochondria
  findings: []
- id: Reactome:R-HSA-9824894
  title: TBK1 is phosphorylated within TBK1:OPTN:Ub-mitochondrial proteins
  findings: []
- id: Reactome:R-HSA-9824897
  title: p-S-TBK1 phosphorylates OPTN
  findings: []
- id: Reactome:R-HSA-9828209
  title: OPTN binds TBK1 within the activated TLR3 complex
  findings: []
- id: Reactome:R-HSA-9840807
  title: OPTN binds ATG9A
  findings: []