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FLASH GENE
Symbol OPTN contributors: mct/npt/pgu - updated : 24-10-2015
HGNC name optineurin
HGNC id 17142
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • leucine zipper motif
  • one zinc finger motif, C2H2 type
  • TBK1 binding site located between AAs 1-127 (N-terminal)
  • tail region (423-577 AAs) of OPTN was necessary for binding with NRL
    • HOMOLOGY
    interspecies ortholog to murine Optn
    Homologene
    FAMILY
    CATEGORY adaptor , regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,nucleus,nucleoplasm
    text myosin VI and OPTN colocalize with secretory vesicles at the plasma membrane
    basic FUNCTION
  • blocks the protective effect of E3-14.7K on tumor necrosis factor-alpha-mediated cell killing (inhibiting cytolysis)
  • critical adaptor that regulates the assembly of TAX1BP1 and post-translationally modified forms of Tax1, leading to sustained NF-kappaB activation
  • involved in the pathogenesis of amyotrophic lateral sclerosis
  • role for myosin VI and optineurin in regulation of fusion pores formed between secretory vesicles and the plasma membrane during the final stages of secretion
  • involved in basic cellular functions including protein trafficking, maintenance of the Golgi apparatus, as well as NFKB pathway, antiviral, and antibacteria signaling
  • important role in the spatial and temporal coordination of PLK1 activity
  • OPTN suppresses nuclear factor-kappa B (NFKB) activity
  • adaptor protein involved in signal transduction, membrane vesicle trafficking and autophagy
  • polyubiquitin-binding protein that has been implicated in regulating cell signaling via its NFKB essential modulator-homologous C-terminal ubiquitin (Ub)-binding region
  • is involved in several functions including regulation of endocytic trafficking, autophagy and signal transduction
  • multifunctional protein involved in cellular morphogenesis, vesicle trafficking, maintenance of the Golgi complex, and transcription activation
  • plays a central role in the adult-onset neuronal intranuclear inclusion disease pathogenesis, and may be a major component of neuronal intranuclear inclusions
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS nervous system
    text playing a putative neuroprotective role in the eye and optic nerve
    PATHWAY
    metabolism
    signaling signal transduction , sensory transduction/vision
    implicated in tumor necrosis factor alpha signaling pathway
    a component HACE1-OPTN axis synergistically suppresses growth and tumorigenicity of lung cancer cells
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
    • protein
  • Huntingtin (HD)
  • Ras-associated protein RAB8
  • transcription factor IIIA
  • adenovirus E3-14.7K
  • binds to the C-terminal region of TBK1 and deletion of the C-terminal 40 residues of TBK1, which prevents interaction with TANK, also abolishes interaction with OPTN
  • interacts cooperatively with TAX1BP1 (OPTN and TAX1BP1 cooperate to modulate Tax1 ubiquitination and NF-kappaB activation)
  • is associated with a myosin phosphatase complex (MP), which antagonizes the mitotic function of PLK1
  • mediates the interaction and colocalisation of TBC1D17 with RAB8A
  • IRF1 mediates IFNG-induced optineurin promoter activation
  • RAB25 associates with OPTN and can recruit this effector protein to endosomal membranes
  • endogenous optineurin is dispensable for NFKB activation but necessary for optimal IRF3 activation in immune cells
  • HACE1 ubiquitylates OPTN and promotes its interaction with p62/SQSTM1 to form the autophagy receptor complex, thus accelerating autophagic flux
  • APP interacts with MAP1LC3B via OPTN/optineurin and is degraded by an autophagic process mediated by the PRKAA1 pathway
  • constitutive interaction of TBK1 with OPTN and the ability of OPTN to bind to ubiquitin chains are essential for TBK1 recruitment and kinase activation on mitochondria
  • OPTN is a positive regulator TBK1 via a bipartite interaction between these molecules
    • cell & other
    REGULATION
    activated by IRF1, that cooperates with NFKB to activate optineurin promoter
    induced by TNF-alpha, interferon
    its expression is induced by cytokines
    Phosphorylated by TBK1 that directly phosphorylated the autophagic adaptor optineurin (OPTN)
    ASSOCIATED DISORDERS
    corresponding disease(s) GLC1E , ALS12
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    in Huntington disease optineurin is present in intranuclear, neuropil and perikaryal inclusions
    Susceptibility
  • to glaucoma with normal tension
  • to Paget disease
    • Variant & Polymorphism other
  • variant M98K modifying initial intraocular pression in patients with primary open angle glaucoma
  • rs1561570 strongly associated with Paget disease
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS