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FLASH GENE
Symbol OPTN contributors: mct/npt/pgu - updated : 24-10-2015
HGNC name optineurin
HGNC id 17142
Corresponding disease
ALS12 amyotrophic lateral sclerosis 12
GLC1E glaucoma, primary open angle 1E
Location 10p13      Physical location : 13.142.081 - 13.180.276
Synonym name
  • Huntingtin interacting protein L
  • tumor necrosis factor alpha-inducible cellular protein containing leucine zipper domains
  • nemo-related protein
  • transcrption factor IIIA-interacting protein
  • glaucoma 1, open angle, E (adult-onset)
  • E3-14.7K-interacting protein
  • Synonym symbol(s) FIP2, NRP, HYPL, TFIIIA-INTP, HIP7, ALS12, GLC1E
    DNA
    TYPE functioning gene
    STRUCTURE 38.20 kb     16 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure
  • three non-coding exons in the 5'-untranslated region and thirteen coding exons
  • TNF activates optineurin promoter through NFKB-binding site in the core promoter
  • a functional IRF1-binding site in the first intron of human optineurin gene that mediates IFNG-induced activation of the promoter
  • MAPPING cloned Y linked N status provisional
    Physical map
    USP6NL 10p13 USP6 N-terminal like ECHDC3 10p14 enoyl Coenzyme A hydratase domain containing 3 C10orf47 10p14 chromosome 10 open reading frame 47 UPF2 10p14-p13 UPF2 regulator of nonsense transcripts homolog (yeast) DHTKD1 10p14 dehydrogenase E1 and transketolase domain containing 1 SEC61A2 10p14 dehydrogenase E1 and transketolase domain containing 1 NUDT5 10p14-p13 nudix (nucleoside diphosphate linked moiety X)-type motif 5 C10orf7 10p13 chromosome 10 open reading frame 7 CAMK1D 10p13 calcium/calmodulin-dependent protein kinase ID DKFZP761F241 10p14 hypothetical protein DKFZp761F241 LOC389939 10 similar to ribosomal protein L5 OPTN 10p14 optineurin MCM10 10p13 MCM10 minichromosome maintenance deficient 10 (S. cerevisiae) LOC221044 10p14 hypothetical protein BC018068 PHYH 10p15-p14 phytanoyl-CoA hydroxylase (Refsum disease) SEPHS1 10p14 selenophosphate synthetase 1 C10orf30 10p14 chromosome 10 open reading frame 30 PRPF18 10p12.33 PRP18 pre-mRNA processing factor 18 homolog (yeast) FLJ10210 C10orf45 10p14 chromosome 10 open reading frame 45 LOC283071 10p14 similar to hypothetical protein 9330140G23 HSP70-4 10p14 likely ortholog of mouse heat shock protein, 70 kDa 4 SUV39H2 10p13 suppressor of variegation 3-9 homolog 2 (Drosophila) DCLRE1C 10p14-p13 DNA cross-link repair 1C (PSO2 homolog, S. cerevisiae) LOC389940 10 similar to seven transmembrane helix receptor FLJ11106 10p13 hypothetical protein FLJ11106
    RNA
    TRANSCRIPTS type messenger
    text three different variants resulting form alternative splicing at the 5'-UTR, but all have the same reading frame
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 - 3597 36 577 - 2008 18385781
    OPTN variant 1
    14 - 3376 36 577 - 2008 18385781
    OPTN variant 2
    15 - 3528 36 577 three to four times less abundant than the variant 1 in trabecular meshwork and nonpigmented ciliary epithelium 2008 18385781
    OPTN variant 3
    16 - 3582 - 577 - 2008 18385781
    OPTN variant 4
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveintestinesmall intestine  highly
    Endocrinepancreas   highly
    Nervousnerve   highly
    Reproductivemale systemtestis  highly
    Urinarykidney    
    Visualeyeretina    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    Muscularstriatumcardiac  
    Muscularstriatumskeletal highly
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
     digestive
    Lymphoid/Immunelymphocyte
    Visualcone photoreceptor Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text trabecular meshwork
    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