Phospho-OPTN (Ser177)

This gene encodes the coiled-coil containing protein optineurin. Optineurin may play a role in normal-tension glaucoma and adult-onset primary open angle glaucoma. Optineurin interacts with adenovirus E3-14.7K protein and may utilize tumor necrosis factor-alpha or Fas-ligand pathways to mediate apoptosis, inflammation or vasoconstriction. Optineurin may also function in cellular morphogenesis and membrane trafficking, vesicle trafficking, and transcription activation through its interactions with the RAB8, huntingtin, and transcription factor IIIA proteins. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

Optineurin

Plays an important role in the maintenance of the Golgi complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8 (PubMed:27534431).
Links myosin VI to the Golgi complex and plays an important role in Golgi ribbon formation (PubMed:27534431).
Plays a role in the activation of innate immune response during viral infection. Mechanistically, recruits TBK1 at the Golgi apparatus, promoting its trans-phosphorylation after RLR or TLR3 stimulation (PubMed:27538435).
In turn, activated TBK1 phosphorylates its downstream partner IRF3 to produce IFN-beta. Plays a neuroprotective role in the eye and optic nerve. May act by regulating membrane trafficking and cellular morphogenesis via a complex that contains Rab8 and hungtingtin (HD). Mediates the interaction of Rab8 with the probable GTPase-activating protein TBC1D17 during Rab8-mediated endocytic trafficking, such as of transferrin receptor (TFRC/TfR); regulates Rab8 recruitment to tubules emanating from the endocytic recycling compartment. Autophagy receptor that interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family; targets ubiquitin-coated bacteria (xenophagy), such as cytoplasmic Salmonella enterica, and appears to function in the same pathway as SQSTM1 and CALCOCO2/NDP52.
(Microbial infection) May constitute a cellular target for adenovirus E3 14.7 and Bluetongue virus protein NS3 to inhibit innate immune response.

AutophagyIEA:UniProtKB-KW
Cell deathManual Assertion Based On ExperimentTAS:ProtInc
Cellular response to unfolded proteinManual Assertion Based On ExperimentIMP:UniProtKB
Defense response to Gram-negative bacteriumManual Assertion Based On ExperimentIMP:UniProtKBGolgi organizationManual Assertion Based On ExperimentIMP:UniProtKB
Golgi ribbon formationManual Assertion Based On ExperimentIDA:UniProtKB
Golgi to plasma membrane protein transportManual Assertion Based On ExperimentIMP:UniProtKB
Innate immune responseIEA:UniProtKB-KW
Negative regulation of I-kappaB kinase/NF-kappaB signalingIEA:Ensembl
Negative regulation of receptor recyclingManual Assertion Based On ExperimentIMP:UniProtKB
Parkin-mediated stimulation of mitophagy in response to mitochondrial depolarizationManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Positive regulation of autophagyManual Assertion Based On ExperimentIDA:GO_Central
Positive regulation of xenophagyManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Protein localization to Golgi apparatusManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIBA:GO_Central
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc

Cytoplasm, perinuclear region
Golgi apparatus
Golgi apparatus, trans-Golgi network
Cytoplasmic vesicle, autophagosome
Cytoplasmic vesicle
Recycling endosome
Found in the perinuclear region and associates with the Golgi apparatus (PubMed:27534431).
Colocalizes with MYO6 and RAB8 at the Golgi complex and in vesicular structures close to the plasma membrane. Localizes to LC3-positive cytoplasmic vesicles upon induction of autophagy.

Glaucoma 1, open angle, E (GLC1E):
A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place.
Glaucoma, normal pressure (NPG):
A primary glaucoma characterized by intraocular pression consistently within the statistically normal population range.
Amyotrophic lateral sclerosis 12 with or without frontotemporal dementia (ALS12):
A form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. ALS12 inheritance can be autosomal dominant or autosomal recessive. There is also sporadic occurrence. ALS12 patients may develop frontotemporal dementia.

Phosphorylated by TBK1, leading to restrict bacterial proliferation in case of infection. Phosphorylation is induced by phorbol esters and decreases its half-time.