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MGP004138

UniProt Annotations

Entry Information
Gene Nameoptineurin
Protein EntryOPTN_HUMAN
UniProt IDQ96CV9
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; IsoId=Q96CV9-1; Sequence=Displayed; Name=2; IsoId=Q96CV9-2; Sequence=VSP_013262; Note=No experimental confirmation available.; Name=3; IsoId=Q96CV9-3; Sequence=VSP_013261;
CautionAccording to some authors (PubMed:12379221) its expression is regulated by intraocular pressure, suggesting a protective role in case of high pressure, while according to other authors (PubMed:12646749), it is not up-regulated in response to pressure elevation. {ECO:0000305|PubMed:12379221, ECO:0000305|PubMed:12646749}.
CautionInteraction of variant GLC1E LYS-50 with Rab8 is reported conflictingly. Coimmunoprecipitation experiments with overexpressed proteins suggested an increased interacion (PubMed:20085643) while yeast-two-hybrid (PubMed:22854040) and protein complentation assays with an equivalent mouse Optn construct (AC Q8K3K8) failed to show an interaction. {ECO:0000305|PubMed:20085643, ECO:0000305|PubMed:22854040}.
DiseaseAmyotrophic lateral sclerosis 12 (ALS12) [MIM:613435]: 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. {ECO:0000269|PubMed:20428114}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseGlaucoma 1, open angle, E (GLC1E) [MIM:137760]: 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. {ECO:0000269|PubMed:11834836, ECO:0000269|PubMed:12939304, ECO:0000269|PubMed:14597044, ECO:0000269|PubMed:15226658, ECO:0000269|PubMed:15326130, ECO:0000269|PubMed:15557444}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseGlaucoma, normal pressure (NPG) [MIM:606657]: A primary glaucoma characterized by intraocular pression consistently within the statistically normal population range. {ECO:0000269|PubMed:15370540}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
DomainThe LIR (LC3-interacting region) motif mediates the interaction with ATG8 family proteins. {ECO:0000269|PubMed:23908376}.
DomainUbiquitin-binding motif (UBAN) is essential for its inhibitory function, subcellular localization and interaction with TBK1.
FunctionPlays an important role in the maintenance of the Golgi complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8. Links myosin VI to the Golgi complex and plays an important role in Golgi ribbon formation. Negatively regulates the induction of IFNB in response to RNA virus infection. Plays a neuroprotective role in the eye and optic nerve. Probably part of the TNF-alpha signaling pathway that can shift the equilibrium toward induction of cell death. 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 recruitnment 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. May constitute a cellular target for adenovirus E3 14.7, an inhibitor of TNF-alpha functions, thereby affecting cell death. {ECO:0000269|PubMed:11834836, ECO:0000269|PubMed:15837803, ECO:0000269|PubMed:20085643, ECO:0000269|PubMed:20174559, ECO:0000269|PubMed:21617041, ECO:0000269|PubMed:22854040}.
InductionUpon TNF and interferon treatments. Up-regulated in direct response to viral infection. {ECO:0000269|PubMed:10807909, ECO:0000269|PubMed:12379221, ECO:0000269|PubMed:12646749, ECO:0000269|PubMed:20174559, ECO:0000269|PubMed:9488477}.
InteractionQ99IB8:- (xeno); NbExp=3; IntAct=EBI-748974, EBI-6858501; Q13023:AKAP6; NbExp=2; IntAct=EBI-748974, EBI-1056102; Q03001:DST; NbExp=2; IntAct=EBI-748974, EBI-310758; O75923:DYSF; NbExp=3; IntAct=EBI-748974, EBI-2799016; Q8IYU2:HACE1; NbExp=15; IntAct=EBI-748974, EBI-308277; P42858:HTT; NbExp=7; IntAct=EBI-748974, EBI-466029; Q00013:MPP1; NbExp=2; IntAct=EBI-748974, EBI-711788; P61006:RAB8A; NbExp=4; IntAct=EBI-748974, EBI-722293; Q14BN4:SLMAP; NbExp=2; IntAct=EBI-748974, EBI-1043216; Q9UNH7:SNX6; NbExp=2; IntAct=EBI-748974, EBI-949294; Q13501:SQSTM1; NbExp=7; IntAct=EBI-748974, EBI-307104; Q9HA65:TBC1D17; NbExp=7; IntAct=EBI-748974, EBI-714625; Q9UHD2:TBK1; NbExp=11; IntAct=EBI-748974, EBI-356402; Q15025:TNIP1; NbExp=3; IntAct=EBI-748974, EBI-357849; Q8WZ42:TTN; NbExp=2; IntAct=EBI-748974, EBI-681210; P04275:VWF; NbExp=2; IntAct=EBI-748974, EBI-981819; Q8IUH5:ZDHHC17; NbExp=2; IntAct=EBI-9091423, EBI-524753;
PtmPhosphorylated by TBK1, leading to restrict bacterial proliferation in case of infection. Phosphorylation is induced by phorbol esters and decreases its half-time. {ECO:0000269|PubMed:10807909, ECO:0000269|PubMed:21617041}.
Sequence CautionSequence=CAI16552.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
Subcellular LocationCytoplasm, perinuclear region. Golgi apparatus. Golgi apparatus, trans-Golgi network. Cytoplasmic vesicle, autophagosome. Cytoplasmic vesicle. Recycling endosome. Note=Found in the perinuclear region and associates with the Golgi apparatus. 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.
SubunitInteracts with HD, Rab8 (RAB8A and/or RAB8B) (active GTP- bound form), GTF3A, TRAF3, TBK1, MYO6 and TFRC. Binds to linear ubiquitin chains. Interacts with LC3 family members MAP1LC3A, MAP1LC3B, GABARAP, GABARAPL1 and GABARAPL2; OPTN phosphorylation increases the asscociation (at least with MAP1LC3B). Self- associates. Interacts with RAB12; the interaction may be indirect. Interacts with E3 14.7 kDa protein of group C human adenovirus. {ECO:0000269|PubMed:10756201, ECO:0000269|PubMed:11137014, ECO:0000269|PubMed:15837803, ECO:0000269|PubMed:20085643, ECO:0000269|PubMed:20174559, ECO:0000269|PubMed:21617041, ECO:0000269|PubMed:22854040, ECO:0000269|PubMed:23357852, ECO:0000269|PubMed:23669351, ECO:0000269|PubMed:23805866, ECO:0000269|PubMed:9488477, ECO:0000269|PubMed:9700202}.
Tissue SpecificityPresent in aqueous humor of the eye (at protein level). Highly expressed in trabecular meshwork. Expressed nonpigmented ciliary epithelium, retina, brain, adrenal cortex, fetus, lymphocyte, fibroblast, skeletal muscle, heart, liver, brain and placenta. {ECO:0000269|PubMed:11834836, ECO:0000269|PubMed:9488477}.
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