InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: OPTN

Summary

InnateDB Protein

IDBP-54470.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

OPTN

Protein Name

optineurin

Synonyms

ALS12; FIP2; GLC1E; HIP7; HYPL; NRP; TFIIIA-INTP;

Species

Homo sapiens

Ensembl Protein

ENSP00000368040

InnateDB Gene

IDBG-54466 (OPTN)

Protein Structure

UniProt Annotation

Function

Plays 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:0000269PubMed:11834836, ECO:0000269PubMed:15837803, ECO:0000269PubMed:20085643, ECO:0000269PubMed:20174559, ECO:0000269PubMed:21617041, ECO:0000269PubMed:22854040}.

Subcellular Localization

Cytoplasm, 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.

Disease Associations

Glaucoma 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:0000269PubMed:11834836, ECO:0000269PubMed:12939304, ECO:0000269PubMed:14597044, ECO:0000269PubMed:15226658, ECO:0000269PubMed:15326130, ECO:0000269PubMed:15557444}. Note=The disease is caused by mutations affecting the gene represented in this entry.Glaucoma, normal pressure (NPG) [MIM:606657]: A primary glaucoma characterized by intraocular pression consistently within the statistically normal population range. {ECO:0000269PubMed:15370540}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Amyotrophic 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:0000269PubMed:20428114}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Present 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:0000269PubMed:11834836, ECO:0000269PubMed:9488477}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 103 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	103 [view]
Protein-Protein	103 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0008022	protein C-terminus binding
GO:0031593	polyubiquitin binding

Biological Process

GO:0000042	protein targeting to Golgi
GO:0000086	G2/M transition of mitotic cell cycle
GO:0000278	mitotic cell cycle
GO:0001920	negative regulation of receptor recycling
GO:0007030	Golgi organization
GO:0007165	signal transduction
GO:0008219	cell death
GO:0016236	macroautophagy
GO:0043001	Golgi to plasma membrane protein transport
GO:0045087	innate immune response (InnateDB)
GO:0050829	defense response to Gram-negative bacterium
GO:0090161	Golgi ribbon formation

Cellular Component

GO:0000139	Golgi membrane
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005794	Golgi apparatus
GO:0005802	trans-Golgi network
GO:0005829	cytosol
GO:0048471	perinuclear region of cytoplasm