Optineurin

OPTN
Identifiers
Aliases	OPTN, ALS12, FIP2, GLC1E, HIP7, HYPL, NRP, TFIIIA-INTP, optineurin
External IDs	OMIM: 602432; MGI: 1918898; GeneCards: OPTN
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2LO4, 2LUE, 5AAZ
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10p13 Start 13,099,449 bp[1] End 13,138,308 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 A1|2 3.15 cM Start 5,025,453 bp[2] End 5,068,862 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in amniotic fluid gastrocnemius muscle muscle of thigh glutes triceps brachii muscle vastus lateralis muscle Skeletal muscle tissue of biceps brachii tendon tendon of biceps brachii thoracic diaphragm Top expressed in neural layer of retina muscle of thigh jejunum iris retinal pigment epithelium spermatid myocardium of ventricle seminiferous tubule interventricular septum knee joint More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein-macromolecule adaptor activity protein C-terminus binding protein binding identical protein binding K63-linked polyubiquitin modification-dependent protein binding metal ion binding polyubiquitin modification-dependent protein binding Cellular component recycling endosome endosome Golgi membrane nucleoplasm autophagosome trans-Golgi network perinuclear region of cytoplasm nucleus Golgi apparatus cytoplasm cytosol recycling endosome membrane cytoplasmic vesicle Biological process Golgi organization cell death negative regulation of I-kappaB kinase/NF-kappaB signaling autophagy G2/M transition of mitotic cell cycle defense response to Gram-negative bacterium negative regulation of receptor recycling vesicle-mediated transport regulation of I-kappaB kinase/NF-kappaB signaling signal transduction Golgi to plasma membrane protein transport parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization positive regulation of xenophagy positive regulation of autophagy Unfolded protein response Golgi ribbon formation immune system process innate immune response protein localization to Golgi apparatus Sources:Amigo / QuickGO
Orthologs Databases NCBI: entry; OMA: entry Species Human Mouse Entrez 10133 71648 Ensembl ENSG00000123240 ENSMUSG00000026672 UniProt Q96CV9 Q8K3K8 RefSeq (mRNA) NM_001008211 NM_001008212 NM_001008213 NM_021980 NM_181848 NM_001356487 RefSeq (protein) NP_001008212 NP_001008213 NP_001008214 NP_068815 NP_862896 NP_001343416 Location (UCSC) Chr 10: 13.1 – 13.14 Mb Chr 2: 5.03 – 5.07 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Optineurin is a protein that in humans is encoded by the OPTN gene.^[5][6][7]

Structure

This gene encodes the coiled-coil containing protein optineurin. Alternative splicing results in multiple transcript variants encoding the same protein.^[7]

Function

Optineurin may function in cellular morphogenesis and membrane trafficking, vesicle trafficking, and transcription activation through its interactions with the RAB8, huntingtin, and transcription factor IIIA proteins. OPTN is a host intrinsic restriction factor against neuroinvasive HSV-1 infection.^[8]

Clinical significance

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.

Interactions

Optineurin has been shown to interact with Huntingtin^[9][10] and RAB8A.^[10]

References

1. GRCh38: Ensembl release 89: ENSG00000123240 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000026672 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Rezaie T, Child A, Hitchings R, Brice G, Miller L, Coca-Prados M, et al. (February 2002). "Adult-onset primary open-angle glaucoma caused by mutations in optineurin". Science. 295 (5557). New York, N.Y.: 1077–1079. Bibcode:2002Sci...295.1077R. doi:10.1126/science.1066901. PMID 11834836. S2CID 23635499.
6. Li Y, Kang J, Horwitz MS (March 1998). "Interaction of an adenovirus E3 14.7-kilodalton protein with a novel tumor necrosis factor alpha-inducible cellular protein containing leucine zipper domains". Molecular and Cellular Biology. 18 (3): 1601–1610. doi:10.1128/mcb.18.3.1601. PMC 108875. PMID 9488477.
7. "Entrez Gene: OPTN optineurin".
8. Ames J, Yadavalli T, Suryawanshi R, Hopkins J, Agelidis A, Patil C, et al. (September 2021). "OPTN is a host intrinsic restriction factor against neuroinvasive HSV-1 infection". Nature Communications. 12 (1) 5401. Bibcode:2021NatCo..12.5401A. doi:10.1038/s41467-021-25642-z. PMC 8437952. PMID 34518549.
9. Faber PW, Barnes GT, Srinidhi J, Chen J, Gusella JF, MacDonald ME (September 1998). "Huntingtin interacts with a family of WW domain proteins". Human Molecular Genetics. 7 (9): 1463–1474. doi:10.1093/hmg/7.9.1463. PMID 9700202.
10. Hattula K, Peränen J (2000). "FIP-2, a coiled-coil protein, links Huntingtin to Rab8 and modulates cellular morphogenesis". Current Biology. 10 (24): 1603–1606. Bibcode:2000CBio...10.1603H. doi:10.1016/S0960-9822(00)00864-2. PMID 11137014. S2CID 12836037.

Further reading

• Sarfarazi M, Rezaie T (December 2003). "Optineurin in primary open angle glaucoma". Ophthalmology Clinics of North America. 16 (4): 529–541. doi:10.1016/S0896-1549(03)00061-0. PMID 14740994.
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (April 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–113. doi:10.1006/abio.1996.0138. PMID 8619474.
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, et al. (April 1997). "Large-scale concatenation cDNA sequencing". Genome Research. 7 (4): 353–358. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
• Sarfarazi M, Child A, Stoilova D, Brice G, Desai T, Trifan OC, et al. (March 1998). "Localization of the fourth locus (GLC1E) for adult-onset primary open-angle glaucoma to the 10p15-p14 region". American Journal of Human Genetics. 62 (3): 641–652. doi:10.1086/301767. PMC 1376961. PMID 9497264.
• Fong KS, de Couet HG (June 1999). "Novel proteins interacting with the leucine-rich repeat domain of human flightless-I identified by the yeast two-hybrid system". Genomics. 58 (2): 146–157. doi:10.1006/geno.1999.5817. PMID 10366446.
• Moreland RJ, Dresser ME, Rodgers JS, Roe BA, Conaway JW, Conaway RC, et al. (May 2000). "Identification of a transcription factor IIIA-interacting protein". Nucleic Acids Research. 28 (9): 1986–1993. doi:10.1093/nar/28.9.1986. PMC 103300. PMID 10756201.
• Schwamborn K, Weil R, Courtois G, Whiteside ST, Israël A (July 2000). "Phorbol esters and cytokines regulate the expression of the NEMO-related protein, a molecule involved in a NF-kappa B-independent pathway". The Journal of Biological Chemistry. 275 (30): 22780–22789. doi:10.1074/jbc.M001500200. PMID 10807909.
• Hales CM, Griner R, Hobdy-Henderson KC, Dorn MC, Hardy D, Kumar R, et al. (October 2001). "Identification and characterization of a family of Rab11-interacting proteins". The Journal of Biological Chemistry. 276 (42): 39067–39075. doi:10.1074/jbc.M104831200. PMID 11495908.
• Vittitow J, Borrás T (October 2002). "Expression of optineurin, a glaucoma-linked gene, is influenced by elevated intraocular pressure". Biochemical and Biophysical Research Communications. 298 (1): 67–74. Bibcode:2002BBRC..298...67V. doi:10.1016/S0006-291X(02)02395-1. PMID 12379221.
• Kamphuis W, Schneemann A (2003). "Optineurin gene expression level in human trabecular meshwork does not change in response to pressure elevation". Ophthalmic Research. 35 (2): 93–96. doi:10.1159/000069133. PMID 12646749. S2CID 41751841.
• Tang S, Toda Y, Kashiwagi K, Mabuchi F, Iijima H, Tsukahara S, et al. (August 2003). "The association between Japanese primary open-angle glaucoma and normal tension glaucoma patients and the optineurin gene". Human Genetics. 113 (3): 276–279. doi:10.1007/s00439-003-0964-y. PMID 12811537. S2CID 24775454.
• Wiggs JL, Auguste J, Allingham RR, Flor JD, Pericak-Vance MA, Rogers K, et al. (August 2003). "Lack of association of mutations in optineurin with disease in patients with adult-onset primary open-angle glaucoma". Archives of Ophthalmology. 121 (8). Chicago: 1181–1183. doi:10.1001/archopht.121.8.1181. PMC 1361284. PMID 12912697.
• Aung T, Ebenezer ND, Brice G, Child AH, Prescott Q, Lehmann OJ, et al. (August 2003). "Prevalence of optineurin sequence variants in adult primary open angle glaucoma: implications for diagnostic testing". Journal of Medical Genetics. 40 (8): 101e–101. doi:10.1136/jmg.40.8.e101. PMC 1735547. PMID 12920093.
• Leung YF, Fan BJ, Lam DS, Lee WS, Tam PO, Chua JK, et al. (September 2003). "Different optineurin mutation pattern in primary open-angle glaucoma". Investigative Ophthalmology & Visual Science. 44 (9): 3880–3884. doi:10.1167/iovs.02-0693. PMID 12939304.
• Alward WL, Kwon YH, Kawase K, Craig JE, Hayreh SS, Johnson AT, et al. (November 2003). "Evaluation of optineurin sequence variations in 1,048 patients with open-angle glaucoma". American Journal of Ophthalmology. 136 (5): 904–910. doi:10.1016/S0002-9394(03)00577-4. PMID 14597044.

External links

• OPTN human gene location in the UCSC Genome Browser.
• OPTN human gene details in the UCSC Genome Browser.