Optineurin Explained

Optineurin is a protein that in humans is encoded by the OPTN gene.^{[1] [2] [3]}

Function

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.^[3] OPTN is a host intrinsic restriction factor against neuroinvasive HSV-1 infection.^[4]

Interactions

Optineurin has been shown to interact with Huntingtin^{[5] [6]} and RAB8A.^[6]

Further reading

• Sarfarazi M, Rezaie T . Optineurin in primary open angle glaucoma . Ophthalmology Clinics of North America . 16 . 4 . 529–41 . Dec 2003 . 14740994 . 10.1016/S0896-1549(03)00061-0 .
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction . Analytical Biochemistry . 236 . 1 . 107–13 . Apr 1996 . 8619474 . 10.1006/abio.1996.0138 .
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . Large-scale concatenation cDNA sequencing . Genome Research . 7 . 4 . 353–8 . Apr 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
• Sarfarazi M, Child A, Stoilova D, Brice G, Desai T, Trifan OC, Poinoosawmy D, Crick RP . 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 . 641–52 . Mar 1998 . 9497264 . 1376961 . 10.1086/301767 .
• Faber PW, Barnes GT, Srinidhi J, Chen J, Gusella JF, MacDonald ME . Huntingtin interacts with a family of WW domain proteins . Human Molecular Genetics . 7 . 9 . 1463–74 . Sep 1998 . 9700202 . 10.1093/hmg/7.9.1463 . free .
• Fong KS, de Couet HG . Novel proteins interacting with the leucine-rich repeat domain of human flightless-I identified by the yeast two-hybrid system . Genomics . 58 . 2 . 146–57 . Jun 1999 . 10366446 . 10.1006/geno.1999.5817 .
• Moreland RJ, Dresser ME, Rodgers JS, Roe BA, Conaway JW, Conaway RC, Hanas JS . Identification of a transcription factor IIIA-interacting protein . Nucleic Acids Research . 28 . 9 . 1986–93 . May 2000 . 10756201 . 103300 . 10.1093/nar/28.9.1986 .
• Schwamborn K, Weil R, Courtois G, Whiteside ST, Israël A . 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 . 22780–9 . Jul 2000 . 10807909 . 10.1074/jbc.M001500200 . free .
• Hattula K, Peränen J . FIP-2, a coiled-coil protein, links Huntingtin to Rab8 and modulates cellular morphogenesis . Current Biology . 10 . 24 . 1603–6 . 2001 . 11137014 . 10.1016/S0960-9822(00)00864-2 . 12836037 . free . 2000CBio...10.1603H .
• Hales CM, Griner R, Hobdy-Henderson KC, Dorn MC, Hardy D, Kumar R, Navarre J, Chan EK, Lapierre LA, Goldenring JR . Identification and characterization of a family of Rab11-interacting proteins . The Journal of Biological Chemistry . 276 . 42 . 39067–75 . Oct 2001 . 11495908 . 10.1074/jbc.M104831200 . free .
• Vittitow J, Borrás T . Expression of optineurin, a glaucoma-linked gene, is influenced by elevated intraocular pressure . Biochemical and Biophysical Research Communications . 298 . 1 . 67–74 . Oct 2002 . 12379221 . 10.1016/S0006-291X(02)02395-1 .
• Kamphuis W, Schneemann A . Optineurin gene expression level in human trabecular meshwork does not change in response to pressure elevation . Ophthalmic Research . 35 . 2 . 93–6 . 2003 . 12646749 . 10.1159/000069133 . 41751841 .
• Tang S, Toda Y, Kashiwagi K, Mabuchi F, Iijima H, Tsukahara S, Yamagata Z . The association between Japanese primary open-angle glaucoma and normal tension glaucoma patients and the optineurin gene . Human Genetics . 113 . 3 . 276–9 . Aug 2003 . 12811537 . 10.1007/s00439-003-0964-y . 24775454 .
• Wiggs JL, Auguste J, Allingham RR, Flor JD, Pericak-Vance MA, Rogers K, LaRocque KR, Graham FL, Broomer B, Del Bono E, Haines JL, Hauser M . Lack of association of mutations in optineurin with disease in patients with adult-onset primary open-angle glaucoma . Archives of Ophthalmology . 121 . 8 . 1181–3 . Aug 2003 . 12912697 . 1361284 . 10.1001/archopht.121.8.1181 .
• Aung T, Ebenezer ND, Brice G, Child AH, Prescott Q, Lehmann OJ, Hitchings RA, Bhattacharya SS . Prevalence of optineurin sequence variants in adult primary open angle glaucoma: implications for diagnostic testing . Journal of Medical Genetics . 40 . 8 . 101e–101 . Aug 2003 . 12920093 . 1735547 . 10.1136/jmg.40.8.e101 .
• Leung YF, Fan BJ, Lam DS, Lee WS, Tam PO, Chua JK, Tham CC, Lai JS, Fan DS, Pang CP . Different optineurin mutation pattern in primary open-angle glaucoma . Investigative Ophthalmology & Visual Science . 44 . 9 . 3880–4 . Sep 2003 . 12939304 . 10.1167/iovs.02-0693 . free .
• Alward WL, Kwon YH, Kawase K, Craig JE, Hayreh SS, Johnson AT, Khanna CL, Yamamoto T, Mackey DA, Roos BR, Affatigato LM, Sheffield VC, Stone EM . Evaluation of optineurin sequence variations in 1,048 patients with open-angle glaucoma . American Journal of Ophthalmology . 136 . 5 . 904–10 . Nov 2003 . 14597044 . 10.1016/S0002-9394(03)00577-4 .

Notes and References

1. Rezaie T, Child A, Hitchings R, Brice G, Miller L, Coca-Prados M, Héon E, Krupin T, Ritch R, Kreutzer D, Crick RP, Sarfarazi M . Adult-onset primary open-angle glaucoma caused by mutations in optineurin . Science . 295 . 5557 . 1077–9 . Feb 2002 . 11834836 . 10.1126/science.1066901 . 2002Sci...295.1077R . 23635499 .
2. Li Y, Kang J, Horwitz MS . 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 . 1601–10 . Mar 1998 . 9488477 . 108875 . 10.1128/mcb.18.3.1601.
3. Web site: Entrez Gene: OPTN optineurin.
4. Ames . Joshua . Yadavalli . Tejabhiram . Suryawanshi . Rahul . Hopkins . James . Agelidis . Alexander . Patil . Chandrashekhar . Fredericks . Brian . Tseng . Henry . Valyi-Nagy . Tibor . Shukla . Deepak . 13 September 2021 . OPTN is a host intrinsic restriction factor against neuroinvasive HSV-1 infection . Nature Communications . en . 12 . 1 . 5401 . 10.1038/s41467-021-25642-z . 34518549 . 8437952 . 2021NatCo..12.5401A . 2041-1723.
5. Faber PW, Barnes GT, Srinidhi J, Chen J, Gusella JF, MacDonald ME . Huntingtin interacts with a family of WW domain proteins . Human Molecular Genetics . 7 . 9 . 1463–74 . Sep 1998 . 9700202 . 10.1093/hmg/7.9.1463 . free .
6. Hattula K, Peränen J . FIP-2, a coiled-coil protein, links Huntingtin to Rab8 and modulates cellular morphogenesis . Current Biology . 10 . 24 . 1603–6 . 2000 . 11137014 . 10.1016/S0960-9822(00)00864-2 . 12836037 . free . 2000CBio...10.1603H .