Optineurin
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Optineurin is a protein that in humans is encoded by the OPTN gene.[4][5][6]
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.[6]
Model organisms
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Normal |
| Fertility | Normal |
| Body weight | Normal |
| Anxiety | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Hot plate | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Normal |
| Haematology | Normal |
| Peripheral blood lymphocytes | Normal |
| Heart weight | Normal |
| Salmonella infection | Normal[7] |
| Citrobacter infection | Normal[8] |
| All tests and analysis from[9][10] |
Model organisms have been used in the study of OPTN function. A conditional knockout mouse line, called Optntm1a(EUCOMM)Wtsi[11][12] was generated as part of the International Knockout Mouse Consortium program – a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists – at the Wellcome Trust Sanger Institute.[13][14][15]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[9][16] Twenty one tests were carried out on mutant mice, however no significant abnormalities were observed.[9]
Interactions
Optineurin has been shown to interact with Huntingtin[17][18] and RAB8A.[18]
References
- ↑ "Diseases that are genetically associated with OPTN view/edit references on wikidata".
- ↑ "Human PubMed Reference:".
- ↑ "Mouse PubMed Reference:".
- ↑ 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 (Feb 2002). "Adult-onset primary open-angle glaucoma caused by mutations in optineurin". Science. 295 (5557): 1077–9. doi:10.1126/science.1066901. PMID 11834836.
- ↑ Li Y, Kang J, Horwitz MS (Mar 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): 1601–10. doi:10.1128/mcb.18.3.1601. PMC 108875
. PMID 9488477. - 1 2 "Entrez Gene: OPTN optineurin".
- ↑ "Salmonella infection data for Optn". Wellcome Trust Sanger Institute.
- ↑ "Citrobacter infection data for Optn". Wellcome Trust Sanger Institute.
- 1 2 3 Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x.
- ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
- ↑ "International Knockout Mouse Consortium".
- ↑ "Mouse Genome Informatics".
- ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
- ↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
- ↑ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
- ↑ Faber PW, Barnes GT, Srinidhi J, Chen J, Gusella JF, MacDonald ME (Sep 1998). "Huntingtin interacts with a family of WW domain proteins". Human Molecular Genetics. 7 (9): 1463–74. doi:10.1093/hmg/7.9.1463. PMID 9700202.
- 1 2 Hattula K, Peränen J (2000). "FIP-2, a coiled-coil protein, links Huntingtin to Rab8 and modulates cellular morphogenesis". Current Biology. 10 (24): 1603–6. doi:10.1016/S0960-9822(00)00864-2. PMID 11137014.
Further reading
- Sarfarazi M, Rezaie T (Dec 2003). "Optineurin in primary open angle glaucoma". Ophthalmology Clinics of North America. 16 (4): 529–41. doi:10.1016/S0896-1549(03)00061-0. PMID 14740994.
- Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (Apr 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
- Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (Apr 1997). "Large-scale concatenation cDNA sequencing". Genome Research. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
- Sarfarazi M, Child A, Stoilova D, Brice G, Desai T, Trifan OC, Poinoosawmy D, Crick RP (Mar 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): 641–52. doi:10.1086/301767. PMC 1376961. PMID 9497264.
- Faber PW, Barnes GT, Srinidhi J, Chen J, Gusella JF, MacDonald ME (Sep 1998). "Huntingtin interacts with a family of WW domain proteins". Human Molecular Genetics. 7 (9): 1463–74. doi:10.1093/hmg/7.9.1463. PMID 9700202.
- Fong KS, de Couet HG (Jun 1999). "Novel proteins interacting with the leucine-rich repeat domain of human flightless-I identified by the yeast two-hybrid system". Genomics. 58 (2): 146–57. doi:10.1006/geno.1999.5817. PMID 10366446.
- Moreland RJ, Dresser ME, Rodgers JS, Roe BA, Conaway JW, Conaway RC, Hanas JS (May 2000). "Identification of a transcription factor IIIA-interacting protein". Nucleic Acids Research. 28 (9): 1986–93. doi:10.1093/nar/28.9.1986. PMC 103300. PMID 10756201.
- Schwamborn K, Weil R, Courtois G, Whiteside ST, Israël A (Jul 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): 22780–9. doi:10.1074/jbc.M001500200. PMID 10807909.
- Hattula K, Peränen J (2001). "FIP-2, a coiled-coil protein, links Huntingtin to Rab8 and modulates cellular morphogenesis". Current Biology. 10 (24): 1603–6. doi:10.1016/S0960-9822(00)00864-2. PMID 11137014.
- Hales CM, Griner R, Hobdy-Henderson KC, Dorn MC, Hardy D, Kumar R, Navarre J, Chan EK, Lapierre LA, Goldenring JR (Oct 2001). "Identification and characterization of a family of Rab11-interacting proteins". The Journal of Biological Chemistry. 276 (42): 39067–75. doi:10.1074/jbc.M104831200. PMID 11495908.
- Vittitow J, Borrás T (Oct 2002). "Expression of optineurin, a glaucoma-linked gene, is influenced by elevated intraocular pressure". Biochemical and Biophysical Research Communications. 298 (1): 67–74. 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): 93–6. doi:10.1159/000069133. PMID 12646749.
- Tang S, Toda Y, Kashiwagi K, Mabuchi F, Iijima H, Tsukahara S, Yamagata Z (Aug 2003). "The association between Japanese primary open-angle glaucoma and normal tension glaucoma patients and the optineurin gene". Human Genetics. 113 (3): 276–9. doi:10.1007/s00439-003-0964-y. PMID 12811537.
- 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 (Aug 2003). "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. doi:10.1001/archopht.121.8.1181. PMC 1361284. PMID 12912697.
- Aung T, Ebenezer ND, Brice G, Child AH, Prescott Q, Lehmann OJ, Hitchings RA, Bhattacharya SS (Aug 2003). "Prevalence of optineurin sequence variants in adult primary open angle glaucoma: implications for diagnostic testing". Journal of Medical Genetics. 40 (8): e101. doi:10.1136/jmg.40.8.e101. PMC 1735547. PMID 12920093.
- Leung YF, Fan BJ, Lam DS, Lee WS, Tam PO, Chua JK, Tham CC, Lai JS, Fan DS, Pang CP (Sep 2003). "Different optineurin mutation pattern in primary open-angle glaucoma". Investigative Ophthalmology & Visual Science. 44 (9): 3880–4. doi:10.1167/iovs.02-0693. PMID 12939304.
- 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 (Nov 2003). "Evaluation of optineurin sequence variations in 1,048 patients with open-angle glaucoma". American Journal of Ophthalmology. 136 (5): 904–10. 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.
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