Optineurin
Optineurin is a protein that in humans is encoded by the OPTN gene.[1][2][3]
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]
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[4] |
| Citrobacter infection | Normal[5] |
| All tests and analysis from[6][7] |
Model organisms have been used in the study of OPTN function. A conditional knockout mouse line, called Optntm1a(EUCOMM)Wtsi[8][9] 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.[10][11][12]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[6][13] Twenty one tests were carried out on mutant mice, however no significant abnormalities were observed.[6]
Interactions
Optineurin has been shown to interact with Huntingtin[14][15] and RAB8A.[15]
References
- ↑ Rezaie T, Child A, Hitchings R, Brice G, Miller L, Coca-Prados M, Heon 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". Mol Cell Biol 18 (3): 1601–10. PMC 108875. PMID 9488477.
- ↑ 3.0 3.1 "Entrez Gene: OPTN optineurin".
- ↑ "Salmonella infection data for Optn". Wellcome Trust Sanger Institute.
- ↑ "Citrobacter infection data for Optn". Wellcome Trust Sanger Institute.
- ↑ 6.0 6.1 6.2 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, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
- ↑ Dolgin E (June 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ↑ Collins FS, Rossant J, Wurst W (January 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 Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
- ↑ Faber, P W; Barnes G T; Srinidhi J; Chen J; Gusella J F; MacDonald M E (Sep 1998). "Huntingtin interacts with a family of WW domain proteins". Hum. Mol. Genet. (ENGLAND) 7 (9): 1463–74. doi:10.1093/hmg/7.9.1463. ISSN 0964-6906. PMID 9700202.
- ↑ 15.0 15.1 Hattula, K; Peränen J (2000). "FIP-2, a coiled-coil protein, links Huntingtin to Rab8 and modulates cellular morphogenesis". Curr. Biol. (England) 10 (24): 1603–6. doi:10.1016/S0960-9822(00)00864-2. ISSN 0960-9822. PMID 11137014.
Further reading
- Sarfarazi M, Rezaie T (2004). "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 et al. (1996). "A "double adaptor" method for improved shotgun library construction.". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
- Yu W, Andersson B, Worley KC et al. (1997). "Large-scale concatenation cDNA sequencing.". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
- Sarfarazi M, Child A, Stoilova D et al. (1998). "Localization of the fourth locus (GLC1E) for adult-onset primary open-angle glaucoma to the 10p15-p14 region.". Am. J. Hum. Genet. 62 (3): 641–52. doi:10.1086/301767. PMC 1376961. PMID 9497264.
- Faber PW, Barnes GT, Srinidhi J et al. (1998). "Huntingtin interacts with a family of WW domain proteins.". Hum. Mol. Genet. 7 (9): 1463–74. doi:10.1093/hmg/7.9.1463. PMID 9700202.
- Fong KS, de Couet HG (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 et al. (2000). "Identification of a transcription factor IIIA-interacting protein.". Nucleic Acids Res. 28 (9): 1986–93. doi:10.1093/nar/28.9.1986. PMC 103300. PMID 10756201.
- Schwamborn K, Weil R, Courtois G et al. (2000). "Phorbol esters and cytokines regulate the expression of the NEMO-related protein, a molecule involved in a NF-kappa B-independent pathway.". J. Biol. Chem. 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.". Curr. Biol. 10 (24): 1603–6. doi:10.1016/S0960-9822(00)00864-2. PMID 11137014.
- Hales CM, Griner R, Hobdy-Henderson KC et al. (2001). "Identification and characterization of a family of Rab11-interacting proteins.". J. Biol. Chem. 276 (42): 39067–75. doi:10.1074/jbc.M104831200. PMID 11495908.
- Vittitow J, Borrás T (2002). "Expression of optineurin, a glaucoma-linked gene, is influenced by elevated intraocular pressure.". Biochem. Biophys. Res. Commun. 298 (1): 67–74. doi:10.1016/S0006-291X(02)02395-1. PMID 12379221.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Kamphuis W, Schneemann A (2003). "Optineurin gene expression level in human trabecular meshwork does not change in response to pressure elevation.". Ophthalmic Res. 35 (2): 93–6. doi:10.1159/000069133. PMID 12646749.
- Tang S, Toda Y, Kashiwagi K et al. (2003). "The association between Japanese primary open-angle glaucoma and normal tension glaucoma patients and the optineurin gene.". Hum. Genet. 113 (3): 276–9. doi:10.1007/s00439-003-0964-y. PMID 12811537.
- Wiggs JL, Auguste J, Allingham RR et al. (2003). "Lack of association of mutations in optineurin with disease in patients with adult-onset primary open-angle glaucoma.". Arch. Ophthalmol. 121 (8): 1181–3. doi:10.1001/archopht.121.8.1181. PMC 1361284. PMID 12912697.
- Aung T, Ebenezer ND, Brice G et al. (2003). "Prevalence of optineurin sequence variants in adult primary open angle glaucoma: implications for diagnostic testing.". J. Med. Genet. 40 (8): e101. doi:10.1136/jmg.40.8.e101. PMC 1735547. PMID 12920093.
- Leung YF, Fan BJ, Lam DS et al. (2003). "Different optineurin mutation pattern in primary open-angle glaucoma.". Invest. Ophthalmol. Vis. Sci. 44 (9): 3880–4. doi:10.1167/iovs.02-0693. PMID 12939304.
- Alward WL, Kwon YH, Kawase K et al. (2003). "Evaluation of optineurin sequence variations in 1,048 patients with open-angle glaucoma.". Am. J. Ophthalmol. 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.