Optineurin

Optineurin
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2LO4​, 2LUE​, 3VTV​, 3VTW​
Identifiers
Symbols	OPTN ; ALS12; FIP2; GLC1E; HIP7; HYPL; NRP; TFIIIA-INTP
External IDs	OMIM: 602432 MGI: 1918898 HomoloGene: 11085 GeneCards: OPTN Gene
Gene ontology Molecular function • TFIIIA-class transcription factor binding • protein binding • protein C-terminus binding • Rab GTPase binding • protein binding, bridging • polyubiquitin binding • identical protein binding • K63-linked polyubiquitin binding Cellular component • Golgi membrane • nucleus • nucleoplasm • cytoplasm • autophagosome • Golgi apparatus • trans-Golgi network • cytosol • cytoplasmic membrane-bounded vesicle • perinuclear region of cytoplasm • recycling endosome Biological process • protein targeting to Golgi • G2/M transition of mitotic cell cycle • mitotic cell cycle • negative regulation of receptor recycling • Golgi organization • signal transduction • cell death • positive regulation of cell proliferation • macroautophagy • wound healing • Golgi to plasma membrane protein transport • regulation of I-kappaB kinase/NF-kappaB signaling • negative regulation of I-kappaB kinase/NF-kappaB signaling • negative regulation of neuron apoptotic process • cytokine secretion • defense response to Gram-negative bacterium • protein homooligomerization • Golgi ribbon formation • xenophagy Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	10133	71648
Ensembl	ENSG00000123240	ENSMUSG00000026672
UniProt	Q96CV9	Q8K3K8
RefSeq (mRNA)	NM_001008211	NM_181848
RefSeq (protein)	NP_001008212	NP_862896
Location (UCSC)	Chr 10: 13.1 – 13.14 Mb	Chr 2: 5.02 – 5.06 Mb
PubMed search

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]

Model organisms

Optn knockout mouse phenotype

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 Optn^{tm1a(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

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 (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.
2. 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.
3. "Entrez Gene: OPTN optineurin".
4. "Salmonella infection data for Optn". Wellcome Trust Sanger Institute.
5. "Citrobacter infection data for Optn". Wellcome Trust Sanger Institute.
6. 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.
7. Mouse Resources Portal, Wellcome Trust Sanger Institute.
8. "International Knockout Mouse Consortium".
9. "Mouse Genome Informatics".
10. 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.
11. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
12. 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.
13. 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.
14. 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.
15. 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.