transcription factor tfiiia


Summary: One of several general transcription factors that are specific for RNA POLYMERASE III. It is a zinc finger (ZINC FINGERS) protein and is required for transcription of 5S ribosomal genes.

Top Publications

  1. Alward W, Kwon Y, Kawase K, Craig J, Hayreh S, Johnson A, et al. Evaluation of optineurin sequence variations in 1,048 patients with open-angle glaucoma. Am J Ophthalmol. 2003;136:904-10 pubmed
    ..1% of all open-angle glaucoma. The Arg545Gln variation is likely to be a nondisease-causing polymorphism. The Met98Lys change may be associated with a fraction of normal-tension glaucoma in patients of Japanese ethnicity. ..
  2. Korańá J, Schaeffer V, Kovacevic I, Clement A, Jungblut B, Behl C, et al. Ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates. J Cell Sci. 2013;126:580-92 pubmed publisher
    ..This study provides evidence for a ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates as well as additional relevance for TBK1 as an upstream regulator of the autophagic pathway. ..
  3. Chen J, Xu L, Li Y. [Study on the optic neuropathy induced response protein gene mutation in Chinese patients with primary open-angle glaucoma]. Zhonghua Yi Xue Za Zhi. 2004;84:1098-102 pubmed
    ..19 mm Hg and a mean defect of visual field from 0.9 to 26. 5dB. The single nucleotide polymorphism (SNP) of OPTN gene may contribute to the pathogenesis of glaucoma in Chinese. ..
  4. Peng Z, Bateman E. Analysis of the 5S rRNA gene promoter from Acanthamoeba castellanii. Mol Microbiol. 2004;52:1123-32 pubmed
  5. Mukhopadhyay A, Komatireddy S, Acharya M, Bhattacharjee A, Mandal A, Thakur S, et al. Evaluation of Optineurin as a candidate gene in Indian patients with primary open angle glaucoma. Mol Vis. 2005;11:792-7 pubmed
    ..Despite a putative mutation (Arg545Gln) in some patients, the present study does not suggest a significant involvement of OPTN in POAG patients of Indian origin. ..
  6. Morton S, Hesson L, Peggie M, Cohen P. Enhanced binding of TBK1 by an optineurin mutant that causes a familial form of primary open angle glaucoma. FEBS Lett. 2008;582:997-1002 pubmed publisher
    ..The OPTN[E50K] mutant associated with Primary Open Angle Glaucoma (POAG) displayed strikingly enhanced binding to TBK1, suggesting that this interaction may contribute to familial POAG caused by this mutation. ..
  7. Hewitt A, Craig J, Mackey D. Complex genetics of complex traits: the case of primary open-angle glaucoma. Clin Exp Ophthalmol. 2006;34:472-84 pubmed
    ..This review explores the genetic mechanisms that have been unequivocally linked to the glaucomatous process and then discusses potential avenues for future breakthroughs. ..
  8. Wang D, Fan B, Chua J, Tam P, Leung C, Lam D, et al. A genome-wide scan maps a novel juvenile-onset primary open-angle glaucoma locus to 15q. Invest Ophthalmol Vis Sci. 2006;47:5315-21 pubmed
    ..The results provide evidence for the mapping of a novel locus for JOAG at 15q22-q24. A further search for the disease-causing gene in this new JOAG locus is in progress. ..
  9. Vittitow J, BORRAS T. Expression of optineurin, a glaucoma-linked gene, is influenced by elevated intraocular pressure. Biochem Biophys Res Commun. 2002;298:67-74 pubmed
    ..3-fold by TNFalpha and 2.6-fold by prolonged DEX treatment. These results demonstrate that OPTN is part of the transcriptome responding to glaucomatous insults and support the protective role of this protein in the trabecular meshwork. ..

More Information


  1. Jansson M, Wadelius C, Rezaie T, Sarfarazi M. Analysis of rare variants and common haplotypes in the optineurin gene in Swedish glaucoma cases. Ophthalmic Genet. 2005;26:85-9 pubmed
    ..These experiments show no association between optineurin and our Swedish cohorts of high-pressure glaucoma cases, either in coding sequence or in haplotype frequency and distribution. ..
  2. Suriyapperuma S, Child A, Desai T, Brice G, Kerr A, Crick R, et al. A new locus (GLC1H) for adult-onset primary open-angle glaucoma maps to the 2p15-p16 region. Arch Ophthalmol. 2007;125:86-92 pubmed
    ..Mapping of the GLC1H locus and eventual identification of its defective gene will help to develop diagnostic tools and effective treatments for this condition. ..
  3. Weisschuh N, Alavi M, Bonin M, Wissinger B. Identification of genes that are linked with optineurin expression using a combined RNAi--microarray approach. Exp Eye Res. 2007;85:450-61 pubmed
  4. Nagabhushana A, Chalasani M, Jain N, Radha V, Rangaraj N, Balasubramanian D, et al. Regulation of endocytic trafficking of transferrin receptor by optineurin and its impairment by a glaucoma-associated mutant. BMC Cell Biol. 2010;11:4 pubmed publisher
    ..These results also have implications for the pathogenesis of glaucoma caused by the E50K mutation because endocytic recycling is vital for maintaining homeostasis. ..
  5. Ginsberg A, King B, Roeder R. Xenopus 5S gene transcription factor, TFIIIA: characterization of a cDNA clone and measurement of RNA levels throughout development. Cell. 1984;39:479-89 pubmed
    ..We report sequence homologies between TFIIIA cDNA and regulatory regions of the Xenopus tmet and 5S RNA genes. Implications of these data for developmental regulation of the TFIIIA and 5S RNA genes are discussed. ..
  6. Brown R, Sander C, Argos P. The primary structure of transcription factor TFIIIA has 12 consecutive repeats. FEBS Lett. 1985;186:271-4 pubmed
    Analysis of the amino acid sequence of transcription factor TFIIIA from Xenopus laevis reveals the presence of 12 repeating structures, each about 30 residues in length...
  7. Ariani F, Longo I, Frezzotti P, Pescucci C, Mari F, Caporossi A, et al. Optineurin gene is not involved in the common high-tension form of primary open-angle glaucoma. Graefes Arch Clin Exp Ophthalmol. 2006;244:1077-82 pubmed
    ..We detected a number of common polymorphisms, including the previously reported p.M98K (Met98Lys) variant. In this population, mutations in the optineurin gene are not associated with adult-onset primary POAG. ..
  8. Yoine M, Ohto M, Onai K, Mita S, Nakamura K. The lba1 mutation of UPF1 RNA helicase involved in nonsense-mediated mRNA decay causes pleiotropic phenotypic changes and altered sugar signalling in Arabidopsis. Plant J. 2006;47:49-62 pubmed
    ..The lba1 mutant provides a good tool for studying NMD in plants. ..
  9. Braun B, Bartholomew B, Kassavetis G, Geiduschek E. Topography of transcription factor complexes on the Saccharomyces cerevisiae 5 S RNA gene. J Mol Biol. 1992;228:1063-77 pubmed
    ..A 90 kDa component that was not previously recognized as an integral part of TFIIIC has been specifically located at the 3' end of the 5 S rRNA gene. ..
  10. Chalasani M, Swarup G, Balasubramanian D. Optineurin and its mutants: molecules associated with some forms of glaucoma. Ophthalmic Res. 2009;42:176-84 pubmed publisher
    ..Our results indicate that several independent mechanisms are likely to be involved in the pathogenesis of glaucoma caused by mutations in optineurin. ..
  11. Lee B, Xu J, Clarkson B, Martinez Yamout M, Dyson H, Case D, et al. Induced fit and "lock and key" recognition of 5S RNA by zinc fingers of transcription factor IIIA. J Mol Biol. 2006;357:275-91 pubmed
  12. Park B, Ying H, Shen X, Park J, Qiu Y, Shyam R, et al. Impairment of protein trafficking upon overexpression and mutation of optineurin. PLoS ONE. 2010;5:e11547 pubmed publisher
    ..The defective protein trafficking may be one of the underlying bases why glaucoma pathology develops in patients with E50K mutation. ..
  13. Brady K, Ponnampalam S, Bumbulis M, Setzer D. Mutations in TFIIIA that increase stability of the TFIIIA-5 S rRNA gene complex: unusual effects on the kinetics of complex assembly and dissociation. J Biol Chem. 2005;280:26743-50 pubmed
    ..Introduction of intercalating amino acids into zinc finger proteins may be a useful tool for producing artificial transcription factors with particularly high in vivo activity. ..
  14. Sahlender D, Roberts R, Arden S, Spudich G, Taylor M, Luzio J, et al. Optineurin links myosin VI to the Golgi complex and is involved in Golgi organization and exocytosis. J Cell Biol. 2005;169:285-95 pubmed
    ..These results show that optineurin links myosin VI to the Golgi complex and plays a central role in Golgi ribbon formation and exocytosis. ..
  15. Funayama T, Ishikawa K, Ohtake Y, Tanino T, Kurosaka D, Kimura I, et al. Variants in optineurin gene and their association with tumor necrosis factor-alpha polymorphisms in Japanese patients with glaucoma. Invest Ophthalmol Vis Sci. 2004;45:4359-67 pubmed
    ..Statistical analysis showed a possible interaction between polymorphisms in the OPTN and the TNF-alpha genes that would increase the risk for glaucoma. ..
  16. Liao X, Clemens K, Tennant L, Wright P, Gottesfeld J. Specific interaction of the first three zinc fingers of TFIIIA with the internal control region of the Xenopus 5 S RNA gene. J Mol Biol. 1992;223:857-71 pubmed
    ..Overall, these studies provide strong support for a model in which the first three zinc fingers of TFIIIA bind with high affinity between nucleotides +80 and +92 of the internal control region of the 5 S RNA gene. ..
  17. Moreland R, Dresser M, Rodgers J, Roe B, Conaway J, Conaway R, et al. Identification of a transcription factor IIIA-interacting protein. Nucleic Acids Res. 2000;28:1986-93 pubmed
    ..In a HeLa cell nuclear extract, recombinant TFIIIA-intP was able to stimulate TFIIIA-dependent transcription of the Xenopus 5S ribosomal RNA gene but not TFIIIA-independent transcription of the human adenovirus VA RNA gene. ..
  18. Aung T, Ebenezer N, Brice G, Child A, Prescott Q, Lehmann O, et al. Prevalence of optineurin sequence variants in adult primary open angle glaucoma: implications for diagnostic testing. J Med Genet. 2003;40:e101 pubmed
  19. Rezaie T, Sarfarazi M. Molecular cloning, genomic structure, and protein characterization of mouse optineurin. Genomics. 2005;85:131-8 pubmed
    ..Gene and protein ocular profiling of Optn is a prerequisite for developing a mouse model for glaucoma. ..
  20. Rakhmanov V, Nikitina N, Zakharova F, Astakhov I, Kvasova M, Vasil ev V, et al. [Mutations and polymorphisms in the genes for myocilin and optineur in as the risk factors of primary open-angle glaucoma]. Genetika. 2005;41:1567-74 pubmed
    ..036; Fisher's exact test) among the POAG patients (6.5%) than among the controls (1%). In the sample examined the E50K mutation, typical of the patients with pseudonormal intraocular pressure glaucoma, was not found. ..
  21. Sripriya S, Nirmaladevi J, George R, Hemamalini A, Baskaran M, Prema R, et al. OPTN gene: profile of patients with glaucoma from India. Mol Vis. 2006;12:816-20 pubmed
    ..The current study suggests a possible role of SNPs rather than mutations in OPTN in POAG pathology in the Indian population. ..
  22. Hauser M, Sena D, Flor J, Walter J, Auguste J, Larocque Abramson K, et al. Distribution of optineurin sequence variations in an ethnically diverse population of low-tension glaucoma patients from the United States. J Glaucoma. 2006;15:358-63 pubmed
    ..The E50K mutation seems to be associated with a severe form of LTG, and although rare, the identification of this sequence variant in patients at risk may help direct appropriate therapy. ..
  23. Schwamborn K, Weil R, Courtois G, Whiteside S, Israel A. 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. 2000;275:22780-9 pubmed
    ..Analogous to NEMO, we find that NRP is associated in a complex with two kinases, suggesting that NRP could play a similar role in another signaling pathway. ..
  24. Osawa T, Mizuno Y, Fujita Y, Takatama M, Nakazato Y, Okamoto K. Optineurin in neurodegenerative diseases. Neuropathology. 2011;31:569-74 pubmed publisher
    ..This study indicates that optineurin is widely distributed in neurodegenerative conditions; however, its significance is obscure. ..
  25. Journo C, Filipe J, About F, Chevalier S, Afonso P, Brady J, et al. NRP/Optineurin Cooperates with TAX1BP1 to potentiate the activation of NF-kappaB by human T-lymphotropic virus type 1 tax protein. PLoS Pathog. 2009;5:e1000521 pubmed publisher
    ..Our data strongly suggest for the first time that NRP is a critical adaptor that regulates the assembly of TAX1BP1 and post-translationally modified forms of Tax1, leading to sustained NF-kappaB activation. ..
  26. Nolte R, Conlin R, Harrison S, Brown R. Differing roles for zinc fingers in DNA recognition: structure of a six-finger transcription factor IIIA complex. Proc Natl Acad Sci U S A. 1998;95:2938-43 pubmed
    ..These results show how TFIIIA can recognize several separated DNA sequences by using fewer fingers than necessary for continuous winding in the major groove. ..
  27. Aung T, Rezaie T, Okada K, Viswanathan A, Child A, Brice G, et al. Clinical features and course of patients with glaucoma with the E50K mutation in the optineurin gene. Invest Ophthalmol Vis Sci. 2005;46:2816-22 pubmed
    ..The findings emphasize the importance of early detection and treatment of glaucoma in such individuals, to minimize visual loss. ..
  28. Deng H, Bigio E, Zhai H, Fecto F, Ajroud K, Shi Y, et al. Differential involvement of optineurin in amyotrophic lateral sclerosis with or without SOD1 mutations. Arch Neurol. 2011;68:1057-61 pubmed publisher
  29. Nagabhushana A, Bansal M, Swarup G. Optineurin is required for CYLD-dependent inhibition of TNF?-induced NF-?B activation. PLoS ONE. 2011;6:e17477 pubmed publisher
    ..These results suggest that optineurin regulates NF-?B activation by mediating interaction of CYLD with ubiquitinated RIP thus facilitating deubiquitination of RIP. ..
  30. Tang S, Toda Y, Kashiwagi K, Mabuchi F, Iijima H, Tsukahara S, et al. The association between Japanese primary open-angle glaucoma and normal tension glaucoma patients and the optineurin gene. Hum Genet. 2003;113:276-9 pubmed
    ..No glaucoma-specific mutations were found in the OPTN gene in Japanese glaucoma patients. However, some novel single-nucleotide polymorphisms (SNPs) in the exons and introns are reported in this paper for the first time. ..
  31. Ayala Lugo R, Pawar H, Reed D, Lichter P, Moroi S, Page M, et al. Variation in optineurin (OPTN) allele frequencies between and within populations. Mol Vis. 2007;13:151-63 pubmed
    ..It is currently not possible to tell how much of the underlying cause of the allele frequency difference is attributable to demographic, technical, or ascertainment differences among the studies. ..
  32. Chalasani M, Radha V, Gupta V, Agarwal N, Balasubramanian D, Swarup G. A glaucoma-associated mutant of optineurin selectively induces death of retinal ganglion cells which is inhibited by antioxidants. Invest Ophthalmol Vis Sci. 2007;48:1607-14 pubmed
    ..This cell death was mediated by oxidative stress. The present findings raise the possibility of antioxidant use for delaying or controlling some forms of glaucoma. ..
  33. Allingham R, Liu Y, Rhee D. The genetics of primary open-angle glaucoma: a review. Exp Eye Res. 2009;88:837-44 pubmed publisher
    ..This review examines what is currently known about the underlying genetic structure, what remains to be learned, and how this may affect our medical management of this major blinding disease...
  34. Sarfarazi M, Rezaie T. Optineurin in primary open angle glaucoma. Ophthalmol Clin North Am. 2003;16:529-41 pubmed
    ..The exact impact of OPTN in the development of all glaucoma phenotypes requires future study. ..
  35. Toda Y, Tang S, Kashiwagi K, Mabuchi F, Iijima H, Tsukahara S, et al. Mutations in the optineurin gene in Japanese patients with primary open-angle glaucoma and normal tension glaucoma. Am J Med Genet A. 2004;125A:1-4 pubmed
    ..The current results suggest that there may be certain racial differences between Japanese and Caucasians with respect to OPTN genotypes. ..
  36. Wiggs J, Auguste J, Allingham R, Flor J, Pericak Vance M, Rogers K, et al. Lack of association of mutations in optineurin with disease in patients with adult-onset primary open-angle glaucoma. Arch Ophthalmol. 2003;121:1181-3 pubmed
    ..This result may indicate that normal-tension glaucoma is not necessarily part of the phenotypic spectrum of adult open-angle glaucoma. ..
  37. Funayama T, Mashima Y, Ohtake Y, Ishikawa K, Fuse N, Yasuda N, et al. SNPs and interaction analyses of noelin 2, myocilin, and optineurin genes in Japanese patients with open-angle glaucoma. Invest Ophthalmol Vis Sci. 2006;47:5368-75 pubmed
    ..The Arg144Gln mutation in OLFM2 is a possible disease-causing mutation in Japanese patients with OAG. Common polymorphisms in OLFM2 and OPTN may interactively contribute to the development of OAG, indicating a polygenic etiology. ..
  38. Foster M, Wuttke D, Radhakrishnan I, Case D, Gottesfeld J, Wright P. Domain packing and dynamics in the DNA complex of the N-terminal zinc fingers of TFIIIA. Nat Struct Biol. 1997;4:605-8 pubmed
    ..Substantial packing interfaces are formed between adjacent fingers, the linkers lose their intrinsic flexibility upon DNA binding, and several lysine side chains implicated in DNA recognition are dynamically disordered. ..
  39. Maruyama H, Morino H, Ito H, Izumi Y, Kato H, Watanabe Y, et al. Mutations of optineurin in amyotrophic lateral sclerosis. Nature. 2010;465:223-6 pubmed publisher
    ..They also indicate that NF-kappaB inhibitors could be used to treat ALS and that transgenic mice bearing various mutations of OPTN will be relevant in developing new drugs for this disorder. ..
  40. Milne C, Segall J. Mapping regions of yeast transcription factor IIIA required for DNA binding, interaction with transcription factor IIIC, and transcription activity. J Biol Chem. 1993;268:11364-71 pubmed
    ..The resultant TFIIIA.DNA complex was defective in recruiting TFIIIC and did not support transcription. ..
  41. Xiao Z, Meng Q, Tsai J, Yuan H, Xu N, Li Y. A novel optineurin genetic mutation associated with open-angle glaucoma in a Chinese family. Mol Vis. 2009;15:1649-54 pubmed
    ..A novel mutation of a Lys322Glu change in OPTN is responsible for this familial case of primary open-angle glaucoma observed in northeastern China. ..
  42. Rezaie T, Waitzman D, Seeman J, Kaufman P, Sarfarazi M. Molecular cloning and expression profiling of optineurin in the rhesus monkey. Invest Ophthalmol Vis Sci. 2005;46:2404-10 pubmed publisher
    ..High similarity of ocular expression and tissue distribution between the two optineurin proteins suggests that this nonhuman primate is a suitable model for the pathophysiology and treatment of human glaucomatous optic neuropathy...
  43. Liu Y, Akafo S, Santiago Turla C, Cohen C, Larocque Abramson K, Qin X, et al. Optineurin coding variants in Ghanaian patients with primary open-angle glaucoma. Mol Vis. 2008;14:2367-72 pubmed
    ..This is the first comprehensive study of OPTN in a single West African population. Our results suggest that coding variants in OPTN may not contribute to the risk for POAG in persons of West African descent. ..
  44. Rothfels K, Rowland O, Segall J. Zinc fingers 1 and 7 of yeast TFIIIA are essential for assembly of a functional transcription complex on the 5 S RNA gene. Nucleic Acids Res. 2007;35:4869-81 pubmed
    ..Disruption of zinc fingers 4, 5 or 6 had minimal effect on the DNA binding and TF activities of TFIIIA. ..
  45. Setzer D, Menezes S, Del Rio S, Hung V, Subramanyan G. Functional interactions between the zinc fingers of Xenopus transcription factor IIIA during 5S rRNA binding. RNA. 1996;2:1254-69 pubmed
  46. Sudhakar C, Nagabhushana A, Jain N, Swarup G. NF-kappaB mediates tumor necrosis factor alpha-induced expression of optineurin, a negative regulator of NF-kappaB. PLoS ONE. 2009;4:e5114 pubmed publisher
    ..In addition these results suggest that there is a negative feedback loop in which TNFalpha-induced NF-kappaB activity mediates expression of optineurin, which itself functions as a negative regulator of NF-kappaB. ..
  47. Fu Y, Bannach O, Chen H, Teune J, Schmitz A, Steger G, et al. Alternative splicing of anciently exonized 5S rRNA regulates plant transcription factor TFIIIA. Genome Res. 2009;19:913-21 pubmed publisher
    ..Most significantly, this study provides the first evidence of ancient exaptation of 5S rRNA in plants, suggesting a novel gene regulation model mediated by the AS of an anciently exonized noncoding element...
  48. Wang C, Weil P. Purification and characterization of Saccharomyces cerevisiae transcription factor IIIA. J Biol Chem. 1989;264:1092-9 pubmed
    ..Characterization of the yeast protein indicates that it shares most, but not all, of the molecular properties of its Xenopus TFIIIA counterpart. ..
  49. Keller B, Volkening K, Droppelmann C, Ang L, Rademakers R, Strong M. Co-aggregation of RNA binding proteins in ALS spinal motor neurons: evidence of a common pathogenic mechanism. Acta Neuropathol. 2012;124:733-47 pubmed publisher
    ..We also conclude that routine IHC-based analysis of spinal MNs may aid in the identification of families not previously suspected to harbor SOD1 mutations. ..
  50. Kryndushkin D, Ihrke G, Piermartiri T, Shewmaker F. A yeast model of optineurin proteinopathy reveals a unique aggregation pattern associated with cellular toxicity. Mol Microbiol. 2012;86:1531-47 pubmed publisher
    ..This study generates a mechanistic framework for investigating how OPTN may trigger pathological changes in ALS and other OPTN-linked neurodegenerative disorders. ..
  51. Lopez Martinez F, Lopez Garrido M, Sanchez Sanchez F, Campos Mollo E, Coca Prados M, Escribano J. Role of MYOC and OPTN sequence variations in Spanish patients with primary open-angle glaucoma. Mol Vis. 2007;13:862-72 pubmed
    ..Overall, our data show that in Spain a minority of adult-onset high-pressure POAG patients carry heterozygous disease-causing mutations in the MYOC gene and that OPTN is not involved in either OHT or POAG. ..
  52. Liu Y, Munro D, Layfield D, Dellinger A, Walter J, Peterson K, et al. Serial analysis of gene expression (SAGE) in normal human trabecular meshwork. Mol Vis. 2011;17:885-93 pubmed
    ..To identify the genes expressed in normal human trabecular meshwork tissue, a tissue critical to the pathogenesis of glaucoma...
  53. Melki R, Belmouden A, Akhayat O, Brezin A, Garchon H. The M98K variant of the OPTINEURIN (OPTN) gene modifies initial intraocular pressure in patients with primary open angle glaucoma. J Med Genet. 2003;40:842-4 pubmed