The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

NRL  -  neural retina leucine zipper

Homo sapiens

Synonyms: D14S46E, NRL-MAF, Neural retina-specific leucine zipper protein, RP27
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of NRL

  • Recessive NRL mutations in patients with clumped pigmentary retinal degeneration and relative preservation of blue cone function [1].
  • Because of its specific pattern of expression, NRL is a candidate gene for retinal diseases [2].
  • PURPOSE: To determine if mutations in the retinal transcription factor gene NRL are associated with retinopathies other than autosomal dominant retinitis pigmentosa (adRP) [3].
  • Here, we show that retinoic acid (RA), a diffusible factor implicated in rod development, activates the expression of NRL in serum-deprived Y79 human retinoblastoma cells and in primary cultures of rat and porcine photoreceptors [4].
  • We have previously shown that neu oncogene-initiated rat mammary carcinomas uniquely over-express neu-related lipocalin (NRL), a member of the calycin protein superfamily [5].

High impact information on NRL

  • A mutation in NRL is associated with autosomal dominant retinitis pigmentosa [6].
  • Our studies establish that NRL is not only essential but is sufficient for rod differentiation and that postmitotic photoreceptor precursors are competent to make binary decisions during early retinogenesis [7].
  • From the Cover: Transformation of cone precursors to functional rod photoreceptors by bZIP transcription factor NRL [7].
  • Ectopic expression of NRL in developing cones can also induce rod-like characteristics and partially suppress cone-specific gene expression [7].
  • Our report presents an unusual clinical phenotype in humans with loss-of-function mutations in NRL [1].

Chemical compound and disease context of NRL

  • The authors investigated the prevalence of immediate (Type I) hypersensitivity to gloves made from natural rubber latex, or NRL, by performing skin-prick tests on 2,166 dental workers over the course of a two-year period (with two one-year intervals) [8].
  • As with clonidine, it evokes hypotension when injected into the NRL region and it completely displaces the [3H]clonidine bound to specific imidazoline-binding sites in human medullary membrane preparations, but it has proved more selective for cerebral imidazoline receptors than clonidine [9].

Biological context of NRL

  • In transient transfection experiments, the mutant protein showed significantly reduced ability to transactivate the rhodopsin promoter, as well as lower synergistic activation with the bZIP transcription factor NRL [10].
  • Interestingly, the mapped CRX transactivation domains were also critical when coexpressed with NRL [11].
  • Here we report that six isoforms of NRL (29-35 kDa) are generated by phosphorylation and expressed specifically in the mammalian retina [12].
  • Loss-of-function NRL alleles have not been described previously in humans, but since the same mutation was present in unaffected family members, it raises the possibility that the abnormal ESCS phenotype in Patient A may result from a digenic mechanism, with a heterozygous NRL mutation and a mutation in another unknown gene [13].
  • NRL is expressed in postmitotic neuronal cells and in lens during embryonic development, but exhibits a retina-specific pattern of expression in the adult [14].

Anatomical context of NRL


Associations of NRL with chemical compounds

  • Deletion analysis revealed that the CRX homeodomain (CRX-HD) plays an important role in the interaction with the NRL leucine zipper [17].
  • Using the yeast two-hybrid method and glutathione S-transferase pull-down assays, we demonstrate that the leucine zipper of NRL can physically interact with CRX [17].
  • We also describe the production of another NRL allergen with the system, Hev b1, which formed large aggregates and gave small yields in purification [18].
  • The monoamine oxidase (MAO) inhibitor tranylcypromine (TCP) (1 nM-10 microM), markedly enhanced [3H]BFI binding in both NRL and cortex [19].
  • BACKGROUND: Immunological cross-reactivity between gutta-percha and natural rubber latex, or NRL, has not been demonstrated clearly despite recent concerns and several suspected cases reported in the literature [20].

Regulatory relationships of NRL


Other interactions of NRL

  • A reciprocal deletion analysis showed that the leucine zipper of NRL is required for interaction with CRX-HD [17].
  • RESULTS: NR2E3 expression was detected shortly after the appearance of NRL in putative immature rods on the foveal edge at Fwk 11 [21].
  • NRL and TBP could be co-immunoprecipitated from bovine retinal nuclear extract [22].
  • METHODS: The coding regions of the NR2E3 and NRL genes and part of the THRB1 coding region were scanned for mutations using single-strand conformation and direct sequencing methods [23].
  • Interestingly, unlike NRL in rat mammary carcinomas, no significant association between NGAL expression and HER-2/neu activation was found in human breast tumors [5].

Analytical, diagnostic and therapeutic context of NRL

  • In both human retinal cell cultures and sections of fetal and adult human retina, NRL is present in the nuclei of developing and mature rods but not cones [12].
  • Both NR2E3 and NRL expression patterns were followed by immunocytochemistry [21].
  • Human bZIP transcription factor gene NRL: structure, genomic sequence, and fine linkage mapping at 14q11.2 and negative mutation analysis in patients with retinal degeneration [14].
  • All samples were subjected to heteroduplex analysis of the three exons of the NRL gene, and HphI restriction digest analysis of exon 2 (to identify the S50T mutation) [24].
  • An indirect competitive immunoassay has been developed using the NRL array biosensor, offering rapid, sensitive detection and quantification of AFB(1) in buffer, corn and nut products [25].


  1. Recessive NRL mutations in patients with clumped pigmentary retinal degeneration and relative preservation of blue cone function. Nishiguchi, K.M., Friedman, J.S., Sandberg, M.A., Swaroop, A., Berson, E.L., Dryja, T.P. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  2. Neural retina-specific leucine zipper gene NRL (D14S46E) maps to human chromosome 14q11.1-q11.2. Yang-Feng, T.L., Swaroop, A. Genomics (1992) [Pubmed]
  3. Mutation screening of patients with Leber Congenital Amaurosis or the enhanced S-Cone Syndrome reveals a lack of sequence variations in the NRL gene. Acar, C., Mears, A.J., Yashar, B.M., Maheshwary, A.S., Andreasson, S., Baldi, A., Sieving, P.A., Iannaccone, A., Musarella, M.A., Jacobson, S.G., Swaroop, A. Mol. Vis. (2003) [Pubmed]
  4. Retinoic Acid Regulates the Expression of Photoreceptor Transcription Factor NRL. Khanna, H., Akimoto, M., Siffroi-Fernandez, S., Friedman, J.S., Hicks, D., Swaroop, A. J. Biol. Chem. (2006) [Pubmed]
  5. Heterogeneous expression of the lipocalin NGAL in primary breast cancers. Stoesz, S.P., Friedl, A., Haag, J.D., Lindstrom, M.J., Clark, G.M., Gould, M.N. Int. J. Cancer (1998) [Pubmed]
  6. A mutation in NRL is associated with autosomal dominant retinitis pigmentosa. Bessant, D.A., Payne, A.M., Mitton, K.P., Wang, Q.L., Swain, P.K., Plant, C., Bird, A.C., Zack, D.J., Swaroop, A., Bhattacharya, S.S. Nat. Genet. (1999) [Pubmed]
  7. From the Cover: Transformation of cone precursors to functional rod photoreceptors by bZIP transcription factor NRL. Oh, E.C., Khan, N., Novelli, E., Khanna, H., Strettoi, E., Swaroop, A. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  8. Natural rubber latex hypersensitivity: incidence and prevalence of type I allergy in the dental professional. Hamann, C.P., Turjanmaa, K., Rietschel, R., Siew, C., Owensby, D., Gruninger, S.E., Sullivan, K.M. Journal of the American Dental Association (1939) (1998) [Pubmed]
  9. I1-imidazoline receptors: an update. Bousquet, P., Dontenwill, M., Greney, H., Feldman, J. Journal of hypertension. Supplement : official journal of the International Society of Hypertension. (1998) [Pubmed]
  10. Leber congenital amaurosis caused by a homozygous mutation (R90W) in the homeodomain of the retinal transcription factor CRX: direct evidence for the involvement of CRX in the development of photoreceptor function. Swaroop, A., Wang, Q.L., Wu, W., Cook, J., Coats, C., Xu, S., Chen, S., Zack, D.J., Sieving, P.A. Hum. Mol. Genet. (1999) [Pubmed]
  11. Functional domains of the cone-rod homeobox (CRX) transcription factor. Chau, K.Y., Chen, S., Zack, D.J., Ono, S.J. J. Biol. Chem. (2000) [Pubmed]
  12. Multiple phosphorylated isoforms of NRL are expressed in rod photoreceptors. Swain, P.K., Hicks, D., Mears, A.J., Apel, I.J., Smith, J.E., John, S.K., Hendrickson, A., Milam, A.H., Swaroop, A. J. Biol. Chem. (2001) [Pubmed]
  13. Mutation analysis of NR2E3 and NRL genes in Enhanced S Cone Syndrome. Wright, A.F., Reddick, A.C., Schwartz, S.B., Ferguson, J.S., Aleman, T.S., Kellner, U., Jurklies, B., Schuster, A., Zrenner, E., Wissinger, B., Lennon, A., Shu, X., Cideciyan, A.V., Stone, E.M., Jacobson, S.G., Swaroop, A. Hum. Mutat. (2004) [Pubmed]
  14. Human bZIP transcription factor gene NRL: structure, genomic sequence, and fine linkage mapping at 14q11.2 and negative mutation analysis in patients with retinal degeneration. Farjo, Q., Jackson, A., Pieke-Dahl, S., Scott, K., Kimberling, W.J., Sieving, P.A., Richards, J.E., Swaroop, A. Genomics (1997) [Pubmed]
  15. FIZ1 is expressed during photoreceptor maturation, and synergizes with NRL and CRX at rod-specific promoters in vitro. Mali, R.S., Zhang, X., Hoerauf, W., Doyle, D., Devitt, J., Loffreda-Wren, J., Mitton, K.P. Exp. Eye Res. (2007) [Pubmed]
  16. Expression of NRL/NGAL (neu-related lipocalin/neutrophil gelatinase-associated lipocalin) during mammalian embryonic development and in inflammation. Zerega, B., Cermelli, S., Michelis, B., Cancedda, R., Cancedda, F.D. Eur. J. Cell Biol. (2000) [Pubmed]
  17. The leucine zipper of NRL interacts with the CRX homeodomain. A possible mechanism of transcriptional synergy in rhodopsin regulation. Mitton, K.P., Swain, P.K., Chen, S., Xu, S., Zack, D.J., Swaroop, A. J. Biol. Chem. (2000) [Pubmed]
  18. Production of Hev b5 as a fluorescent biotin-binding tripartite fusion protein in insect cells. Nordlund, H.R., Laitinen, O.H., Uotila, S.T., Kulmala, M., Kalkkinen, N., Kulomaa, M.S. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  19. Binding of [3H]2-(2-benzofuranyl)-2-imidazoline (BFI) to human brain: potentiation by tranylcypromine. Wiest, S.A., Steinberg, M.I. Life Sci. (1997) [Pubmed]
  20. Cross-reactivity between gutta-percha and natural rubber latex: assumptions vs. reality. Hamann, C., Rodgers, P.A., Alenius, H., Halsey, J.F., Sullivan, K. Journal of the American Dental Association (1939) (2002) [Pubmed]
  21. Expression of photoreceptor-specific nuclear receptor NR2E3 in rod photoreceptors of fetal human retina. Bumsted O'Brien, K.M., Cheng, H., Jiang, Y., Schulte, D., Swaroop, A., Hendrickson, A.E. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
  22. The minimal transactivation domain of the basic motif-leucine zipper transcription factor NRL interacts with TATA-binding protein. Friedman, J.S., Khanna, H., Swain, P.K., Denicola, R., Cheng, H., Mitton, K.P., Weber, C.H., Hicks, D., Swaroop, A. J. Biol. Chem. (2004) [Pubmed]
  23. Shared mutations in NR2E3 in enhanced S-cone syndrome, Goldmann-Favre syndrome, and many cases of clumped pigmentary retinal degeneration. Sharon, D., Sandberg, M.A., Caruso, R.C., Berson, E.L., Dryja, T.P. Arch. Ophthalmol. (2003) [Pubmed]
  24. NRL S50T mutation and the importance of 'founder effects' in inherited retinal dystrophies. Bessant, D.A., Payne, A.M., Plant, C., Bird, A.C., Swaroop, A., Bhattacharya, S.S. Eur. J. Hum. Genet. (2000) [Pubmed]
  25. Indirect competitive immunoassay for detection of aflatoxin B(1) in corn and nut products using the array biosensor. Sapsford, K.E., Taitt, C.R., Fertig, S., Moore, M.H., Lassman, M.E., Maragos, C.M., Shriver-Lake, L.C. Biosensors & bioelectronics. (2006) [Pubmed]
WikiGenes - Universities