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ZACN  -  zinc activated ligand-gated ion channel

Homo sapiens

Synonyms: L2, LGICZ, LGICZ1, Ligand-gated ion channel zinc-activated 1, Ligand-gated ion-channel receptor L2, ...
 
 
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Disease relevance of LGICZ1

 

High impact information on LGICZ1

  • Five consecutive triple base pairs flank the helical junction where the 3' nucleotide of L2, C27, adopts a cytidine 27 N3-cytidine 14 2'-OH hydrogen bonding interaction with the C14-G7 base pair [3].
  • The cell cycle control gene ZAC/PLAGL1 is imprinted--a strong candidate gene for transient neonatal diabetes [5].
  • In particular, ZAC / PLAGL1 is a transcriptional regulator of the type 1 receptor for pituitary adenylate cyclase-activating polypeptide, which is the most potent known insulin secretagog and an important mediator of autocrine control of insulin secretion in the pancreatic islet [5].
  • Here we investigate ZAC status in pituitary tumors to evaluate its role in pituitary tumorigenesis [6].
  • ZAC is highly expressed in the anterior pituitary gland, and its ablation by antisense targeting promotes pituitary cell proliferation [6].
 

Biological context of LGICZ1

 

Anatomical context of LGICZ1

  • Transcripts of ZAC subunits were detected in human placenta, trachea, spinal cord, stomach, and fetal brain [7].
  • Cloning and expression of ligand-gated ion-channel receptor L2 in central nervous system [8].
  • Immunostained tissue sections revealed that L2-like immunoreactivity was dominantly expressed in the hippocampal CA3 pyramidal cells and in the polymorphic layer of the dentate gyrus [8].
  • The RT-PCR studies confirmed L2 mRNA expression in hippocampus, striatum, amygdala, and thalamus in adult brain [8].
  • We have cloned L2 cDNA derived from human caudate nucleus and characterized the exon-intron structure as follows: (1) The L2 protein has four transmembrane regions (M1-M4) and a long cytoplasmic loop between M3 and M4 [8].
 

Associations of LGICZ1 with chemical compounds

  • This protein (ZAC) contains all of the motifs that are characteristic of Cys loop channel subunits but cannot be assigned to any of the four established families on the basis of sequence similarity [7].
  • The L2 protein shares partial homology with serotonin receptors 5HT3A and 5HT3B [8].
  • L1-L2 interactions were not significantly disrupted by treatment with high salt concentrations (2 M NaCl), weak detergents, and urea concentrations of up to 2 M, further indicating that L1 binding by this domain is mediated by strong hydrophobic interactions [10].
  • The L2 protein remained associated with capsomers on disassembly by treatment with DTT [11].
  • We used C. trachomatis serovar L2 and a mutant CHO K1 cell line with a genetic deficiency in folate metabolism as a host for chlamydial growth [12].
 

Analytical, diagnostic and therapeutic context of LGICZ1

  • Western blots revealed that L2 protein confers sugar chains on the extracellular side [8].
  • Antibodies directed toward these epitopes detect L2 proteins of HPV11, -16, and -18, but not of HPV1 and -8, in Western immunoblots and enzyme-linked immunosorbent assays [13].
  • Based on immunofluorescence and coimmunoprecipitation analyses, the L2 region interacting with dynein is mapped to the C-terminal 40 amino acids [14].
  • Similarly, in vivo DNA vaccination using HPV L1 or L2 expression constructs produces only weak immune responses [15].
  • To characterize such virus-like particles more fully, cryoelectron microscopy and image analysis techniques were used to generate three-dimensional reconstructions of capsids produced by vaccinia virus recombinants (V capsids) that expressed human papillomavirus type 1 L1 protein only or both L1 and L2 proteins [16].

References

  1. A Sequential splicing mechanism promotes selection of an optimal exon by repositioning a downstream 5' splice site in preprotachykinin pre-mRNA. Nasim, F.H., Spears, P.A., Hoffmann, H.M., Kuo, H.C., Grabowski, P.J. Genes Dev. (1990) [Pubmed]
  2. Pathogenesis of human papillomaviruses in differentiating epithelia. Longworth, M.S., Laimins, L.A. Microbiol. Mol. Biol. Rev. (2004) [Pubmed]
  3. A loop 2 cytidine-stem 1 minor groove interaction as a positive determinant for pseudoknot-stimulated -1 ribosomal frameshifting. Cornish, P.V., Hennig, M., Giedroc, D.P. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  4. Zac1 (Lot1), a potential tumor suppressor gene, and the gene for epsilon-sarcoglycan are maternally imprinted genes: identification by a subtractive screen of novel uniparental fibroblast lines. Piras, G., El Kharroubi, A., Kozlov, S., Escalante-Alcalde, D., Hernandez, L., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Stewart, C.L. Mol. Cell. Biol. (2000) [Pubmed]
  5. The cell cycle control gene ZAC/PLAGL1 is imprinted--a strong candidate gene for transient neonatal diabetes. Kamiya, M., Judson, H., Okazaki, Y., Kusakabe, M., Muramatsu, M., Takada, S., Takagi, N., Arima, T., Wake, N., Kamimura, K., Satomura, K., Hermann, R., Bonthron, D.T., Hayashizaki, Y. Hum. Mol. Genet. (2000) [Pubmed]
  6. The expression of the antiproliferative gene ZAC is lost or highly reduced in nonfunctioning pituitary adenomas. Pagotto, U., Arzberger, T., Theodoropoulou, M., Grübler, Y., Pantaloni, C., Saeger, W., Losa, M., Journot, L., Stalla, G.K., Spengler, D. Cancer Res. (2000) [Pubmed]
  7. A novel class of ligand-gated ion channel is activated by Zn2+. Davies, P.A., Wang, W., Hales, T.G., Kirkness, E.F. J. Biol. Chem. (2003) [Pubmed]
  8. Cloning and expression of ligand-gated ion-channel receptor L2 in central nervous system. Houtani, T., Munemoto, Y., Kase, M., Sakuma, S., Tsutsumi, T., Sugimoto, T. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  9. Complete nucleotide sequence of reovirus L2 gene and deduced amino acid sequence of viral mRNA guanylyltransferase. Seliger, L.S., Zheng, K., Shatkin, A.J. J. Biol. Chem. (1987) [Pubmed]
  10. Interactions between papillomavirus L1 and L2 capsid proteins. Finnen, R.L., Erickson, K.D., Chen, X.S., Garcea, R.L. J. Virol. (2003) [Pubmed]
  11. Organization of the major and minor capsid proteins in human papillomavirus type 33 virus-like particles. Sapp, M., Volpers, C., Müller, M., Streeck, R.E. J. Gen. Virol. (1995) [Pubmed]
  12. Biochemical evidence for the existence of thymidylate synthase in the obligate intracellular parasite Chlamydia trachomatis. Fan, H.Z., McClarty, G., Brunham, R.C. J. Bacteriol. (1991) [Pubmed]
  13. Development of type-specific and cross-reactive serological probes for the minor capsid protein of human papillomavirus type 33. Volpers, C., Sapp, M., Komly, C.A., Richalet-Secordel, P., Streeck, R.E. J. Virol. (1993) [Pubmed]
  14. Identification of a dynein interacting domain in the papillomavirus minor capsid protein l2. Florin, L., Becker, K.A., Lambert, C., Nowak, T., Sapp, C., Strand, D., Streeck, R.E., Sapp, M. J. Virol. (2006) [Pubmed]
  15. Enhancement of capsid gene expression: preparing the human papillomavirus type 16 major structural gene L1 for DNA vaccination purposes. Leder, C., Kleinschmidt, J.A., Wiethe, C., Müller, M. J. Virol. (2001) [Pubmed]
  16. Three-dimensional structure of vaccinia virus-produced human papillomavirus type 1 capsids. Hagensee, M.E., Olson, N.H., Baker, T.S., Galloway, D.A. J. Virol. (1994) [Pubmed]
 
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