HGNC Approved Gene Symbol: DNASE1L2
Cytogenetic location: 16p13.3 Genomic coordinates (GRCh38): 16:2,236,444-2,238,711 (from NCBI)
Germino et al. (1992) identified a DNASE1L2 exon while sequencing a cosmid from the PKD1 (601313) region on 16p13.3. Using the sequence of this exon for RT-PCR and searches of EST databases, Rodriguez et al. (1997) cloned DNASE1L2 cDNAs. The predicted 299-amino acid DNASE1L2 protein contains a 21-amino acid signal peptide. The amino acid sequence of DNASE1L2 is 56% identical to that of DNASE1 (125505). By RT-PCR, the authors detected DNASE1L2 expression in fetal and adult brain.
Using RT-PCR, Shiokawa et al. (2004) detected DNASE1L2 expression in all tissues examined except colon. Peripheral blood leukocytes showed a second DNASE1L2 transcript, and by PCR of a leukocyte cDNA library, Shiokawa et al. (2004) cloned this splice variant, which they called DNASE1L2S. The deduced 278-amino acid protein lacks a proline-rich domain found in the full-length protein, which the authors called DNASE1L2L. DNASE1L2S also differs from the brain-specific DNASE1L2 splice variant identified by Rodriguez et al. (1997).
Shiokawa et al. (2004) characterized the DNase activities of full-length DNASE1L2L and the DNASE1L2S variant following expression in human embryonic kidney cells. Both isoforms showed identical enzymatic properties, with strong endonuclease activity in the presence of both Ca(2+) and Mg(2+). No activity was detected in the absence of either cation, but either Co(2+) or Mn(2+) could replace the combination of Ca(2+) and Mg(2+). Both enzymes showed a pH optimum of 5.6, and both were inhibited by increasing NaCl concentration. Two inflammatory cytokines, TNFA (191160) and IL1B (147720), induced endogenous DNAS1L2 expression in a keratinocyte cell line via the NFKB (see 164011) pathway. However, several other interferons and interleukins, as well as dibutyryl cAMP, had no effect on DNAS1L2 expression levels.
Shiokawa et al. (2004) determined that the DNAS1L2 gene contains 7 exons and spans about 2.0 kb. The 5-prime flanking region contains no TATA or CAAT boxes, but it has 2 GC boxes. Using a reporter gene assay, Shiokawa et al. (2004) identified an NFKB-responsive element in the 5-prime flanking region.
Germino et al. (1992) identified the DNASE1L2 gene on chromosome 16p13.3.
Germino, G. G., Weinstat-Saslow, D., Himmelbauer, H., Gillespie, G. A. J., Somlo, S., Wirth, B., Barton, N., Harris, K. L., Frischauf, A.-M., Reeders, S. T. The gene for autosomal dominant polycystic kidney disease lies in a 750-kb CpG-rich region. Genomics 13: 144-151, 1992. [PubMed: 1577479] [Full Text: https://doi.org/10.1016/0888-7543(92)90214-d]
Rodriguez, A. M., Rodin, D., Nomura, H., Morton, C. C., Weremowicz, S., Schneider, M. C. Identification, localization, and expression of two novel human genes similar to deoxyribonuclease I. Genomics 42: 507-513, 1997. [PubMed: 9205125] [Full Text: https://doi.org/10.1006/geno.1997.4748]
Shiokawa, D., Matsushita, T., Kobayashi, T., Matsumoto, Y., Tanuma, S. Characterization of the human DNAS1L2 gene the molecular mechanism for its transcriptional activation induced by inflammatory cytokines. Genomics 84: 95-105, 2004. [PubMed: 15203207] [Full Text: https://doi.org/10.1016/j.ygeno.2004.02.003]