Alternative titles; symbols
HGNC Approved Gene Symbol: ZRANB2
Cytogenetic location: 1p31.1 Genomic coordinates (GRCh38) : 1:71,063,291-71,081,035 (from NCBI)
ZRANB2 is an evolutionarily conserved zinc finger protein that plays a role in mRNA processing (Plambeck et al., 2003).
Nakano et al. (1998) isolated 2 transcripts, ZIS1 and ZIS2, from a human fetal brain cDNA library. ZIS1 and ZIS2 correspond to the human ortholog of the rat Zis (zinc finger, splicing) gene. Comparison of the cDNA sequence with its corresponding genomic clone showed that both transcripts have an open reading frame of 1,011 basepairs, encoding a 337-amino acid protein. Due to differential splicing, ZIS1 has 10 exons while ZIS2 has 11. The 2 transcripts share the first 9 exons, but ZIS1 lacks exon 10 and instead has a longer exon 11 and a longer 3-prime untranslated region. Northern blot analysis identified 2 ubiquitously expressed transcripts of 5.2 and 3.2 kb. Two additional transcripts of 3.9 and 1.9 kb were seen at high levels in fetal brain and kidney. Both ZIS proteins have a zinc finger domain, a nuclear localization signal, an asp-glu region, and a ser/arg-rich region.
Using Northern blot analysis, Adams et al. (2000) detected ZNF265 transcripts of 3.5, 5.2, and 6.7 kb in all adult and fetal human tissues examined. A 9.0-kb transcript was also present in kidney and lung, and a 1.9-kb transcript was also present in adult, but not fetal, heart and skeletal muscle.
By FISH analysis using a ZIS genomic clone, Nakano et al. (1998) mapped the ZIS gene to chromosome 1p22.1-p21.3. They confirmed this result using a radiation hybrid mapping panel.
Using FISH, Adams et al. (2000) mapped the ZRANB2 gene to chromosome 1p31. They mapped the mouse gene to chromosome 3q.
Plambeck et al. (2003) showed that the conserved cys-containing motifs of human ZRANB2 were zinc-binding domains. By NMR analysis, they found that the structure was a variant of the zinc ribbon class of zinc-binding domains. An RNA gel-shift assay demonstrated that the zinc-binding domain of ZRANB2 bound cyclin B1 (CCNB1; 123836) mRNA.
Using human ZRANB2 as bait in a yeast 2-hybrid screen, Mangs et al. (2006) identified human XE7 (AKAP17A; 312095) as an interacting protein. They demonstrated that XE7 functioned as an alternative splicing regulator that interacted with both ZRANB2 and ASF (SRSF1; 600812) via its RS-rich region. Confocal microscopy demonstrated colocalization of XE7, ZRANB2, and ASF in nuclei of human cells.
Wang et al. (2016) identified zranb2 as a cytoplasmic lipopolysaccharide (LPS)-binding protein that was abundantly expressed in zebrafish eggs and embryos. Zebrafish zranb2 also bound gram-negative bacteria and functioned as an antibacterial effector molecule with direct bactericidal activity that required N-terminal residues 11 through 37, consisting of the first zinc finger RAN-binding (ZNFRBZ) domain. Injection of recombinant zranb2 into early embryos enhanced resistance to pathogenic bacteria, and this effect was abrogated by anti-zranb2 antibody. Wang et al. (2016) concluded that zranb2 is a maternal LPS-binding protein with an immunologic role that protects early zebrafish embryos from pathogen attack.
Adams, D. J., van der Weyden, L., Kovacic, A., Lovicu, F. J., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Ioannou, P. A., Morris, B. J. Chromosome localization and characterization of the mouse and human zinc finger protein 265 gene. Cytogenet. Cell Genet. 88: 68-73, 2000. [PubMed: 10773668] [Full Text: https://doi.org/10.1159/000015487]
Mangs, A. H., Speirs, H. J. L., Goy, C., Adams, D. J., Markus, M. A., Morris, B. J. XE7: a novel splicing factor that interacts with ASF/SF2 and ZNF265. Nucleic Acids Res. 34: 49776-4986, 2006.
Nakano, M., Yoshiura, K., Oikawa, M., Miyoshi, O., Yamada, K., Kondo, S., Miwa, N., Soeda, E., Jinno, Y., Fujii, T., Niikawa, N. Identification, characterization and mapping of the human ZIS (zinc-finger, splicing) gene. Gene 225: 59-65, 1998. [PubMed: 9931435] [Full Text: https://doi.org/10.1016/s0378-1119(98)00536-8]
Plambeck, C. A., Kwan, A. H. Y., Adams, D. J., Westman, B. J., van der Weyden, L., Medcalf, R. L., Morris, B. J., Mackay, J. P. The structure of the zinc finger domain from human splicing factor ZNF265 fold. J. Biol. Chem. 278: 22805-22811, 2003. [PubMed: 12657633] [Full Text: https://doi.org/10.1074/jbc.M301896200]
Wang, X., Du, X., Li, H., Zhang, S. Identification of the zinc finger protein ZRANB2 as a novel maternal lipopolysaccharide-binding protein that protects embryos of zebrafish against gram-negative bacterial infections. J. Biol. Chem. 291: 4019-4034, 2016. [PubMed: 26740623] [Full Text: https://doi.org/10.1074/jbc.M115.679167]