The International Journal of Biochemistry & Cell Biology 40 (2008) 2353–2357 Available online at www.sciencedirect.com Molecules in focus ZRANB2: Structural and functional insights into a novel splicing protein A. Helena Mangs, Brian J. Morris ∗ Basic & Clinical Genomics Laboratory, School of Medical Sciences and Bosch Institute, Building F13, The University of Sydney, NSW 2006, Australia Received 16 August 2007; received in revised form 17 August 2007; accepted 20 August 2007 Available online 24 August 2007 Abstract ZRANB2 was identified originally in a differential display experiment on 2-day and 10-day primary cultures of rat juxtaglomerular cells. During prolonged culture it was found to undergo down-regulation in concert with renin, the archetypical constituent of these cells. ZRANB2 has two zinc fingers that form a novel fold and show striking homology to Ran-binding protein domains. Human ZRANB2 mRNA is alternatively spliced to give two variants with different 3 ′ ends. ZRANB2 has homologues across a range of species, the N-terminal end being particularly conserved. ZRANB2 is present in the nucleus of human cells. It binds to mRNA, as well as the essential splicing factors U170K and U2AF 35 and the novel splicing component SFRS17A (formerly known as XE7). ZRANB2 is one of 20 genes up-regulated in grade III ovarian serous papillary carcinoma. Here, we review current knowledge surrounding ZRANB2. © 2007 Elsevier Ltd. All rights reserved. Keywords: Zinc finger proteins; Renin; Splicing factor; Alternative splicing 1. Introduction Zinc finger Ran-binding domain-containing protein 2 (ZRANB2), originally known as ‘Zis’ and then ‘ZNF265’, was first identified in renal juxtaglumerular (JG) cells (Karginova et al., 1997). JG cells are found in the afferent arterioles of the glomerulus. These cells synthesize and release renin, the key rate-determining enzyme of the renin–angiotensin system whose main function is to regulate arterial blood pressure and salt and water homeostasis. During prolonged culture of JG cells renin expression is down-regulated. In an attempt ∗ Corresponding author. Tel.: +61 2 9351 3688; fax: +61 2 9351 2227. E-mail address: brianm@medsci.usyd.edu.au (B.J. Morris). to identify factors that control renin expression, differ- ential display was performed on 2- and 10-day cultures of rat JG cells. This led to the initial identification of Zis as a unique mRNA that was down-regulated in concert with renin during this period (Karginova et al., 1997). We found that in humans ZRANB2 is localized on chromosome 1p31 (Adams et al., 2000). Expression is not confined to renin mRNA-containing cells but is ubiq- uitous (Adams et al., 2000). We then went on to show that ZRANB2 can regulate alternative splicing and that it interacts with several splicing proteins (Adams et al., 2001; Mangs et al., 2006). 2. Structure ZRANB2 has two zinc finger domains, a C-terminal Ser/Arg-rich (SR) domain and a glutamic acid-rich 1357-2725/$ – see front matter © 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.biocel.2007.08.007