Date: Mon, 15 Oct 2001 14:58:15 \-0700 To: Gillian Millburn (Genetics) <gm119@XXXX> From: Gerard Manning <gerard-manning@XXXX> Subject: Novel kinase: WSCK WSCK is a predicted novel receptor tyrosine kinase. It was discovered in a computational screen for kinase domains in fly genomic sequence; the initial HMM hit was extended using Genewise gene finding and overlapping ESTs, giving a full open reading frame ((TrEMBL: P83097) and flanking UTRs . The 2980nt predicted transcript encodes an 809 AA protein with 5' and 3' UTRs and a polyA tail, if a single base is inserted into the genomic sequence to correct a predicted frameshift. The sequence predicts a receptor-like protein, with a signal peptide from 1-32 and a single transmembrane domain in the region of 418-463 (different methods predict different co-ordinates within that region). The putative extracellular region includes a WSC domain from 42-115, a full fibronectin type III (FnIII) repeat from 129-233 and a partial FnIII repeat from 248-286. The WSC domain has been weakly ascribed a role in carbohydrate binding. FnIII domains are common in extracellular regions of cell surface proteins, especially receptor tyrosine kinases and cytokine receptors and may bind heparin or other cell surface proteins. The putative intracellular region has a divergent kinase domain from 511-770 which is most similar to tyrosine kinase domains from the tie/tek and FGF-R families of receptor tyrosine kinases, though the similarity of kinases within these families is much higher to each other than to WSCK. The divergence of this sequence cautions against strong conclusions from the homology or that this is a fully functional kinase domain. However, the relationship to FGF receptor kinases may be relevant to the carbohydrate and heparin-binding properties of the WSC and FnIII domains, given that FGF binding to receptor is dependent on heparin binding; WSCK could speculatively be a FGF co-receptor. The sequence is almost completely covered by 15 ESTs (excluding the frameshift region), from a variety of libraries: 5 from embryo (LD library), 5 from head (1 from GH library, 4 from RH normalized head library), 1 from ovary (GM), 1 from larval/pupal stages (LP) and three from S2 cells (SD library). The sequence maps as a two-exon transcript to 96A13-16, between predicted gene CG6668, a conserved novel protein, and Syx 18, encoding a t-SNARE. \-Gerard Manning.