Subject: Novel kinase: Dyrk3 Dyrk3 is a novel Drosophila kinase belonging to the Dyrk family. 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 and flanking UTRs (TrEMBL: P83102). The sequence is most similar to human Dyrk2 (75% identity in kinase domain, 72% in a 397 AA extended overlap, excluding the divergent first 202 AA and the last 25 AA of fly Dyrk3). There are two other Dyrk family members in Drosophila: mnb (Dyrk1) and smi35A (Dyrk2), and two in C. elegans (F49E11.1 and T04C10.1). mnb and T04C10.1 are likely orthologous to human genes Dyrk1 and mnb, while Drosophila Dyrk3 and F49E11.1 appear to be orthologous to human Dyrk2 and Dyrk3. smi35A and human Dyrk4 are outliers to this group, whose orthology is not clear. 18 ESTs cover most of the sequence, including 15 from embryo (14 from the RE normalized library, 1 from the LD library), ovary (1 GM library clone), adult head (1 HL clone) and S2 cells (1 SD clone). 10 of the RE ESTs show alternative splicing, with an extended first exon and missing second exon, but this is in the 5' UTR and does not affect the protein sequence. The single S2 clone (SD25722) also skips the second exon, and extends the first exon even further. Dyrk3 maps to 102EF; a partial sequence of this gene including an intron has been published to Genbank (gi|5081375) as 'unknown telomeric protein gene' and annotated as mapping to telomeric heterochromatin. This is the site of insertion of a hsp70-white+ transgene, stock 118E-15 in Cryderman et al (EMBO J. (1999), 18:3724-35 ). \-Gerard Manning.