title: Comparative analysis of the Kekkon molecules, related members of the LIG superfamily.
abstract: Leucine-rich repeats (LRRs) and immunoglobulin (Ig) domains represent two of the most abundant sequence elements in metazoan proteomes. Despite this prevalence, comparatively few molecules containing both LRR and Ig (LIG) modules exist, and fewer still have been functionally defined. One LIG whose function has been investigated is the Drosophila protein Kekkon1 (Kek1). In vivo studies have demonstrated a role for Kek1 in Epidermal Growth Factor Receptor (EGFR) signaling and have suggested a role in neuronal pathfinding. Kek1 is the founding member of the Kek family, a group of six Drosophila transmembrane proteins that contain seven LRRs and a single Ig in their extracellular domains. While this arrangement of domains predicts a possible role as cell adhesion molecules (CAMs), to date little is known about the function or evolutionary relationship of these additional Kek molecules. Here we report that orthologs of Kek1, Kek2, Kek5, and Kek6 exist in the mosquito, Anopheles gambiae, and the honeybee, Apis mellifera, indicating that this family has been conserved for ~300 million years of evolutionary time. Comparative sequence analyses reveal remarkable identity among these orthologs, primarily in their extracellular regions. In contrast, the intracellular regions are more divergent, exhibiting only small pockets of conservation. In addition, we provide support for the general notion that these molecules may share common functions as CAMs, by demonstrating that Kek family members can form homotypic and heterotypic complexes.
authors.affiliation: Department of Biology, Indiana University, Jordan Hall, 1001 E 3rd Street, Bloomington, IN 47405, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: MacLaren
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Evans
authors.forename: Diego
authors.initials: D
authors.lastname: Alvarado
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Duffy
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016000:Cluster Analysis; D019295:Computational Biology; D017124:Conserved Sequence / Q000235:genetics; D030561:Databases, Nucleic Acid; D029721:Drosophila Proteins / Q000235:genetics*; D019143:Evolution, Molecular; D007136:Immunoglobulins / Q000235:genetics*; D047468:Immunoprecipitation; D007313:Insecta / Q000235:genetics*; D000090263:Leucine-Rich Repeat Proteins; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D029721:Drosophila Proteins; D007136:Immunoglobulins; D000090263:Leucine-Rich Repeat Proteins; D008565:Membrane Proteins; D011506:Proteins; C105053:Kek1 protein, Drosophila; D017027:Protein Tyrosine Phosphatases