title: Ancient divergence of a complex family of immune-type receptor genes.
abstract: Multigene families of activating/inhibitory receptors belonging to the immunoglobulin superfamily (IgSF) regulate immunological and other cell-cell interactions. A new family of such genes, termed modular domain immune-type receptors (MDIRs), has been identified in the clearnose skate (Raja eglanteria), a phylogenetically ancient vertebrate. At least five different major forms of predicted MDIR proteins are comprised of four different subfamilies of IgSF ectodomains of the intermediate (I)- or C2-set. The predicted number of individual IgSF ectodomains in MDIRs varies from one to six. MDIR1 contains a positively charged transmembrane residue and MDIR2 and MDIR3 each possesses at least one immunoreceptor tyrosine-based inhibitory motif in their cytoplasmic regions. MDIR4 and MDIR5 lack characteristic activating/inhibitory signalling motifs. MDIRs are encoded in a particularly large and complex multigene family. MDIR domains exhibit distant sequence similarity to mammalian CMRF-35-like molecules, polymeric immunoglobulin receptors, triggering receptors expressed on myeloid cells (TREMs), TREM-like transcripts, NKp44 and FcR homologs, as well as to sequences identified in several different vertebrate genomes. Phylogenetic analyses suggest that MDIRs are representative members of an extended family of IgSF genes that diverged before or very early in evolution of the vertebrates and subsequently came to occupy multiple, fully independent distributions in the present day.
authors.affiliation: Department of Pediatrics, University of South Florida College of Medicine, and USF/ACH Children's Research Institute, 830 First Street South, St. Petersburg, FL, 33701, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Cannon
authors.forename: Robert N
authors.initials: RN
authors.lastname: Haire
authors.forename: M Gail
authors.initials: MG
authors.lastname: Mueller
authors.forename: Ronda T
authors.initials: RT
authors.lastname: Litman
authors.forename: Donna D
authors.initials: DD
authors.lastname: Eason
authors.forename: Deborah
authors.initials: D
authors.lastname: Tinnemore
authors.forename: Chris T
authors.initials: CT
authors.lastname: Amemiya
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ota
authors.forename: Gary W
authors.initials: GW
authors.lastname: Litman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D014644:Genetic Variation; D007136:Immunoglobulins / Q000276:immunology*; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000145:classification* / Q000235:genetics*; D012860:Skates, Fish / Q000235:genetics / Q000276:immunology*
chemical_list: D007136:Immunoglobulins; D011971:Receptors, Immunologic