title: Genes encoding human killer-cell Ig-like receptors with D1 and D2 extracellular domains all contain untranslated pseudoexons encoding a third Ig-like domain.
abstract: Human killer-cell immunoglobulin-like receptors (KIR) show three types of organization of their extracellular domains: D0-D1-D2 in KIR3D, D1-D2 in the majority of KIR2D, and D0-D2 in KIR2DL4 and the novel KIR2DL5. The gene for a KIR2DL3 variant, which has a D1-D2 structure, has been shown previously to have a nonexpressed region (pseudoexon 3) that is paralogous to the exon encoding the D0 domain of other KIR. This pseudoexon is not expressed because it is skipped during splicing of pre-mRNA. In this study, we demonstrate that all eight genes encoding human KIR with D1-D2 configuration (KIR2DL1-KIR2DL3, KIR2DS1-KIR2DS5) have similarly untranslated pseudoexons. Whereas the pseudoexons of four of these KIR genes bear nonsense mutations and/or altered splicing sites, the pseudoexons in the other four KIR genes have no major structural abnormalities, indicating that other mechanisms are responsible for inactivation of their exons 3. A comparison of the sequences on pseudoexons 3 with the paralogous expressed exons suggests that an exonic splicing enhancer may be necessary for the expression of exon 3 in KIR genes.
authors.affiliation: Department of Structural Biology, Stanford University School of Medicine, CA 94305, USA.
authors.forename: C
authors.initials: C
authors.lastname: Vilches
authors.forename: M J
authors.initials: MJ
authors.lastname: Pando
authors.forename: P
authors.initials: P
authors.lastname: Parham
mesh_terms: D000328:Adult; D001483:Base Sequence; D018076:DNA, Complementary; D005091:Exons; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D011544:Pseudogenes; D011971:Receptors, Immunologic / Q000737:chemistry / Q000145:classification / Q000235:genetics*; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054344:Receptors, KIR2DL3; D054345:Receptors, KIR2DL4; D012689:Sequence Homology, Nucleic Acid; D014407:Tumor Cells, Cultured
chemical_list: D018076:DNA, Complementary; C515078:KIR2DL3 protein, human; C515079:KIR2DL4 protein, human; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054344:Receptors, KIR2DL3; D054345:Receptors, KIR2DL4