title: The silent KIR3DP1 gene (CD158c) is transcribed and might encode a secreted receptor in a minority of humans, in whom the KIR3DP1, KIR2DL4 and KIR3DL1/KIR3DS1 genes are duplicated.
abstract: Killer-cell Ig-like receptors (KIR) are structurally and functionally diverse, and enable human NK cells to survey the expression of individual HLA class I molecules, often altered in infections and tumors. Multiple events of non-reciprocal recombination have contributed to the rapid diversification of KIR. We show that approximately 4.5% of the individuals of a Caucasoid population bear a recombinant allele of KIR3DP1, officially designed KIR3DP1*004, that associates tightly with gene duplications of KIR3DP1, KIR2DL4 and KIR3DL1/KIR3DS1. The KIR3DP1 gene is normally silent, but the recombinant allele carries a novel promoter sequence and, as a consequence, is transcribed in all tested individuals. Messenger RNA of KIR3DP1*004 is made up of six exons; of these, exons 1-5 are similar to, and spliced like, those encoding the leader peptide and Ig-domains of KIR3D. By contrast, exon 6 is homologous to no other human KIR sequence, but only to possible homologs in chimpanzees and rhesus macaques, and encodes a short hydrophilic tail. The putative KIR3DP1*004 product, like those of the related genes LAIR-2 and LILRA3/ILT6/LIR4, is predicted to be secreted to the extracellular medium rather than anchored to the cell membrane.
authors.affiliation: Servicio de Inmunología, Hospital Universitario Puerta de Hierro, Madrid, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Gómez-Lozano
authors.forename: Ernesto
authors.initials: E
authors.lastname: Estefanía
authors.forename: Fionnuala
authors.initials: F
authors.lastname: Williams
authors.forename: Iris
authors.initials: I
authors.lastname: Halfpenny
authors.forename: Derek
authors.initials: D
authors.lastname: Middleton
authors.forename: Rosario
authors.initials: R
authors.lastname: Solís
authors.forename: Carlos
authors.initials: C
authors.lastname: Vilches
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D020440:Gene Duplication; D020868:Gene Silencing; D006239:Haplotypes; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D054340:Receptors, KIR; D054345:Receptors, KIR2DL4; D054341:Receptors, KIR3DL1; D054349:Receptors, KIR3DS1; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D011995:Recombination, Genetic; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
chemical_list: C515079:KIR2DL4 protein, human; C515083:KIR3DL1 protein, human; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054345:Receptors, KIR2DL4; D054341:Receptors, KIR3DL1; D054349:Receptors, KIR3DS1; D011993:Recombinant Fusion Proteins