Siglec-15: an immune system Siglec conserved throughout vertebrate evolution.
Siglecs are vertebrate cell-surface receptors that recognize sialylated glycans. Here we have identified and characterized a novel Siglec, named Siglec-15. Siglec-15 is a type-I transmembrane protein consisting of: (i) two immunoglobulin (Ig)-like domains, (ii) a transmembrane domain containing a lysine residue, and (iii) a short cytoplasmic tail. Siglec-15 is expressed on macrophages and/or dendritic cells of human spleen and lymph nodes. We show that the extracellular domain of Siglec-15 preferentially recognizes the Neu5Acalpha2-6GalNAcalpha- structure. Siglec-15 associates with the activating adaptor proteins DNAX activation protein (DAP)12 and DAP10 via its lysine residue in the transmembrane domain, implying that it functions as an activating signaling molecule. Siglec-15 is the second human Siglec identified to have an activating signaling potential; unlike Siglec-14, however, it does not have an inhibitory counterpart. Orthologs of Siglec-15 are present not only in mammals but also in other branches of vertebrates; in contrast, no other known Siglec expressed in the immune system has been conserved throughout vertebrate evolution. Thus, Siglec-15 probably plays a conserved, regulatory role in the immune system of vertebrates.
Angata
Takashi
T
Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan. takashi-angata@aist.go.jp
Tabuchi
Yukako
Y
Nakamura
Kazunori
K
Nakamura
Mitsuru
M
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006801:Humans; D007107:Immune System / Q000276:immunology*; D007136:Immunoglobulins / Q000235:genetics* / Q000378:metabolism*; D037102:Lectins / Q000235:genetics* / Q000378:metabolism*; D008024:Ligands; D008198:Lymph Nodes / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010802:Phylogeny; D011971:Receptors, Immunologic / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D013154:Spleen / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; C120528:HCST protein, human; D007136:Immunoglobulins; D037102:Lectins; D008024:Ligands; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; C527037:SIGLEC15 protein, human; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C110546:TYROBP protein, human