Cloning and characterization of human Siglec-11. A recently evolved signaling molecule that can interact with SHP-1 and SHP-2 and is expressed by tissue macrophages, including brain microglia.
Siglecs are sialic acid-recognizing animal lectins of the immunoglobulin superfamily. We have cloned and characterized a novel human molecule, Siglec-11, that belongs to the subgroup of CD33/Siglec-3-related Siglecs. As with others in this subgroup, the cytosolic domain of Siglec-11 is phosphorylated at tyrosine residue(s) upon pervanadate treatment of cells and then recruits the protein-tyrosine phosphatases SHP-1 and SHP-2. However, Siglec-11 has several novel features relative to the other CD33/Siglec-3-related Siglecs. First, it binds specifically to alpha2-8-linked sialic acids. Second, unlike other CD33/Siglec-3-related Siglecs, Siglec-11 was not found on peripheral blood leukocytes. Instead, we observed its expression on macrophages in various tissues, such as liver Kupffer cells. Third, it was also expressed on brain microglia, thus becoming the second Siglec to be found in the nervous system. Fourth, whereas the Siglec-11 gene is on human chromosome 19, it lies outside the previously described CD33/Siglec-3-related Siglec cluster on this chromosome. Fifth, analyses of genome data bases indicate that Siglec-11 has no mouse ortholog and that it is likely to be the last canonical human Siglec to be reported. Finally, although Siglec-11 shows marked sequence similarity to human Siglec-10 in its extracellular domain, the cytosolic tail appears only distantly related. Analysis of genomic regions surrounding the Siglec-11 gene suggests that it is actually a chimeric molecule that arose from relatively recent gene duplication and recombination events, involving the extracellular domain of a closely related ancestral Siglec gene (which subsequently became a pseudogene) and a transmembrane and cytosolic tail derived from another ancestral Siglec.
Angata
Takashi
T
Glycobiology Research and Training Center, Department of Medicine, University of California, San Diego, La Jolla, California 92093-0687, USA.
Kerr
Sheena C
SC
Greaves
David R
DR
Varki
Nissi M
NM
Crocker
Paul R
PR
Varki
Ajit
A
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001065:Appendix / Q000166:cytology / Q000378:metabolism; D001483:Base Sequence; D001921:Brain / Q000502:physiology*; D003001:Cloning, Molecular; D019143:Evolution, Molecular; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D008565:Membrane Proteins; D017628:Microglia / Q000502:physiology*; D008969:Molecular Sequence Data; D009928:Organ Specificity; D014066:Palatine Tonsil / Q000166:cytology / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011544:Pseudogenes; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D063268:Sialic Acid Binding Ig-like Lectin 3; D014158:Transcription, Genetic; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; D008565:Membrane Proteins; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D012333:RNA, Messenger; D063268:Sialic Acid Binding Ig-like Lectin 3; C571163:CD33 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C571165:Cd33 protein, mouse; C464442:SIGLEC11 protein, human; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse