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. Author manuscript; available in PMC: 2024 Apr 1.
Published in final edited form as: Mol Aspects Med. 2022 Aug 18;90:101117. doi: 10.1016/j.mam.2022.101117

Figure 1. Mammalian Siglecs.

Figure 1.

Siglecs in humans, chimpanzees, rhesus macaques, common marmosets, and mice are depicted. Mammalian Siglecs can be classified into two groups: conserved Siglecs, including Sialoadhesin/Siglec-1, CD22/Siglec-2, MAG/Siglec-4, and Siglec-15, are conserved among these species (and possibly among tetrapods); CD33/Siglec-3-related Siglecs show significant species-to-species variations. Siglec-13 was lost in humans. Siglec-17 is a functional protein in marmoset (New World monkey); the transcript of its ortholog (SIGLEC17P) is expressed in humans and great apes but does not yield functional protein due to mutations (human: single-nucleotide deletion in exon 1; chimpanzee and gorilla: five-nucleotide deletion in exon 2; orangutan: insertion of two 61-nucleotide repeats in exon 2). SIGLEC5 gene in common marmoset has a frameshift mutation in exon 2 (encoding V-set domain) but otherwise intact, and thus included.

N-terminal V-set Ig-like domain of Siglecs recognizes sialic acid (Sia) and contains several conserved residues involved in Sia recognition. Human Siglec-XII has a mutation at the essential Arg residue involved in Sia recognition, and thus lost the ability to recognize Sia, whereas great ape counterpart has the Arg and preferentially recognizes Neu5Gc.

Intracellular domain of most Siglecs contains a sequence motif called ITIM, which interacts with nonreceptor-type protein tyrosine phosphatase SHP-1 (gene: PTPN6) and negatively regulates leukocyte activities. A few Siglecs have a positively charged amino acid residue in the transmembrane domain, which interact with adapter protein DAP12 (gene: TYROBP) and transduce positive regulatory signal by way of protein tyrosine kinase SYK (gene: SYK).

Human cell types that express each Siglec are as follows: Siglec-1: macrophages; CD22/Siglec-2: B lymphocytes; CD33/Siglec-3: myeloid precursor cells, monocytes, macrophages, microglia, dendritic cells, and mast cells; MAG/Siglec-4: Schwann cells and oligodendrocytes; Siglec-5: neutrophils, monocytes, macrophages, and B lymphocytes; Siglec-6: placental trophoblasts, B lymphocytes, and mast cells; Siglec-7: natural killer cells, monocytes, macrophages, dendritic cells, and mast cells; Siglec-8: eosinophils and mast cells; Siglec-9: neutrophils, monocytes, macrophages, and dendritic cells; Siglec-10: B lymphocytes, monocytes, macrophages, and dendritic cells; Siglec-11: macrophages and microglia; Siglec-XII: macrophages and luminal epithelial cells; Siglec-14: neutrophils, monocytes, and macrophages; Siglec-15: osteoclasts and macrophage subsets; and Siglec-16: macrophages and microglia. Note that this list is not exhaustive, as tissue and systemic milieu may influence the expression of Siglecs.

Modified from Figure 35.1 (prepared by Dr. Richard Cummings (Harvard Medical School)) in Chapter 35 “I-type lectins”, Essentials of Glycobiology (4th edition), Cold Spring Harbor Press.