Molecular features of Siglec-H. (A) Predicted protein sequence of Siglec-H. Asterisks indicate positions of the 3 cysteine residues in domain 1 that are characteristic of siglecs. Open circles underlie residues in Siglec-H that are predicted to be important for sialic acid binding, including the critical arginine on the F β-strand.²²  Potential N-linked glycosylation sites are shown by open boxes. The β-strands (A, A′, B, and C etc) shown in domain 1 are predicted by alignment with hSiglec-7.²³  The slanted line indicates the predicted leader peptide cleavage site and the vertical lines show positions of intron-exon boundaries deduced from comparisons of the cDNA and gDNA sequences. Domains 1 and 2, the linker, the transmembrane region, and cytoplasmic tail are indicated. (B) Genomic organization of Siglec-h. Exons are shown as filled bars and introns as lines. L indicates leader peptide; V, domain 1 (V-set immunoglobulin-like); and C2, domain 2 (C2-set immunoglobulin-like). Numbers underlie nucleotide residues in cDNA, beginning at the start codon. Numbers in brackets indicate intron phases. (C) Alignment of the mouse Siglec-H with the closest matching rat, mouse, and human siglecs and a human siglec-like sequence. Identical residues are boxed in black and similar residues in gray. Accession numbers are as follows: mSiglec-H, AAZ81614; rSiglec-H, XP_341867; mCD33, AAB30843; hCD33, AAA51948; and hSiglec-L2, XP_290822.