Synonyms for siglec or Related words with siglec

siglecs              sialoadhesin              nectin              pilr              psgl              btla              ceacam              dectin              plexin              macrosialin              ulbp              ephrina              dcir              sirp              tnfrsf              emilin              glypican              tetraspanin              langerin              neuropilin              sorla              fzd              hcell              rlrs              endosialin              ficolin              crig              ifnar              mhcii              tigit              sialomucin              fccri              cubilin              ifngr              selectin              prominin              hspg              aicl              galectin              megalin              rhamm              mincle              syndecan              gitr              counterstructure              mhci              icosl              nucleolin              intergrin              galectins             

Examples of "siglec"
The first described candidate Siglec was Sialoadhesin (Siglec-1/CD169) a lectin-like adhesion protein on macrophages. Parallel studies by Ajit Varki and colleagues on the previously cloned CD22 (a B cell surface protein involved in adhesion and activation) showed direct evidence for sialic acid recognition. The subsequent cloning of Sialoadhesin by Crocker revealed homology to CD22 (Siglec-2), CD33 (Siglec-3) and myelin-associated glycoprotein (MAG/Siglec-4), leading to the proposal for a family of "Sialoadhesins". Varki then suggested the term Siglec as a better alternative and as a subset of I-type (Ig-type) lectins. This nomenclature was agreed upon and has been adopted by almost all investigators working on these molecules (by convention, Siglecs are always capitalised.) Several additional Siglecs (Siglecs 5–12) have been identified in humans that are highly similar in structure to CD33 and so are collectively referred to as "CD33-related Siglecs". Further Siglecs have been identified including Siglec-14 and Siglec-15. Some Siglecs are absolutely conserved between mice and humans including Sialoadhesin, CD22, MAG and Siglec-15. Others such as Siglec-8 and Siglec-9 have homologues in mice and rats (Siglec-F and Siglec-E respectively in both). Humans have a higher number of Siglecs than mice and so the numbering system was based on the human proteins.
While Siglec-8 ligation does not cause mast cell apoptosis, it inhibits FcεRIα-mediated Ca flux and release of prostaglandin D2 and histamine. However, the release of IL-8 is not prevented by Siglec-8 ligation in mast cells. In experiments using the rat basophilic leukemia cell line RBL-2H3 stably transfected with Siglec-8, the inhibitory effect of Siglec-8 ligation on FcεRIα-mediated degranulation and Ca flux was found to be dependent on the intact ITIM. There are no published data regarding the function of Siglec-8 on basophils.
Siglec-14 contains an arginine residue in its transmembrane region. This binds to the ITAM-containing DAP10 and DAP12 proteins. When bound to its ligand, Siglec-14 leads to activation of cellular signalling pathways via the DAP10 and DAP12 proteins. These proteins up-regulate phosphorylation cascades involving numerous cellular proteins, leading to cellular activation. Siglec-14 appears to co-localise with Siglec-5, and as this protein inhibits cellular signalling pathways, co-ordinate opposing functions within immune cells.
Two splice variants of Siglec-8 exist. The initially characterized form contains 431 amino acid residues in total, 47 of which comprise an uncharacteristically short cytoplasmic tail compared to most CD33-associated siglecs. Subsequently, a longer form of Siglec-8, initially termed Siglec-8L, that contains 499 amino acid residues was identified. This longer form of Siglec-8 shares the same extracellular region but includes a longer cytoplasmic tail with two tyrosine-based motifs (an immunoreceptor tyrosine-based inhibitory motif [ITIM] and an immunoreceptor tyrosine-based switch motif [ITSM]). Both forms of Siglec-8 are found in eosinophils and contain a V-set domain with lectin activity and two C2-type Ig repeat domains in the extracellular region. Given that the longer version is felt to be the normal version, the term Siglec-8 is best used to refer to the 499 amino acid version, while the 431 amino acid version is best referred to as the “short form” of Siglec-8.
Sialic acid-binding Ig-like lectin 8 is a protein that in humans is encoded by the "SIGLEC8" gene. This gene is located on chromosome 19q13.4, about 330 kb downstream of the SIGLEC9 gene. Within the siglec family of transmembrane proteins, Siglec-8 belongs to the CD33-related siglec subfamily, a subfamily that has undergone rapid evolution.
While "SIGLEC8" and mouse "Siglecf " do not appear to derive from the same ancestral gene (they are paralogous, not orthologous), they share a binding preference for 6′-sulfo-sialyl Lewis X and 6′-sulfated sialyl "N"-acetyl-D-lactosamine, similar but distinct patterns of cellular expression, and similar inhibitory functions. For example, Siglec-F is expressed by eosinophils, like Siglec-8, but is also expressed by alveolar macrophages and has not been detected on mouse mast cells or basophils. This functional convergence of Siglec-8 and Siglec-F has permitted in vivo studies to be performed in mouse models of eosinophil-mediated disorders that may provide information about the human system. In a chicken ovalbumin (OVA) model of allergic airway inflammation, the Siglec-F knockout mouse exhibits increased lung eosinophilia, enhanced inflammation, delayed resolution, and exacerbated peribronchial fibrosis. Antibody ligation of Siglec-F has also been shown to inhibit eosinophil-mediated intestinal inflammation and airway remodeling in OVA challenge models. The ST3Gal-III enzyme is necessary for the generation of the natural Siglec-F ligand, which remains unknown but is induced by IL-4 and IL-13 in the airway. Loss of this enzyme leads to enhanced allergic eosinophilic airway inflammation. Despite evidence that Siglec-F binds specifically to 6′-sulfo-sialyl Lewis X and 6′-sulfated sialyl "N"-acetyl-D-lactosamine, in which galactose is sulfated at carbon 6, mice deficient in the two known galactose 6-"O"-sulfotransferases, keratan sulfate galactose 6-"O"-sulfotransferase (KSGal6ST) and chondroitin 6-"O"-sulfotransferase 1 (C6ST-1), express equivalent levels of Siglec-F ligand. These models may shed some light on the regulation of human eosinophil biology by Siglec-8 and the production of natural Siglec-8 ligands in humans. Also like Siglec-8, Siglec-F ligation leads to the apoptosis of eosinophils. However, Siglec-F–induced eosinophil apoptosis is mediated by a mechanism distinct from that employed by Siglec-8, hindering direct comparisons between the mouse and human systems. Siglec-F-induced apoptosis is mediated by caspase activation in mouse eosinophils and does not involve ROS, in contrast to the mechanism reported in Siglec-8–induced apoptosis of human eosinophils. This apoptotic mechanism also does not involve Src family kinases, SHP-1, or NADPH.
Due to its high level of sequence homology with CD33 (Siglec-3), Siglec-8 is grouped within the CD33-related siglec subfamily. This family is composed of a rapidly evolving group of siglecs that share 50–99% sequence identity. Most members of the subfamily also possess conserved cytoplasmic ITIM and ITIM-like sequences.
It binds sialic acids, therefore is a member of the SIGLEC family of lectins.
In addition, baboon eosinophils as well as monocytes, a subset of lymphocytes, and neutrophils express on their cell surface a protein or proteins that are recognized by polyclonal human Siglec-8-specific antibody, consistent with genetic analyses indicating the existence of a Siglec-8 ortholog in this species. However, the 2C4, 2E2, and 7C9 monoclonal antibodies against human Siglec-8 were not found to bind to targets on baboon cells, indicating that these particular epitopes are not conserved.
Potential glycan ligands for Siglec-8 have been screened by glycan array. The glycan NeuAcα2–3(6-O-sulfo)Galβ1–4[Fucα1–3]GlcNAc, also known as 6′-sulfo-sialyl Lewis X, binds with high affinity to both Siglec-8 and to a mouse siglec, Siglec-F, which appears to have acquired a similar but not identical function and pattern of expression to human Siglec-8 through convergent evolution (the two siglecs are not orthologous). Rescreening on a more expanded glycan array reconfirmed this finding, but also identified a second closely related ligand in which the fucose is absent (NeuAcα2–3(6-O-sulfo)Galβ1–4GlcNAc, or 6′-sulfated sialyl N-acetyl-D-lactosamine. These interactions are quite specific; no binding could be detected between these siglecs and unsulfated sialyl Lewis X or sialyl Lewis X sulfated at carbon 6 of GlcNAc (6-sulfo-sialyl Lewis X) rather than carbon 6 of galactose as in 6′-sulfo-sialyl Lewis X. Similarly, no other siglecs bind effectively to these Siglec-8 ligands, as demonstrated by selective binding to eosinophils in human blood of a polymer decorated with 6′-sulfo-sialyl Lewis X. The natural ligand or ligands for Siglec-8 have not yet been positively identified, but ongoing studies have determined that there are sialidase-sensitive glycoprotein ligands for Siglec-F in mouse airways that require the activity of the α2,3 sialyltransferase 3 (ST3Gal-III) enzyme for their generation.
At the tissue level, Siglec-8 mRNA was found to be most highly expressed in lung, PBMCs, spleen, and kidney.
Siglec-7 is also used in binding to pathogens such as "Campylobacter jejuni". This occurs in a sialic acid-dependent manner and brings NK cells and monocytes, on which Siglec-7 is expressed, into contact with these bacteria. The NK cell is then able to kill these foreign pathogens.
Like most but not all other Siglecs, Siglec-10 bears an ITIM (Immunoreceptor tyrosine-based inhibitory motif) within its cytoplasmic domain. Siglec-10 is a ligand for CD52, the target of the therapeutic monoclonal antibody Alemtuzumab. It is also reported to bind to Vascular adhesion protein 1 (VAP-1) and to the co-stimulatory molecule CD24 also known as HSA (Heat-stable antigen).
Consistent with the role of most siglecs and the presence of the intracellular ITIM, Siglec-8 has been found to function as an inhibitory immunoregulatory receptor. Ligation of Siglec-8 induces apoptosis in eosinophils, and, surprisingly, the normally pro-survival cytokines interleukin (IL)-5 and GM-CSF have been found to potentiate this apoptotic effect. IL-33, which activates and maintains eosinophils, also exerts a similar potentiating effect on Siglec-8-induced apoptosis. Inhibitor studies demonstrate that apoptosis induced by crosslinking Siglec-8 through the use of an anti-Siglec-8 mAb and a secondary antibody is mediated sequentially through reactive oxygen species (ROS) production, loss of mitochondrial membrane potential, and caspase activation. In the presence of IL-5, the loss of mitochondrial membrane integrity is accelerated and the secondary crosslinking antibody is no longer necessary to induce apoptosis. IL-5 stimulation also appears to alter the mode of cell death of eosinophils induced by Siglec-8 ligation in that cell death becomes a caspase-independent process. Costimulation of the IL-5 receptor and Siglec-8 leads to a type of cell death resembling regulated necrosis that is promoted by MEK1/ERK signaling. Because inhibition of MEK1 does not alter ROS generation but the ROS inhibitor diphenyleneiodonium inhibits ERK1/2 phosphorylation and cell death, the production of ROS appears to be upstream of MEK1/ERK signaling in this pathway. Cell death induced by Siglec-8 in the presence of IL-33, in contrast, is mediated primarily by a caspase-dependent pathway, and IL-33 is capable of synergizing with IL-5 in potentiating cell death induced by Siglec-8 ligation.
CD33 or Siglec-3 (sialic acid binding Ig-like lectin 3, SIGLEC3, SIGLEC-3, gp67, p67) is a transmembrane receptor expressed on cells of myeloid lineage. It is usually considered myeloid-specific, but it can also be found on some lymphoid cells.
Myelin-associated glycoprotein (MAG, Siglec-4) is a cell membrane glycoprotein that is a member of the SIGLEC family of proteins and is a functional ligand of the NOGO-66 receptor, NgR. MAG is believed to be involved in myelination during nerve regeneration.
Siglec-8 is expressed by human eosinophils, mast cells, and, to a lesser extent, basophils. It has thus garnered attention as a molecule that is uniquely expressed by immune effector cells involved in asthma and allergy. In both eosinophils and mast cells, Siglec-8 is expressed late in development. Siglec-8 transcript and protein are detectable at day 12 during the in vitro differentiation of eosinophils from cord blood precursors, whereas the transcription factor GATA-1 peaks at day 2 and the secondary granule protein MBP-1 peaks at day 4 in this differentiation system. In mast cells generated from CD34+ precursors, Siglec-8 expression peaks at 4 weeks of differentiation, in parallel with FcεRIα surface expression.
Sialic acid-binding Ig-like lectin 10 is a protein that in humans is encoded by the "SIGLEC10" gene. The mouse orthologue is Siglec G.
This table briefly summarises the cellular distribution of each human/primate Siglec; the linkage specificity each has for sialic acid binding; the number of C2-Ig domains it contains; and whether it contains an ITIM or a positive residue to bind ITAM-containing adaptor proteins. References in the column headings correspond to all information displayed in that column, unless other references are shown. Siglec-12 information is referenced by only, excluding the linkage specificity.
Siglec-8 was first identified by CD33 homology screening of ESTs from a cDNA library generated from a patient diagnosed with idiopathic hypereosinophilic syndrome and was originally termed SAF-2 (sialoadhesin family 2).