SIGLEC6

SIGLEC6
Identifiers
Gene ontology
Molecular function	protein binding carbohydrate binding
Cellular component	integral component of membrane extracellular region plasma membrane integral component of plasma membrane membrane
Biological process	cell-cell signaling cell adhesion
Sources:Amigo / QuickGO

Ensembl				ENSG00000105492	n/a
UniProt	O43699	n/a
RefSeq (mRNA)	NM_001177547 NM_001177548 NM_001177549 NM_001245 NM_198845 NM_198846	n/a
RefSeq (protein)	NP_001171018 NP_001171019 NP_001171020 NP_001236 NP_942142 NP_942143	n/a
Location (UCSC)	Chr 19: 51.52 – 51.53 Mb	n/a
PubMed search	[2]	n/a

Wikidata

View/Edit Human

Sialic acid-binding Ig-like lectin 6 is a

Expression

Siglec-6 was first found to be expressed in placental tissue,

cells. This monoclonal antibody also bound to nearly all human peripheral blood B cells, although more recent reports have not replicated this finding.^{[6] [7]} Siglec-6 has also been found to be highly expressed on human Other than

Ligand binding

Siglec-6 was identified in a screen for

biology have been identified. Initial studies found that Siglec-6 binds to sialyl-Tn antigen (Neu5Acα2–6GalNAcα) but not to Tn antigen (GalNAcα), 6′-sialyl-lactose (Neu5Acα2–6Galβ1–4Glc), or 3′-sialyl-lactose (Neu5Acα2–3Galβ1–4Glc).^[4] Further characterization of the glycan binding specificity of Siglec-6 revealed that Siglec-6, consistent with other members of the Siglec family, requires the carboxyl group on sialic acid, but is unique in that it does not require the glycolyl group of sialic acid for binding.^[17]

Signaling and function

Siglec-6 contains in its cytoplasmic domain two known signaling motifs identified as an immunoreceptor tyrosine-based inhibitory motif (ITIM) and an immunoreceptor tyrosine-based switch motif (ITSM).^[4] Based on the presence of these motifs, it was presumed that Siglec-6 exerts an inhibitory effect on signaling cascades initiated by an immunoreceptor tyrosine-based activation motif (ITAM)-bearing receptor through the recruitment and activation of protein tyrosine phosphatases like SHP-1/2.

Placental trophoblasts

By introducing mutated versions of Siglec-6 lacking the key

Mast cells

Antibody ligation of Siglec-6 on human CD34+ progenitor-derived mast cells inhibited GM-CSF secretion and slightly reduced degranulation in response to IgE crosslinking, although IL-8 secretion in response to stimulation was not similarly affected.^[19] This observation of Siglec-6 inhibitory function on mast cells was expanded to human skin-derived mast cells and the G protein-coupled receptors MRGPRX2 and C5aR, in addition to the ITAM-bearing FcεRI.^[9] Antibody ligation of Siglec-6 reduced mast cell degranulation in response to lower levels of the stimuli that act through these receptors. However, much more potent inhibition was observed by co-crosslinking Siglec-6 and FcεRI through the use of a secondary crosslinking antibody or the use of streptavidin-based tetramers of antibodies targeting Siglec-6 and FcεRI.^[9] Additionally, the inhibitory effect of Siglec-6 ligation remained for at least 4.5 hours, perhaps due to the observed stability of the receptor on the cell surface following antibody ligation, suggesting that the receptor may continue to participate in inhibitory signaling for prolonged periods of time.

Exhausted tissue-like B cells

Knockdown of SIGLEC6 using siRNA in exhausted tissue-like B cells from HIV-infected individuals enhances the ability of these cells to proliferate or secrete CCL3 or IL-6 upon stimulation.^[6] The lack of known Siglec-6 ligand in this system suggests that Siglec-6 may be reducing responsiveness of these cells through tonic signaling.

References

External links

• SIGLEC6+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.