Siglec-15 - Revision history

Carole Weaver: /* Glycogene microarray */

2011-03-30T23:37:46Z

Glycogene microarray

Carole Weaver: /* Related GBPs */

2011-03-18T22:26:29Z

Related GBPs

Carole Weaver: /* Progress toward understanding this GBP paradigm */

2010-08-06T17:32:33Z

Progress toward understanding this GBP paradigm

Carole Weaver at 21:56, 6 July 2010

2010-07-06T21:56:54Z

Carole Weaver at 22:02, 21 June 2010

2010-06-21T22:02:40Z

Takashi Angata at 12:09, 19 May 2010

2010-05-19T12:09:20Z

Takashi Angata at 12:02, 19 May 2010

2010-05-19T12:02:57Z

Takashi Angata at 00:35, 14 May 2010

2010-05-14T00:35:22Z

Heather Buschman: /* Acknowledgements */

2010-05-13T18:04:43Z

Acknowledgements

Heather Buschman: Created page with 'Siglec-15 serves as a paradigm for several siglecs, including Siglec-14Angata, T., Hayakawa, T., Yamanaka, M., Varki, A. & Nakamura, M. Discovery of Siglec-14, a novel siali…'

2010-04-06T21:49:49Z

Created page with 'Siglec-15 serves as a paradigm for several siglecs, including Siglec-14<ref>Angata, T., Hayakawa, T., Yamanaka, M., Varki, A. & Nakamura, M. Discovery of Siglec-14, a novel siali…'

New page

Siglec-15 serves as a paradigm for several siglecs, including Siglec-14<ref>Angata, T., Hayakawa, T., Yamanaka, M., Varki, A. & Nakamura, M. Discovery of Siglec-14, a novel sialic acid receptor undergoing concerted evolution with Siglec-5 in primates. Faseb J 20, 1964-1973 (2006).</ref>, Siglec-16<ref>Cao, H. et al. SIGLEC16 encodes a DAP12-associated receptor expressed in macrophages that evolved from its inhibitory counterpart SIGLEC11 and has functional and non-functional alleles in humans. Eur J Immunol 38, 2303-2315 (2008).</ref> and Siglec-H<ref>Zhang, J. et al. Characterization of Siglec-H as a novel endocytic receptor expressed on murine plasmacytoid dendritic cell precursors. Blood 107, 3600-3608 (2006).</ref><ref>Blasius, A. L., Cella, M., Maldonado, J., Takai, T. & Colonna, M. Siglec-H is an IPC-specific receptor that modulates type I IFN secretion through DAP12. Blood 107, 2474-2476 (2006).</ref>, that contain a basic amino acid within the transmembrane domain<ref>Delputte, P. L. et al. Porcine arterivirus attachment to the macrophage-specific receptor sialoadhesin is dependent on the sialic81, 9546-9550 (2007).</ref>. This leads to association of these siglecs with a transmembrane adaptor protein containing an immunoreceptor tyrosine based activation motif (ITAM). Siglec-15 is unusual compared to other siglecs that share this paradigm in two respects. Firstly it can associate with two ITAM containing adaptors, DAP12 and DAP10, whereas Siglec-14, Siglec-16, and Siglec-H show a restricted association with DAP12. Siglec-15 is also unusual in having four cysteine residues in the V-set domain predicted to result in an inter-sheet disulfide that is absent from all other known siglecs. These potentially ‘activating’ siglecs are expressed on myeloid cells and dendritic cells and may be involved in innate responses to pathogen challenge.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
As yet, no CFG Participating Investigators (PIs) have contributed to Siglec-15, but contributors to the related Siglec-H include Marco Colonna and Paul Crocker.

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===

 
=== Cellular expression ===

 
=== Structure ===

 
=== Biological roles of GBP-ligand interaction ===

 
== CFG resources used in investigations ==
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=Siglec-15&maxresults=20 CFG database search results for Siglec-15].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===
The CFG has generated Siglec-15-deficient ES cells that will permit generation of a Siglec-15-deficient mouse in the future. Two [https://www.functionalglycomics.org/static/consortium/resources/DataCoreFsigH.shtml Siglec-H-deficient mouse lines] (Siglec-H-conditional knockout and Siglec-H-total knockout) were also generated and are currently under investigation.

=== Glycan array ===

== Related GBPs ==
Siglec-14, Siglec-16, Siglec-H

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Paul Crocker, James Paulson

@@ Line 31: / Line 31: @@
 === Glycogene microarray ===
-No data available.
+No data available. Probes for human Siglec-15 were included on version 4 of the CFG glycogene microarray.
 === Knockout mouse lines ===

@@ Line 5: / Line 5: @@
 == Progress toward understanding this GBP paradigm ==
+This section documents what is currently known about Siglec-15, its carbohydrate ligand(s), and how they interact to mediate cell communication.
 === Carbohydrate ligands ===
 Human Siglec-15 has been shown to prefer the sialyl Tn (Neu5Ac&alpha;2-6GalNAc&alpha;1-) structure, while mouse Siglec-15 recognizes both sialyl Tn and 3'-sialyl Lac[NAc] (Neu5Ac&alpha;2-3Gal&beta;1-4Glc[NAc]) structures<ref name="Angata 2007"/>.
@@ Line 22: / Line 22: @@
 === Biological roles of GBP-ligand interaction ===
 As yet, no clear biological roles for the GBP-ligand interaction have been shown for Siglec-15. Considering the absence of reported cases of Sia&alpha;2-6GalNAc&alpha;1- structure in pathogens<ref>Angata, T. & Varki, A. Chemical diversity in the sialic acids and related alpha-keto acids: an evolutionary perspective. Chem Rev 102, 439-469 (2002)</ref>, the ligand for Siglec-15 may be of endogenous origin.
 == CFG resources used in investigations ==

@@ Line 1: / Line 1: @@
-Siglec-15<ref name="Angata 2007">Angata, T., Tabuchi, Y., Nakamura, K. & Nakamura, M. Siglec-15: an immune system Siglec conserved throughout vertebrate evolution. Glycobiology 17, 838-846 (2007).</ref> serves as a paradigm for several siglecs, including Siglec-14<ref>Angata, T., Hayakawa, T., Yamanaka, M., Varki, A. & Nakamura, M. Discovery of Siglec-14, a novel sialic acid receptor undergoing concerted evolution with Siglec-5 in primates. FASEB J 20, 1964-1973 (2006).</ref><ref>Yamanaka, M., Kato, Y., Angata, T. & Narimatsu, H. Deletion polymorphism of SIGLEC14 and its functional implications. Glycobiology 19, 841-846 (2009)</ref>, Siglec-16<ref>Cao, H. et al. SIGLEC16 encodes a DAP12-associated receptor expressed in macrophages that evolved from its inhibitory counterpart SIGLEC11 and has functional and non-functional alleles in humans. Eur J Immunol 38, 2303-2315 (2008).</ref> and Siglec-H<ref>Zhang, J. et al. Characterization of Siglec-H as a novel endocytic receptor expressed on murine plasmacytoid dendritic cell precursors. Blood 107, 3600-3608 (2006).</ref><ref>Blasius, A. L., Cella, M., Maldonado, J., Takai, T. & Colonna, M. Siglec-H is an IPC-specific receptor that modulates type I IFN secretion through DAP12. Blood 107, 2474-2476 (2006).</ref>, that contain a basic amino acid within the transmembrane domain. This leads to association of these siglecs with a transmembrane adaptor protein containing an immunoreceptor tyrosine based activation motif (ITAM). Siglec-15 is unusual compared to other siglecs that share this paradigm in two respects. Firstly it can associate with two ITAM containing adaptors, DAP12 and DAP10, whereas Siglec-14, Siglec-16, and Siglec-H show a restricted association with DAP12. Siglec-15 is also unusual in having four cysteine residues in the V-set domain predicted to result in an inter-sheet disulfide that is absent from all other known siglecs. These potentially ‘activating’ siglecs are expressed on myeloid cells and dendritic cells and may be involved in innate responses to pathogen challenge.
+Siglec-15<ref name="Angata 2007">Angata, T., Tabuchi, Y., Nakamura, K. & Nakamura, M. Siglec-15: an immune system Siglec conserved throughout vertebrate evolution. Glycobiology 17, 838-846 (2007).</ref> serves as a paradigm for several siglecs, including Siglec-14<ref>Angata, T., Hayakawa, T., Yamanaka, M., Varki, A. & Nakamura, M. Discovery of Siglec-14, a novel sialic acid receptor undergoing concerted evolution with Siglec-5 in primates. FASEB J 20, 1964-1973 (2006).</ref><ref>Yamanaka, M., Kato, Y., Angata, T. & Narimatsu, H. Deletion polymorphism of SIGLEC14 and its functional implications. Glycobiology 19, 841-846 (2009)</ref>, Siglec-16<ref>Cao, H. et al. SIGLEC16 encodes a DAP12-associated receptor expressed in macrophages that evolved from its inhibitory counterpart SIGLEC11 and has functional and non-functional alleles in humans. Eur J Immunol 38, 2303-2315 (2008).</ref> and Siglec-H<ref>Zhang, J. et al. Characterization of Siglec-H as a novel endocytic receptor expressed on murine plasmacytoid dendritic cell precursors. Blood 107, 3600-3608 (2006).</ref><ref>Blasius, A. L., Cella, M., Maldonado, J., Takai, T. & Colonna, M. Siglec-H is an IPC-specific receptor that modulates type I IFN secretion through DAP12. Blood 107, 2474-2476 (2006).</ref>, that contain a basic amino acid within the transmembrane domain. This leads to association of these siglecs with a transmembrane adaptor protein containing an immunoreceptor tyrosine based activation motif (ITAM). Siglec-15 is unusual compared to other siglecs that share this paradigm in two respects. For one, it can associate with two ITAM containing adaptors, DAP12 and DAP10, whereas Siglec-14, Siglec-16, and Siglec-H show a restricted association with DAP12. In addition, Siglec-15 is unusual in having four cysteine residues in the V-set domain predicted to result in an inter-sheet disulfide that is absent from all other known siglecs. These potentially ‘activating’ siglecs are expressed on myeloid cells and dendritic cells and may be involved in innate responses to pathogen challenge.
 == CFG Participating Investigators contributing to the understanding of this paradigm ==
@@ Line 7: / Line 7: @@
 === Carbohydrate ligands ===
-Human Siglec-15 has been shown to prefer sialyl Tn (Neu5Ac&alpha;2-6GalNAc&alpha;1-) structure, while mouse Siglec-15 recognize both sialyl Tn and 3'-sialyl Lac[NAc] (Neu5Ac&alpha;2-3Gal&beta;1-4Glc[NAc]) structures<ref name="Angata 2007"/>.
+Human Siglec-15 has been shown to prefer the sialyl Tn (Neu5Ac&alpha;2-6GalNAc&alpha;1-) structure, while mouse Siglec-15 recognizes both sialyl Tn and 3'-sialyl Lac[NAc] (Neu5Ac&alpha;2-3Gal&beta;1-4Glc[NAc]) structures<ref name="Angata 2007"/>.
@@ Line 16: / Line 16: @@
 <br>
 === Structure ===
-Siglec-15 has two Ig-like domains, followed by a single-pass transmembrane domain and a short cytoplasmic tail. Siglec-15 is unusual compared to other siglecs, in that it has four cysteine residues in the V-set domain predicted to result in an inter-sheet disulfide that is absent from all other known siglecs.
+Siglec-15 has two Ig-like domains, followed by a single-pass transmembrane domain and a short cytoplasmic tail. Siglec-15 is unusual compared to other siglecs in that it has four cysteine residues in the V-set domain predicted to result in an inter-sheet disulfide that is absent from all other known siglecs.
-The transmembrane domain of Siglec-15 contains a basic amino acid. This leads to association with a transmembrane adaptor protein containing an immunoreceptor tyrosine based activation motif (ITAM), DAP12 and DAP10. A stretch of conserved amino acids (containing a tyrosine residue) is found in the cytoplasmic tail of human and mouse Siglec-15, while its functional importance is not yet known.
+The transmembrane domain of Siglec-15 contains a basic amino acid. This leads to association with a transmembrane adaptor protein containing an immunoreceptor tyrosine based activation motif (ITAM), DAP12 and DAP10. A stretch of conserved amino acids (containing a tyrosine residue) is found in the cytoplasmic tail of human and mouse Siglec-15, although its functional importance is not yet known.
 === Biological roles of GBP-ligand interaction ===
-As yet, no clear biological roles for GBP-ligand interaction have been shown for Siglec-15. Considering the absence of reported case of Sia&alpha;2-6GalNAc&alpha;1- structure in pathogens<ref>Angata, T. & Varki, A. Chemical diversity in the sialic acids and related alpha-keto acids: an evolutionary perspective. Chem Rev 102, 439-469 (2002)</ref>, the ligand for Siglec-15 may be of endogenous origin.
+As yet, no clear biological roles for the GBP-ligand interaction have been shown for Siglec-15. Considering the absence of reported cases of Sia&alpha;2-6GalNAc&alpha;1- structure in pathogens<ref>Angata, T. & Varki, A. Chemical diversity in the sialic acids and related alpha-keto acids: an evolutionary perspective. Chem Rev 102, 439-469 (2002)</ref>, the ligand for Siglec-15 may be of endogenous origin.

@@ Line 16: / Line 16: @@
 === Structure ===
 Siglec-15 has two Ig-like domains, followed by a single-pass transmembrane domain and a short cytoplasmic tail. Siglec-15 is unusual compared to other siglecs, in that it has four cysteine residues in the V-set domain predicted to result in an inter-sheet disulfide that is absent from all other known siglecs.
-The transmembrane domain of Siglec-15 contains a basic amino acid. This leads to association with a transmembrane adaptor protein containing an immunoreceptor tyrosine based activation motif (ITAM), DAP12 and DAP10.<br/>
+The transmembrane domain of Siglec-15 contains a basic amino acid. This leads to association with a transmembrane adaptor protein containing an immunoreceptor tyrosine based activation motif (ITAM), DAP12 and DAP10. A stretch of conserved amino acids (containing a tyrosine residue) is found in the cytoplasmic tail of human and mouse Siglec-15, while its functional importance is not yet known.
 <br>
 === Biological roles of GBP-ligand interaction ===
-As yet, no clear biological roles for GBP-ligand interaction is shown for Siglec-15. Considering the absence of reported case of Sia&alpha;2-6GalNAc&alpha;1- structure in pathogens<ref>Angata, T. & Varki, A. Chemical diversity in the sialic acids and related alpha-keto acids: an evolutionary perspective. Chem Rev 102, 439-469 (2002)</ref>, the ligand for Siglec-15 may be of endogenous origin.
+As yet, no clear biological roles for GBP-ligand interaction have been shown for Siglec-15. Considering the absence of reported case of Sia&alpha;2-6GalNAc&alpha;1- structure in pathogens<ref>Angata, T. & Varki, A. Chemical diversity in the sialic acids and related alpha-keto acids: an evolutionary perspective. Chem Rev 102, 439-469 (2002)</ref>, the ligand for Siglec-15 may be of endogenous origin.
 <br>

@@ Line 16: / Line 16: @@
 === Structure ===
 Siglec-15 has two Ig-like domains, followed by a single-pass transmembrane domain and a short cytoplasmic tail. Siglec-15 is unusual compared to other siglecs, in that it has four cysteine residues in the V-set domain predicted to result in an inter-sheet disulfide that is absent from all other known siglecs.
-The transmembrane domain of Siglec-15 contains a basic amino acid. This leads to association with a transmembrane adaptor protein containing an immunoreceptor tyrosine based activation motif (ITAM), DAP12 and DAP10.
+The transmembrane domain of Siglec-15 contains a basic amino acid. This leads to association with a transmembrane adaptor protein containing an immunoreceptor tyrosine based activation motif (ITAM), DAP12 and DAP10.<br/>
-A stretch of conserved amino acids containing a tyrosine residue is found in he cytoplasmic tail of mammalian Siglec-15, while its functional importance is not yet known.
+A stretch of conserved amino acids containing a tyrosine residue is found in the cytoplasmic tail of human and mouse Siglec-15, while its functional importance is not yet known.
 <br>
 === Biological roles of GBP-ligand interaction ===
-As yet, no clear biological roles for GBP-ligand interaction is shown for Siglec-15. Given the near-absence of Sia&alpha;2-6Gal[NAc] structure in pathogens, **to be edited further**
+As yet, no clear biological roles for GBP-ligand interaction is shown for Siglec-15. Considering the absence of reported case of Sia&alpha;2-6GalNAc&alpha;1- structure in pathogens<ref>Angata, T. & Varki, A. Chemical diversity in the sialic acids and related alpha-keto acids: an evolutionary perspective. Chem Rev 102, 439-469 (2002)</ref>, the ligand for Siglec-15 may be of endogenous origin.
 <br>
@@ Line 28: / Line 28: @@
 === Glycan profiling ===
 <br>
 === Glycogene microarray ===
 <br>
@@ Line 36: / Line 38: @@
 The CFG has generated Siglec-15-deficient ES cells that will permit generation of a Siglec-15-deficient mouse in the future. Two [https://www.functionalglycomics.org/static/consortium/resources/DataCoreFsigH.shtml Siglec-H-deficient mouse lines] (Siglec-H-conditional knockout and Siglec-H-total knockout) were also generated and are currently under investigation.
 === Glycan array ===
+<br>
 == Related GBPs ==
 Siglec-14, Siglec-16, Siglec-H

@@ Line 42: / Line 42: @@
 == Related GBPs ==
-Siglec-14, Siglec-16, Siglec-H
+Siglec-14, Siglec-16, Siglec-H [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=Siglec-H&maxresults=20 (CFG data)].
 == References ==

← Older revision		Revision as of 18:04, 13 May 2010
Line 40:		Line 40:

	== Acknowledgements ==		== Acknowledgements ==
−	The CFG is grateful to the following PIs for their contributions to this wiki page: Paul Crocker, James Paulson	+	The CFG is grateful to the following PIs for their contributions to this wiki page: Takashi Angata, Paul Crocker, James Paulson