CFGparadigms - User contributions [en]

DC-SIGN

2011-03-21T13:58:33Z

Irma van Die:

Dendritic cell-specific intracellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin (DC-SIGN, CD209) is a C-type lectin that plays roles in both cell-cell and host-pathogen interactions, and thus serves as a model for both processes. This glycan-binding protein (GBP) paradigm also serves as a model for other members of the C-type lectin family expressed on dendritic cells. 
DC-SIGN is a type II membrane protein with a short aminoterminal cytoplasmic tail, a neck region and a single carboxyl terminal carbohydrate recognition domain (CRD)<ref name="Geijtenbeek 2000">Geijtenbeek TB, Torensma R, van Vliet SJ, van Duijnhoven GC, Adema GJ, van Kooyk Y and Figdor CG. 2000. Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell. 100:575-585</ref>. The primary structure of the CRD contains conserved residues consistent with classical mannose-specific CRDs <ref name="Feinberg 2001">Feinberg H, Mitchell DA, Drickamer K and Weis WI. 2001. Structural basis for selective recognition of oligosaccharides by DC-SIGN and DC-SIGNR. Science. 294:2163-2166</ref>. Multivalent binding of glycan ligands by DC-SIGN is dependent on correct organization and presentation of the CRDs at the neck domains, which are crucial for tetramerization of DC-SIGN <ref>Yu QD, Oldring AP, Powlesland AS, Tso CK, Yang C, Drickamer K and Taylor ME. 2009. Autonomous tetramerization domains in the glycan-binding receptors DC-SIGN and DC-SIGNR. J Mol Biol. 387:1075-1080</ref>. The cytoplasmic tail of DC-SIGN contains internalization motifs involved in the ligand-induced internalization of DC-SIGN <ref>Engering A, Geijtenbeek TB, van Vliet SJ, Wijers M, van Liempt E, Demaurex N, Lanzavecchia A, Fransen J, Figdor CG, Piguet V and van Kooyk Y. 2002. The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells. J Immunol. 168:2118-2126</ref>, and can activate signaling pathways <ref>Caparros E, Munoz P, Sierra-Filardi E, Serrano-Gomez D, Puig-Kroger A, Rodriguez-Fernandez JL, Mellado M, Sancho J, Zubiaur M and Corbi AL. 2006. DC-SIGN ligation on dendritic cells results in ERK and PI3k activation and modulates cytokine production. Blood. 107:3950-3958</ref><ref>Gringhuis SI, den Dunnen J, Litjens M, van Het Hof B, van Kooyk Y and Geijtenbeek TB. 2007. C-type lectin DC-SIGN modulates toll-like receptor signaling via raf-1 kinase-dependent acetylation of transcription factor NF-kb. Immunity. 26:605-616</ref><ref>Gringhuis SI, den Dunnen J, Litjens M, van der Vlist M and Geijtenbeek TB. 2009. Carbohydrate-specific signaling through the DC-SIGN signalosome tailors immunity to ''Mycobacterium tuberculosis'', HIV-1 and ''Helicobacter pylori''. Nat Immunol. 10:1081-1088</ref>.
In mice several DC-SIGN-related proteins have been identified (SIGNR1-SIGNR8) <ref>Powlesland AS, Ward EM, Sadhu SK, Guo Y, Taylor ME and Drickamer K. 2006. Widely divergent biochemical properties of the complete set of mouse DC-SIGN-related proteins. J Biol Chem. 281:20440-20449</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==

Many investigators, both CFG Participating Investigators (PIs) and non-PIs using CFG resources, have led extensive studies on DC-SIGN, particularly regarding structure-function relationships, interactions with pathogens, and signaling functions in dendritic cells.
* PIs working on DC-SIGN include: Pedro Bonay, Angel Corbi, Kurt Drickamer, Juan Garcia-Vallejo, Donald Harn, Kayo Inaba, Benhur Lee, Olivier Neyrolles, Irma van Die, Yvette van Kooyk, William Weis, Martin Wild
* Non-PIs who have used CFG resources to study DC-SIGN include: Brigitte Gicquel, Arne Skerra, Ralph Steinman

== Progress toward understanding this GBP paradigm ==
This section documents what is currently known about DC-SIGN, its carbohydrate ligand(s), and how they interact to mediate cell communication. Further information about DC-SIGN can be found in its [http://www.functionalglycomics.org/glycomics/molecule/jsp/viewGbpMolecule.jsp?gbpId=cbp_hum_Ctlect_00121&sideMenu=no GBP Molecule Page] in the CFG database.
=== Carbohydrate ligands ===
DC-SIGN recognizes both internal branched mannose residues as well as terminal di-mannoses, α1-3 and α1-4 fucosylated glycan structures and certain N-aceltylglucosamine containing molecules on self proteins and/or pathogens <ref name="Feinberg 2001"/><ref name="Guo 2004">Guo Y, Feinberg H, Conroy E, Mitchell DA, Alvarez R, Blixt O, Taylor ME, Weis WI and Drickamer K. 2004. Structural basis for distinct ligand-binding and targeting properties of the receptors DC-SIGN and DC-SIGNR. Nat Struct Mol Biol. 11:591-598</ref><ref>Mitchell DA, Fadden AJ and Drickamer K. 2001. A novel mechanism of carbohydrate recognition by the C-type lectins DC-SIGN and DC-SIGNR. Subunit organization and binding to multivalent ligands. J Biol Chem. 276:28939-28945</ref><ref name="Liempt 2006">van Liempt E, Bank CM, Mehta P, Garcia-Vallejo JJ, Kawar ZS, Geyer R, Alvarez RA, Cummings RD, Kooyk Y and van Die I. 2006. Specificity of DC-SIGN for mannose- and fucose-containing glycans. FEBS Lett. 580:6123-6131</ref> 
''Endogenous ligands include''
*Lewis blood group antigens LeX, LeA, LeY and LeB <ref>Bogoevska V, Horst A, Klampe B, Lucka L, Wagener C and Nollau P. 2006. CEACAM1, an adhesion molecule of human granulocytes, is fucosylated by fucosyltransferase IX and interacts with DC-SIGN of dendritic cells via Lewis X residues. Glycobiology. 16:197-209</ref><ref>Bogoevska V, Nollau P, Lucka L, Grunow D, Klampe B, Uotila LM, Samsen A, Gahmberg CG and Wagener C. 2007. DC-SIGN binds ICAM-3 isolated from peripheral human leukocytes through Lewis X residues. Glycobiology. 17:324-333</ref><ref name="Garcia 2008">Garcia-Vallejo JJ, van Liempt E, da Costa Martins P, Beckers C, van het Hof B, Gringhuis SI, Zwaginga JJ, van Dijk W, Geijtenbeek TB, van Kooyk Y and van Die I. 2008. DC-SIGN mediates adhesion and rolling of dendritic cells on primary human umbilical vein endothelial cells through Lewis Y antigen expressed on ICAM-2. Mol Immunol. 45:2359-2369</ref><ref>Naarding MA, Ludwig IS, Groot F, Berkhout B, Geijtenbeek TB, Pollakis G and Paxton WA. 2005. Lewis x component in human milk binds DC-SIGN and inhibits HIV-1 transfer to CD4+ t lymphocytes. J Clin Invest. 115:3256-3264</ref><ref name="Nonaka 2008">Nonaka M, Ma BY, Murai R, Nakamura N, Baba M, Kawasaki N, Hodohara K, Asano S and Kawasaki T. 2008. Glycosylation-dependent interactions of C-type lectin DC-SIGN with colorectal tumor-associated Lewis glycans impair the function and differentiation of monocyte-derived dendritic cells. J Immunol. 180:3347-3356</ref> 
''Glycan ligands from pathogens include''
*''Mycobacterium tuberculosis'' lipoarabinomannan (ManLAM) and hexamannosylated phosphatidylinositol mannoside PIM6 <ref>Maeda N, Nigou J, Herrmann JL, Jackson M, Amara A, Lagrange PH, Puzo G, Gicquel B and Neyrolles O. 2003. The cell surface receptor DC-SIGN discriminates between mycobacterium species through selective recognition of the mannose caps on lipoarabinomannan. J Biol Chem. 278:5513-5516</ref><ref>Driessen NN, Ummels R, Maaskant JJ, Gurcha SS, Besra GS, Ainge GD, Larsen DS, Painter GF, Vandenbroucke-Grauls CM, Geurtsen J and Appelmelk BJ. 2009. Role of phosphatidylinositol mannosides in the interaction between mycobacteria and DC-SIGN. Infect Immun. 77:4538-4547</ref>
*''Schistosoma mansoni'' glycans LeX, GalNAcβ1-4(Fucα1-3)GlcNAc-R (LDNF) and Fucα1-3Galβ1-4(Fucα1-3)GlcNAc-R (pseudo-LeY) <ref>van Die I, van Vliet SJ, Nyame AK, Cummings RD, Bank CM, Appelmelk B, Geijtenbeek TB and van Kooyk Y. 2003. The dendritic cell-specific C-type lectin DC-SIGN is a receptor for ''Schistosoma mansoni'' egg antigens and recognizes the glycan antigen Lewis x. Glycobiology. 13:471-478</ref><ref>Meyer S, van Liempt E, Imberty A, van Kooyk Y, Geyer H, Geyer R and van Die I. 2005. DC-SIGN mediates binding of dendritic cells to authentic pseudo-Lewis Y glycolipids of ''Schistosoma mansoni'' cercariae, the first parasite-specific ligand of DC-SIGN. J Biol Chem. 280:37349-37359</ref>
*Virus-associated high-mannose type glycans <ref>Feinberg H, Castelli R, Drickamer K, Seeberger PH and Weis WI. 2007. Multiple modes of binding enhance the affinity of DC-SIGN for high mannose N-linked glycans found on viral glycoproteins. J Biol Chem. 282:4202-4209</ref><ref>Lozach PY, Lortat-Jacob H, de Lacroix de Lavalette A, Staropoli I, Foung S, Amara A, Houles C, Fieschi F, Schwartz O, Virelizier JL, Arenzana-Seisdedos F and Altmeyer R. 2003. DC-SIGN and L-SIGN are high affinity binding receptors for hepatitis c virus glycoprotein E2. J Biol Chem. 278:20358-20366</ref>
*''Candida albicans'' N-linked mannan <ref>Cambi A, Netea MG, Mora-Montes HM, Gow NA, Hato SV, Lowman DW, Kullberg BJ, Torensma R, Williams DL and Figdor CG. 2008. Dendritic cell interaction with ''Candida albicans'' critically depends on N-linked mannan. J Biol Chem. 283:20590-20599</ref>
*''Escherichia coli'' K12 ''N''-acetylglucosamine (GlcNAc) residues within core LPS <ref name="Zhang 2006">Zhang P, Snyder S, Feng P, Azadi P, Zhang S, Bulgheresi S, Sanderson KE, He J, Klena J and Chen T. 2006. Role of N-acetylglucosamine within core lipopolysaccharide of several species of gram-negative bacteria in targeting DC-SIGN (CD209). J Immunol. 177:4002-4011</ref>
*''Neisseria meningitides'' GlcNAcβ1-3Galβ1-4Glc-R oligosaccharide of lgtB outer core LPS <ref name="Steeghs 2006">Steeghs L, van Vliet SJ, Uronen-Hansson H, van Mourik A, Engering A, Sanchez-Hernandez M, Klein N, Callard R, van Putten JP, van der Ley P, van Kooyk Y and van de Winkel JG. 2006. ''Neisseria meningitidis'' expressing Lgtb lipopolysaccharide targets DC-SIGN and modulates dendritic cell function. Cell Microbiol. 8:316-325</ref>
*''Helicobacter pylori'' LPS-associated LeX glycan antigens <ref name="Bergman 2004">Bergman MP, Engering A, Smits HH, van Vliet SJ, van Bodegraven AA, Wirth HP, Kapsenberg ML, Vandenbroucke-Grauls CM, van Kooyk Y and Appelmelk BJ. 2004. ''Helicobacter py''lori modulates the T helper cell 1/T helper cell 2 balance through phase-variable interaction between lipopolysaccharide and DC-SIGN. J Exp Med. 200:979-990</ref>
 
=== Cellular expression of GBP and ligands ===

DC-SIGN is expressed on dendritic cells and dendritic cell-like macrophages. Pathogens expressing DC-SIGN ligands include: ''Mycobacterium tuberculosis'', ''Schistosoma mansoni'', ''Candida albicans'', ''Escherichia coli'', ''Neisseria meningitides'', ''Helicobacter pylori'', and others (see above).
 

=== Biosynthesis of ligands ===
Glycans on viruses 
High mannose oligosaccharides on viral envelope proteins that are ligands for DC-SIGN result from incomplete processing of glycans in the pathway for biosynthesis of complex N-linked glycans ([http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/geMolecule.jsp?slideNumber=default GT Database]).
 
Glycans on bacteria 
The biosynthesis pathways for the bacterial lipopolysaccharides have been extensively studied and the gene families responsible for the expression of different glycan sequences have been characterized.<ref name”Raetz2002”>Raetz CR and Whitfield C (2002) Lipopolysaccharide endotoxins. Annu. Rev. Biochem. 71, 635-700</ref>
 
The mycobacterial transferases for synthesis of the lipo-arabinomannan (LAM) core and the extended ManLAM structures have been characterized.<ref name”Tam2009”>Tam, P-H and Lowary, TL (2009) Recent advances in mycobacterial cell wall glycan biosynthesis. Cur. Opin Struct. Biol. 13, 618-625</ref>
 
Glycans on fungi 
Biosynthesis mannans on fungi has been well studied in a number of species. For example, in the yeast S. cerevisiae, the KRE2/MNT1 genes encode mannosyltransferases that synthesize both N- and O-linked mannans.<ref name”Lussier1999”>Lussier, M, Sdicu, A-M and Bussey, H (1999) The KTR and MNN1 mannosyltransferase families of Saccharomyces cerevisiae. Biochim. Biophys. Acta 1426, 323-334</ref>
 
Glycans on parasites 
Some data give insight in the biosynthesis of DC-SIGN ligands in parasitic helminths. In Schistosoma mansoni <ref>DeBose-Boyd R, Nyame AK, Cummings RD. 1996. Schistosoma mansoni: characterization of an α1-3 fucosyltransferase in adult parasites. Exp Parasitol. 82: 1-10</ref><ref>Marques Jr ET Jr, Ichikawa Y, Strand M, August JT, Hart GW, Schnaar RL. 2001. Fucosyltransferases in ''Schistosoma mansoni'' development. Glycobiology 11: 249-59</ref> and ''Haemonchus contortus'' <ref>DeBose-Boyd RA, Nyame AK, Jasmer DP, Cummings RD. 1998. The ruminant parasite ''Haemonchus contortus'' expresses an α1,3-fucosyltransferase capable of synthesizing the Lewis x and sialyl Lewis x antigens. Glycoconjugate J. 15: 789-98</ref> α1,3-fucosyltransferases have been identified, which may be involved in generation of Galβ1-4(Fucα1-3)GlcNAc-R (Lewis X), and/or GalNAcβ1-4(Fucα1-3)GlcNAc-R (LDNF). Combined transcriptome (putative glycosyltransferase genes) and glycome analyses of Schistosoma revealed that female schistosomes synthesize preferably terminal LacNAc and Lewis X, whereas male worms synthesize more LDN/LDNF antigens <ref>Hokke CH, Fitzpatrick JM and Hoffmann KF. 2007. Integrating transcriptome, proteome and glycome analyses of Schistosoma biology. Trends in Parasitology 23: 165-174</ref>.

=== Structure ===
[[image:DC-SIGN_4.jpg]] 
Crystal structures of the CRD of DC-SIGN bound to a mannose-containing oligosaccharide and lacto-N-fucopentaose have been analyzed.<ref name="Feinberg 2001"/><ref name="Guo 2004"/> The first structure can be used to model the binding of the outer portion of a high mannose oligosaccharide and the second structure shows how the Lewisx trisaccharide fits into the binding site. The high mannose oligosaccharide makes extensive interactions in an extended binding site, while the more rigid Lewisx oligosaccharide binds primarily through the fucose residues, with some additional stabilizing interactions with the galactose. The overall structure of the tetrameric extracellular domain has been deduced from crystal structures of the repeats in the neck domain of the related protein DC-SIGNR (L-SIGN)<ref name="Feinberg 2009">Feinberg, H, Tso, CKW, Taylor, ME, Drickamer, K and Weis, WI. 2009. Segmented helical structure of the neck region of the glycan-binding receptor DC-SIGNR. J Mol Biol 394:613-620</ref> and oligomeric C-terminal fragments of DC-SIGN that contain the CRD<ref name="Feinberg 2005">Feinberg, H, Guo, Y, Mitchell, DA, Drickamer, K and Weis, WI. 2005. Extended neck regions stabilze tetramers of the receptors DC-SIGN and DC-SIGNR. J Biol Chem 280:1327-1335</ref>.
 

=== Biological roles of GBP-ligand interaction ===
''Biological roles for DC-SIGN include'':
*DC-SIGN mediates interactions between dendritic cells (DCs) and resting T cells <ref name="Geijtenbeek 2000"/> and between DCs and neutrophils <ref>van Gisbergen KP, Sanchez-Hernandez M, Geijtenbeek TB and van Kooyk Y. 2005. Neutrophils mediate immune modulation of dendritic cells through glycosylation-dependent interactions between MAC-1 and DC-SIGN. J Exp Med. 201:1281-1292</ref>.
*DC-SIGN contributes to adhesion and rolling of DCs on primary human umbilical vein endothelial cells <ref>Geijtenbeek TB, Krooshoop DJ, Bleijs DA, van Vliet SJ, van Duijnhoven GC, Grabovsky V, Alon R, Figdor CG and van Kooyk Y. 2000. DC-SIGN-ICAM-2 interaction mediates dendritic cell trafficking. Nat Immunol. 1:353-357</ref><ref name="Garcia 2008"/>
*interactions of DC-SIGN with Lewis antigens on colorectal tumor cells impair the function and differentiation of dendritic cells <ref name="Nonaka 2008"/>
*DC-SIGN can mediate bacterial adherence and phagocytosis <ref name="Zhang 2006"/>.
*viruses target DC-SIGN to promote infection and spread to cells <ref>Geijtenbeek TB, Kwon DS, Torensma R, van Vliet SJ, van Duijnhoven GC, Middel J, Cornelissen IL, Nottet HS, KewalRamani VN, Littman DR, Figdor CG and van Kooyk Y. 2000. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell. 100:587-597</ref><ref>Navarro-Sanchez E, Altmeyer R, Amara A, Schwartz O, Fieschi F, Virelizier JL, Arenzana-Seisdedos F and Despres P. 2003. Dendritic-cell-specific ICAM3-grabbing non-integrin is essential for the productive infection of human dendritic cells by mosquito-cell-derived dengue viruses. EMBO Rep. 4:723-728</ref><ref>Simmons G, Reeves JD, Grogan CC, Vandenberghe LH, Baribaud F, Whitbeck JC, Burke E, Buchmeier MJ, Soilleux EJ, Riley JL, Doms RW, Bates P and Pohlmann S. 2003. DC-SIGN and DC-SIGNR bind Ebola glycoproteins and enhance infection of macrophages and endothelial cells. Virology. 305:115-123</ref><ref>Hodges A, Sharrocks K, Edelmann M, Baban D, Moris A, Schwartz O, Drakesmith H, Davies K, Kessler B, McMichael A and Simmons A. 2007. Activation of the lectin DC-SIGN induces an immature dendritic cell phenotype triggering Rho-GTPase activity required for HIV-1 replication. Nat Immunol. 8:569-577</ref>
*activation of DC-SIGN by pathogens can contribute to T helper type 1 (Th)1 cell activity <ref name="Steeghs 2006"/><ref>van Stijn CM, Meyer S, van den Broek M, Bruijns SC, van Kooyk Y, Geyer R and van Die I. 2010. ''Schistosoma mansoni'' worm glycolipids induce an inflammatory phenotype in human dendritic cells by cooperation of TLR4 and DC-SIGN. Mol Immunol. 47:1544-1552</ref>
*some pathogens target DC-SIGN to suppress Th1 cell development <ref name="Bergman 2004"/><ref>Geijtenbeek TB, Van Vliet SJ, Koppel EA, Sanchez-Hernandez M, Vandenbroucke-Grauls CM, Appelmelk B and Van Kooyk Y. 2003. Mycobacteria target DC-SIGN to suppress dendritic cell function. J Exp Med. 197:7-17</ref>
* the murine DC-SIGN homologue SIGNR3 contributes to early host defense against Mycobacterium tuberculosis <ref>Tanne A, Ma B, Boudou F, Tailleux L, Botella H, Badell E, Levillain F, Taylor ME, Drickamer K, Nigou J, Dobos KM, Puzo G, Vestweber D, Wild MK, Marcinko M, Sobieszczuk P, Stewart L, Lebus D, Gicquel B, Neyrolles O. 2009. A murine DC-SIGN homologue contributes to early host defense against ''Mycobacterium tub''erculosis. J Exp Med 206: 2205-2220</ref>
 

== 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=DC-SIGN&maxresults=20 CFG database search results for DC-SIGN].

=== Glycan profiling ===

 
=== Glycogene microarray ===
Probes for human DC-SIGN have been included in all versions of the CFG glycogene chip.
 

=== Knockout mouse lines ===

Knockout mice for three potential DC-SIGN orthologues ([https://www.functionalglycomics.org/static/consortium/resources/DataCoreFdc.shtml DC-SIGN], [https://www.functionalglycomics.org/static/consortium/resources/DataCoreFsr1.shtml SIGNR1], and [https://www.functionalglycomics.org/static/consortium/resources/DataCoreFsr3.shtml SIGNR3]) were created by the CFG and distributed to PIs, and their [http://www.functionalglycomics.org/glycomics/publicdata/phenotyping.jsp phenotypes] were analyzed.

=== Glycan array ===

Glycan array analysis <ref name="Guo 2004"/><ref name="Liempt 2006"/>and synthetic oligosaccharides were used to elucidate DC-SIGN [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_GLYCAN_v2_52_06122003 glycan-binding specificity] and analyze the mechanism of specific glycan binding. See all glycan array results for [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=dc-sign&cat=coreh DC-SIGN here]. See glycan array screening results for these related GBPs: [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=langerin&cat=coreh langerin,] [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=DCIR&cat=coreh DCIR,] and [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=DC-SIGNR&cat=coreh DC-SIGNR.]

== Related GBPs ==
Other dendritic cell lectins include langerin [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=langerin&maxresults=20 (CFG data)], DCIR [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=DCIR&maxresults=20 (CFG data)], and DCAR. Paralogs on other cells include DC-SIGNR [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=DC-SIGNR&maxresults=20 (CFG data)].

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Kurt Drickamer, Irma van Die, Yvette van Kooyk

DC-SIGN

2010-06-15T13:18:11Z

Irma van Die:

Dendritic cell-specific intracellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin (DC-SIGN, CD209) is a C-type lectin that plays roles in both cell-cell and host-pathogen interactions, and thus serves as a model for both processes. This glycan-binding protein (GBP) paradigm also serves as a model for other members of the C-type lectin family expressed on dendritic cells. 
DC-SIGN is a type II membrane protein with a short aminoterminal cytoplasmic tail, a neck region and a single carboxyl terminal carbohydrate recognition domain (CRD)<ref name="Geijtenbeek 2000">Geijtenbeek TB, Torensma R, van Vliet SJ, van Duijnhoven GC, Adema GJ, van Kooyk Y and Figdor CG. 2000. Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell. 100:575-585</ref>. The primary structure of the CRD contains conserved residues consistent with classical mannose-specific CRDs <ref name="Feinberg 2001">Feinberg H, Mitchell DA, Drickamer K and Weis WI. 2001. Structural basis for selective recognition of oligosaccharides by DC-SIGN and DC-SIGNR. Science. 294:2163-2166</ref>. Multivalent binding of glycan ligands by DC-SIGN is dependent on correct organization and presentation of the CRDs at the neck domains, which are crucial for tetramerization of DC-SIGN <ref>Yu QD, Oldring AP, Powlesland AS, Tso CK, Yang C, Drickamer K and Taylor ME. 2009. Autonomous tetramerization domains in the glycan-binding receptors DC-SIGN and DC-SIGNR. J Mol Biol. 387:1075-1080</ref>. The cytoplasmic tail of DC-SIGN contains internalization motives involved in the ligand-induced internalization of DC-SIGN <ref>Engering A, Geijtenbeek TB, van Vliet SJ, Wijers M, van Liempt E, Demaurex N, Lanzavecchia A, Fransen J, Figdor CG, Piguet V and van Kooyk Y. 2002. The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells. J Immunol. 168:2118-2126</ref>, and can activate signaling pathways <ref>Caparros E, Munoz P, Sierra-Filardi E, Serrano-Gomez D, Puig-Kroger A, Rodriguez-Fernandez JL, Mellado M, Sancho J, Zubiaur M and Corbi AL. 2006. DC-SIGN ligation on dendritic cells results in ERK and PI3k activation and modulates cytokine production. Blood. 107:3950-3958</ref><ref>Gringhuis SI, den Dunnen J, Litjens M, van Het Hof B, van Kooyk Y and Geijtenbeek TB. 2007. C-type lectin DC-SIGN modulates toll-like receptor signaling via raf-1 kinase-dependent acetylation of transcription factor NF-kb. Immunity. 26:605-616</ref><ref>Gringhuis SI, den Dunnen J, Litjens M, van der Vlist M and Geijtenbeek TB. 2009. Carbohydrate-specific signaling through the DC-SIGN signalosome tailors immunity to ''Mycobacterium tuberculosis'', HIV-1 and ''Helicobacter pylori''. Nat Immunol. 10:1081-1088</ref>.
In mice several DC-SIGN-related proteins have been identified (SIGNR1-SIGNR8) <ref>Powlesland AS, Ward EM, Sadhu SK, Guo Y, Taylor ME and Drickamer K. 2006. Widely divergent biochemical properties of the complete set of mouse DC-SIGN-related proteins. J Biol Chem. 281:20440-20449</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==

Many investigators, both CFG Participating Investigators (PIs) and non-PIs using CFG resources, have led extensive studies on DC-SIGN, particularly regarding structure-function relationships, interactions with pathogens, and signaling functions in dendritic cells.
* PIs working on DC-SIGN include: Pedro Bonay, Angel Corbi, Kurt Drickamer, Juan Garcia-Vallejo, Donald Harn, Kayo Inaba, Benhur Lee, Olivier Neyrolles, Irma van Die, Yvette van Kooyk, William Weis, Martin Wild
* Non-PIs who have used CFG resources to study DC-SIGN include: Brigitte Gicquel, Arne Skerra, Ralph Steinman

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===
DC-SIGN recognizes both internal branched mannose residues as well as terminal di-mannoses, α1-3 and α1-4 fucosylated glycan structures and certain N-aceltylglucosamine containing molecules on self proteins and/or pathogens <ref name="Feinberg 2001"/><ref name="Guo 2004">Guo Y, Feinberg H, Conroy E, Mitchell DA, Alvarez R, Blixt O, Taylor ME, Weis WI and Drickamer K. 2004. Structural basis for distinct ligand-binding and targeting properties of the receptors DC-SIGN and DC-SIGNR. Nat Struct Mol Biol. 11:591-598</ref><ref>Mitchell DA, Fadden AJ and Drickamer K. 2001. A novel mechanism of carbohydrate recognition by the C-type lectins DC-SIGN and DC-SIGNR. Subunit organization and binding to multivalent ligands. J Biol Chem. 276:28939-28945</ref><ref name="Liempt 2006">van Liempt E, Bank CM, Mehta P, Garcia-Vallejo JJ, Kawar ZS, Geyer R, Alvarez RA, Cummings RD, Kooyk Y and van Die I. 2006. Specificity of DC-SIGN for mannose- and fucose-containing glycans. FEBS Lett. 580:6123-6131</ref> 
''Endogenous ligands include''
*Lewis blood group antigens LeX, LeA, LeY and LeB <ref>Bogoevska V, Horst A, Klampe B, Lucka L, Wagener C and Nollau P. 2006. CEACAM1, an adhesion molecule of human granulocytes, is fucosylated by fucosyltransferase IX and interacts with DC-SIGN of dendritic cells via Lewis X residues. Glycobiology. 16:197-209</ref><ref>Bogoevska V, Nollau P, Lucka L, Grunow D, Klampe B, Uotila LM, Samsen A, Gahmberg CG and Wagener C. 2007. DC-SIGN binds ICAM-3 isolated from peripheral human leukocytes through Lewis X residues. Glycobiology. 17:324-333</ref><ref name="Garcia 2008">Garcia-Vallejo JJ, van Liempt E, da Costa Martins P, Beckers C, van het Hof B, Gringhuis SI, Zwaginga JJ, van Dijk W, Geijtenbeek TB, van Kooyk Y and van Die I. 2008. DC-SIGN mediates adhesion and rolling of dendritic cells on primary human umbilical vein endothelial cells through Lewis Y antigen expressed on ICAM-2. Mol Immunol. 45:2359-2369</ref><ref>Naarding MA, Ludwig IS, Groot F, Berkhout B, Geijtenbeek TB, Pollakis G and Paxton WA. 2005. Lewis x component in human milk binds DC-SIGN and inhibits HIV-1 transfer to CD4+ t lymphocytes. J Clin Invest. 115:3256-3264</ref><ref name="Nonaka 2008">Nonaka M, Ma BY, Murai R, Nakamura N, Baba M, Kawasaki N, Hodohara K, Asano S and Kawasaki T. 2008. Glycosylation-dependent interactions of C-type lectin DC-SIGN with colorectal tumor-associated Lewis glycans impair the function and differentiation of monocyte-derived dendritic cells. J Immunol. 180:3347-3356</ref> 
''Glycan ligands from pathogens include''
*''Mycobacterium tuberculosis'' lipoarabinomannan (ManLAM) and hexamannosylated phosphatidylinositol mannoside PIM6 <ref>Maeda N, Nigou J, Herrmann JL, Jackson M, Amara A, Lagrange PH, Puzo G, Gicquel B and Neyrolles O. 2003. The cell surface receptor DC-SIGN discriminates between mycobacterium species through selective recognition of the mannose caps on lipoarabinomannan. J Biol Chem. 278:5513-5516</ref><ref>Driessen NN, Ummels R, Maaskant JJ, Gurcha SS, Besra GS, Ainge GD, Larsen DS, Painter GF, Vandenbroucke-Grauls CM, Geurtsen J and Appelmelk BJ. 2009. Role of phosphatidylinositol mannosides in the interaction between mycobacteria and DC-SIGN. Infect Immun. 77:4538-4547</ref>
*''Schistosoma mansoni'' glycans LeX, GalNAcβ1-4(Fucα1-3)GlcNAc-R (LDNF) and Fucα1-3Galβ1-4(Fucα1-3)GlcNAc-R (pseudo-LeY) <ref>van Die I, van Vliet SJ, Nyame AK, Cummings RD, Bank CM, Appelmelk B, Geijtenbeek TB and van Kooyk Y. 2003. The dendritic cell-specific C-type lectin DC-SIGN is a receptor for ''Schistosoma mansoni'' egg antigens and recognizes the glycan antigen Lewis x. Glycobiology. 13:471-478</ref><ref>Meyer S, van Liempt E, Imberty A, van Kooyk Y, Geyer H, Geyer R and van Die I. 2005. DC-SIGN mediates binding of dendritic cells to authentic pseudo-Lewis Y glycolipids of ''Schistosoma mansoni'' cercariae, the first parasite-specific ligand of DC-SIGN. J Biol Chem. 280:37349-37359</ref>
*Virus-associated high-mannose type glycans <ref>Feinberg H, Castelli R, Drickamer K, Seeberger PH and Weis WI. 2007. Multiple modes of binding enhance the affinity of DC-SIGN for high mannose N-linked glycans found on viral glycoproteins. J Biol Chem. 282:4202-4209</ref><ref>Lozach PY, Lortat-Jacob H, de Lacroix de Lavalette A, Staropoli I, Foung S, Amara A, Houles C, Fieschi F, Schwartz O, Virelizier JL, Arenzana-Seisdedos F and Altmeyer R. 2003. DC-SIGN and L-SIGN are high affinity binding receptors for hepatitis c virus glycoprotein E2. J Biol Chem. 278:20358-20366</ref>
*''Candida albicans'' N-linked mannan <ref>Cambi A, Netea MG, Mora-Montes HM, Gow NA, Hato SV, Lowman DW, Kullberg BJ, Torensma R, Williams DL and Figdor CG. 2008. Dendritic cell interaction with ''Candida albicans'' critically depends on N-linked mannan. J Biol Chem. 283:20590-20599</ref>
*''Escherichia coli'' K12 ''N''-acetylglucosamine (GlcNAc) residues within core LPS <ref name="Zhang 2006">Zhang P, Snyder S, Feng P, Azadi P, Zhang S, Bulgheresi S, Sanderson KE, He J, Klena J and Chen T. 2006. Role of N-acetylglucosamine within core lipopolysaccharide of several species of gram-negative bacteria in targeting DC-SIGN (CD209). J Immunol. 177:4002-4011</ref>
*''Neisseria meningitides'' GlcNAcβ1-3Galβ1-4Glc-R oligosaccharide of lgtB outer core LPS <ref name="Steeghs 2006">Steeghs L, van Vliet SJ, Uronen-Hansson H, van Mourik A, Engering A, Sanchez-Hernandez M, Klein N, Callard R, van Putten JP, van der Ley P, van Kooyk Y and van de Winkel JG. 2006. ''Neisseria meningitidis'' expressing Lgtb lipopolysaccharide targets DC-SIGN and modulates dendritic cell function. Cell Microbiol. 8:316-325</ref>
*''Helicobacter pylori'' LPS-associated LeX glycan antigens <ref name="Bergman 2004">Bergman MP, Engering A, Smits HH, van Vliet SJ, van Bodegraven AA, Wirth HP, Kapsenberg ML, Vandenbroucke-Grauls CM, van Kooyk Y and Appelmelk BJ. 2004. ''Helicobacter py''lori modulates the T helper cell 1/T helper cell 2 balance through phase-variable interaction between lipopolysaccharide and DC-SIGN. J Exp Med. 200:979-990</ref>
 
=== Cellular expression ===

DC-SIGN is expressed on dendritic cells and dendritic cell-like macrophages
 
=== Structure ===
Crystal structures of DC-SIGN bound to high-mannose oligosaccharide and lacto-N-fucopentaose have been analyzed <ref name="Feinberg 2001"/><ref name="Guo 2004"/>
 
=== Biological roles of GBP-ligand interaction ===
''Biological roles for DC-SIGN include'':
*DC-SIGN mediates interactions between dendritic cells (DCs) and resting T cells <ref name="Geijtenbeek 2000"/> and between DCs and neutrophils <ref>van Gisbergen KP, Sanchez-Hernandez M, Geijtenbeek TB and van Kooyk Y. 2005. Neutrophils mediate immune modulation of dendritic cells through glycosylation-dependent interactions between MAC-1 and DC-SIGN. J Exp Med. 201:1281-1292</ref>.
*DC-SIGN contributes to adhesion and rolling of DCs on primary human umbilical vein endothelial cells <ref>Geijtenbeek TB, Krooshoop DJ, Bleijs DA, van Vliet SJ, van Duijnhoven GC, Grabovsky V, Alon R, Figdor CG and van Kooyk Y. 2000. DC-SIGN-ICAM-2 interaction mediates dendritic cell trafficking. Nat Immunol. 1:353-357</ref><ref name="Garcia 2008"/>
*interactions of DC-SIGN with Lewis antigens on colorectal tumor cells impair the function and differentiation of dendritic cells <ref name="Nonaka 2008"/>
*DC-SIGN can mediate bacterial adherence and phagocytosis <ref name="Zhang 2006"/>.
*viruses target DC-SIGN to promote infection and spread to cells <ref>Geijtenbeek TB, Kwon DS, Torensma R, van Vliet SJ, van Duijnhoven GC, Middel J, Cornelissen IL, Nottet HS, KewalRamani VN, Littman DR, Figdor CG and van Kooyk Y. 2000. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell. 100:587-597</ref><ref>Navarro-Sanchez E, Altmeyer R, Amara A, Schwartz O, Fieschi F, Virelizier JL, Arenzana-Seisdedos F and Despres P. 2003. Dendritic-cell-specific ICAM3-grabbing non-integrin is essential for the productive infection of human dendritic cells by mosquito-cell-derived dengue viruses. EMBO Rep. 4:723-728</ref><ref>Simmons G, Reeves JD, Grogan CC, Vandenberghe LH, Baribaud F, Whitbeck JC, Burke E, Buchmeier MJ, Soilleux EJ, Riley JL, Doms RW, Bates P and Pohlmann S. 2003. DC-SIGN and DC-SIGNR bind Ebola glycoproteins and enhance infection of macrophages and endothelial cells. Virology. 305:115-123</ref><ref>Hodges A, Sharrocks K, Edelmann M, Baban D, Moris A, Schwartz O, Drakesmith H, Davies K, Kessler B, McMichael A and Simmons A. 2007. Activation of the lectin DC-SIGN induces an immature dendritic cell phenotype triggering Rho-GTPase activity required for HIV-1 replication. Nat Immunol. 8:569-577</ref>
*activation of DC-SIGN by pathogens can contribute to T helper type 1 (Th)1 cell activity <ref name="Steeghs 2006"/><ref>van Stijn CM, Meyer S, van den Broek M, Bruijns SC, van Kooyk Y, Geyer R and van Die I. 2010. ''Schistosoma mansoni'' worm glycolipids induce an inflammatory phenotype in human dendritic cells by cooperation of TLR4 and DC-SIGN. Mol Immunol. 47:1544-1552</ref>
*some pathogens target DC-SIGN to suppress Th1 cell development <ref name="Bergman 2004"/><ref>Geijtenbeek TB, Van Vliet SJ, Koppel EA, Sanchez-Hernandez M, Vandenbroucke-Grauls CM, Appelmelk B and Van Kooyk Y. 2003. Mycobacteria target DC-SIGN to suppress dendritic cell function. J Exp Med. 197:7-17</ref>
* the murine DC-SIGN homologue SIGNR3 contributes to early host defense against Mycobacterium tuberculosis <ref>Tanne A, Ma B, Boudou F, Tailleux L, Botella H, Badell E, Levillain F, Taylor ME, Drickamer K, Nigou J, Dobos KM, Puzo G, Vestweber D, Wild MK, Marcinko M, Sobieszczuk P, Stewart L, Lebus D, Gicquel B, Neyrolles O. 2009. A murine DC-SIGN homologue contributes to early host defense against ''Mycobacterium tub''erculosis. J Exp Med 206: 2205-2220</ref>
 
== 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=DC-SIGN&maxresults=20 CFG database search results for DC-SIGN].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

Knockout mice for three potential DC-SIGN orthologues ([https://www.functionalglycomics.org/static/consortium/resources/DataCoreFdc.shtml DC-SIGN], [https://www.functionalglycomics.org/static/consortium/resources/DataCoreFsr1.shtml SIGNR1], and [https://www.functionalglycomics.org/static/consortium/resources/DataCoreFsr3.shtml SIGNR3]) were created by the CFG and distributed to PIs, and their [http://www.functionalglycomics.org/glycomics/publicdata/phenotyping.jsp phenotypes] were analyzed.

=== Glycan array ===

Glycan array analysis <ref name="Guo 2004"/><ref name="Liempt 2006"/>and synthetic oligosaccharides were used to elucidate DC-SIGN glycan-binding specificity and analyze the mechanism of specific glycan binding.

== Related GBPs ==
Other dendritic cell lectins include langerin, DCIR, and DCAR. Paralogs on other cells include DC-SIGNR.

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Kurt Drickamer, Irma van Die, Yvette van Kooyk

DC-SIGN

2010-06-15T12:40:18Z

Irma van Die:

Dendritic cell-specific intracellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin (DC-SIGN, CD209) is a C-type lectin that plays roles in both cell-cell and host-pathogen interactions, and thus serves as a model for both processes. This glycan-binding protein (GBP) paradigm also serves as a model for other members of the C-type lectin family expressed on dendritic cells. 
DC-SIGN is a type II membrane protein with a short aminoterminal cytoplasmic tail, a neck region and a single carboxyl terminal carbohydrate recognition domain (CRD)<ref name="Geijtenbeek 2000">Geijtenbeek TB, Torensma R, van Vliet SJ, van Duijnhoven GC, Adema GJ, van Kooyk Y and Figdor CG. 2000. Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell. 100:575-585</ref>. The primary structure of the CRD contains conserved residues consistent with classical mannose-specific CRDs <ref>Feinberg H, Mitchell DA, Drickamer K and Weis WI. 2001. Structural basis for selective recognition of oligosaccharides by DC-SIGN and DC-SIGNR. Science. 294:2163-2166</ref>. Multivalent binding of glycan ligands by DC-SIGN is dependent on correct organization and presentation of the CRDs at the neck domains, which are crucial for tetramerization of DC-SIGN <ref>Yu QD, Oldring AP, Powlesland AS, Tso CK, Yang C, Drickamer K and Taylor ME. 2009. Autonomous tetramerization domains in the glycan-binding receptors DC-SIGN and DC-SIGNR. J Mol Biol. 387:1075-1080</ref>. The cytoplasmic tail of DC-SIGN contains internalization motives involved in the ligand-induced internalization of DC-SIGN <ref>Engering A, Geijtenbeek TB, van Vliet SJ, Wijers M, van Liempt E, Demaurex N, Lanzavecchia A, Fransen J, Figdor CG, Piguet V and van Kooyk Y. 2002. The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells. J Immunol. 168:2118-2126</ref>, and can activate signaling pathways <ref>Caparros E, Munoz P, Sierra-Filardi E, Serrano-Gomez D, Puig-Kroger A, Rodriguez-Fernandez JL, Mellado M, Sancho J, Zubiaur M and Corbi AL. 2006. DC-SIGN ligation on dendritic cells results in ERK and PI3k activation and modulates cytokine production. Blood. 107:3950-3958</ref><ref>Gringhuis SI, den Dunnen J, Litjens M, van Het Hof B, van Kooyk Y and Geijtenbeek TB. 2007. C-type lectin DC-SIGN modulates toll-like receptor signaling via raf-1 kinase-dependent acetylation of transcription factor NF-kb. Immunity. 26:605-616</ref><ref>Gringhuis SI, den Dunnen J, Litjens M, van der Vlist M and Geijtenbeek TB. 2009. Carbohydrate-specific signaling through the DC-SIGN signalosome tailors immunity to Mycobacterium tuberculosis, HIV-1 and Helicobacter pylori. Nat Immunol. 10:1081-1088</ref>.
In mice several DC-SIGN-related proteins have been identified (SIGNR1-SIGNR8) <ref>Powlesland AS, Ward EM, Sadhu SK, Guo Y, Taylor ME and Drickamer K. 2006. Widely divergent biochemical properties of the complete set of mouse DC-SIGN-related proteins. J Biol Chem. 281:20440-20449</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==

Many investigators, both CFG Participating Investigators (PIs) and non-PIs using CFG resources, have led extensive studies on DC-SIGN, particularly regarding structure-function relationships, interactions with pathogens, and signaling functions in dendritic cells.
* PIs working on DC-SIGN include: Pedro Bonay, Angel Corbi, Kurt Drickamer, Juan Garcia-Vallejo, Donald Harn, Kayo Inaba, Benhur Lee, Olivier Neyrolles, Irma van Die, Yvette van Kooyk, William Weis, Martin Wild
* Non-PIs who have used CFG resources to study DC-SIGN include: Brigitte Gicquel, Arne Skerra, Ralph Steinman

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===
DC-SIGN recognizes both internal branched mannose residues as well as terminal di-mannoses, α1-3 and α1-4 fucosylated glycan structures and certain N-aceltylglucosamine containing molecules on self proteins and/or pathogens <ref>Feinberg H, Mitchell DA, Drickamer K and Weis WI. 2001. Structural basis for selective recognition of oligosaccharides by DC-SIGN and DC-SIGNR. Science. 294:2163-2166</ref><ref>Guo Y, Feinberg H, Conroy E, Mitchell DA, Alvarez R, Blixt O, Taylor ME, Weis WI and Drickamer K. 2004. Structural basis for distinct ligand-binding and targeting properties of the receptors DC-SIGN and DC-SIGNR. Nat Struct Mol Biol. 11:591-598</ref><ref>Mitchell DA, Fadden AJ and Drickamer K. 2001. A novel mechanism of carbohydrate recognition by the C-type lectins DC-SIGN and DC-SIGNR. Subunit organization and binding to multivalent ligands. J Biol Chem. 276:28939-28945</ref><ref>van Liempt E, Bank CM, Mehta P, Garcia-Vallejo JJ, Kawar ZS, Geyer R, Alvarez RA, Cummings RD, Kooyk Y and van Die I. 2006. Specificity of DC-SIGN for mannose- and fucose-containing glycans. FEBS Lett. 580:6123-6131</ref> 
''Endogenous ligands include''
*Lewis blood group antigens LeX, LeA, LeY and LeB <ref>Bogoevska V, Horst A, Klampe B, Lucka L, Wagener C and Nollau P. 2006. CEACAM1, an adhesion molecule of human granulocytes, is fucosylated by fucosyltransferase IX and interacts with DC-SIGN of dendritic cells via Lewis X residues. Glycobiology. 16:197-209</ref><ref>Bogoevska V, Nollau P, Lucka L, Grunow D, Klampe B, Uotila LM, Samsen A, Gahmberg CG and Wagener C. 2007. DC-SIGN binds ICAM-3 isolated from peripheral human leukocytes through Lewis X residues. Glycobiology. 17:324-333</ref><ref name="Garcia 2008">Garcia-Vallejo JJ, van Liempt E, da Costa Martins P, Beckers C, van het Hof B, Gringhuis SI, Zwaginga JJ, van Dijk W, Geijtenbeek TB, van Kooyk Y and van Die I. 2008. DC-SIGN mediates adhesion and rolling of dendritic cells on primary human umbilical vein endothelial cells through Lewis Y antigen expressed on ICAM-2. Mol Immunol. 45:2359-2369</ref><ref>Naarding MA, Ludwig IS, Groot F, Berkhout B, Geijtenbeek TB, Pollakis G and Paxton WA. 2005. Lewis x component in human milk binds DC-SIGN and inhibits HIV-1 transfer to CD4+ t lymphocytes. J Clin Invest. 115:3256-3264</ref><ref>Nonaka M, Ma BY, Murai R, Nakamura N, Baba M, Kawasaki N, Hodohara K, Asano S and Kawasaki T. 2008. Glycosylation-dependent interactions of C-type lectin DC-SIGN with colorectal tumor-associated Lewis glycans impair the function and differentiation of monocyte-derived dendritic cells. J Immunol. 180:3347-3356</ref> 
''Glycan ligands from pathogens include''
*''Mycobacterium tuberculosis'' lipoarabinomannan (ManLAM) and hexamannosylated phosphatidylinositol mannoside PIM6 <ref>Maeda N, Nigou J, Herrmann JL, Jackson M, Amara A, Lagrange PH, Puzo G, Gicquel B and Neyrolles O. 2003. The cell surface receptor DC-SIGN discriminates between mycobacterium species through selective recognition of the mannose caps on lipoarabinomannan. J Biol Chem. 278:5513-5516</ref><ref>Driessen NN, Ummels R, Maaskant JJ, Gurcha SS, Besra GS, Ainge GD, Larsen DS, Painter GF, Vandenbroucke-Grauls CM, Geurtsen J and Appelmelk BJ. 2009. Role of phosphatidylinositol mannosides in the interaction between mycobacteria and DC-SIGN. Infect Immun. 77:4538-4547</ref>
*''Schistosoma mansoni'' glycans LeX, GalNAcβ1-4(Fucα1-3)GlcNAc-R (LDNF) and Fucα1-3Galβ1-4(Fucα1-3)GlcNAc-R (pseudo-LeY) <ref>van Die I, van Vliet SJ, Nyame AK, Cummings RD, Bank CM, Appelmelk B, Geijtenbeek TB and van Kooyk Y. 2003. The dendritic cell-specific C-type lectin DC-SIGN is a receptor for Schistosoma mansoni egg antigens and recognizes the glycan antigen Lewis x. Glycobiology. 13:471-478</ref><ref>Meyer S, van Liempt E, Imberty A, van Kooyk Y, Geyer H, Geyer R and van Die I. 2005. DC-SIGN mediates binding of dendritic cells to authentic pseudo-Lewis Y glycolipids of Schistosoma mansoni cercariae, the first parasite-specific ligand of DC-SIGN. J Biol Chem. 280:37349-37359</ref>
*Virus-associated high-mannose type glycans <ref>Feinberg H, Castelli R, Drickamer K, Seeberger PH and Weis WI. 2007. Multiple modes of binding enhance the affinity of DC-SIGN for high mannose N-linked glycans found on viral glycoproteins. J Biol Chem. 282:4202-4209</ref><ref>Lozach PY, Lortat-Jacob H, de Lacroix de Lavalette A, Staropoli I, Foung S, Amara A, Houles C, Fieschi F, Schwartz O, Virelizier JL, Arenzana-Seisdedos F and Altmeyer R. 2003. DC-SIGN and L-SIGN are high affinity binding receptors for hepatitis c virus glycoprotein E2. J Biol Chem. 278:20358-20366</ref>
*''Candida albicans'' N-linked mannan <ref>Cambi A, Netea MG, Mora-Montes HM, Gow NA, Hato SV, Lowman DW, Kullberg BJ, Torensma R, Williams DL and Figdor CG. 2008. Dendritic cell interaction with Candida albicans critically depends on N-linked mannan. J Biol Chem. 283:20590-20599</ref>
*''Escherichia coli'' K12 ''N''-acetylglucosamine (GlcNAc) residues within core LPS <ref name="Zhang 2006">Zhang P, Snyder S, Feng P, Azadi P, Zhang S, Bulgheresi S, Sanderson KE, He J, Klena J and Chen T. 2006. Role of N-acetylglucosamine within core lipopolysaccharide of several species of gram-negative bacteria in targeting DC-SIGN (CD209). J Immunol. 177:4002-4011</ref>
*''Neisseria meningitides'' GlcNAcβ1-3Galβ1-4Glc-R oligosaccharide of lgtB outer core LPS <ref name="Steeghs 2006">Steeghs L, van Vliet SJ, Uronen-Hansson H, van Mourik A, Engering A, Sanchez-Hernandez M, Klein N, Callard R, van Putten JP, van der Ley P, van Kooyk Y and van de Winkel JG. 2006. Neisseria meningitidis expressing Lgtb lipopolysaccharide targets DC-SIGN and modulates dendritic cell function. Cell Microbiol. 8:316-325</ref>
*''Helicobacter pylori'' LPS-associated LeX glycan antigens <ref name="Bergman 2004">Bergman MP, Engering A, Smits HH, van Vliet SJ, van Bodegraven AA, Wirth HP, Kapsenberg ML, Vandenbroucke-Grauls CM, van Kooyk Y and Appelmelk BJ. 2004. Helicobacter pylori modulates the T helper cell 1/T helper cell 2 balance through phase-variable interaction between lipopolysaccharide and DC-SIGN. J Exp Med. 200:979-990</ref>
 
=== Cellular expression ===

DC-SIGN is expressed on dendritic cells and dendritic cell-like macrophages
 
=== Structure ===

 
=== Biological roles of GBP-ligand interaction ===
''Biological roles for DC-SIGN include'':
*mediating interactions between dendritic cells (DCs) and resting T cells <ref name="Geijtenbeek 2000"/> and between DCs and neutrophils <ref>van Gisbergen KP, Sanchez-Hernandez M, Geijtenbeek TB and van Kooyk Y. 2005. Neutrophils mediate immune modulation of dendritic cells through glycosylation-dependent interactions between MAC-1 and DC-SIGN. J Exp Med. 201:1281-1292</ref>.
*contributing to adhesion and rolling of DCs on primary human umbilical vein endothelial cells <ref>Geijtenbeek TB, Krooshoop DJ, Bleijs DA, van Vliet SJ, van Duijnhoven GC, Grabovsky V, Alon R, Figdor CG and van Kooyk Y. 2000. DC-SIGN-ICAM-2 interaction mediates dendritic cell trafficking. Nat Immunol. 1:353-357</ref><ref name="Garcia 2008"/>
*interactions of DC-SIGN with Lewis antigens on colorectal tumor cells impair the function and differentiation of dendritic cells <ref>Nonaka M, Ma BY, Murai R, Nakamura N, Baba M, Kawasaki N, Hodohara K, Asano S and Kawasaki T. 2008. Glycosylation-dependent interactions of C-type lectin DC-SIGN with colorectal tumor-associated Lewis glycans impair the function and differentiation of monocyte-derived dendritic cells. J Immunol. 180:3347-3356</ref>
*mediates bacterial adherence and phagocytosis <ref name="Zhang 2006"/>.
*viruses target DC-SIGN to promote infection and spread to cells <ref>Geijtenbeek TB, Kwon DS, Torensma R, van Vliet SJ, van Duijnhoven GC, Middel J, Cornelissen IL, Nottet HS, KewalRamani VN, Littman DR, Figdor CG and van Kooyk Y. 2000. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell. 100:587-597</ref><ref>Navarro-Sanchez E, Altmeyer R, Amara A, Schwartz O, Fieschi F, Virelizier JL, Arenzana-Seisdedos F and Despres P. 2003. Dendritic-cell-specific ICAM3-grabbing non-integrin is essential for the productive infection of human dendritic cells by mosquito-cell-derived dengue viruses. EMBO Rep. 4:723-728</ref><ref>references</ref><ref>Simmons G, Reeves JD, Grogan CC, Vandenberghe LH, Baribaud F, Whitbeck JC, Burke E, Buchmeier MJ, Soilleux EJ, Riley JL, Doms RW, Bates P and Pohlmann S. 2003. DC-SIGN and DC-SIGNR bind Ebola glycoproteins and enhance infection of macrophages and endothelial cells. Virology. 305:115-123</ref><ref>Hodges A, Sharrocks K, Edelmann M, Baban D, Moris A, Schwartz O, Drakesmith H, Davies K, Kessler B, McMichael A and Simmons A. 2007. Activation of the lectin DC-SIGN induces an immature dendritic cell phenotype triggering Rho-GTPase activity required for HIV-1 replication. Nat Immunol. 8:569-577</ref>
*activation of DC-SIGN by pathogens can contribute to T helper type 1 (Th)1 cell activity <ref name="Steeghs 2006"/><ref>van Stijn CM, Meyer S, van den Broek M, Bruijns SC, van Kooyk Y, Geyer R and van Die I. 2010. Schistosoma mansoni worm glycolipids induce an inflammatory phenotype in human dendritic cells by cooperation of TLR4 and DC-SIGN. Mol Immunol. 47:1544-1552</ref>
*some pathogens target DC-SIGN to suppress Th1 cell development <ref name="Bergman 2004"/><ref>Geijtenbeek TB, Van Vliet SJ, Koppel EA, Sanchez-Hernandez M, Vandenbroucke-Grauls CM, Appelmelk B and Van Kooyk Y. 2003. Mycobacteria target DC-SIGN to suppress dendritic cell function. J Exp Med. 197:7-17</ref>
* the murine DC-SIGN homologue SIGNR3 contributes to early host defense against Mycobacterium tuberculosis <ref>Tanne A, Ma B, Boudou F, Tailleux L, Botella H, Badell E, Levillain F, Taylor ME, Drickamer K, Nigou J, Dobos KM, Puzo G, Vestweber D, Wild MK, Marcinko M, Sobieszczuk P, Stewart L, Lebus D, Gicquel B, Neyrolles O. 2009. A murine DC-SIGN homologue contributes to early host defense against Mycobacterium tuberculosis. J Exp Med 206: 2205-2220</ref>
 
== 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=DC-SIGN&maxresults=20 CFG database search results for DC-SIGN].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

Knockout mice for three potential DC-SIGN orthologues ([https://www.functionalglycomics.org/static/consortium/resources/DataCoreFdc.shtml DC-SIGN], [https://www.functionalglycomics.org/static/consortium/resources/DataCoreFsr1.shtml SIGNR1], and [https://www.functionalglycomics.org/static/consortium/resources/DataCoreFsr3.shtml SIGNR3]) were created by the CFG and distributed to PIs, and their [http://www.functionalglycomics.org/glycomics/publicdata/phenotyping.jsp phenotypes] were analyzed.

=== Glycan array ===

Glycan array analysis and synthetic oligosaccharides were used to elucidate DC-SIGN glycan-binding specificity and analyze the mechanism of specific glycan binding.

== Related GBPs ==
Other dendritic cell lectins include langerin, DCIR, and DCAR. Paralogs on other cells include DC-SIGNR.

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Kurt Drickamer, Irma van Die, Yvette van Kooyk

Macrophage galactose lectin (MGL)

2010-06-15T11:51:03Z

Irma van Die:

Macrophage galactose binding lectin (MGL) is the best studied of the multiple C-type lectins on macrophages <ref name="Kawasaki 1986">Kawasaki T, Ii M, Kozutsumi Y and Yamashina I. 1986. Isolation and characterization of a receptor lectin specific for galactose/N-acetylgalactosamine from macrophages. Carbohydr Res. 151:197-206</ref><ref name="Suzuki 1996">Suzuki N, Yamamoto K, Toyoshima S, Osawa T and Irimura T. 1996. Molecular cloning and expression of cDNA encoding human macrophage C-type lectin. Its unique carbohydrate binding specificity for Tn antigen. J Immunol. 156:128-135</ref>. It is also representative of the subclass of C-type lectins that bind galactose-related sugars. MGL consists of one CRD domain and contains cytoplasmic internalization motifs for endocytosis. No signaling properties have been described yet for MGL. Human MGL (CD301) and rat MGL are encoded by a single gene, whereas mice contain two MGL copies, mMGL-1 and mMGL-2 that differ in carbohydrate specificity <ref name=Tsuiji 2002">Tsuiji M, Fujimori M, Ohashi Y, Higashi N, Onami TM, Hedrick SM and Irimura T. 2002. Molecular cloning and characterization of a novel mouse macrophage C-type lectin, mMGL2, which has a distinct carbohydrate specificity from mMGL1. J Biol Chem. 277:28892-28901</ref><ref name="Singh 2009">Singh SK, Streng-Ouwehand I, Litjens M, Weelij DR, Garca-Vallejo JJ, van Vliet SJ, Saeland E, van Kooyk Y. 2009. Characterization of murine MGL1 and MGL2 C-type lectins: distinct glycan specificities and tumor binding properties. Mol Immunol 46: 1240-1249</ref><ref name="Higashi 2002">Higashi N, Fujioka K, Denda-Nagai K, Hashimoto S, Nagai S, Sato T, Fujita Y, Morikawa A, Tsuiji M, Miyata-Takeuchi M, Sano Y, Suzuki N, Yamamoto K, Matsushima K and Irimura T. 2002. The macrophage C-type lectin specific for galactose/N-acetylgalactosamine is an endocytic receptor expressed on monocyte-derived immature dendritic cells. J Biol Chem. 277:20686-20693</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
In addition to creating the knockout for the two mouse forms of MGL, PIs have been involved in extensive studies of binding specificity and mechanism of ligand binding as well as the role of the receptor in macrophage signaling.
* PIs working on MGL include: Nicolai Bovin, Kurt Drickamer, Toshisuke Kawasaki, Cheng Liu, Yvette van Kooyk, Hui Wu
* Non-PIs with who have used CFG resources to study MGL include: Siamon Gordon, Alan Saltiel
* PIs working on MGL-related glycan-binding proteins (GBPs), particularly Mincle, include: Anthony dApice, Joshua Fierer, Rikard Holmdahl, Christopher O'Callaghan, Judy Teale, Christine Wells
* Non-PIs with who have used resources to study related members of this paradigm group include: Roland Lang, Ulrich Maus, Gunnar Nilsson, Kenneth Rock

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===
*mMGL1 binds Lewis X and Lewis A structures, whereas mMGL2 recognizes N-acetylgalactosamine (GalNAc) and galactose, including the O-linked Tn-antigen and TF-antigen <ref name=Tsuiji 2002"/><ref name="Singh 2009"/>
*hMGL binds terminal α- and β-linked GalNAc residues on glycoproteins, glycolipids and bacterial LPS, including Tn antigen and GalNAcβ1-4GlcNAc-R (LDN) antigens <ref name="Suzuki 1996"/><ref name="Van Vliet 2005">van Vliet SJ, van Liempt E, Saeland E, Aarnoudse CA, Appelmelk B, Irimura T, Geijtenbeek TB, Blixt O, Alvarez R, van Die I and van Kooyk Y. 2005. Carbohydrate profiling reveals a distinctive role for the C-type lectin MGL in the recognition of helminth parasites and tumor antigens by dendritic cells. Int Immunol. 17:661-669</ref><ref>van Sorge NM, Bleumink NM, van Vliet SJ, Saeland E, van der Pol WL, van Kooyk Y and van Putten JP. 2009. N-glycosylated proteins and distinct lipooligosaccharide glycoforms of Campylobacter jejuni target the human C-type lectin receptor MGL. Cell Microbiol. 11:1768-1781</ref><ref>Saeland E, van Vliet SJ, Backstrom M, van den Berg VC, Geijtenbeek TB, Meijer GA and van Kooyk Y. 2007. The C-type lectin mgl expressed by dendritic cells detects glycan changes on Muc1 in colon carcinoma. Cancer Immunol Immunother. 56:1225-1236</ref>
 
=== Cellular expression ===
MGL is expressed on DCs and macrophages <ref name="Higashi 2002"/><ref>van Vliet SJ, Gringhuis SI, Geijtenbeek TB and van Kooyk Y. 2006. Regulation of effector T cells by antigen-presenting cells via interaction of the C-type lectin MGL with CD45. Nat Immunol. 7:1200-1208</ref>
 

=== Structure ===

 
=== Biological roles of GBP-ligand interaction ===
*MGL is a highly efficient internalization receptor <ref name="Higashi 2002"/><ref>Valladeau J, Duvert-Frances V, Pin JJ, Kleijmeer MJ, Ait-Yahia S, Ravel O, Vincent C, Vega F, Jr., Helms A, Gorman D, Zurawski SM, Zurawski G, Ford J and Saeland S. 2001. Immature human dendritic cells express asialoglycoprotein receptor isoforms for efficient receptor-mediated endocytosis. J Immunol. 167:5767-5774</ref>
*hMGL regulates T-cell receptor mediated signaling and T-cell dependent cytokine responses <ref>van Vliet SJ, Gringhuis SI, Geijtenbeek TB and van Kooyk Y. 2006. Regulation of effector T cells by antigen-presenting cells via interaction of the C-type lectin MGL with CD45. Nat Immunol. 7:1200-1208</ref>
*mMGL1 promotes adipose tissue inflammation and insulin resistance <ref>Westcott DJ, Delproposto JB, Geletka LM, Wang T, Singer K, Saltiel AR, Lumeng CN. 2009. MGL1 promotes adipose tissue inflammation and insulin resistance by regulating 7/4hi monocytes in obesity. J Exp Med 206: 3143-56</ref>
*mMGL2 promotes enhances both MHC class II and class I presentation antigen in DC <ref>Singh SK, Streng-Ouwehand I, Litjens M, Kalay H, Saeland E, Van Kooyk Y. 2010. Tumour-associated glycan modifications of antigen enhance MGL2 dependent uptake and MHC class I restricted CD8 T cell responses. Int. J. Cancer, in press</ref>

 
== 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=MGL&maxresults=20 CFG database search results for MGL].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===
Knockouts for one of the mouse orthologs of MGL was distributed by the CFG and the [https://www.functionalglycomics.org/glycomics/publicdata/phenotyping.jsp phenotype] was analyzed.

=== Glycan array ===
The glycan-binding specificity of human and mouse versions of MGL have been analyzed by glycan array screening <ref name="Van Vliet 2005"/><ref name="Singh 2009"/>.

== Related GBPs ==
Other C-type lectins on macrophages include the mannose receptor, mincle <ref>Wells CA, Salvage-Jones JA, Li X, Hitchens K, Butcher S, Murray RZ, Beckhouse AG, Lo YL, Manzanero S, Cobbold C, Schroder K, Ma B, Orr S, Stewart L, Lebus D, Sobieszczuk P, Hume DA, Stow J, Blanchard H, Ashman RB. 2008. The macrophage-inducible C-type lectin, mincle, is an essential component of the innate immune response to Candida albicans. J Immunol 180: 7404-7413</ref>, macrophage C- type lectin (MCL), and dectin-1.

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Kurt Drickamer, Yvette van Kooyk

Macrophage galactose lectin (MGL)

2010-06-15T11:47:03Z

Irma van Die:

Macrophage galactose binding lectin (MGL) is the best studied of the multiple C-type lectins on macrophages <ref name="Kawasaki 1986">Kawasaki T, Ii M, Kozutsumi Y and Yamashina I. 1986. Isolation and characterization of a receptor lectin specific for galactose/N-acetylgalactosamine from macrophages. Carbohydr Res. 151:197-206</ref><ref name="Suzuki 1996">Suzuki N, Yamamoto K, Toyoshima S, Osawa T and Irimura T. 1996. Molecular cloning and expression of cDNA encoding human macrophage C-type lectin. Its unique carbohydrate binding specificity for Tn antigen. J Immunol. 156:128-135</ref>. It is also representative of the subclass of C-type lectins that bind galactose-related sugars. MGL consists of one CRD domain and contains cytoplasmic internalization motifs for endocytosis. No signaling properties have been described yet for MGL. Human MGL (CD301) and rat MGL are encoded by a single gene, whereas mice contain two MGL copies, mMGL-1 and mMGL-2 that differ in carbohydrate specificity <ref name=Tsuiji 2002">Tsuiji M, Fujimori M, Ohashi Y, Higashi N, Onami TM, Hedrick SM and Irimura T. 2002. Molecular cloning and characterization of a novel mouse macrophage C-type lectin, mMGL2, which has a distinct carbohydrate specificity from mMGL1. J Biol Chem. 277:28892-28901</ref><ref name="Singh 2009">Singh SK, Streng-Ouwehand I, Litjens M, Weelij DR, Garca-Vallejo JJ, van Vliet SJ, Saeland E, van Kooyk Y. 2009. Characterization of murine MGL1 and MGL2 C-type lectins: distinct glycan specificities and tumor binding properties. Mol Immunol 46: 1240-1249</ref><ref name="Higashi 2002">Higashi N, Fujioka K, Denda-Nagai K, Hashimoto S, Nagai S, Sato T, Fujita Y, Morikawa A, Tsuiji M, Miyata-Takeuchi M, Sano Y, Suzuki N, Yamamoto K, Matsushima K and Irimura T. 2002. The macrophage C-type lectin specific for galactose/N-acetylgalactosamine is an endocytic receptor expressed on monocyte-derived immature dendritic cells. J Biol Chem. 277:20686-20693</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
In addition to creating the knockout for the two mouse forms of MGL, PIs have been involved in extensive studies of binding specificity and mechanism of ligand binding as well as the role of the receptor in macrophage signaling.
* PIs working on MGL include: Nicolai Bovin, Kurt Drickamer, Toshisuke Kawasaki, Cheng Liu, Yvette van Kooyk, Hui Wu
* Non-PIs with who have used CFG resources to study MGL include: Siamon Gordon, Alan Saltiel
* PIs working on MGL-related glycan-binding proteins (GBPs), particularly Mincle, include: Anthony dApice, Joshua Fierer, Rikard Holmdahl, Christopher O'Callaghan, Judy Teale, Christine Wells
* Non-PIs with who have used resources to study related members of this paradigm group include: Roland Lang, Ulrich Maus, Gunnar Nilsson, Kenneth Rock

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===
*mMGL1 binds Lewis X and Lewis A structures, whereas mMGL2 recognizes N-acetylgalactosamine (GalNAc) and galactose, including the O-linked Tn-antigen and TF-antigen <ref name=Tsuiji 2002"/><ref name="Singh 2009"/>
*hMGL binds terminal α- and β-linked GalNAc residues on glycoproteins, glycolipids and bacterial LPS, including Tn antigen and GalNAcβ1-4GlcNAc-R (LDN) antigens <ref name="Suzuki 1996"/><ref name="Van Vliet 2005">van Vliet SJ, van Liempt E, Saeland E, Aarnoudse CA, Appelmelk B, Irimura T, Geijtenbeek TB, Blixt O, Alvarez R, van Die I and van Kooyk Y. 2005. Carbohydrate profiling reveals a distinctive role for the C-type lectin MGL in the recognition of helminth parasites and tumor antigens by dendritic cells. Int Immunol. 17:661-669</ref><ref>van Sorge NM, Bleumink NM, van Vliet SJ, Saeland E, van der Pol WL, van Kooyk Y and van Putten JP. 2009. N-glycosylated proteins and distinct lipooligosaccharide glycoforms of Campylobacter jejuni target the human C-type lectin receptor MGL. Cell Microbiol. 11:1768-1781</ref><ref>Saeland E, van Vliet SJ, Backstrom M, van den Berg VC, Geijtenbeek TB, Meijer GA and van Kooyk Y. 2007. The C-type lectin mgl expressed by dendritic cells detects glycan changes on Muc1 in colon carcinoma. Cancer Immunol Immunother. 56:1225-1236</ref>
 
=== Cellular expression ===
MGL is expressed on DCs and macrophages <ref name="Higashi 2002"/><ref>van Vliet SJ, Gringhuis SI, Geijtenbeek TB and van Kooyk Y. 2006. Regulation of effector T cells by antigen-presenting cells via interaction of the C-type lectin MGL with CD45. Nat Immunol. 7:1200-1208</ref>.
 
=== Structure ===

 
=== Biological roles of GBP-ligand interaction ===
*MGL is a highly efficient internalization receptor <ref name="Higashi 2002"/><ref>Valladeau J, Duvert-Frances V, Pin JJ, Kleijmeer MJ, Ait-Yahia S, Ravel O, Vincent C, Vega F, Jr., Helms A, Gorman D, Zurawski SM, Zurawski G, Ford J and Saeland S. 2001. Immature human dendritic cells express asialoglycoprotein receptor isoforms for efficient receptor-mediated endocytosis. J Immunol. 167:5767-5774</ref>
*hMGL regulates T-cell receptor mediated signaling and T-cell dependent cytokine responses <ref>van Vliet SJ, Gringhuis SI, Geijtenbeek TB and van Kooyk Y. 2006. Regulation of effector T cells by antigen-presenting cells via interaction of the C-type lectin MGL with CD45. Nat Immunol. 7:1200-1208</ref>
*mMGL1 promotes adipose tissue inflammation and insulin resistance <ref>Westcott DJ, Delproposto JB, Geletka LM, Wang T, Singer K, Saltiel AR, Lumeng CN. 2009. MGL1 promotes adipose tissue inflammation and insulin resistance by regulating 7/4hi monocytes in obesity. J Exp Med 206: 3143-56</ref>
*mMGL2 promotes enhances both MHC class II and class I presentation antigen in DC <ref>Singh SK, Streng-Ouwehand I, Litjens M, Kalay H, Saeland E, Van Kooyk Y. 2010. Tumour-associated glycan modifications of antigen enhance MGL2 dependent uptake and MHC class I restricted CD8 T cell responses. Int. J. Cancer, in press</ref>

 
== 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=MGL&maxresults=20 CFG database search results for MGL].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===
Knockouts for one of the mouse orthologs of MGL was distributed by the CFG and the [https://www.functionalglycomics.org/glycomics/publicdata/phenotyping.jsp phenotype] was analyzed.

=== Glycan array ===
The glycan-binding specificity of human and mouse versions of MGL have been analyzed by glycan array screening <ref name="Van Vliet 2005"/><ref name="Singh 2009"/>.

== Related GBPs ==
Other C-type lectins on macrophages include the mannose receptor, mincle <ref>Wells CA, Salvage-Jones JA, Li X, Hitchens K, Butcher S, Murray RZ, Beckhouse AG, Lo YL, Manzanero S, Cobbold C, Schroder K, Ma B, Orr S, Stewart L, Lebus D, Sobieszczuk P, Hume DA, Stow J, Blanchard H, Ashman RB. 2008. The macrophage-inducible C-type lectin, mincle, is an essential component of the innate immune response to Candida albicans. J Immunol 180: 7404-7413</ref>, macrophage C- type lectin (MCL), and dectin-1.

== References ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Kurt Drickamer, Yvette van Kooyk

Macrophage galactose lectin (MGL)

2010-06-15T11:39:54Z

Irma van Die:

Macrophage galactose binding lectin (MGL) is the best studied of the multiple C-type lectins on macrophages <ref name="Kawasaki 1986">Kawasaki T, Ii M, Kozutsumi Y and Yamashina I. 1986. Isolation and characterization of a receptor lectin specific for galactose/N-acetylgalactosamine from macrophages. Carbohydr Res. 151:197-206</ref><ref>Suzuki N, Yamamoto K, Toyoshima S, Osawa T and Irimura T. 1996. Molecular cloning and expression of cDNA encoding human macrophage C-type lectin. Its unique carbohydrate binding specificity for Tn antigen. J Immunol. 156:128-135</ref>. It is also representative of the subclass of C-type lectins that bind galactose-related sugars. MGL consists of one CRD domain and contains cytoplasmic internalization motifs for endocytosis. No signaling properties have been described yet for MGL. Human MGL (CD301) and rat MGL are encoded by a single gene, whereas mice contain two MGL copies, mMGL-1 and mMGL-2 that differ in carbohydrate specificity <ref name=Tsuiji 2002">Tsuiji M, Fujimori M, Ohashi Y, Higashi N, Onami TM, Hedrick SM and Irimura T. 2002. Molecular cloning and characterization of a novel mouse macrophage C-type lectin, mMGL2, which has a distinct carbohydrate specificity from mMGL1. J Biol Chem. 277:28892-28901</ref><ref name="Singh 2009">Singh SK, Streng-Ouwehand I, Litjens M, Weelij DR, Garca-Vallejo JJ, van Vliet SJ, Saeland E, van Kooyk Y. 2009. Characterization of murine MGL1 and MGL2 C-type lectins: distinct glycan specificities and tumor binding properties. Mol Immunol 46: 1240-1249</ref><ref name="Higashi 2002">Higashi N, Fujioka K, Denda-Nagai K, Hashimoto S, Nagai S, Sato T, Fujita Y, Morikawa A, Tsuiji M, Miyata-Takeuchi M, Sano Y, Suzuki N, Yamamoto K, Matsushima K and Irimura T. 2002. The macrophage C-type lectin specific for galactose/N-acetylgalactosamine is an endocytic receptor expressed on monocyte-derived immature dendritic cells. J Biol Chem. 277:20686-20693</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
In addition to creating the knockout for the two mouse forms of MGL, PIs have been involved in extensive studies of binding specificity and mechanism of ligand binding as well as the role of the receptor in macrophage signaling.
* PIs working on MGL include: Nicolai Bovin, Kurt Drickamer, Toshisuke Kawasaki, Cheng Liu, Yvette van Kooyk, Hui Wu
* Non-PIs with who have used CFG resources to study MGL include: Siamon Gordon, Alan Saltiel
* PIs working on MGL-related glycan-binding proteins (GBPs), particularly Mincle, include: Anthony dApice, Joshua Fierer, Rikard Holmdahl, Christopher O'Callaghan, Judy Teale, Christine Wells
* Non-PIs with who have used resources to study related members of this paradigm group include: Roland Lang, Ulrich Maus, Gunnar Nilsson, Kenneth Rock

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===
*mMGL1 binds Lewis X and Lewis A structures, whereas mMGL2 recognizes N-acetylgalactosamine (GalNAc) and galactose, including the O-linked Tn-antigen and TF-antigen <ref name=Tsuiji 2002"/><ref name="Singh 2009"/>
*hMGL binds terminal α- and β-linked GalNAc residues on glycoproteins, glycolipids and bacterial LPS, including Tn antigen and GalNAcβ1-4GlcNAc-R (LDN) antigens <ref name="Van Vliet 2005">van Vliet SJ, van Liempt E, Saeland E, Aarnoudse CA, Appelmelk B, Irimura T, Geijtenbeek TB, Blixt O, Alvarez R, van Die I and van Kooyk Y. 2005. Carbohydrate profiling reveals a distinctive role for the C-type lectin MGL in the recognition of helminth parasites and tumor antigens by dendritic cells. Int Immunol. 17:661-669</ref><ref>van Sorge NM, Bleumink NM, van Vliet SJ, Saeland E, van der Pol WL, van Kooyk Y and van Putten JP. 2009. N-glycosylated proteins and distinct lipooligosaccharide glycoforms of Campylobacter jejuni target the human C-type lectin receptor MGL. Cell Microbiol. 11:1768-1781</ref><ref>Saeland E, van Vliet SJ, Backstrom M, van den Berg VC, Geijtenbeek TB, Meijer GA and van Kooyk Y. 2007. The C-type lectin mgl expressed by dendritic cells detects glycan changes on Muc1 in colon carcinoma. Cancer Immunol Immunother. 56:1225-1236</ref>
 
=== Cellular expression ===
MGL is expressed on DCs and macrophages <ref name="Higashi 2002"/><ref>van Vliet SJ, Gringhuis SI, Geijtenbeek TB and van Kooyk Y. 2006. Regulation of effector T cells by antigen-presenting cells via interaction of the C-type lectin MGL with CD45. Nat Immunol. 7:1200-1208</ref>.
 
=== Structure ===

 
=== Biological roles of GBP-ligand interaction ===
*MGL is a highly efficient internalization receptor <ref name="Higashi 2002"/><ref>Valladeau J, Duvert-Frances V, Pin JJ, Kleijmeer MJ, Ait-Yahia S, Ravel O, Vincent C, Vega F, Jr., Helms A, Gorman D, Zurawski SM, Zurawski G, Ford J and Saeland S. 2001. Immature human dendritic cells express asialoglycoprotein receptor isoforms for efficient receptor-mediated endocytosis. J Immunol. 167:5767-5774</ref>
*hMGL regulates T-cell receptor mediated signaling and T-cell dependent cytokine responses <ref>van Vliet SJ, Gringhuis SI, Geijtenbeek TB and van Kooyk Y. 2006. Regulation of effector T cells by antigen-presenting cells via interaction of the C-type lectin MGL with CD45. Nat Immunol. 7:1200-1208</ref>
*mMGL1 promotes adipose tissue inflammation and insulin resistance <ref>Westcott DJ, Delproposto JB, Geletka LM, Wang T, Singer K, Saltiel AR, Lumeng CN. 2009. MGL1 promotes adipose tissue inflammation and insulin resistance by regulating 7/4hi monocytes in obesity. J Exp Med 206: 3143-56</ref>
*mMGL2 promotes enhances both MHC class II and class I presentation antigen in DC <ref>Singh SK, Streng-Ouwehand I, Litjens M, Kalay H, Saeland E, Van Kooyk Y. 2010. Tumour-associated glycan modifications of antigen enhance MGL2 dependent uptake and MHC class I restricted CD8 T cell responses. Int. J. Cancer, in press</ref>

 
== 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=MGL&maxresults=20 CFG database search results for MGL].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===
Knockouts for one of the mouse orthologs of MGL was distributed by the CFG and the [https://www.functionalglycomics.org/glycomics/publicdata/phenotyping.jsp phenotype] was analyzed.

=== Glycan array ===
The glycan-binding specificity of human and mouse versions of MGL have been analyzed by glycan array screening.

== Related GBPs ==
Other C-type lectins on macrophages include the mannose receptor, mincle, macrophage C- type lectin (MCL), and dectin-1.

== References ==
<references/>
* Singh SK, Streng-Ouwehand I, Litjens M, Weelij DR, Garca-Vallejo JJ, van Vliet SJ, Saeland E, van Kooyk Y (2009) Characterization of murine MGL1 and MGL2 C-type lectins: distinct glycan specificities and tumor binding properties. Mol Immunol 46, 1240-1249.
* Westcott DJ, Delproposto JB, Geletka LM, Wang T, Singer K, Saltiel AR, Lumeng CN (2009) MGL1 promotes adipose tissue inflammation and insulin resistance by regulating 7/4hi monocytes in obesity. J Exp Med 206, 3143-56.
* van Vliet SJ, van Liempt E, Saeland E, Aarnoudse CA, Appelmelk B, Irimura T, Geijtenbeek TBH, Blixt O, Alvarez R, van Die I, van Kooyk Y (2005) Carbohydrate profiling reveals a distinctive role for the C-type lectin MGL in the recognition of helminth parasites and tumor antigens by dendritic cells. Int Immunol 17, 661-669.
* Wells CA, Salvage-Jones JA, Li X, Hitchens K, Butcher S, Murray RZ, Beckhouse AG, Lo YL, Manzanero S, Cobbold C, Schroder K, Ma B, Orr S, Stewart L, Lebus D, Sobieszczuk P, Hume DA, Stow J, Blanchard H, Ashman RB (2008) The macrophage-inducible C-type lectin, mincle, is an essential component of the innate immune response to Candida albicans. J Immunol 180, 7404-7413.

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Kurt Drickamer, Yvette van Kooyk

Macrophage galactose lectin (MGL)

2010-06-15T11:21:54Z

Irma van Die:

Macrophage galactose binding lectin (MGL) is the best studied of the multiple C-type lectins on macrophages <ref name="Kawasaki 1986">Kawasaki T, Ii M, Kozutsumi Y and Yamashina I. 1986. Isolation and characterization of a receptor lectin specific for galactose/N-acetylgalactosamine from macrophages. Carbohydr Res. 151:197-206</ref><ref>Suzuki N, Yamamoto K, Toyoshima S, Osawa T and Irimura T. 1996. Molecular cloning and expression of cDNA encoding human macrophage C-type lectin. Its unique carbohydrate binding specificity for Tn antigen. J Immunol. 156:128-135</ref>. It is also representative of the subclass of C-type lectins that bind galactose-related sugars. MGL consists of one CRD domain and contains cytoplasmic internalization motifs for endocytosis. No signaling properties have been described yet for MGL. Human MGL (CD301) and rat MGL are encoded by a single gene, whereas mice contain two MGL copies, mMGL-1 and mMGL-2 that differ in carbohydrate specificity <ref name=Tsuiji 2002">Tsuiji M, Fujimori M, Ohashi Y, Higashi N, Onami TM, Hedrick SM and Irimura T. 2002. Molecular cloning and characterization of a novel mouse macrophage C-type lectin, mMGL2, which has a distinct carbohydrate specificity from mMGL1. J Biol Chem. 277:28892-28901</ref><ref name="Singh 2009">Singh SK, Streng-Ouwehand I, Litjens M, Weelij DR, Garca-Vallejo JJ, van Vliet SJ, Saeland E, van Kooyk Y. 2009. Characterization of murine MGL1 and MGL2 C-type lectins: distinct glycan specificities and tumor binding properties. Mol Immunol 46: 1240-1249</ref><ref name="Higashi 2002">Higashi N, Fujioka K, Denda-Nagai K, Hashimoto S, Nagai S, Sato T, Fujita Y, Morikawa A, Tsuiji M, Miyata-Takeuchi M, Sano Y, Suzuki N, Yamamoto K, Matsushima K and Irimura T. 2002. The macrophage C-type lectin specific for galactose/N-acetylgalactosamine is an endocytic receptor expressed on monocyte-derived immature dendritic cells. J Biol Chem. 277:20686-20693</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==
In addition to creating the knockout for the two mouse forms of MGL, PIs have been involved in extensive studies of binding specificity and mechanism of ligand binding as well as the role of the receptor in macrophage signaling.
* PIs working on MGL include: Nicolai Bovin, Kurt Drickamer, Toshisuke Kawasaki, Cheng Liu, Yvette van Kooyk, Hui Wu
* Non-PIs with who have used CFG resources to study MGL include: Siamon Gordon, Alan Saltiel
* PIs working on MGL-related glycan-binding proteins (GBPs), particularly Mincle, include: Anthony dApice, Joshua Fierer, Rikard Holmdahl, Christopher O'Callaghan, Judy Teale, Christine Wells
* Non-PIs with who have used resources to study related members of this paradigm group include: Roland Lang, Ulrich Maus, Gunnar Nilsson, Kenneth Rock

== Progress toward understanding this GBP paradigm ==

=== Carbohydrate ligands ===
*mMGL1 binds Lewis X and Lewis A structures, whereas mMGL2 recognizes N-acetylgalactosamine (GalNAc) and galactose, including the O-linked Tn-antigen and TF-antigen <ref name=Tsuiji 2002"/><ref name="Singh 2009"/>
*hMGL binds terminal α- and β-linked GalNAc residues on glycoproteins, glycolipids and bacterial LPS, including Tn antigen and GalNAcβ1-4GlcNAc-R (LDN) antigens <ref name="Van Vliet 2005">van Vliet SJ, van Liempt E, Saeland E, Aarnoudse CA, Appelmelk B, Irimura T, Geijtenbeek TB, Blixt O, Alvarez R, van Die I and van Kooyk Y. 2005. Carbohydrate profiling reveals a distinctive role for the C-type lectin MGL in the recognition of helminth parasites and tumor antigens by dendritic cells. Int Immunol. 17:661-669</ref><ref>van Sorge NM, Bleumink NM, van Vliet SJ, Saeland E, van der Pol WL, van Kooyk Y and van Putten JP. 2009. N-glycosylated proteins and distinct lipooligosaccharide glycoforms of Campylobacter jejuni target the human C-type lectin receptor MGL. Cell Microbiol. 11:1768-1781</ref><ref>Saeland E, van Vliet SJ, Backstrom M, van den Berg VC, Geijtenbeek TB, Meijer GA and van Kooyk Y. 2007. The C-type lectin mgl expressed by dendritic cells detects glycan changes on Muc1 in colon carcinoma. Cancer Immunol Immunother. 56:1225-1236</ref>
 
=== Cellular expression ===
MGL is expressed on DCs and macrophages <ref name="Higashi 2002"/><ref>van Vliet SJ, Gringhuis SI, Geijtenbeek TB and van Kooyk Y. 2006. Regulation of effector T cells by antigen-presenting cells via interaction of the C-type lectin MGL with CD45. Nat Immunol. 7:1200-1208</ref>.
 
=== 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=MGL&maxresults=20 CFG database search results for MGL].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===
Knockouts for one of the mouse orthologs of MGL was distributed by the CFG and the [https://www.functionalglycomics.org/glycomics/publicdata/phenotyping.jsp phenotype] was analyzed.

=== Glycan array ===
The glycan-binding specificity of human and mouse versions of MGL have been analyzed by glycan array screening.

== Related GBPs ==
Other C-type lectins on macrophages include the mannose receptor, mincle, macrophage C- type lectin (MCL), and dectin-1.

== References ==
<references/>
* Singh SK, Streng-Ouwehand I, Litjens M, Weelij DR, Garca-Vallejo JJ, van Vliet SJ, Saeland E, van Kooyk Y (2009) Characterization of murine MGL1 and MGL2 C-type lectins: distinct glycan specificities and tumor binding properties. Mol Immunol 46, 1240-1249.
* Westcott DJ, Delproposto JB, Geletka LM, Wang T, Singer K, Saltiel AR, Lumeng CN (2009) MGL1 promotes adipose tissue inflammation and insulin resistance by regulating 7/4hi monocytes in obesity. J Exp Med 206, 3143-56.
* van Vliet SJ, van Liempt E, Saeland E, Aarnoudse CA, Appelmelk B, Irimura T, Geijtenbeek TBH, Blixt O, Alvarez R, van Die I, van Kooyk Y (2005) Carbohydrate profiling reveals a distinctive role for the C-type lectin MGL in the recognition of helminth parasites and tumor antigens by dendritic cells. Int Immunol 17, 661-669.
* Wells CA, Salvage-Jones JA, Li X, Hitchens K, Butcher S, Murray RZ, Beckhouse AG, Lo YL, Manzanero S, Cobbold C, Schroder K, Ma B, Orr S, Stewart L, Lebus D, Sobieszczuk P, Hume DA, Stow J, Blanchard H, Ashman RB (2008) The macrophage-inducible C-type lectin, mincle, is an essential component of the innate immune response to Candida albicans. J Immunol 180, 7404-7413.

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Kurt Drickamer, Yvette van Kooyk

Macrophage galactose lectin (MGL)

2010-06-15T10:58:09Z

Irma van Die:

DC-SIGN

2010-06-13T08:31:02Z

Irma van Die:

DC-SIGN

2010-06-12T17:34:24Z

Irma van Die:

'''DC-SIGN''' 
Dendritic cell-specific intracellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin (DC-SIGN, CD209) is a C-type lectin that plays roles in both cell-cell and host-pathogen interactions, and thus serves as a model for both processes. This glycan-binding protein (GBP) paradigm also serves as a model for other members of the C-type lectin family expressed on dendritic cells. 
DC-SIGN is a type II membrane protein with a short aminoterminal cytoplasmic tail, a neck region and a single carboxyl terminal carbohydrate recognition domain (CRD)<ref>Geijtenbeek TB, Torensma R, van Vliet SJ, van Duijnhoven GC, Adema GJ, van Kooyk Y and Figdor CG. 2000. Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell. 100:575-585</ref>. The primary structure of the CRD contains conserved residues consistent with classical mannose-specific CRDs <ref>Feinberg H, Mitchell DA, Drickamer K and Weis WI. 2001. Structural basis for selective recognition of oligosaccharides by DC-SIGN and DC-SIGNR. Science. 294:2163-2166</ref>. Multivalent binding of glycan ligands by DC-SIGN is dependent on correct organization and presentation of the CRDs at the neck domains, which are crucial for tetramerization of DC-SIGN <ref>Yu QD, Oldring AP, Powlesland AS, Tso CK, Yang C, Drickamer K and Taylor ME. 2009. Autonomous tetramerization domains in the glycan-binding receptors DC-SIGN and DC-SIGNR. J Mol Biol. 387:1075-1080</ref>. The cytoplasmic tail of DC-SIGN contains internalization motives involved in the ligand-induced internalization of DC-SIGN <ref>Engering A, Geijtenbeek TB, van Vliet SJ, Wijers M, van Liempt E, Demaurex N, Lanzavecchia A, Fransen J, Figdor CG, Piguet V and van Kooyk Y. 2002. The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells. J Immunol. 168:2118-2126</ref>, and can activate signaling pathways <ref>Caparros E, Munoz P, Sierra-Filardi E, Serrano-Gomez D, Puig-Kroger A, Rodriguez-Fernandez JL, Mellado M, Sancho J, Zubiaur M and Corbi AL. 2006. DC-SIGN ligation on dendritic cells results in ERK and PI3k activation and modulates cytokine production. Blood. 107:3950-3958</ref><ref>Gringhuis SI, den Dunnen J, Litjens M, van Het Hof B, van Kooyk Y and Geijtenbeek TB. 2007. C-type lectin DC-SIGN modulates toll-like receptor signaling via raf-1 kinase-dependent acetylation of transcription factor NF-kb. Immunity. 26:605-616</ref><ref>Gringhuis SI, den Dunnen J, Litjens M, van der Vlist M and Geijtenbeek TB. 2009. Carbohydrate-specific signaling through the DC-SIGN signalosome tailors immunity to Mycobacterium tuberculosis, HIV-1 and Helicobacter pylori. Nat Immunol. 10:1081-1088</ref>.

== CFG Participating Investigators contributing to the understanding of this paradigm ==

Many investigators, both CFG Participating Investigators (PIs) and non-PIs using CFG resources, have led extensive studies on DC-SIGN, particularly regarding structure-function relationships, interactions with pathogens, and signaling functions in dendritic cells.
* PIs working on DC-SIGN include: Pedro Bonay, Angel Corbi, Kurt Drickamer, Juan Garcia-Vallejo, Donald Harn, Kayo Inaba, Benhur Lee, Olivier Neyrolles, Irma van Die, Yvette van Kooyk, William Weis, Martin Wild
* Non-PIs who have used CFG resources to study DC-SIGN include: Brigitte Gicquel, Arne Skerra, Ralph Steinman

== 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=DC-SIGN&maxresults=20 CFG database search results for DC-SIGN].

=== Glycan profiling ===

 
=== Glycogene microarray ===

 
=== Knockout mouse lines ===

Knockout mice for three potential DC-SIGN orthologues ([https://www.functionalglycomics.org/static/consortium/resources/DataCoreFdc.shtml DC-SIGN], [https://www.functionalglycomics.org/static/consortium/resources/DataCoreFsr1.shtml SIGNR1], and [https://www.functionalglycomics.org/static/consortium/resources/DataCoreFsr3.shtml SIGNR3]) were created by the CFG and distributed to PIs, and their [http://www.functionalglycomics.org/glycomics/publicdata/phenotyping.jsp phenotypes] were analyzed.

=== Glycan array ===

Glycan array analysis and synthetic oligosaccharides were used to elucidate DC-SIGN glycan-binding specificity and analyze the mechanism of specific glycan binding.

== Related GBPs ==
Other dendritic cell lectins include langerin, DCIR, and DCAR. Paralogs on other cells include DC-SIGNR.

== References ==
<references/>
* Tanne A, Ma B, Boudou F, Tailleux L, Botella H, Badell E, Levillain F, Taylor ME, Drickamer K, Nigou J, Dobos KM, Puzo G, Vestweber D, Wild MK, Marcinko M, Sobieszczuk P, Stewart L, Lebus D, Gicquel B, Neyrolles O (2009) A murine DC-SIGN homologue contributes to early host defense against Mycobacterium tuberculosis. J Exp Med 206, 2205-2220.
* Powlesland AS, Ward EM, Sadhu SK, Guo Y, Taylor ME, Drickamer K (2006) Novel mouse homologs of human DC-SIGN: Widely divergent biochemical properties of the complete set of mouse DC-SIGN-related proteins. J Biol Chem 281, 20440-20449.
* Van Liempt E, Bank CM, Mehta P, Garci A-Vallejo JJ, Kawar ZS, Geyer R, Alvarez RA, Cummings RD, van Kooyk Y, van Die I (2006) Specificity of DC-SIGN for mannose- and fucose-containing glycans. FEBS Lett 580, 6123-6131.
* Guo Y, Feinberg H, Conroy E, Mitchell DA, Alvarez R, Blixt O, Taylor ME, Weis WI, Drickamer K (2004) Structural basis for distinct ligand-binding and targeting properties of the receptors DC-SIGN and DC-SIGNR. Nat Struct Mol Biol 11, 591-598.

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Kurt Drickamer, Irma van Die, Yvette van Kooyk