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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)[1]. The primary structure of the CRD contains conserved residues consistent with classical mannose-specific CRDs [2]. 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 [3]. The cytoplasmic tail of DC-SIGN contains internalization motives involved in the ligand-induced internalization of DC-SIGN [4], and can activate signaling pathways [5][6][7].


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


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 CFG database search results for DC-SIGN.

Glycan profiling

Glycogene microarray

Knockout mouse lines

Knockout mice for three potential DC-SIGN orthologues (DC-SIGN, SIGNR1, and SIGNR3) were created by the CFG and distributed to PIs, and their 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.


  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  • 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.


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

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