InterPro domain: IPR016186

Lectins occur in plants, animals, bacteria and viruses. Initially described for their carbohydrate-binding activity [ 1 ], they are now recognised as a more diverse group of proteins, some of which are involved in protein-protein, protein-lipid or protein-nucleic acid interactions [ 2 ]. There are at least twelve structural families of lectins, of which C-type (Ca+-dependent) lectins is one. C-type lectins can be further divided into seven subgroups based on additional non-lectin domains and gene structure: (I) hyalectans, (II) asialoglycoprotein receptors, (III) collectins, (IV) selectins, (V) NK group transmembrane receptors, (VI) macrophage mannose receptors, and (VII) simple (single domain) lectins [ 3 ].

The term 'C-type lectin domain' was introduced to distinguish a carbohydrate-recognition domain (CRD) which is present in all Ca2+-dependent lectins, but not in other types of animal lectins. However, there are proteins with modules similar in overall structure to CRDs that serve functions other than sugar binding. Therefore, a more general term C-type lectin-like domain was introduced to refer to such domains, although both terms are sometimes used interchangeably [ 4 ].

This superfamily represents a structural domain found in C-type lectins, as well as in other proteins, including:

• The C-terminal domain of invasin [ 5 ] and intimin [ 6 ].
• Link domain, which includes the Link module of tumor necrosis factor-inducible gene 6 protein (TSG-6) [ 7 ] (a hyaladherin with important roles in inflammation and ovulation) and the hyaluronan binding domain of CD44 (which contains extra N-terminal beta-strand and C-terminal beta-hairpin) [ 8 ]. The Link domain may have emerged as a result of a deletion of the long loop region from an ancestral canonical C-type lectin domain [ 9 ].
• Endostatin [ 10 ] and the endostatin domain of collagen alpha 1 (XV) [ 11 ], these domains being decorated with many insertions in the common fold.

1. The structural basis for carbohydrate recognition by lectins. Adv. Exp. Med. Biol. 491, 1-16
2. Animal lectins: a historical introduction and overview. Biochim. Biophys. Acta 1572, 187-97
3. Divergent roles for C-type lectins expressed by cells of the innate immune system. Mol. Immunol. 41, 1109-21
4. The C-type lectin-like domain superfamily. FEBS J. 272, 6179-217
5. Crystal structure of invasin: a bacterial integrin-binding protein. Science 286, 291-5
6. Crystal structure of enteropathogenic Escherichia coli intimin-receptor complex. Nature 405, 1073-7
7. The link module from ovulation- and inflammation-associated protein TSG-6 changes conformation on hyaluronan binding. J. Biol. Chem. 278, 49261-70
8. Structure of the regulatory hyaluronan binding domain in the inflammatory leukocyte homing receptor CD44. Mol. Cell 13, 483-96
9. The protein fold of the hyaluronate-binding proteoglycan tandem repeat domain of link protein, aggrecan and CD44 is similar to that of the C-type lectin superfamily. FEBS Lett. 388, 211-6
10. Zinc-dependent dimers observed in crystals of human endostatin. Proc. Natl. Acad. Sci. U.S.A. 95, 10443-8
11. Endostatins derived from collagens XV and XVIII differ in structural and binding properties, tissue distribution and anti-angiogenic activity. J. Mol. Biol. 301, 1179-90