Chitinase-like lectins


Structure of murine Ym1 with modelled glucosamine

Beta-strands in the TIM domain are shown in light blue and those in the small insertion domain in yellow.  Glucosamine is shown in dark blue.  Protein Data Bank structure ID: 1E9L.
Structure of human YKL-40 with bound GlcNAc oligomer
Beta-strands are coloured as described above.  The GlcNAc oligomer is shown in dark blue.  Protein Data Bank structure ID: 1HJW.
Abbreviations and Synonyms
AMCase: acidic mammalian chitinase, CHIA, eosinophil chemotactic factor (human, erroneous designation), chitinase family protein 2, 3, YNL.
CHIT1: chitinase-1, chitotriosidase-1.
Ym1: Chitinase 3-like 3, eosinophil chemotactic cytokine, ECF-L.
Ym2: Chitinase 3-like 4
YKL-40: Chitinase 3-like 1, human cartilage glycoprotein 39, hcGP-39.
YKL-39: chitinase 3-like 2, chondrocyte protein 39.
CHID1: chitinase domain containing 1, stabilin-1 interacting chitinase-like protein, SI-CLP.
DIAC: di-N-acetylchitobiase, CTBS, CTB
OVGP: oviductin, oviduct-specific/oviductal glycoprotein, OGP, estrogen-dependent oviduct protein, EGP, mucin 9, CHIT5.
BCLP1/2: brain chitinase-like protein 1/2


The chitinase-like lectins are mammalian proteins which belong to the glycoside hydrolase family 18.  This is a family of soluble, intracellular or secreted proteins which have a triose-phosphate isomerase (TIM) barrel-like structure, sometimes with the insertion of a small alpha + beta domain.

Glycoside hydrolase family 18 proteins in mammals

Glycoside hydrolase family 18 includes chitinases and non-enzymatic chitinase-like proteins from viruses, bacteria, plants, fungi, protozoa and invertebrates as well as higher animals.  Chitinases cleave chitin, a polymer of N-acetylglucosamine (GlcNAc) that is a common structural molecule in fungi and invertebrates, and contain the conserved sequence motif DXXDXDXE, in which the glutamate is the catalytic residue.  Chitinase-like proteins are structurally homologous to chitinases but lack the essential catalytic residues.  Chitin is not found in vertebrates, but vertebrates do possess a small number of closely-related active chitinases.  In mammals these are represented primarily by acidic mammalian chitinase (AMCase) and chitotriosidase, both of which appear to have roles in the immune system.  Eukaryotes also possess di-N-acetylchitobiase, a lysosomal enzyme involved in the degradation of N-linked glycoproteins, which is distantly related to AMCase and chitotriosidase.  In mammals, but not other vertebrates, there are non-enzymatic chitinase-like proteins very similar to AMCase and chitotriosidase, such as YKL-40.  Preservation of the hydrophobic substrate binding cleft, and consequently of high affinity binding to chito-oligosaccharides, has been demonstrated in some of these proteins, which have been termed chitinase-like lectins or Chi-lectins.  Finally, stabilin-1 interacting chitinase-like protein (SI-CLP, CHID1) is a non-enzymatic protein of unknown function which is distantly related to other mammalian glycoside hydrolase family 18 proteins and is conserved in eukaryotes.

Potential mammalian chitinase-like lectins

YKL-40 (Human cartilage glycoprotein-39, chitinase 3-like protein 1) is a mammalian protein which in humans is expressed by a variety of cell types including synovial cells, chondrocytes and smooth muscle cells, and neutrophils and macrophages.  Expression appears to be induced by a change in the extracellular matrix environment, is thought to have a role in development, tissue remodelling and inflammation, and has been associated with diseases including arthritis, cancer and liver fibrosis.  YKL-40 binds specifically to collagen triple helices and regulates cleavage and fibril formation.  YKL-40 binds chitin and chito-oligosaccharides using 9 GlcNAc-binding subsites.  The short chito-oligosaccharides which prime hyaluronic acid synthesis and are retained at reducing ends of hyaluronic acid molecules in mammals are suggested carbohydrate ligands for YKL-40; hyaluronic acid is associated with similar processes to YKL-40.  Heparan sulphate, found on proteoglycans, is also a potential ligand and cell surface receptor for YKL-40.  YKL-39 is a protein of unknown function closely related to YKL-40 and present in humans and other primates.

Ym1 is a murine protein secreted in large quantities by peritoneal macrophages upon nematode infection and is a marker for alternatively activated macrophages, which exert anti-inflammatory effects and promote wound healing, as well as combating parasitic infections.  The function of Ym1 is not known, and there is conflicting evidence regarding both chitinase activity (weak or absent) and sugar-binding activity.  SPR studies suggested that Ym1 exhibits calcium-independent binding at low pH to glucosamine (GlcN) and galactosamine (GalN), and especially to oligomers of these sugars, including heparin, but not to the unsubstituted or N-acetylated sugar.  GlcN was modelled into a putative sugar binding site at the centre of the TIM barrel in the first crystal structure of Ym1 (above left), but a very high resolution structure of uncomplexed Ym1 suggests that the electron density of water molecules may have been mistaken for a monosaccharide.  Furthermore, crystals of Ym1 complexed with GlcN or GlcNAc polymers could not be obtained.  A lack of conservation in Ym1 of residues involved in ligand binding in YKL-40 support the conclusion that Ym1 does not bind chito-oligosaccharides.  Ym2 is a murine protein of unknown function closely related to Ym1. 

Oviductin is a mammalian protein secreted by oviductal epithelial cells and has a role in fertilization and early embryo development.  Uniquely among glycoside hydrolase family 18 proteins, it has an O-glycosylated mucin-like region following the chitinase-like domain.  Carbohydrate binding has yet to be investigated in oviductin. 

Potential chitinase-like lectins in non-mammals

Non-enzymatic chitinase-like proteins are found across a range of organisms.  Notable examples are the Drosophila melanogaster imaginal disc growth factor proteins, which stimulate cell proliferation in common with the mammalian chitinase-like protein YKL-40, but are only distantly related to mammalian glycoside hydrolase family 18 proteins, displaying around 25% sequence identity.  A chitinase-like protein from oyster, Clp1 (CAI96029) has recently been described which binds chitin and exhibits similar functional properties to YKL-40.  Clp1, along with paralogues Clp2 and Clp3, shares a relatively recent common ancestor with mammalian glycoside hydrolase family 18 members (with the exceptions of di-N-acetylchitobiase and CHID1) and has around 35% sequence identity to human chitotriosidase.


This page last updated:
Wednesday, 01 January 2014
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Contact information: This site is supported by:
Kurt Drickamer
Division of Molecular Biosciences
Faculty of Natural Sciences
Imperial College London