Intelectin

Xenopus embryonic epidermal lectin
Monomeric structure of XEEL-CRD with bound D-glycerol 1-phosphate. The protein is colored using a blue-red gradient from the N- to the C- terminus. Calcium ions are shown as green spheres and the coordinated water molecules are shown as red spheres.
Identifiers
Organism	Xenopus laevis
Symbol	itln1
Entrez	398574
HomoloGene	111044
PDB	4WN0
RefSeq (mRNA)	NM_001089101.1
RefSeq (Prot)	NP_001082570.1
UniProt	Q800K0

Human intelectin-1
Monomeric structure of human intelectin with bound allyl-beta-D-galactofuranose. The protein is colored using a blue-red gradient from the N- to the C- terminus. Calcium ions are shown as green spheres and the coordinated water molecules are shown as red spheres.
Identifiers
Symbol	ITLN1
Alt. symbols	hIntL-1
Entrez	55600
HUGO	18259
OMIM	609873
PDB	4WMY
RefSeq	NP_060095
UniProt	Q8WWA0
Other data
Locus	Chr. 1 q21.3

Intelectins are lectins (carbohydrate-binding proteins) expressed in humans and other chordates. Humans express two types of intelectins encoded by ITLN1 and ITLN2 genes respectively. Several intelectins bind microbe-specific carbohydrate residues. Therefore, intelectins have been proposed to function as immune lectins. Even though intelectins contain fibrinogen-like domain found in the ficolins family of immune lectins, there is significant structural divergence. Thus, intelectins may not function through the same lectin-complement pathway. Most intelectins are still poorly characterized and they may have diverse biological roles. Human intelectin-1 (hIntL-1) has also been shown to bind lactoferrin, but the functional consequence has yet to be elucidated. Additionally, hIntL-1 is a major component of asthmatic mucus and may be involved in insulin physiology as well.

The first intelectin was discovered in Xenopus laevis oocyte and is named XL35 or XCGL-1.X. laevis oocyte also contains a closely related XCGL-2. In addition, X. laevis embryos secrete Xenopus embryonic epidermal lectin into the environmental water, presumably to bind microbes. XSL-1 and XSL-2 are also expressed in X. laevis serum when stimulated with lipopolysaccharide. Two additional intestinal intelectins are disovered in X. laevis

Human has two intelectins: hIntL-1 (omentin) and hIntL-2. Mouse also has two intelectins: mIntL-1 and mIntL-2.

Several lines of evidence suggest that intelectins recognize microbes and may function as an innate immune defense protein. Tunicate intelectin is an opsonin for phagocytosis by hemocyte. Amphioxus intelectin has been shown to agglutinate bacteria. In zebrafish and rainbow trout, intelectin expression is stimulated upon microbial exposure. Mammals such as sheep and mice also upregulate intelectin expression upon parasitic infection. Increase in intelectin expression upon microbial exposure support the hypothesis that intelectins play a role in the immune system.

Although intelectins require calcium ion for function, the sequences bear no resemblance to C-type lectins. In addition, merely around 50 amino acids (the fibronogen-like domain) align with any known protein, specifically the ficolin family. The first structural details of an intelectin comes from the crystal structure of selenomethionine-labeled XEEL carbohydrate-recognition domain (Se-Met XEEL-CRD) solved by Se-SAD. XEEL-CRD was expressed and Se-Met-labeled in High Five insect cells using a recombinant baculovirus. The fibrinogen-like fold is conserved despite amino acid sequence divergence. However, extensive insertions are present in intelectin compared to ficolins, thus making intelectin a distinct lectin structural class. The Se-Met XEEL-CRD structure then enables the structure solution by molecular replacement of D-glycerol 1-phosphate (GroP)-bound XEEL-CRD, apo-human intelectin-1 (hIntL-1), and galactofuranose-bound hIntL-1.