Natural killer cell receptor-like, C-type lectin-like domain (IPR033992)

Short name: NKR-like_CTLD

Overlapping homologous superfamilies

Domain relationships

  • C-type lectin-like (IPR001304)
    • Natural killer cell receptor-like, C-type lectin-like domain (IPR033992)


This entry represents a C-type lectin-like domain (CTLD) of the type found in natural killer cell receptors (NKRs), including proteins similar to oxidized low density lipoprotein (OxLDL) receptor (LOX-1), CD94, CD69, NKG2-A and -D, osteoclast inhibitory lectin (OCIL), dendritic cell-associated C-type lectin-1 (dectin-1), human myeloid inhibitory C-type lectin-like receptor (MICL), mast cell-associated functional antigen (MAFA), killer cell lectin-like receptors: subfamily F, member 1 (KLRF1) and subfamily B, member 1 (KLRB1), and lys49 receptors. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins [PMID: 16336259].

NKRs are variously associated with activation or inhibition of natural killer (NK) cells. Activating NKRs stimulate cytolysis by NK cells of virally infected or transformed cells; inhibitory NKRs block cytolysis upon recognition of markers of healthy self cells. Most Lys49 receptors are inhibitory; some are stimulatory. OCIL inhibits NK cell function via binding to the receptor NKRP1D. Murine OCIL in addition to inhibiting NK cell function inhibits osteoclast differentiation [PMID: 15123656]. MAFA clusters with the type I Fc epsilon receptor (FcepsilonRI) and inhibits the mast cells secretory response to FcepsilonRI stimulus [PMID: 9765598, PMID: 12217400]. CD72 is a regulator of B cell receptor signaling [PMID: 11999169]. NKG2D is an activating receptor for stress-induced antigens; human NKG2D ligands include the stress induced MHC-I homologs, MICA, MICB, and ULBP family of glycoproteins. Several NKRs have a carbohydrate-binding capacity which is not mediated through calcium ions (e.g. OCIL binds a range of high molecular weight sulfated glycosaminoglycans including dextran sulfate, fucoidan, and gamma-carrageenan sugars) [PMID: 11323699]. Dectin-1 binds fungal beta-glucans and is involved in the innate immune responses to fungal pathogens [PMID: 11470510, PMID: 16341139]. MAFA binds saccharides having terminal alpha-D mannose residues in a calcium-dependent manner. LOX-1 is the major receptor for OxLDL in endothelial cells and thought to play a role in the pathology of atherosclerosis [PMID: 15695803, PMID: 27160316]. Some NKRs exist as homodimers (e.g.Lys49, NKG2D, CD69, LOX-1) and some as heterodimers (e.g. CD94/NKG2A). Dectin-1 can function as a monomer in vitro.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
  • cd03593 (CLECT_NK_receptors_like)