KLRK1
Description
The KLRK1 (killer cell lectin like receptor K1) is a protein-coding gene located on chromosome 12.
NKG2D is an activating receptor (transmembrane protein) belonging to the NKG2 family of C-type lectin-like receptors. NKG2D is encoded by KLRK1 (killer cell lectin like receptor K1) gene which is located in the NK-gene complex (NKC) situated on chromosome 6 in mice and chromosome 12 in humans. In mice, it is expressed by NK cells, NK1.1+ T cells, γδ T cells, activated CD8+ αβ T cells and activated macrophages. In humans, it is expressed by NK cells, γδ T cells and CD8+ αβ T cells. NKG2D recognizes induced-self proteins from MIC and RAET1/ULBP families which appear on the surface of stressed, malignant transformed, and infected cells.
== Structure == Human NKG2D receptor complex assembles into a hexameric structure. NKG2D itself forms a homodimer whose ectodomains serve for ligand binding. Each NKG2D monomer is associated with DAP10 dimer. This association is maintained by ionic interaction of a positively charged arginine present in a transmembrane segment of NKG2D and negatively charged aspartic acids within both transmembrane regions of DAP10 dimer. DAP10 functions as an adaptor protein and transduces the signal after the ligand binding by recruiting the p85 subunit of PI3K and Grb2-Vav1 complex which are responsible for subsequent downstream events.
The KLRK1 gene encodes the NKG2D protein, which acts as an activating and costimulatory receptor in immunosurveillance. Upon binding to various stress-inducible ligands on tumor cells and virus-infected cells, NKG2D triggers innate immune responses in activated NK cells, resulting in cytotoxicity. It also serves as a costimulatory receptor for TCR in CD8(+) T-cell mediated adaptive immunity, amplifying T-cell activation. This receptor promotes perforin-mediated elimination of ligand-expressing tumor cells. NKG2D signaling involves calcium influx, leading to TNF-alpha expression. It plays a role in NK cell-mediated bone marrow graft rejection and may regulate NK cell differentiation and survival. NKG2D binds to ligands from various MHC class I-related glycoprotein subfamilies, including MICA, MICB, RAET1E, RAET1G, RAET1L/ULBP6, ULBP1, ULBP2, ULBP3 (ULBP2>ULBP1>ULBP3), and ULBP4.
KLRK1 is also known as CD314, D12S2489E, KLR, NKG2-D, NKG2D.
