NKG2D

NKG2D

Target · Activating immune receptor

NKG2D Killer cell lectin like receptor K1 · NKG2-D type II integral membrane protein

NKG2D (killer cell lectin like receptor K1, KLRK1, CD314) is an activating and costimulatory receptor on natural killer cells and CD8+ T cells. It detects stress-inducible ligands on tumour cells and virus-infected cells and helps trigger their elimination. Browse Assay Genie's current range of NKG2D research reagents below, or read on for the biology behind the target.

Cell membrane receptorActivating NK cell receptorBinds MICA and ULBP ligands
216 aa
Protein length
~25 kDa
Molecular weight
12p13.2
Gene locus
C-type lectin
Receptor class
Target information

What is NKG2D (killer cell lectin like receptor K1)?

NKG2D functions as an activating and costimulatory receptor involved in immunosurveillance. It binds cellular stress-inducible ligands displayed at the surface of autologous tumour cells and virus-infected cells. On activated natural killer (NK) cells it provides both stimulatory and costimulatory innate immune signals that lead to cytotoxic activity, including perforin-mediated elimination of ligand-expressing tumour cells. Signalling involves calcium influx and culminates in the expression of TNF. On CD8+ T cells, NKG2D acts as a costimulatory receptor for the T-cell receptor (TCR), amplifying T-cell activation in adaptive immune responses. It also participates in NK cell-mediated bone marrow graft rejection and may play a regulatory role in the differentiation and survival of NK cells.

NKG2D recognises several subfamilies of MHC class I-related glycoproteins, including MICA, MICB, RAET1E, RAET1G, RAET1L/ULBP6, ULBP1, ULBP2, ULBP3 and ULBP4, with a reported preference order of ULBP2 over ULBP1 over ULBP3. Surface expression of these ligands marks stressed cells for recognition by the immune system, which is why the receptor and its ligands are considered therapeutic targets in immune diseases and cancers. The KLRK1 gene encodes a member of the NKG2 family, located within the NK complex, a region containing several C-type lectin genes preferentially expressed in NK cells. The encoded transmembrane protein has a type II membrane orientation and a C-type lectin domain. Read-through transcription exists between this gene and the upstream KLRC4 family member.

The gene was previously named killer cell lectin-like receptor subfamily K, member 1, and carries the aliases NKG2-D, KLR and D12S2489E, as well as the CD designation CD314. Orthologous Klrk1 genes are present in mouse and rat.

Tumour immunosurveillance

NKG2D detects stress-inducible ligands on autologous tumour cells and promotes perforin-mediated killing, making it central to studies of immune recognition of cancer.

NK cell biology

The receptor drives stimulatory responses and cytotoxicity in activated NK cells and may regulate their differentiation and survival.

T-cell costimulation

NKG2D amplifies TCR-driven activation of CD8+ T cells, offering a model for costimulatory signalling in adaptive immunity.

Antiviral and transplant immunology

Recognition of ligands on virus-infected cells and a role in NK-mediated bone marrow graft rejection link NKG2D to infection and transplantation research.

Background

NKG2D frequently asked questions

What does NKG2D do?

NKG2D is an activating and costimulatory receptor on NK cells and CD8+ T cells. It binds stress-inducible ligands on tumour and virus-infected cells, triggering cytotoxic activity, perforin-mediated killing and TNF expression, and amplifies TCR-driven T-cell activation.

What other names does NKG2D go by?

NKG2D is encoded by KLRK1, the HGNC symbol for killer cell lectin like receptor K1. Aliases include NKG2-D, KLR, CD314 and D12S2489E, and the UniProt name is NKG2-D type II integral membrane protein. Earlier gene naming used killer cell lectin-like receptor subfamily K, member 1.

Is NKG2D conserved across species and which ligands does it bind?

Mouse and rat both have an ortholog named Klrk1. Human NKG2D binds MICA, MICB, RAET1E, RAET1G, RAET1L/ULBP6 and ULBP1 to ULBP4. Check the datasheet of any product for its validated reactivity.

Explore

Related targets

NKG2D ligands, other NK cell lectin-like receptors and effector cytokines relevant to NK and T-cell activation.

Gene and protein annotations from HGNC, NCBI Gene and UniProt P26718; product specifications from Assay Genie datasheets.

NKG2D Product listing