Killer cell lectin-like receptor subfamily K member 1, NK cell receptor D, NKG2-D-activating NK receptor, CD314, D12S2489E, KLR, DNA Segment On Chromosome 12 (Unique) 2489 Expressed Sequence, Killer Cell Lectin Like Receptor K1, NKG2-D, Killer Cell Lectin-Like Receptor Subfamily K, Member 1, KLRK1, CD314 Antigen


NKG2-D type II integral membrane protein is a transmembrane protein belonging to the NKG2 family of C-type lectin-like receptors.NKG2D is encoded by KLRK1 gene which is located in the NK-gene complex (NKC) situated on chromosome 6 in mice and chromosome 12 in humans.Functions as an activating and costimulatory receptor involved in immunosurveillance upon binding to various cellular stress-inducible ligands displayed at the surface of autologous tumor cells and virus-infected cells. Provides both stimulatory and costimulatory innate immune responses on activated killer (NK) cells, leading to cytotoxic activity. Acts as a costimulatory receptor for T-cell receptor (TCR) in CD8 T-cell-mediated adaptive immune responses by amplifying T-cell activation. Stimulates perforin-mediated elimination of ligand-expressing tumor cells. Signaling involves calcium influx, culminating in the expression of TNF-alpha. Participates in NK cell-mediated bone marrow graft rejection. May play a regulatory role in differentiation and survival of NK cells. Binds to ligands belonging to various subfamilies of MHC class I-related glycoproteins including MICA, MICB, RAET1E, RAET1G, RAET1L/ULBP6, ULBP1, ULBP2, ULBP3 (ULBP2>ULBP1>ULBP3) and ULBP4.

Drug Information

Drugs in clinical trials: 3
Latest Research Phase: Phase 2 Clinical

Drug Name





Clinical Trials


IPH-2301, IPH-23XX, JNJ-4500, JNJ-64304500, NNC-0142-002, NNC-0142-0002, NNC-0142-0000-0002, NN-8555

Phase 2 Clinical


Alopecia Areata, Arthritis, Rheumatoid, Celiac Disease, Inflammation, Crohn Disease


GSK-2862277, 2862277

Phase 2 Clinical

Glaxosmithkline Plc

Respiration Disorders, Respiratory Distress Syndrome, Adult, Acute Lung Injury



Phase 1 Clinical

Eli Lilly And Company

Chronic Urticaria, Dermatitis, Atopic



Phase 1 Clinical

Heat Biologics

Solid tumours, Neoplasms

NKG2D CAR-T Cell therapy (Yake Biotechnology)

Phase 1 Clinical

Shanghai YaKe Biotechnology Co Ltd

Leukemia, Myeloid, Acute


MK-6105, ASLAN-004, CSL-334

Phase 1 Clinical

Csl Ltd, Merck Sharp & Dohme Corp

Dermatitis, Atopic, Hypersensitivity

NKG2D CAR-T cell therapy (Uwell Biopharma)



Uwell Biopharma





Pelican Therapeutics Inc

Rejection of organ transplantation




Neoplasms, Inflammation, Autoimmune Diseases of the Nervous System





The genomic organization of NKG2C, E, F, and D receptor genes in the human natural killer gene complex

Glienke J., Sobanov Y., Brostjan C., Steffens C., Nguyen C., Lehrach H., Hofer E., Francis F.,

Immunogenetics 48:163-173(1998)

Conservation and variation in human and common chimpanzee CD94 and NKG2 genes

Shum B.P., Flodin L.R., Muir D.G., Rajalingam R., Khakoo S.I., Cleland S., Guethlein L.A., Uhrberg M., Parham P.,

J. Immunol. 168:240-252(2002)

Complete sequencing and characterization of 21,243 full-length human cDNAs

Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., Sugano S.,

Nat. Genet. 36:40-45(2004)

The finished DNA sequence of human chromosome 12

Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Gibbs R.A.,

Nature 440:346-351(2006)

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)

The MGC Project Team,

Genome Res. 14:2121-2127(2004)

An activating immunoreceptor complex formed by NKG2D and DAP10

Wu J., Song Y., Bakker A.B.H., Bauer S., Spies T., Lanier L.L., Phillips J.H.,

Science 285:730-732(1999)

DAP10 and DAP12 form distinct, but functionally cooperative, receptor complexes in natural killer cells

Wu J., Cherwinski H., Spies T., Phillips J.H., Lanier L.L.,

J. Exp. Med. 192:1059-1068(2000)

Costimulation of CD8alphabeta T cells by NKG2D via engagement by MIC induced on virus-infected cells

Groh V., Rhinehart R., Randolph-Habecker J., Topp M.S., Riddell S.R., Spies T.,

Nat. Immunol. 2:255-260(2001)

UL16-binding proteins, novel MHC class I-related proteins, bind to NKG2D and activate multiple signaling pathways in primary NK cells

Sutherland C.L., Chalupny N.J., Schooley K., VandenBos T., Kubin M., Cosman D.,

J. Immunol. 168:671-679(2002)

Lymphocyte activation via NKG2D: towards a new paradigm in immune recognition?

Vivier E., Tomasello E., Paul P.,

Curr. Opin. Immunol. 14:306-311(2002)