NKG2D_HUMAN
ID NKG2D_HUMAN Reviewed; 216 AA.
AC P26718; A8K7K5; A8K7P4; Q9NR41;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 2.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=NKG2-D type II integral membrane protein;
DE AltName: Full=Killer cell lectin-like receptor subfamily K member 1;
DE AltName: Full=NK cell receptor D;
DE AltName: Full=NKG2-D-activating NK receptor;
DE AltName: CD_antigen=CD314;
GN Name=KLRK1; Synonyms=D12S2489E, NKG2D;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALA-72.
RX PubMed=2007850; DOI=10.1084/jem.173.4.1017;
RA Houchins J.P., Yabe T., McSherry C., Bach F.H.;
RT "DNA sequence analysis of NKG2, a family of related cDNA clones encoding
RT type II integral membrane proteins on human natural killer cells.";
RL J. Exp. Med. 173:1017-1020(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-72.
RX PubMed=9683661; DOI=10.1007/s002510050420;
RA Glienke J., Sobanov Y., Brostjan C., Steffens C., Nguyen C., Lehrach H.,
RA Hofer E., Francis F.;
RT "The genomic organization of NKG2C, E, F, and D receptor genes in the human
RT natural killer gene complex.";
RL Immunogenetics 48:163-173(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALA-72.
RA Kothapalli R., Kusmartseva I., Loughran T.P. Jr.;
RT "Identification and characterization of the NKG2D gene from large granular
RT lymphocytic leukemia (LGL) cells.";
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALA-72.
RX PubMed=11751968; DOI=10.4049/jimmunol.168.1.240;
RA Shum B.P., Flodin L.R., Muir D.G., Rajalingam R., Khakoo S.I., Cleland S.,
RA Guethlein L.A., Uhrberg M., Parham P.;
RT "Conservation and variation in human and common chimpanzee CD94 and NKG2
RT genes.";
RL J. Immunol. 168:240-252(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spleen, and Stomach;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ALA-72.
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP FUNCTION IN CYTOTOXICITY ACTIVATION, INTERACTION WITH HCST, AND SUBCELLULAR
RP LOCATION.
RX PubMed=10426994; DOI=10.1126/science.285.5428.730;
RA Wu J., Song Y., Bakker A.B.H., Bauer S., Spies T., Lanier L.L.,
RA Phillips J.H.;
RT "An activating immunoreceptor complex formed by NKG2D and DAP10.";
RL Science 285:730-732(1999).
RN [10]
RP INTERACTION WITH HCST, AND SUBCELLULAR LOCATION.
RX PubMed=11015446; DOI=10.1084/jem.192.7.1059;
RA Wu J., Cherwinski H., Spies T., Phillips J.H., Lanier L.L.;
RT "DAP10 and DAP12 form distinct, but functionally cooperative, receptor
RT complexes in natural killer cells.";
RL J. Exp. Med. 192:1059-1068(2000).
RN [11]
RP FUNCTION IN CYTOTOXICITY ACTIVATION AND VIRAL INFECTION, AND FUNCTION AS A
RP RECEPTOR FOR MICA.
RX PubMed=11224526; DOI=10.1038/85321;
RA Groh V., Rhinehart R., Randolph-Habecker J., Topp M.S., Riddell S.R.,
RA Spies T.;
RT "Costimulation of CD8alphabeta T cells by NKG2D via engagement by MIC
RT induced on virus-infected cells.";
RL Nat. Immunol. 2:255-260(2001).
RN [12]
RP FUNCTION AS A RECEPTOR FOR MICA; MICB; ULBP1; ULBP2, ULBP3, AND INDUCTION.
RX PubMed=11777960; DOI=10.4049/jimmunol.168.2.671;
RA Sutherland C.L., Chalupny N.J., Schooley K., VandenBos T., Kubin M.,
RA Cosman D.;
RT "UL16-binding proteins, novel MHC class I-related proteins, bind to NKG2D
RT and activate multiple signaling pathways in primary NK cells.";
RL J. Immunol. 168:671-679(2002).
RN [13]
RP REVIEW, AND ALTERNATIVE SPLICING.
RX PubMed=11973127; DOI=10.1016/s0952-7915(02)00337-0;
RA Vivier E., Tomasello E., Paul P.;
RT "Lymphocyte activation via NKG2D: towards a new paradigm in immune
RT recognition?";
RL Curr. Opin. Immunol. 14:306-311(2002).
RN [14]
RP FUNCTION IN CYTOTOXICITY ACTIVATION, AND FUNCTION AS A RECEPTOR FOR RAET1E;
RP RAET1G AND ULBP2.
RX PubMed=15240696; DOI=10.4049/jimmunol.173.2.1078;
RA Bacon L., Eagle R.A., Meyer M., Easom N., Young N.T., Trowsdale J.;
RT "Two human ULBP/RAET1 molecules with transmembrane regions are ligands for
RT NKG2D.";
RL J. Immunol. 173:1078-1084(2004).
RN [15]
RP INTERACTION WITH HCST, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15294961; DOI=10.4049/jimmunol.173.4.2470;
RA Rosen D.B., Araki M., Hamerman J.A., Chen T., Yamamura T., Lanier L.L.;
RT "A Structural basis for the association of DAP12 with mouse, but not human,
RT NKG2D.";
RL J. Immunol. 173:2470-2478(2004).
RN [16]
RP SUBUNIT, AND MUTAGENESIS OF ARG-66.
RX PubMed=15894612; DOI=10.1073/pnas.0502439102;
RA Garrity D., Call M.E., Feng J., Wucherpfennig K.W.;
RT "The activating NKG2D receptor assembles in the membrane with two signaling
RT dimers into a hexameric structure.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:7641-7646(2005).
RN [17]
RP TISSUE SPECIFICITY.
RX PubMed=16444266; DOI=10.1038/nm1352;
RA Chan C.W., Crafton E., Fan H.-N., Flook J., Yoshimura K., Skarica M.,
RA Brockstedt D., Dubensky T.W., Stins M.F., Lanier L.L., Pardoll D.M.,
RA Housseau F.;
RT "Interferon-producing killer dendritic cells provide a link between innate
RT and adaptive immunity.";
RL Nat. Med. 12:207-213(2006).
RN [18]
RP INTERACTION WITH RAET1L.
RX PubMed=19658097; DOI=10.1002/eji.200939502;
RA Eagle R.A., Traherne J.A., Hair J.R., Jafferji I., Trowsdale J.;
RT "ULBP6/RAET1L is an additional human NKG2D ligand.";
RL Eur. J. Immunol. 39:3207-3216(2009).
RN [19]
RP REVIEW, AND FUNCTION.
RX PubMed=21898152; DOI=10.1007/s00018-011-0797-0;
RA Zafirova B., Wensveen F.M., Gulin M., Polic B.;
RT "Regulation of immune cell function and differentiation by the NKG2D
RT receptor.";
RL Cell. Mol. Life Sci. 68:3519-3529(2011).
RN [20]
RP REVIEW, AND FUNCTION AS A RECEPTOR FOR MHC CLASS I-RELATED GLYCOPROTEINS.
RX PubMed=23298206; DOI=10.1146/annurev-immunol-032712-095951;
RA Raulet D.H., Gasser S., Gowen B.G., Deng W., Jung H.;
RT "Regulation of ligands for the NKG2D activating receptor.";
RL Annu. Rev. Immunol. 31:413-441(2013).
RN [21]
RP INTERACTION WITH CEACAM1.
RX PubMed=23696226; DOI=10.1002/eji.201242676;
RA Hosomi S., Chen Z., Baker K., Chen L., Huang Y.H., Olszak T., Zeissig S.,
RA Wang J.H., Mandelboim O., Beauchemin N., Lanier L.L., Blumberg R.S.;
RT "CEACAM1 on activated NK cells inhibits NKG2D-mediated cytolytic function
RT and signaling.";
RL Eur. J. Immunol. 43:2473-2483(2013).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 89-216 IN COMPLEX WITH MICA, AND
RP TISSUE SPECIFICITY.
RX PubMed=10426993; DOI=10.1126/science.285.5428.727;
RA Bauer S., Groh V., Wu J., Steinle A., Phillips J.H., Lanier L.L., Spies T.;
RT "Activation of NK cells and T cells by NKG2D, a receptor for stress-
RT inducible MICA.";
RL Science 285:727-729(1999).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 93-216 IN COMPLEX WITH ULBP3.
RX PubMed=11754823; DOI=10.1016/s1074-7613(01)00241-2;
RA Radaev S., Rostro B., Brooks A.G., Colonna M., Sun P.D.;
RT "Conformational plasticity revealed by the cocrystal structure of NKG2D and
RT its class I MHC-like ligand ULBP3.";
RL Immunity 15:1039-1049(2001).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 88-215.
RX PubMed=12679019; DOI=10.1016/s0969-2126(03)00047-9;
RA McFarland B.J., Kortemme T., Yu S.F., Baker D., Strong R.K.;
RT "Symmetry recognizing asymmetry: analysis of the interactions between the
RT C-type lectin-like immunoreceptor NKG2D and MHC class I-like ligands.";
RL Structure 11:411-422(2003).
RN [25] {ECO:0007744|PDB:4S0U}
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 90-215 IN COMPLEX WITH RAET1L.
RX PubMed=28559451; DOI=10.1126/scisignal.aai8904;
RA Zuo J., Willcox C.R., Mohammed F., Davey M., Hunter S., Khan K., Antoun A.,
RA Katakia P., Croudace J., Inman C., Parry H., Briggs D., Malladi R.,
RA Willcox B.E., Moss P.;
RT "A disease-linked ULBP6 polymorphism inhibits NKG2D-mediated target cell
RT killing by enhancing the stability of NKG2D ligand binding.";
RL Sci. Signal. 10:0-0(2017).
CC -!- FUNCTION: Functions as an activating and costimulatory receptor
CC involved in immunosurveillance upon binding to various cellular stress-
CC inducible ligands displayed at the surface of autologous tumor cells
CC and virus-infected cells. Provides both stimulatory and costimulatory
CC innate immune responses on activated killer (NK) cells, leading to
CC cytotoxic activity. Acts as a costimulatory receptor for T-cell
CC receptor (TCR) in CD8(+) T-cell-mediated adaptive immune responses by
CC amplifying T-cell activation. Stimulates perforin-mediated elimination
CC of ligand-expressing tumor cells. Signaling involves calcium influx,
CC culminating in the expression of TNF-alpha. Participates in NK cell-
CC mediated bone marrow graft rejection. May play a regulatory role in
CC differentiation and survival of NK cells. Binds to ligands belonging to
CC various subfamilies of MHC class I-related glycoproteins including
CC MICA, MICB, RAET1E, RAET1G, RAET1L/ULBP6, ULBP1, ULBP2, ULBP3
CC (ULBP2>ULBP1>ULBP3) and ULBP4. {ECO:0000269|PubMed:10426994,
CC ECO:0000269|PubMed:11224526, ECO:0000269|PubMed:11777960,
CC ECO:0000269|PubMed:15240696, ECO:0000269|PubMed:19658097,
CC ECO:0000269|PubMed:21898152, ECO:0000269|PubMed:23298206,
CC ECO:0000269|PubMed:28559451}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Heterohexamer composed of two
CC subunits of KLRK1 and four subunits of HCST/DAP10. Interacts (via
CC transmembrane domain) with HCST/DAP10 (via transmembrane domain); the
CC interaction is required for KLRK1 NK cell surface and induces NK cell-
CC mediated cytotoxicity. Does not interact with TYROBP. Interacts with
CC CEACAM1; recruits PTPN6 that dephosphorylates VAV1 (PubMed:23696226).
CC {ECO:0000269|PubMed:10426993, ECO:0000269|PubMed:10426994,
CC ECO:0000269|PubMed:11015446, ECO:0000269|PubMed:11754823,
CC ECO:0000269|PubMed:15294961, ECO:0000269|PubMed:15894612,
CC ECO:0000269|PubMed:23696226}.
CC -!- INTERACTION:
CC P26718; Q29983: MICA; NbExp=2; IntAct=EBI-458344, EBI-1031130;
CC P26718; Q08493-2: PDE4C; NbExp=3; IntAct=EBI-458344, EBI-12169289;
CC P26718; Q8TD07: RAET1E; NbExp=4; IntAct=EBI-458344, EBI-16365677;
CC P26718; Q8TD07-1: RAET1E; NbExp=2; IntAct=EBI-458344, EBI-16747021;
CC P26718; Q8TD07-2: RAET1E; NbExp=2; IntAct=EBI-458344, EBI-16417277;
CC P26718; Q8TD07-5: RAET1E; NbExp=2; IntAct=EBI-458344, EBI-16747044;
CC P26718; Q8TD07-6: RAET1E; NbExp=2; IntAct=EBI-458344, EBI-16747033;
CC P26718; Q6H3X3: RAET1G; NbExp=6; IntAct=EBI-458344, EBI-458334;
CC P26718; Q5VY80: RAET1L; NbExp=4; IntAct=EBI-458344, EBI-16364752;
CC P26718; Q9BZM6: ULBP1; NbExp=2; IntAct=EBI-458344, EBI-16365037;
CC P26718; Q9BZM5: ULBP2; NbExp=6; IntAct=EBI-458344, EBI-3919993;
CC P26718; Q9BZM4: ULBP3; NbExp=4; IntAct=EBI-458344, EBI-1032551;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10426994,
CC ECO:0000269|PubMed:11015446, ECO:0000269|PubMed:15294961}; Single-pass
CC type II membrane protein {ECO:0000269|PubMed:10426994,
CC ECO:0000269|PubMed:11015446, ECO:0000269|PubMed:15294961}.
CC Note=Colocalized with HCST on the cell surface.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=1;
CC Comment=A number of isoforms are produced.;
CC Name=1;
CC IsoId=P26718-1; Sequence=Displayed;
CC -!- TISSUE SPECIFICITY: Expressed in natural killer (NK) cells, CD8(+)
CC alpha-beta and gamma-delta T-cells. Expressed on essentially all
CC CD56+CD3- NK cells from freshly isolated PBMC. Expressed in interferon-
CC producing killer dendritic cells (IKDCs). {ECO:0000269|PubMed:10426993,
CC ECO:0000269|PubMed:15294961, ECO:0000269|PubMed:16444266}.
CC -!- INDUCTION: Up-regulated by interleukin IL15 in primary NK cells.
CC {ECO:0000269|PubMed:11777960}.
CC -!- MISCELLANEOUS: Is not capable of signal transduction by itself, but
CC operates through the adapter protein HCST (PubMed:10426994 and
CC PubMed:15894612). Some families of ligands for human and mouse KLRK1
CC receptors have been characterized being very similar in structure and
CC highly likely to be orthologs. In humans, an additional distinct
CC subfamily of ligands (MICA and MICB) differs structurally, having an
CC extra MHC alpha 3-like domain (PubMed:23298206).
CC {ECO:0000305|PubMed:23298206}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/KLRK1ID41094ch12p13.html";
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC Note=NKG-2D;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Ctlect_246";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X54870; CAA38652.1; -; mRNA.
DR EMBL; AJ001687; CAA04925.1; -; Genomic_DNA.
DR EMBL; AJ001688; CAA04925.1; JOINED; Genomic_DNA.
DR EMBL; AJ001689; CAA04925.1; JOINED; Genomic_DNA.
DR EMBL; AF461811; AAL65233.1; -; mRNA.
DR EMBL; AF260135; AAF86973.1; -; mRNA.
DR EMBL; AF260136; AAF86974.1; -; mRNA.
DR EMBL; AK292059; BAF84748.1; -; mRNA.
DR EMBL; AK292020; BAF84709.1; -; mRNA.
DR EMBL; AC022075; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471094; EAW96178.1; -; Genomic_DNA.
DR EMBL; BC039836; AAH39836.1; -; mRNA.
DR CCDS; CCDS8623.1; -. [P26718-1]
DR PIR; PT0375; PT0375.
DR RefSeq; NP_001186734.1; NM_001199805.1.
DR RefSeq; NP_031386.2; NM_007360.3.
DR PDB; 1HYR; X-ray; 2.70 A; A/B=80-216.
DR PDB; 1KCG; X-ray; 2.60 A; A/B=93-216.
DR PDB; 1MPU; X-ray; 2.50 A; A=80-216.
DR PDB; 4PDC; X-ray; 1.99 A; A/B/C/D=93-215.
DR PDB; 4S0U; X-ray; 2.35 A; A/B=90-215.
DR PDBsum; 1HYR; -.
DR PDBsum; 1KCG; -.
DR PDBsum; 1MPU; -.
DR PDBsum; 4PDC; -.
DR PDBsum; 4S0U; -.
DR AlphaFoldDB; P26718; -.
DR SMR; P26718; -.
DR BioGRID; 116576; 39.
DR CORUM; P26718; -.
DR DIP; DIP-31100N; -.
DR IntAct; P26718; 9.
DR MINT; P26718; -.
DR STRING; 9606.ENSP00000240618; -.
DR TCDB; 1.C.111.1.13; the regiiiGama (regiiiGama) family.
DR GlyGen; P26718; 3 sites.
DR iPTMnet; P26718; -.
DR PhosphoSitePlus; P26718; -.
DR BioMuta; KLRK1; -.
DR DMDM; 128370; -.
DR MassIVE; P26718; -.
DR MaxQB; P26718; -.
DR PaxDb; P26718; -.
DR PeptideAtlas; P26718; -.
DR PRIDE; P26718; -.
DR ProteomicsDB; 54365; -. [P26718-1]
DR ABCD; P26718; 36 sequenced antibodies.
DR Antibodypedia; 23295; 687 antibodies from 36 providers.
DR DNASU; 22914; -.
DR Ensembl; ENST00000240618.11; ENSP00000240618.6; ENSG00000213809.9. [P26718-1]
DR Ensembl; ENST00000540818.5; ENSP00000446003.1; ENSG00000213809.9. [P26718-1]
DR GeneID; 100528032; -.
DR GeneID; 22914; -.
DR KEGG; hsa:100528032; -.
DR KEGG; hsa:22914; -.
DR MANE-Select; ENST00000240618.11; ENSP00000240618.6; NM_007360.4; NP_031386.2.
DR UCSC; uc009zhj.4; human. [P26718-1]
DR CTD; 100528032; -.
DR CTD; 22914; -.
DR DisGeNET; 100528032; -.
DR DisGeNET; 22914; -.
DR GeneCards; KLRK1; -.
DR HGNC; HGNC:18788; KLRK1.
DR HPA; ENSG00000213809; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 611817; gene.
DR neXtProt; NX_P26718; -.
DR OpenTargets; ENSG00000213809; -.
DR PharmGKB; PA128394594; -.
DR VEuPathDB; HostDB:ENSG00000213809; -.
DR eggNOG; KOG4297; Eukaryota.
DR GeneTree; ENSGT00940000154558; -.
DR HOGENOM; CLU_049894_9_1_1; -.
DR InParanoid; P26718; -.
DR OrthoDB; 1201127at2759; -.
DR PhylomeDB; P26718; -.
DR TreeFam; TF336674; -.
DR PathwayCommons; P26718; -.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR Reactome; R-HSA-2172127; DAP12 interactions.
DR Reactome; R-HSA-2424491; DAP12 signaling.
DR SignaLink; P26718; -.
DR SIGNOR; P26718; -.
DR BioGRID-ORCS; 100528032; 8 hits in 177 CRISPR screens.
DR BioGRID-ORCS; 22914; 7 hits in 1066 CRISPR screens.
DR EvolutionaryTrace; P26718; -.
DR GeneWiki; KLRK1; -.
DR Pharos; P26718; Tbio.
DR PRO; PR:P26718; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P26718; protein.
DR Bgee; ENSG00000213809; Expressed in granulocyte and 93 other tissues.
DR ExpressionAtlas; P26718; baseline and differential.
DR Genevisible; P26718; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0042288; F:MHC class I protein binding; IEA:Ensembl.
DR GO; GO:0032394; F:MHC class Ib receptor activity; IEA:Ensembl.
DR GO; GO:0038023; F:signaling receptor activity; IDA:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IEA:Ensembl.
DR GO; GO:0030101; P:natural killer cell activation; TAS:BHF-UCL.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IDA:UniProtKB.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IDA:CACAO.
DR GO; GO:2000502; P:negative regulation of natural killer cell chemotaxis; IDA:CACAO.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; IEA:Ensembl.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IEA:Ensembl.
DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; IDA:UniProtKB.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0031295; P:T cell costimulation; TAS:BHF-UCL.
DR CDD; cd03593; CLECT_NK_receptors_like; 1.
DR Gene3D; 3.10.100.10; -; 1.
DR InterPro; IPR001304; C-type_lectin-like.
DR InterPro; IPR016186; C-type_lectin-like/link_sf.
DR InterPro; IPR016187; CTDL_fold.
DR InterPro; IPR042169; NKG2D.
DR InterPro; IPR033992; NKR-like_CTLD.
DR PANTHER; PTHR47494; PTHR47494; 1.
DR Pfam; PF00059; Lectin_C; 1.
DR SMART; SM00034; CLECT; 1.
DR SUPFAM; SSF56436; SSF56436; 1.
DR PROSITE; PS50041; C_TYPE_LECTIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Cell membrane;
KW Differentiation; Disulfide bond; Glycoprotein; Immunity; Innate immunity;
KW Lectin; Membrane; Receptor; Reference proteome; Signal-anchor;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..216
FT /note="NKG2-D type II integral membrane protein"
FT /id="PRO_0000046665"
FT TOPO_DOM 1..51
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 52..72
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 73..216
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 98..213
FT /note="C-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT CARBOHYD 131
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 163
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 202
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 96..105
FT DISULFID 99..110
FT DISULFID 127..211
FT DISULFID 189..203
FT VARIANT 72
FT /note="T -> A (in dbSNP:rs2255336)"
FT /evidence="ECO:0000269|PubMed:11751968,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:2007850,
FT ECO:0000269|PubMed:9683661, ECO:0000269|Ref.3"
FT /id="VAR_013295"
FT VARIANT 177
FT /note="N -> S (in dbSNP:rs2306182)"
FT /id="VAR_030738"
FT MUTAGEN 66
FT /note="R->A: Inhibits association with the HCST signaling
FT dimer."
FT /evidence="ECO:0000269|PubMed:15894612"
FT CONFLICT 186
FT /note="K -> R (in Ref. 5; BAF84709)"
FT /evidence="ECO:0000305"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:4PDC"
FT STRAND 103..106
FT /evidence="ECO:0007829|PDB:4PDC"
FT STRAND 109..118
FT /evidence="ECO:0007829|PDB:4PDC"
FT HELIX 120..128
FT /evidence="ECO:0007829|PDB:4PDC"
FT TURN 129..131
FT /evidence="ECO:0007829|PDB:4PDC"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:4PDC"
FT TURN 140..143
FT /evidence="ECO:0007829|PDB:4PDC"
FT HELIX 144..148
FT /evidence="ECO:0007829|PDB:4PDC"
FT STRAND 153..159
FT /evidence="ECO:0007829|PDB:4PDC"
FT TURN 161..163
FT /evidence="ECO:0007829|PDB:4PDC"
FT STRAND 166..168
FT /evidence="ECO:0007829|PDB:4PDC"
FT STRAND 176..178
FT /evidence="ECO:0007829|PDB:4S0U"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:4PDC"
FT STRAND 185..193
FT /evidence="ECO:0007829|PDB:4PDC"
FT TURN 194..196
FT /evidence="ECO:0007829|PDB:4PDC"
FT STRAND 197..201
FT /evidence="ECO:0007829|PDB:4PDC"
FT STRAND 207..213
FT /evidence="ECO:0007829|PDB:4PDC"
SQ SEQUENCE 216 AA; 25304 MW; 387F85D483D79B0F CRC64;
MGWIRGRRSR HSWEMSEFHN YNLDLKKSDF STRWQKQRCP VVKSKCRENA SPFFFCCFIA
VAMGIRFIIM VTIWSAVFLN SLFNQEVQIP LTESYCGPCP KNWICYKNNC YQFFDESKNW
YESQASCMSQ NASLLKVYSK EDQDLLKLVK SYHWMGLVHI PTNGSWQWED GSILSPNLLT
IIEMQKGDCA LYASSFKGYI ENCSTPNTYI CMQRTV
