ID NKG2D_HUMAN Reviewed; 216 AA. AC P26718; A8K7K5; A8K7P4; Q9NR41; DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1992, sequence version 1. DT 01-MAY-2013, entry version 129. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). 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 RT encoding type II integral membrane proteins on human natural killer RT cells."; RL J. Exp. Med. 173:1017-1020(1991). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9683661; DOI=10.1007/s002510050420; RA Glienke J., Sobanov Y., Brostjan C., Steffens C., Nguyen C., RA Lehrach H., Hofer E., Francis F.; RT "The genomic organization of NKG2C, E, F, and D receptor genes in the RT human natural killer gene complex."; RL Immunogenetics 48:163-173(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Kothapalli R., Kusmartseva I., Loughran T.P. Jr.; RT "Identification and characterization of the NKG2D gene from large RT granular lymphocytic leukemia (LGL) cells."; RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT THR-72. RX PubMed=11751968; RA Shum B.P., Flodin L.R., Muir D.G., Rajalingam R., Khakoo S.I., RA Cleland S., Guethlein L.A., Uhrberg M., Parham P.; RT "Conservation and variation in human and common chimpanzee CD94 and RT NKG2 genes."; RL J. Immunol. 168:240-252(2002). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-72. 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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], AND VARIANT THR-72. 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., RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., RA 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., RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., RA 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., RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., RA Kucherlapati R., Weinstock G., 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], AND VARIANT THR-72. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] 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 [10] 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 RT innate and adaptive immunity."; RL Nat. Med. 12:207-213(2006). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 89-216 IN COMPLEX WITH MICA. 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., RA 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 [12] 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 RT NKG2D and its class I MHC-like ligand ULBP3."; RL Immunity 15:1039-1049(2001). RN [13] 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 RT the C-type lectin-like immunoreceptor NKG2D and MHC class I-like RT ligands."; RL Structure 11:411-422(2003). CC -!- FUNCTION: Receptor for MICA, MICB, ULBP1, ULBP2, ULBP3 CC (ULBP2>ULBP1>ULBP3) and ULBP4. Plays a role as a receptor for the CC recognition of MHC class I HLA-E molecules by NK cells and some CC cytotoxic T-cells. Involved in the immune surveillance exerted by CC T- and B-lymphocytes. CC -!- SUBUNIT: Homodimer. Interacts with DAP10. The interaction with CC DAP10 is required for NKG2D cell surface expression. CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane CC protein. 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: Natural killer cells. Expressed on essentially CC all CD56+CD3- NK cells from freshly isolated PBMC. Also detected CC in gamma-delta cells and CD8+ alpha-beta T-cells. Expressed in CC interferon-producing killer dendritic cells (IKDCs). CC -!- MISCELLANEOUS: Structurally distinct families of ligands for mouse CC and human NKG2D receptors have been characterized. They might be CC orthologs. CC -!- SIMILARITY: Contains 1 C-type lectin domain. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and 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 http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs 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 IPI; IPI00473104; -. DR PIR; PT0375; PT0375. DR RefSeq; NP_001186734.1; NM_001199805.1. DR RefSeq; NP_031386.2; NM_007360.3. DR UniGene; Hs.387787; -. 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 PDBsum; 1HYR; -. DR PDBsum; 1KCG; -. DR PDBsum; 1MPU; -. DR ProteinModelPortal; P26718; -. DR DIP; DIP-31100N; -. DR IntAct; P26718; 4. DR STRING; 9606.ENSP00000240618; -. DR PhosphoSite; P26718; -. DR DMDM; 128370; -. DR PaxDb; P26718; -. DR PRIDE; P26718; -. DR Ensembl; ENST00000240618; ENSP00000240618; ENSG00000213809. DR Ensembl; ENST00000540818; ENSP00000446003; ENSG00000213809. DR GeneID; 100528032; -. DR GeneID; 22914; -. DR KEGG; hsa:100528032; -. DR KEGG; hsa:22914; -. DR UCSC; uc001qyc.3; human. DR CTD; 100528032; -. DR CTD; 22914; -. DR GeneCards; GC12M010524; -. DR H-InvDB; HIX0020427; -. DR HGNC; HGNC:18788; KLRK1. DR HPA; CAB021896; -. DR MIM; 611817; gene. DR neXtProt; NX_P26718; -. DR PharmGKB; PA128394594; -. DR eggNOG; NOG315914; -. DR HOGENOM; HOG000220925; -. DR HOVERGEN; HBG052629; -. DR InParanoid; P26718; -. DR KO; K06728; -. DR Reactome; REACT_6900; Immune System. DR EvolutionaryTrace; P26718; -. DR NextBio; 43595; -. DR ArrayExpress; P26718; -. DR Bgee; P26718; -. DR CleanEx; HS_KLRK1; -. DR Genevestigator; P26718; -. DR GermOnline; ENSG00000183542; Homo sapiens. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0009897; C:external side of plasma membrane; IEA:Compara. DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc. DR GO; GO:0030246; F:carbohydrate binding; IEA:InterPro. DR GO; GO:0032394; F:MHC class Ib receptor activity; IEA:Compara. DR GO; GO:0004872; F:receptor activity; TAS:ProtInc. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Compara. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IEA:Compara. DR GO; GO:0030101; P:natural killer cell activation; TAS:BHF-UCL. DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IEA:Compara. DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; IEA:Compara. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IEA:Compara. DR GO; GO:0050776; P:regulation of immune response; TAS:Reactome. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; IEA:Compara. DR GO; GO:0031295; P:T cell costimulation; TAS:BHF-UCL. DR Gene3D; 3.10.100.10; -; 1. DR InterPro; IPR001304; C-type_lectin. DR InterPro; IPR016186; C-type_lectin-like. DR InterPro; IPR016187; C-type_lectin_fold. DR Pfam; PF00059; Lectin_C; 1. DR SMART; SM00034; CLECT; 1. DR SUPFAM; SSF56436; C-type_lectin_fold; 1. DR PROSITE; PS00615; C_TYPE_LECTIN_1; FALSE_NEG. DR PROSITE; PS50041; C_TYPE_LECTIN_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Complete proteome; Disulfide bond; KW Glycoprotein; Lectin; Membrane; Polymorphism; Receptor; KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix. FT CHAIN 1 216 NKG2-D type II integral membrane protein. FT /FTId=PRO_0000046665. FT TOPO_DOM 1 51 Cytoplasmic (Potential). FT TRANSMEM 52 72 Helical; Signal-anchor for type II FT membrane protein; (Potential). FT TOPO_DOM 73 216 Extracellular (Potential). FT DOMAIN 98 213 C-type lectin. FT CARBOHYD 131 131 N-linked (GlcNAc...) (Potential). FT CARBOHYD 163 163 N-linked (GlcNAc...) (Potential). FT CARBOHYD 202 202 N-linked (GlcNAc...) (Potential). FT DISULFID 96 105 FT DISULFID 99 110 FT DISULFID 127 211 FT DISULFID 189 203 FT VARIANT 72 72 A -> T (in allele NKG2-D*02; FT dbSNP:rs2255336). FT /FTId=VAR_013295. FT VARIANT 177 177 N -> S (in dbSNP:rs2306182). FT /FTId=VAR_030738. FT CONFLICT 186 186 K -> R (in Ref. 5; BAF84709). FT STRAND 96 99 FT STRAND 104 106 FT STRAND 110 118 FT HELIX 120 129 FT TURN 140 142 FT HELIX 144 148 FT STRAND 151 159 FT TURN 161 163 FT STRAND 166 168 FT STRAND 176 178 FT STRAND 180 182 FT STRAND 188 193 FT TURN 194 196 FT STRAND 197 201 FT STRAND 207 213 SQ SEQUENCE 216 AA; 25274 MW; C22F6BD533D7800E CRC64; MGWIRGRRSR HSWEMSEFHN YNLDLKKSDF STRWQKQRCP VVKSKCRENA SPFFFCCFIA VAMGIRFIIM VAIWSAVFLN SLFNQEVQIP LTESYCGPCP KNWICYKNNC YQFFDESKNW YESQASCMSQ NASLLKVYSK EDQDLLKLVK SYHWMGLVHI PTNGSWQWED GSILSPNLLT IIEMQKGDCA LYASSFKGYI ENCSTPNTYI CMQRTV //