ID NKG2D_RAT Reviewed; 215 AA. AC O70215; DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1998, sequence version 1. DT 24-JAN-2024, entry version 141. 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=NK lectin-like receptor; DE Short=NKLLR; DE AltName: Full=NKG2-D-activating NK receptor; DE AltName: Full=NKR-P2; DE AltName: CD_antigen=CD314; GN Name=Klrk1; Synonyms=Nkg2d, Nkrp2; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC STRAIN=Fischer 344; TISSUE=Natural killer cell; RX PubMed=9620593; DOI=10.1093/intimm/10.4.379; RA Berg S.F., Dissen E., Westgaard I.H., Fossum S.; RT "Molecular characterization of rat NKR-P2, a lectin-like receptor expressed RT by NK cells and resting T cells."; RL Int. Immunol. 10:379-385(1998). RN [2] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=15048723; DOI=10.1002/eji.200324793; RA Alli R., Savithri B., Das S., Varalakshmi C., Rangaraj N., Khar A.; RT "Involvement of NKR-P2/NKG2D in DC-mediated killing of tumor targets: RT indicative of a common, innate, target-recognition paradigm?"; RL Eur. J. Immunol. 34:1119-1126(2004). 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. CC {ECO:0000269|PubMed:15048723}. 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. Can form disulfide-bonded heterodimer with CD94 CC (By similarity). Interacts with CEACAM1; recruits PTPN6 that CC dephosphorylates VAV1 (By similarity). {ECO:0000250, CC ECO:0000250|UniProtKB:P26718}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type II CC membrane protein {ECO:0000250}. Note=Colocalized with HCST on the cell CC surface. {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Expressed by natural killer cells and by resting CC thoracic duct CD4+ and CD8+ T-cells, but not by thymocytes or other CC hemopoietic cells. Expressed by DC cells. {ECO:0000269|PubMed:15048723, CC ECO:0000269|PubMed:9620593}. CC -!- MISCELLANEOUS: Is not capable of signal transduction by itself, but CC operates through the adapter protein HCST. {ECO:0000250}. 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; AF009511; AAC40092.1; -; mRNA. DR RefSeq; NP_598196.1; NM_133512.2. DR RefSeq; XP_006237139.1; XM_006237077.3. DR AlphaFoldDB; O70215; -. DR SMR; O70215; -. DR STRING; 10116.ENSRNOP00000071035; -. DR GlyCosmos; O70215; 3 sites, No reported glycans. DR GlyGen; O70215; 3 sites. DR PhosphoSitePlus; O70215; -. DR PaxDb; 10116-ENSRNOP00000012886; -. DR GeneID; 24934; -. DR KEGG; rno:24934; -. DR UCSC; RGD:3180; rat. DR AGR; RGD:3180; -. DR CTD; 22914; -. DR RGD; 3180; Klrk1. DR VEuPathDB; HostDB:ENSRNOG00000061739; -. DR eggNOG; KOG4297; Eukaryota. DR HOGENOM; CLU_049894_9_1_1; -. DR InParanoid; O70215; -. DR OrthoDB; 4893801at2759; -. DR PhylomeDB; O70215; -. DR TreeFam; TF336674; -. DR Reactome; R-RNO-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell. DR Reactome; R-RNO-2424491; DAP12 signaling. DR PRO; PR:O70215; -. DR Proteomes; UP000002494; Chromosome 4. DR Bgee; ENSRNOG00000061739; Expressed in spleen and 15 other cell types or tissues. DR ExpressionAtlas; O70215; baseline and differential. DR Genevisible; O70215; RN. DR GO; GO:0009986; C:cell surface; IDA:RGD. DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD. DR GO; GO:0005886; C:plasma membrane; ISO:RGD. DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; ISO:RGD. DR GO; GO:0019900; F:kinase binding; ISO:RGD. DR GO; GO:0042288; F:MHC class I protein binding; ISO:RGD. DR GO; GO:0032394; F:MHC class Ib receptor activity; ISO:RGD. DR GO; GO:0038023; F:signaling receptor activity; ISO:RGD. 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; ISO:RGD. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISO:RGD. DR GO; GO:0030101; P:natural killer cell activation; ISO:RGD. DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; ISO:RGD. DR GO; GO:2000502; P:negative regulation of natural killer cell chemotaxis; ISO:RGD. DR GO; GO:0006809; P:nitric oxide biosynthetic process; ISO:RGD. DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD. DR GO; GO:0030887; P:positive regulation of myeloid dendritic cell activation; IDA:RGD. DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; ISS:UniProtKB. DR GO; GO:0002860; P:positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target; IMP:RGD. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISO:RGD. DR GO; GO:0032729; P:positive regulation of type II interferon production; ISO:RGD. DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; ISO:RGD. DR CDD; cd03593; CLECT_NK_receptors_like; 1. DR Gene3D; 3.10.100.10; Mannose-Binding Protein A, subunit A; 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; NKG2-D TYPE II INTEGRAL MEMBRANE PROTEIN; 1. DR PANTHER; PTHR47494:SF1; NKG2-D TYPE II INTEGRAL MEMBRANE PROTEIN; 1. DR Pfam; PF00059; Lectin_C; 1. DR SMART; SM00034; CLECT; 1. DR SUPFAM; SSF56436; C-type lectin-like; 1. DR PROSITE; PS50041; C_TYPE_LECTIN_2; 1. PE 2: Evidence at transcript level; KW Adaptive immunity; Cell membrane; Differentiation; Disulfide bond; KW Glycoprotein; Immunity; Innate immunity; Lectin; Membrane; Receptor; KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix. FT CHAIN 1..215 FT /note="NKG2-D type II integral membrane protein" FT /id="PRO_0000046670" FT TOPO_DOM 1..51 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 52..74 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255" FT TOPO_DOM 75..215 FT /note="Extracellular" FT /evidence="ECO:0000255" FT DOMAIN 105..211 FT /note="C-type lectin" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040" FT REGION 14..35 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 120 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 130 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 162 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 95..104 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040" FT DISULFID 98..109 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040" FT DISULFID 126..210 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040" FT DISULFID 188..202 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040" SQ SEQUENCE 215 AA; 24438 MW; B49C0364613031AF CRC64; MSKCHNYDLK PAKWDTSQEH QKQRSALPTS RPGENGIIRR RSSIEELKIS PLFVVRVLVA AMTIRFTVIT LTWLAVFITL LCNKEVSVSS REGYCGPCPN DWICHRNNCY QFFNENKAWN QSQASCLSQN SSLLKIYSKE EQDFLKLVKS YHWMGLVQSP ANGSWQWEDG SSLSPNELTL VKTPSGTCAV YGSSFKAYTE DCSNPNTYIC MKRAV //