ID KLRD1_MOUSE Reviewed; 179 AA. AC O54707; O54708; DT 07-JUL-2009, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1998, sequence version 1. DT 24-JAN-2024, entry version 152. DE RecName: Full=Natural killer cells antigen CD94; DE AltName: Full=Killer cell lectin-like receptor subfamily D member 1; DE AltName: CD_antigen=CD94; GN Name=Klrd1; Synonyms=Cd94; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLU-83. RC STRAIN=C57BL/6J, and CB.17 SCID; RX PubMed=9464811; DOI=10.1002/eji.1830271222; RA Vance R.E., Tanamachi D.M., Hanke T., Raulet D.H.; RT "Cloning of a mouse homolog of CD94 extends the family of C-type lectins on RT murine natural killer cells."; RL Eur. J. Immunol. 27:3236-3241(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=C57BL/6J; RX PubMed=9600963; DOI=10.1073/pnas.95.11.6320; RA Ho E.L., Heusel J.W., Brown M.G., Matsumoto K., Scalzo A.A., Yokoyama W.M.; RT "Murine Nkg2d and Cd94 are clustered within the natural killer complex and RT are expressed independently in natural killer cells."; RL Proc. Natl. Acad. Sci. U.S.A. 95:6320-6325(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=C57BL/6J; TISSUE=Mammary gland; RA Butcher S., Cottage A., Cook G.P.; RT "Mouse natural killer cell receptors homologous to human CD94 and NKG2-D."; RL Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Cecum; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLU-83. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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). CC -!- FUNCTION: Immune receptor involved in self-nonself discrimination. In CC complex with KLRC1 or KLRC2 on cytotoxic and regulatory lymphocyte CC subsets, recognizes non-classical major histocompatibility (MHC) class CC Ib molecule MHC-E loaded with self-peptides derived from the signal CC sequence of classical MHC class Ia and non-classical MHC class Ib CC molecules. Enables cytotoxic cells to monitor the expression of MHC CC class I molecules in healthy cells and to tolerate self. Primarily CC functions as a ligand binding subunit as it lacks the capacity to CC signal. {ECO:0000250|UniProtKB:Q13241}. CC -!- FUNCTION: KLRD1-KLRC1 acts as an immune inhibitory receptor. Key CC inhibitory receptor on natural killer (NK) cells that regulates their CC activation and effector functions. Dominantly counteracts T cell CC receptor signaling on a subset of memory/effector CD8-positive T cells CC as part of an antigen-driven response to avoid autoimmunity. On CC intraepithelial CD8-positive gamma-delta regulatory T cells triggers CC TGFB1 secretion, which in turn limits the cytotoxic programming of CC intraepithelial CD8-positive alpha-beta T cells, distinguishing CC harmless from pathogenic antigens. In MHC-E-rich tumor CC microenvironment, acts as an immune inhibitory checkpoint and may CC contribute to progressive loss of effector functions of NK cells and CC tumor-specific T cells, a state known as cell exhaustion. Upon MHC-E- CC peptide binding, transmits intracellular signals through KLRC1 CC immunoreceptor tyrosine-based inhibition motifs (ITIMs) by recruiting CC INPP5D/SHIP-1 and INPPL1/SHIP-2 tyrosine phosphatases to ITIMs, and CC ultimately opposing signals transmitted by activating receptors through CC dephosphorylation of proximal signaling molecules. CC {ECO:0000250|UniProtKB:Q13241}. CC -!- FUNCTION: KLRD1-KLRC2 acts as an immune activating receptor. On CC cytotoxic lymphocyte subsets recognizes MHC-E loaded with signal CC sequence-derived peptides from non-classical MHC class Ib MHC-G CC molecules, likely playing a role in the generation and effector CC functions of adaptive NK cells and in maternal-fetal tolerance during CC pregnancy. Regulates the effector functions of terminally CC differentiated cytotoxic lymphocyte subsets, and in particular may play CC a role in adaptive NK cell response to viral infection. Upon MHC-E- CC peptide binding, transmits intracellular signals via the adapter CC protein TYROBP/DAP12, triggering the phosphorylation of proximal CC signaling molecules and cell activation. CC {ECO:0000250|UniProtKB:Q13241}. CC -!- SUBUNIT: Can form disulfide-bonded heterodimer with NKG2 family members CC KLRC1 and KLRC2. KLRD1-KLRC1 heterodimer interacts with peptide-bound CC MHC-E-B2M heterotrimeric complex. KLRD1 plays a prominent role in CC directly interacting with MHC-E. KLRD1-KLRC1 interacts with much higher CC affinity with peptide-bound MHC-E-B2M than KLRD1-KLRC2. Interacts with CC the adapter protein TYROBP/DAP12; this interaction is required for cell CC surface expression and cell activation. {ECO:0000250|UniProtKB:Q13241}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q13241}; CC Single-pass type II membrane protein {ECO:0000255}. 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; AF030311; AAC28243.1; -; mRNA. DR EMBL; AF030312; AAC28244.1; -; mRNA. DR EMBL; AF057714; AAC33713.1; -; mRNA. DR EMBL; AF039025; AAD02116.1; -; mRNA. DR EMBL; AK136548; BAE23039.1; -; mRNA. DR EMBL; CH466523; EDK99936.1; -; Genomic_DNA. DR EMBL; BC117112; AAI17113.1; -; mRNA. DR EMBL; BC120854; AAI20855.1; -; mRNA. DR CCDS; CCDS57456.1; -. DR RefSeq; NP_034784.1; NM_010654.3. DR RefSeq; XP_006505718.1; XM_006505655.1. DR AlphaFoldDB; O54707; -. DR SMR; O54707; -. DR ComplexPortal; CPX-5900; CD94-NKG2A natural killer receptor complex. DR ComplexPortal; CPX-5902; CD94-NKG2C natural killer receptor complex. DR ComplexPortal; CPX-5904; CD94-NKG2E natural killer receptor complex. DR STRING; 10090.ENSMUSP00000107694; -. DR GlyCosmos; O54707; 2 sites, No reported glycans. DR GlyGen; O54707; 2 sites. DR PhosphoSitePlus; O54707; -. DR EPD; O54707; -. DR PaxDb; 10090-ENSMUSP00000107694; -. DR ProteomicsDB; 263559; -. DR Antibodypedia; 11712; 927 antibodies from 37 providers. DR DNASU; 16643; -. DR Ensembl; ENSMUST00000112063.9; ENSMUSP00000107694.3; ENSMUSG00000030165.17. DR GeneID; 16643; -. DR KEGG; mmu:16643; -. DR UCSC; uc009egd.2; mouse. DR AGR; MGI:1196275; -. DR CTD; 3824; -. DR MGI; MGI:1196275; Klrd1. DR VEuPathDB; HostDB:ENSMUSG00000030165; -. DR eggNOG; KOG4297; Eukaryota. DR GeneTree; ENSGT00940000160107; -. DR HOGENOM; CLU_049894_9_3_1; -. DR InParanoid; O54707; -. DR OMA; RFICERK; -. DR OrthoDB; 3814553at2759; -. DR PhylomeDB; O54707; -. DR TreeFam; TF336674; -. DR Reactome; R-MMU-2172127; DAP12 interactions. DR Reactome; R-MMU-2424491; DAP12 signaling. DR BioGRID-ORCS; 16643; 0 hits in 77 CRISPR screens. DR PRO; PR:O54707; -. DR Proteomes; UP000000589; Chromosome 6. DR RNAct; O54707; Protein. DR Bgee; ENSMUSG00000030165; Expressed in peripheral lymph node and 50 other cell types or tissues. DR ExpressionAtlas; O54707; baseline and differential. DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0043235; C:receptor complex; ISO:MGI. DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW. DR GO; GO:0062082; F:HLA-E specific inhibitory MHC class Ib receptor activity; ISO:MGI. DR GO; GO:0023024; F:MHC class I protein complex binding; ISO:MGI. DR GO; GO:0023030; F:MHC class Ib protein binding, via antigen binding groove; ISO:MGI. DR GO; GO:1990405; F:protein antigen binding; ISO:MGI. DR GO; GO:0004888; F:transmembrane signaling receptor activity; IBA:GO_Central. DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW. DR GO; GO:0002228; P:natural killer cell mediated immunity; ISO:MGI. DR GO; GO:0045953; P:negative regulation of natural killer cell mediated cytotoxicity; ISS:UniProtKB. DR GO; GO:0001915; P:negative regulation of T cell mediated cytotoxicity; ISS:UniProtKB. DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; ISO:MGI. DR GO; GO:0032814; P:regulation of natural killer cell activation; NAS:ComplexPortal. DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; ISS:UniProtKB. 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; IPR033992; NKR-like_CTLD. DR PANTHER; PTHR22800; C-TYPE LECTIN PROTEINS; 1. DR PANTHER; PTHR22800:SF246; NATURAL KILLER CELLS ANTIGEN CD94; 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. DR Genevisible; O54707; MM. PE 2: Evidence at transcript level; KW Adaptive immunity; Cell membrane; Disulfide bond; Glycoprotein; Immunity; KW Innate immunity; Lectin; Membrane; Receptor; Reference proteome; KW Signal-anchor; Transmembrane; Transmembrane helix. FT CHAIN 1..179 FT /note="Natural killer cells antigen CD94" FT /id="PRO_0000378458" FT TOPO_DOM 1..10 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 11..31 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255" FT TOPO_DOM 32..179 FT /note="Extracellular" FT /evidence="ECO:0000255" FT DOMAIN 68..175 FT /note="C-type lectin" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040" FT CARBOHYD 93 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 109 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 58..70 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040" FT DISULFID 59 FT /note="Interchain (with C-116 in KLRC1/NGK2A)" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040" FT DISULFID 61..72 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040" FT DISULFID 89..174 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040" FT DISULFID 152..166 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040" FT VARIANT 83 FT /note="K -> E" FT /evidence="ECO:0000269|PubMed:9464811, ECO:0000269|Ref.5" SQ SEQUENCE 179 AA; 20808 MW; DD343419E93B3465 CRC64; MAVSRITRWR LMSVIFGIKC LFLMVTLGVL LINSFTIQNI QSTPSPTTTV EFQEVSECCV CLDKWVGHQC NCYFISKEEK SWKRSRDFCA SQNSSLLQPQ SRNELSFMNF SQTFFWIGMH YSEKRNAWLW EDGTVPSKDL FPEFSVIRPE HCIVYSPSKS VSAESCENKN RYICKKLPI //