KLRD1_MOUSE
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 03-AUG-2022, entry version 144.
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}.
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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 GlyGen; O54707; 2 sites.
DR PhosphoSitePlus; O54707; -.
DR EPD; O54707; -.
DR PaxDb; O54707; -.
DR PRIDE; O54707; -.
DR ProteomicsDB; 263559; -.
DR Antibodypedia; 11712; 880 antibodies from 37 providers.
DR DNASU; 16643; -.
DR Ensembl; ENSMUST00000112063; ENSMUSP00000107694; ENSMUSG00000030165.
DR GeneID; 16643; -.
DR KEGG; mmu:16643; -.
DR UCSC; uc009egd.2; mouse.
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; GWIGYQC; -.
DR OrthoDB; 1389571at2759; -.
DR PhylomeDB; O54707; -.
DR TreeFam; TF336674; -.
DR Reactome; R-MMU-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR Reactome; R-MMU-2172127; DAP12 interactions.
DR Reactome; R-MMU-2424491; DAP12 signaling.
DR BioGRID-ORCS; 16643; 0 hits in 72 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 tissues.
DR ExpressionAtlas; O54707; baseline and differential.
DR Genevisible; O54707; MM.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
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; IC: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; -; 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 Pfam; PF00059; Lectin_C; 1.
DR SMART; SM00034; CLECT; 1.
DR SUPFAM; SSF56436; SSF56436; 1.
DR PROSITE; PS50041; C_TYPE_LECTIN_2; 1.
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
