KLRD1_MACMU
ID KLRD1_MACMU Reviewed; 179 AA.
AC Q9MZK9; Q9GK91; Q9MZK7; Q9MZK8;
DT 15-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 25-MAY-2022, entry version 119.
DE RecName: Full=Natural killer cells antigen CD94;
DE AltName: Full=Killer cell lectin-like receptor subfamily D member 1;
DE AltName: Full=NK cell receptor;
DE AltName: CD_antigen=CD94;
GN Name=KLRD1; Synonyms=CD94;
OS Macaca mulatta (Rhesus macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9544;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
RX PubMed=10866118; DOI=10.1007/s002510050650;
RA LaBonte M.L., Levy D.B., Letvin N.L.;
RT "Characterization of rhesus monkey CD94/NKG2 family members and
RT identification of novel transmembrane-deleted forms of NKG2-A, B, C, and
RT D.";
RL Immunogenetics 51:496-499(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=11261935; DOI=10.1007/s002510000289;
RA Kravitz R.H., Grendell R.L., Slukvin I.I., Golos T.G.;
RT "Selective expression of NKG2-A and NKG2-C mRNAs and novel alternative
RT splicing of 5' exons in rhesus monkey decidua.";
RL Immunogenetics 53:69-73(2001).
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=CD94-A;
CC IsoId=Q9MZK9-1; Sequence=Displayed;
CC Name=2; Synonyms=CD94-B;
CC IsoId=Q9MZK9-2; Sequence=VSP_003055;
CC Name=3; Synonyms=CD94 alt;
CC IsoId=Q9MZK9-3; Sequence=VSP_003054;
CC -!- TISSUE SPECIFICITY: Natural killer cells.
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DR EMBL; AF190931; AAF74527.1; -; mRNA.
DR EMBL; AF190932; AAF74528.1; -; mRNA.
DR EMBL; AF190933; AAF74529.1; -; mRNA.
DR EMBL; AF294886; AAG34498.1; -; mRNA.
DR RefSeq; NP_001028000.1; NM_001032828.1.
DR RefSeq; XP_015006475.1; XM_015150989.1.
DR AlphaFoldDB; Q9MZK9; -.
DR SMR; Q9MZK9; -.
DR STRING; 9544.ENSMMUP00000024061; -.
DR GeneID; 574145; -.
DR KEGG; mcc:574145; -.
DR CTD; 3824; -.
DR eggNOG; KOG4297; Eukaryota.
DR InParanoid; Q9MZK9; -.
DR Proteomes; UP000006718; Unplaced.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IBA:GO_Central.
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; IBA:GO_Central.
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 Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein; Lectin;
KW Membrane; Receptor; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..179
FT /note="Natural killer cells antigen CD94"
FT /id="PRO_0000046588"
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 83
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 132
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 VAR_SEQ 1..34
FT /note="MAVFKTTLWRLISGTLGIICLSLMATLGILLKNS -> MAA (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:10866118"
FT /id="VSP_003054"
FT VAR_SEQ 105
FT /note="L -> LQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10866118"
FT /id="VSP_003055"
FT VARIANT 139
FT /note="Y -> D"
SQ SEQUENCE 179 AA; 20607 MW; 06212B4494527F07 CRC64;
MAVFKTTLWR LISGTLGIIC LSLMATLGIL LKNSFTKLSV EPAYTPGPNI ELQKDSDCCS
CHEKWVGYRC NCYFISSEEK TWNESRHFCA SQKSSLLQLQ NRDELDFMSS SQHFYWIGLS
YSEEHTAWLW ENGSALSQYL FPSFETFKPK NCIAYNSKGN ALDESCETKN RYICKQQLI
