ID KLRD1_CANLF Reviewed; 179 AA.
AC Q38HS3;
DT 07-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT 22-NOV-2005, sequence version 1.
DT 27-MAR-2024, entry version 112.
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 Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Jochum C., Venkataraman G.M., Beste M., Graves S.S., Storb R.;
RT "Canis familiaris CD94 cDNA.";
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
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; DQ228356; ABB16421.1; -; mRNA.
DR RefSeq; NP_001041500.1; NM_001048035.1.
DR RefSeq; XP_005636778.1; XM_005636721.1.
DR AlphaFoldDB; Q38HS3; -.
DR SMR; Q38HS3; -.
DR STRING; 9615.ENSCAFP00000035934; -.
DR GlyCosmos; Q38HS3; 2 sites, No reported glycans.
DR PaxDb; 9612-ENSCAFP00000035934; -.
DR Ensembl; ENSCAFT00000043457.4; ENSCAFP00000035934.1; ENSCAFG00000013459.6.
DR Ensembl; ENSCAFT00030035673.1; ENSCAFP00030031110.1; ENSCAFG00030019329.1.
DR GeneID; 611360; -.
DR KEGG; cfa:611360; -.
DR CTD; 3824; -.
DR VGNC; VGNC:42486; KLRD1.
DR eggNOG; KOG4297; Eukaryota.
DR InParanoid; Q38HS3; -.
DR OMA; RFICERK; -.
DR OrthoDB; 3814553at2759; -.
DR TreeFam; TF336674; -.
DR Reactome; R-CFA-2424491; DAP12 signaling.
DR Proteomes; UP000002254; Chromosome 27.
DR Proteomes; UP000694429; Chromosome 27.
DR Proteomes; UP000694542; Unplaced.
DR Proteomes; UP000805418; Unplaced.
DR Bgee; ENSCAFG00000013459; Expressed in spleen and 39 other cell types or tissues.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C: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:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
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; 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.
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_0000378457"
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 125
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"
SQ SEQUENCE 179 AA; 20473 MW; F4BDF3520045E2CB CRC64;
MAVSQTTLWN LISGILGVIC LLLMTTMGIL LKNLLLTESI QPTLSPGPIT ELQKGSDCCS
CPKRWIGHQC NCYLFFDELK SWTESRDFCA SQNSSLLHIQ NRDELRFVSS SKYFYWIGVY
YSKENGTWLW ENGLALPQDL LQTIQTFDTK KCVIYSSSHS VLDVSCEDKS RFICKQELM
//
