KLRD1_BOVIN
ID KLRD1_BOVIN Reviewed; 190 AA.
AC Q863H3; A3R3C2; A3R3C3; A3R3C4;
DT 07-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT 07-JUL-2009, sequence version 2.
DT 25-MAY-2022, entry version 95.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS SER-65; LEU-85; SER-96 AND
RP LEU-116.
RX PubMed=12672064; DOI=10.1002/eji.200323710;
RA Storset A.K., Slettedal I.O., Williams J.L., Law A., Dissen E.;
RT "Natural killer cell receptors in cattle: a bovine killer cell
RT immunoglobulin-like receptor multigene family contains members with
RT divergent signaling motifs.";
RL Eur. J. Immunol. 33:980-990(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS SER-65; LEU-85; SER-96; LEU-116;
RP LEU-155; THR-167; SER-168 AND HIS-176.
RX PubMed=17285285; DOI=10.1007/s00251-006-0189-z;
RA Birch J., Ellis S.A.;
RT "Complexity in the cattle CD94/NKG2 gene families.";
RL Immunogenetics 59:273-280(2007).
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; AF422180; AAP33622.1; -; mRNA.
DR EMBL; EF081290; ABO15594.1; -; mRNA.
DR EMBL; EF081291; ABO15595.1; -; mRNA.
DR EMBL; EF081292; ABO15596.1; -; mRNA.
DR RefSeq; NP_001002890.1; NM_001002890.1.
DR AlphaFoldDB; Q863H3; -.
DR SMR; Q863H3; -.
DR STRING; 9913.ENSBTAP00000037681; -.
DR PaxDb; Q863H3; -.
DR PRIDE; Q863H3; -.
DR GeneID; 444877; -.
DR KEGG; bta:444877; -.
DR CTD; 3824; -.
DR eggNOG; KOG4297; Eukaryota.
DR HOGENOM; CLU_049894_9_3_1; -.
DR InParanoid; Q863H3; -.
DR OrthoDB; 1389571at2759; -.
DR TreeFam; TF336674; -.
DR Proteomes; UP000009136; 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: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; -; 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..190
FT /note="Natural killer cells antigen CD94"
FT /id="PRO_0000378460"
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..190
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 79..186
FT /note="C-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT CARBOHYD 104
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 69..81
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 72..83
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 100..185
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 163..177
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT VARIANT 65
FT /note="L -> S (in allele CD94-01 and allele CD94-03)"
FT /evidence="ECO:0000269|PubMed:12672064,
FT ECO:0000269|PubMed:17285285"
FT VARIANT 85
FT /note="F -> L (in allele CD94-01 and allele CD94-03)"
FT /evidence="ECO:0000269|PubMed:12672064,
FT ECO:0000269|PubMed:17285285"
FT VARIANT 96
FT /note="G -> S (in allele CD94-01 and allele CD94-03)"
FT /evidence="ECO:0000269|PubMed:12672064,
FT ECO:0000269|PubMed:17285285"
FT VARIANT 116
FT /note="P -> L (in allele CD94-01 and allele CD94-03)"
FT /evidence="ECO:0000269|PubMed:12672064,
FT ECO:0000269|PubMed:17285285"
FT VARIANT 155
FT /note="F -> L (in allele CD94-04)"
FT /evidence="ECO:0000269|PubMed:17285285"
FT VARIANT 167
FT /note="N -> T (in allele CD94-04)"
FT /evidence="ECO:0000269|PubMed:17285285"
FT VARIANT 168
FT /note="P -> S (in allele CD94-03)"
FT /evidence="ECO:0000269|PubMed:17285285"
FT VARIANT 176
FT /note="Y -> H (in allele CD94-04)"
FT /evidence="ECO:0000269|PubMed:17285285"
SQ SEQUENCE 190 AA; 21927 MW; 080610DBC5676240 CRC64;
MAAFRTTAWR LISGVLGVIC LVLMAALGVL LKNSLTKRSV QPGPSADLQE EYNLHEEEES
CLGCLGSGCY SCQEKWIGYQ CNCYFISNEL KTWKDGRDFC VSHNSSLLQI QTRNEPAFMK
FSTSFYWIGL SYDEEHHAWL WEDNSTLSQD LLPFFKSVNP KNCIMYNPRG RILDAYCEKK
FRYICKQQLI
