KLRD1_PONPY
ID KLRD1_PONPY Reviewed; 179 AA.
AC Q8MHY9; Q8MHY8; Q8MJI3; Q8MJI4;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 25-MAY-2022, entry version 81.
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: Full=Popy-CD94;
DE AltName: CD_antigen=CD94;
GN Name=KLRD1; Synonyms=CD94;
OS Pongo pygmaeus (Bornean orangutan).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9600;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12077248; DOI=10.4049/jimmunol.169.1.220;
RA Guethlein L.A., Flodin L.R., Adams E.J., Parham P.;
RT "NK cell receptors of the orangutan (Pongo pygmaeus): a pivotal species for
RT tracking the coevolution of killer cell Ig-like receptors with MHC-C.";
RL J. Immunol. 169:220-229(2002).
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 -!- TISSUE SPECIFICITY: Natural killer cells.
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; AF470380; AAM78480.1; -; mRNA.
DR EMBL; AF470381; AAM78481.1; -; mRNA.
DR EMBL; AF470382; AAM78482.1; -; mRNA.
DR EMBL; AF470383; AAM78483.1; -; mRNA.
DR EMBL; AF470384; AAM78484.1; -; mRNA.
DR EMBL; AF470385; AAM78485.1; -; mRNA.
DR AlphaFoldDB; Q8MHY9; -.
DR SMR; Q8MHY9; -.
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: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: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; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..179
FT /note="Natural killer cells antigen CD94"
FT /id="PRO_0000046590"
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 VARIANT 24
FT /note="T -> M (in allele CD94*02 and allele CD94*05)"
FT /id="VAR_019064"
FT VARIANT 135
FT /note="A -> S (in allele CD94*03 and allele CD94*05)"
FT /id="VAR_019065"
SQ SEQUENCE 179 AA; 20520 MW; 674489E5FBD95CFA CRC64;
MAVFKTTLWW LISGTLGIIC LSLTATLGIL LKNSFTKLSI EPAFTPGPDI ELQKDSDCCS
CQEKWVGYRC NCYFISSEQK TWNESRHLCA SQKSSLLQLQ NTDELDFMSS SQQFYWIGLS
YSEEHTAWLW ENGSALSQYL FPLFETFNPK NCIAYNPNGN ALDESCEDKN RYICKQQLI
