ID KLRD1_PANTR Reviewed; 179 AA.
AC Q9MZ41;
DT 15-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 24-JAN-2024, entry version 139.
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 Pan troglodytes (Chimpanzee).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9598;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10894168; DOI=10.1016/s1074-7613(00)80219-8;
RA Khakoo S.I., Rajalingam R., Shum B.P., Weidenbach K., Flodin L., Muir D.G.,
RA Canavez F., Cooper S.L., Valiante N.M., Lanier L.L., Parham P.;
RT "Rapid evolution of NK cell receptor systems demonstrated by comparison of
RT chimpanzees and humans.";
RL Immunity 12:687-698(2000).
RN [2]
RP ALTERNATIVE SPLICING.
RX PubMed=11751968; DOI=10.4049/jimmunol.168.1.240;
RA Shum B.P., Flodin L.R., Muir D.G., Rajalingam R., Khakoo S.I., Cleland S.,
RA Guethlein L.A., Uhrberg M., Parham P.;
RT "Conservation and variation in human and common chimpanzee CD94 and NKG2
RT genes.";
RL J. Immunol. 168:240-252(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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=CD94-A;
CC IsoId=Q9MZ41-1; Sequence=Displayed;
CC Name=2; Synonyms=CD94-B;
CC IsoId=Q9MZ41-2; Sequence=VSP_003056;
CC -!- TISSUE SPECIFICITY: Natural killer cells.
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DR EMBL; AF259054; AAF86964.1; -; mRNA.
DR RefSeq; NP_001009062.1; NM_001009062.1. [Q9MZ41-1]
DR RefSeq; XP_009423053.1; XM_009424778.2.
DR RefSeq; XP_016778010.1; XM_016922521.1.
DR AlphaFoldDB; Q9MZ41; -.
DR SMR; Q9MZ41; -.
DR STRING; 9598.ENSPTRP00000057110; -.
DR GlyCosmos; Q9MZ41; 2 sites, No reported glycans.
DR PaxDb; 9598-ENSPTRP00000057110; -.
DR Ensembl; ENSPTRT00000065546.3; ENSPTRP00000057110.3; ENSPTRG00000004671.7. [Q9MZ41-1]
DR GeneID; 450156; -.
DR KEGG; ptr:450156; -.
DR CTD; 3824; -.
DR eggNOG; KOG4297; Eukaryota.
DR GeneTree; ENSGT00940000160107; -.
DR HOGENOM; CLU_049894_9_3_1; -.
DR InParanoid; Q9MZ41; -.
DR OMA; RFICERK; -.
DR OrthoDB; 3814553at2759; -.
DR TreeFam; TF336674; -.
DR Proteomes; UP000002277; Chromosome 12.
DR Bgee; ENSPTRG00000004671; Expressed in lung and 20 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:0043235; C:receptor complex; IEA:Ensembl.
DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR GO; GO:0062082; F:HLA-E specific inhibitory MHC class Ib receptor activity; IEA:Ensembl.
DR GO; GO:0023024; F:MHC class I protein complex binding; IEA:Ensembl.
DR GO; GO:0023030; F:MHC class Ib protein binding, via antigen binding groove; IEA:Ensembl.
DR GO; GO:1990405; F:protein antigen binding; IEA:Ensembl.
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; IEA:Ensembl.
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; Alternative splicing; Cell membrane; Disulfide bond;
KW Glycoprotein; Immunity; Innate immunity; Lectin; Membrane; Receptor;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..179
FT /note="Natural killer cells antigen CD94"
FT /id="PRO_0000046589"
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 105
FT /note="L -> LQ (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_003056"
SQ SEQUENCE 179 AA; 20493 MW; 7244D99E8D9587E7 CRC64;
MAVFKTTLWR LISGTLGIIC LSLMATLGIL LKNSFTKLSI EPAFTPGPNI ELQKDSDCCS
CQEKWVGYRC NCYFISSEQK TWNESRHLCA SQKSSLLQLQ NTDELDFMSS SQQFYWIGLS
YSEEHTAWLW ENGSALSQYL FPSFETFNPK NCIAYNPNGN ALDESCEDKN RYICKQQLI
//
