NKG2A_PANTR
ID NKG2A_PANTR Reviewed; 233 AA.
AC Q95MI5; Q9MYM6;
DT 15-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2002, sequence version 2.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=NKG2-A/NKG2-B type II integral membrane protein;
DE AltName: Full=CD159 antigen-like family member A;
DE AltName: Full=NK cell receptor A;
DE AltName: Full=NKG2-A/B-activating NK receptor;
DE AltName: CD_antigen=CD159a;
GN Name=KLRC1; Synonyms=NKG2A;
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].
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 NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, AND VARIANTS LEU-79 AND
RP ARG-231.
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 inhibitory receptor involved in self-nonself
CC discrimination. In complex with KLRD1 on cytotoxic and regulatory
CC lymphocyte subsets, recognizes non-classical major histocompatibility
CC (MHC) class Ib molecule MHC-E loaded with self-peptides derived from
CC the signal sequence of classical MHC class Ia molecules. Enables
CC cytotoxic cells to monitor the expression of MHC class I molecules in
CC healthy cells and to tolerate self. Upon MHC-E-peptide binding,
CC transmits intracellular signals through two immunoreceptor tyrosine-
CC based inhibition motifs (ITIMs) by recruiting INPP5D/SHP-1 and
CC INPPL1/SHP-2 tyrosine phosphatases to ITIMs, and ultimately opposing
CC signals transmitted by activating receptors through dephosphorylation
CC of proximal signaling molecules. Key inhibitory receptor on natural
CC killer (NK) cells that regulates their activation and effector
CC functions. Dominantly counteracts T cell receptor signaling on a subset
CC of memory/effector CD8-positive T cells as part of an antigen-driven
CC response to avoid autoimmunity. On intraepithelial CD8-positive gamma-
CC delta regulatory T cells triggers TGFB1 secretion, which in turn limits
CC the cytotoxic programming of intraepithelial CD8-positive alpha-beta T
CC cells, distinguishing harmless from pathogenic antigens. In MHC-E-rich
CC tumor 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.
CC {ECO:0000250|UniProtKB:P26715}.
CC -!- SUBUNIT: Heterodimer with KLRD1; disulfide-linked. KLRD1-KLRC1
CC heterodimer interacts with peptide-bound MHC-E-B2M heterotrimeric
CC complex. Competes with KLRC2 for its interaction with MHC-E. Interacts
CC (via ITIM) with INPP5D/SHIP-1 and INPPL1/SHIP-2 (via SH2 domain).
CC {ECO:0000250|UniProtKB:P26715}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P26715};
CC Single-pass type II membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=NKG2-A;
CC IsoId=Q95MI5-1; Sequence=Displayed;
CC Name=NKG2-B;
CC IsoId=Q95MI5-2; Sequence=VSP_003066;
CC -!- TISSUE SPECIFICITY: Natural killer cells.
CC -!- DOMAIN: The cytosolic N-terminus contains two immunoreceptor tyrosine-
CC based inhibitory motifs (ITIMs), which are essential for the
CC association with INPP5D/SHIP-1 and INPPL1/SHIP-2 phosphatases and
CC functional inhibition. {ECO:0000250|UniProtKB:P26715}.
CC -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:P26715}.
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; AF259055; AAF86965.1; -; mRNA.
DR EMBL; AF259056; AAF86966.1; -; mRNA.
DR EMBL; AF350005; AAK83792.1; -; mRNA.
DR RefSeq; NP_001009048.2; NM_001009048.2. [Q95MI5-1]
DR RefSeq; XP_009423042.2; XM_009424767.2. [Q95MI5-1]
DR AlphaFoldDB; Q95MI5; -.
DR SMR; Q95MI5; -.
DR STRING; 9598.ENSPTRP00000054743; -.
DR PaxDb; Q95MI5; -.
DR Ensembl; ENSPTRT00000062196; ENSPTRP00000054750; ENSPTRG00000029778. [Q95MI5-2]
DR Ensembl; ENSPTRT00000067984; ENSPTRP00000059579; ENSPTRG00000029778. [Q95MI5-1]
DR GeneID; 450131; -.
DR KEGG; ptr:450131; -.
DR CTD; 3821; -.
DR eggNOG; ENOG502S6IE; Eukaryota.
DR GeneTree; ENSGT00940000164619; -.
DR HOGENOM; CLU_049894_9_2_1; -.
DR InParanoid; Q95MI5; -.
DR OMA; KEWLIYS; -.
DR OrthoDB; 1161111at2759; -.
DR TreeFam; TF336674; -.
DR Proteomes; UP000002277; Chromosome 12.
DR Bgee; ENSPTRG00000029778; Expressed in prefrontal cortex and 11 other tissues.
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: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; ISS:UniProtKB.
DR GO; GO:0023024; F:MHC class I protein complex 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:0002305; P:CD8-positive, gamma-delta intraepithelial T cell differentiation; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0002769; P:natural killer cell inhibitory signaling pathway; 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 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 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; Alternative splicing; Cell membrane; Disulfide bond;
KW Glycoprotein; Immunity; Innate immunity; Lectin; Membrane; Phosphoprotein;
KW Receptor; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..233
FT /note="NKG2-A/NKG2-B type II integral membrane protein"
FT /id="PRO_0000046661"
FT TOPO_DOM 1..70
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 71..93
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 94..233
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 118..231
FT /note="C-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 6..11
FT /note="Immunoreceptor tyrosine-based inhibition motif
FT (ITIM)"
FT /evidence="ECO:0000250|UniProtKB:P26715"
FT MOTIF 38..43
FT /note="Immunoreceptor tyrosine-based inhibition motif
FT (ITIM)"
FT /evidence="ECO:0000250|UniProtKB:P26715"
FT COMPBIAS 1..16
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 8
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P26715"
FT MOD_RES 40
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P26715"
FT CARBOHYD 102
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 180
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 116
FT /note="Interchain (with C-59 in KLRD1)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 119..130
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 147..229
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 208..221
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT VAR_SEQ 96..113
FT /note="Missing (in isoform NKG2-B)"
FT /evidence="ECO:0000305"
FT /id="VSP_003066"
FT VARIANT 79
FT /note="I -> L (in allele NKG2-A*03)"
FT /evidence="ECO:0000269|PubMed:11751968"
FT /id="VAR_018698"
FT VARIANT 231
FT /note="H -> R (in allele NKG2-A*03)"
FT /evidence="ECO:0000269|PubMed:11751968"
FT /id="VAR_018699"
SQ SEQUENCE 233 AA; 26212 MW; AE94BEA3A0209984 CRC64;
MDNQGVIYSD LNLPPNPKRQ QRKPKGNKSS ILATEQEITY AELNLQKASQ DFQENDKTYH
CKDLPSAPEK LIVGILGIIC LILMASVVTI VVIPSTLIQR HNNSSLNTRT QKARHCGHCP
EEWITYSNSC YYIGKERRTW EESLLACTSK NSGLLSIDNE EEMKFLSIIS PSSWIGVFRN
SSHHPWVTIN GLAFKHEIKD SDNAELNCAV LQVNGLKSAQ CGSSIIYHCK HKL
