UniProtKB - Q13241 (KLRD1_HUMAN)
Natural killer cells antigen CD94
KLRD1
Functioni
Immune receptor involved in self-nonself discrimination. In complex with KLRC1 or KLRC2 on cytotoxic and regulatory lymphocyte subsets, recognizes non-classical major histocompatibility (MHC) class Ib molecule HLA-E loaded with self-peptides derived from the signal sequence of classical MHC class Ia and non-classical MHC class Ib molecules (PubMed:9486650, PubMed:10023772, PubMed:18083576, PubMed:18064301, PubMed:9754572).
Enables cytotoxic cells to monitor the expression of MHC class I molecules in healthy cells and to tolerate self (PubMed:9430220, PubMed:12387742, PubMed:18064301).
Primarily functions as a ligand binding subunit as it lacks the capacity to signal.
7 PublicationsKLRD1-KLRC1 acts as an immune inhibitory receptor. Key inhibitory receptor on natural killer (NK) cells that regulates their activation and effector functions (PubMed:9486650, PubMed:9430220, PubMed:9485206, PubMed:30860984).
Dominantly counteracts T cell receptor signaling on a subset of memory/effector CD8-positive T cells as part of an antigen-driven response to avoid autoimmunity (PubMed:12387742).
On intraepithelial CD8-positive gamma-delta regulatory T cells triggers TGFB1 secretion, which in turn limits the cytotoxic programming of intraepithelial CD8-positive alpha-beta T cells, distinguishing harmless from pathogenic antigens (PubMed:18064301).
In HLA-E-rich tumor microenvironment, acts as an immune inhibitory checkpoint and may contribute to progressive loss of effector functions of NK cells and tumor-specific T cells, a state known as cell exhaustion (PubMed:30503213, PubMed:30860984).
Upon HLA-E-peptide binding, transmits intracellular signals through KLRC1 immunoreceptor tyrosine-based inhibition motifs (ITIMs) by recruiting INPP5D/SHIP-1 and INPPL1/SHIP-2 tyrosine phosphatases to ITIMs, and ultimately opposing signals transmitted by activating receptors through dephosphorylation of proximal signaling molecules (PubMed:9485206, PubMed:12165520).
8 PublicationsKLRD1-KLRC2 acts as an immune activating receptor (PubMed:9655483, PubMed:15940674).
On cytotoxic lymphocyte subsets recognizes HLA-E loaded with signal sequence-derived peptides from non-classical MHC class Ib HLA-G molecules, likely playing a role in the generation and effector functions of adaptive NK cells and in maternal-fetal tolerance during pregnancy (PubMed:9754572, PubMed:30134159).
Regulates the effector functions of terminally differentiated cytotoxic lymphocyte subsets, and in particular may play a role in adaptive NK cell response to viral infection (PubMed:21825173, PubMed:20952657).
Upon HLA-E-peptide binding, transmits intracellular signals via the adapter protein TYROBP/DAP12, triggering the phosphorylation of proximal signaling molecules and cell activation (PubMed:9655483, PubMed:15940674).
6 Publications(Microbial infection) Viruses like human cytomegalovirus have evolved an escape mechanism whereby virus-induced down-regulation of host MHC class I molecules is coupled to the binding of viral peptides to HLA-E, restoring HLA-E expression and inducing HLA-E-dependent NK cell immune tolerance to infected cells. Recognizes HLA-E in complex with human cytomegalovirus UL40-derived peptide (VMAPRTLIL) and inhibits NK cell cytotoxicity.
2 Publications(Microbial infection) May recognize HLA-E in complex with HIV-1 gag/Capsid protein p24-derived peptide (AISPRTLNA) on infected cells and may inhibit NK cell cytotoxicity, a mechanism that allows HIV-1 to escape immune recognition.
1 Publication(Microbial infection) Upon SARS-CoV-2 infection, may contribute to functional exhaustion of cytotoxic NK cells and CD8-positive T cells (PubMed:32859121).
On NK cells, may recognize HLA-E in complex with SARS-CoV-2 S/Spike protein S1-derived peptide (LQPRTFLL) expressed on the surface of lung epithelial cells, inducing NK cell exhaustion and dampening antiviral immune surveillance (PubMed:32859121).
1 PublicationGO - Molecular functioni
- carbohydrate binding Source: UniProtKB-KW
- HLA-E specific inhibitory MHC class Ib receptor activity Source: UniProtKB
- MHC class Ib protein binding, via antigen binding groove Source: UniProtKB
- MHC class I protein complex binding Source: UniProtKB
- protein antigen binding Source: UniProtKB
- transmembrane signaling receptor activity Source: GO_Central
GO - Biological processi
- adaptive immune response Source: UniProtKB-KW
- cell surface receptor signaling pathway Source: ProtInc
- natural killer cell mediated immunity Source: UniProtKB
- negative regulation of natural killer cell mediated cytotoxicity Source: UniProtKB
- negative regulation of T cell mediated cytotoxicity Source: UniProtKB
- positive regulation of natural killer cell mediated cytotoxicity Source: UniProtKB
- regulation of natural killer cell activation Source: ComplexPortal
- stimulatory C-type lectin receptor signaling pathway Source: UniProtKB
Keywordsi
Molecular function | Receptor |
Biological process | Adaptive immunity, Immunity, Innate immunity |
Ligand | Lectin |
Enzyme and pathway databases
PathwayCommonsi | Q13241 |
Reactomei | R-HSA-198933, Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell R-HSA-2172127, DAP12 interactions R-HSA-2424491, DAP12 signaling |
SignaLinki | Q13241 |
Names & Taxonomyi
Protein namesi | Recommended name: Natural killer cells antigen CD94Alternative name(s): KP43 Killer cell lectin-like receptor subfamily D member 1 NK cell receptor CD_antigen: CD941 Publication |
Gene namesi | Name:KLRD1 Synonyms:CD94 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6378, KLRD1 |
MIMi | 602894, gene |
neXtProti | NX_Q13241 |
VEuPathDBi | HostDB:ENSG00000134539 |
Subcellular locationi
Plasma membrane
- Cell membrane 2 Publications; Single-pass type II membrane protein Sequence analysis
Plasma Membrane
- external side of plasma membrane Source: GO_Central
- integral component of plasma membrane Source: UniProtKB
- plasma membrane Source: ComplexPortal
Other locations
- receptor complex Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 10 | CytoplasmicSequence analysis | 10 | |
Transmembranei | 11 – 31 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 21 | |
Topological domaini | 32 – 179 | ExtracellularSequence analysisAdd BLAST | 148 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 79 | Q → A: Has no impact on the affinity for HLA-E. 1 Publication | 1 | |
Mutagenesisi | 112 | Q → A: Abolishes binding to HLA-E. 1 Publication | 1 | |
Mutagenesisi | 114 | F → A: Abolishes binding to HLA-E. 1 Publication | 1 | |
Mutagenesisi | 146 | T → A: Has no impact on the affinity for HLA-E. 1 Publication | 1 | |
Mutagenesisi | 148 | N → A: Has no impact on the affinity for HLA-E. 1 Publication | 1 | |
Mutagenesisi | 158 | N → A: Has no impact on the affinity for HLA-E. 1 Publication | 1 | |
Mutagenesisi | 160 | N → A: Abolishes binding to HLA-E. 1 Publication | 1 | |
Mutagenesisi | 162 | L → A: Abolishes binding to HLA-E. 1 Publication | 1 | |
Mutagenesisi | 163 | D → A: Impairs binding to HLA-E. 1 Publication | 1 | |
Mutagenesisi | 164 | E → A: Impairs binding to HLA-E. 1 Publication | 1 | |
Mutagenesisi | 168 | D → A: Reduces binding to HLA-E. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 3824 |
OpenTargetsi | ENSG00000134539 |
PharmGKBi | PA30167 |
Miscellaneous databases
Pharosi | Q13241, Tbio |
Genetic variation databases
BioMutai | KLRD1 |
DMDMi | 334302835 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000046587 | 1 – 179 | Natural killer cells antigen CD94Add BLAST | 179 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 58 ↔ 70 | 2 Publications | ||
Disulfide bondi | 59 | Interchain (with C-116 in KLRC1/NGK2A)2 Publications | ||
Disulfide bondi | 61 ↔ 72 | 4 Publications | ||
Glycosylationi | 83 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 89 ↔ 174 | 4 Publications | ||
Glycosylationi | 132 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 152 ↔ 166 | 4 Publications |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
jPOSTi | Q13241 |
MassIVEi | Q13241 |
PaxDbi | Q13241 |
PeptideAtlasi | Q13241 |
PRIDEi | Q13241 |
ProteomicsDBi | 59243 [Q13241-1] 59244 [Q13241-2] 59245 [Q13241-3] |
PTM databases
GlyGeni | Q13241, 2 sites |
iPTMneti | Q13241 |
PhosphoSitePlusi | Q13241 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000134539, Expressed in granulocyte and 141 other tissues |
ExpressionAtlasi | Q13241, baseline and differential |
Genevisiblei | Q13241, HS |
Organism-specific databases
HPAi | ENSG00000134539, Tissue enhanced (lymphoid) |
Interactioni
Subunit structurei
Can form disulfide-bonded heterodimer with NKG2 family members KLRC1 and KLRC2 (PubMed:18083576, PubMed:18332182, PubMed:18448674, PubMed:9655483). KLRD1-KLRC1 heterodimer interacts with peptide-bound HLA-E-B2M heterotrimeric complex. KLRD1 plays a prominent role in directly interacting with HLA-E (PubMed:18083576). KLRD1-KLRC1 interacts with much higher affinity with peptide-bound HLA-E-B2M than KLRD1-KLRC2 (PubMed:9486650, PubMed:10428963).
Interacts with the adapter protein TYROBP/DAP12; this interaction is required for cell surface expression and cell activation (PubMed:9655483, PubMed:15940674).
6 PublicationsBinary interactionsi
Q13241
With | #Exp. | IntAct |
---|---|---|
KLRC1 [P26715] | 5 | EBI-9018174,EBI-9018187 |
GO - Molecular functioni
- MHC class Ib protein binding, via antigen binding groove Source: UniProtKB
- protein antigen binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 110023, 132 interactors |
ComplexPortali | CPX-2502, CD94-NKG2A natural killer receptor complex CPX-5901, CD94-NKG2C natural killer receptor complex CPX-5903, CD94-NKG2E natural killer receptor complex |
IntActi | Q13241, 3 interactors |
STRINGi | 9606.ENSP00000371333 |
Miscellaneous databases
RNActi | Q13241, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q13241 |
SMRi | Q13241 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q13241 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 68 – 175 | C-type lectinPROSITE-ProRule annotationAdd BLAST | 108 |
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG4297, Eukaryota |
GeneTreei | ENSGT00940000160107 |
InParanoidi | Q13241 |
OMAi | GWIGYQC |
TreeFami | TF336674 |
Family and domain databases
CDDi | cd03593, CLECT_NK_receptors_like, 1 hit |
Gene3Di | 3.10.100.10, 1 hit |
InterProi | View protein in InterPro IPR001304, C-type_lectin-like IPR016186, C-type_lectin-like/link_sf IPR016187, CTDL_fold IPR033992, NKR-like_CTLD |
Pfami | View protein in Pfam PF00059, Lectin_C, 1 hit |
SMARTi | View protein in SMART SM00034, CLECT, 1 hit |
SUPFAMi | SSF56436, SSF56436, 1 hit |
PROSITEi | View protein in PROSITE PS50041, C_TYPE_LECTIN_2, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAVFKTTLWR LISGTLGIIC LSLMSTLGIL LKNSFTKLSI EPAFTPGPNI
60 70 80 90 100
ELQKDSDCCS CQEKWVGYRC NCYFISSEQK TWNESRHLCA SQKSSLLQLQ
110 120 130 140 150
NTDELDFMSS SQQFYWIGLS YSEEHTAWLW ENGSALSQYL FPSFETFNTK
160 170
NCIAYNPNGN ALDESCEDKN RYICKQQLI
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF6WZH4 | F6WZH4_HUMAN | Natural killer cells antigen CD94 | KLRD1 | 158 | Annotation score: | ||
F5GX94 | F5GX94_HUMAN | Natural killer cells antigen CD94 | KLRD1 | 106 | Annotation score: | ||
E9PCX9 | E9PCX9_HUMAN | Natural killer cells antigen CD94 | KLRD1 | 72 | Annotation score: | ||
F5H2B7 | F5H2B7_HUMAN | Natural killer cells antigen CD94 | KLRD1 | 139 | Annotation score: | ||
H0YFB8 | H0YFB8_HUMAN | Natural killer cells antigen CD94 | KLRD1 | 51 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_050103 | 25 | S → A3 PublicationsCorresponds to variant dbSNP:rs10772256Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_003052 | 1 – 34 | MAVFK…LLKNS → MAA in isoform 3. 1 PublicationAdd BLAST | 34 | |
Alternative sequenceiVSP_003053 | 105 | L → LQ in isoform 2. Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U30610 mRNA Translation: AAC50291.1 Y14287, Y14288 Genomic DNA Translation: CAA74663.1 AJ000673 Genomic DNA Translation: CAA04230.1 AJ000001 mRNA Translation: CAA03845.1 AB009597 mRNA Translation: BAA24450.1 AB010084 Genomic DNA Translation: BAA24451.1 AC022075 Genomic DNA No translation available. BC028009 mRNA Translation: AAH28009.1 |
CCDSi | CCDS8621.1 [Q13241-1] CCDS8622.1 [Q13241-3] |
RefSeqi | NP_001107868.1, NM_001114396.1 [Q13241-1] NP_002253.1, NM_002262.3 [Q13241-1] NP_031360.1, NM_007334.2 [Q13241-3] XP_016874780.1, XM_017019291.1 |
Genome annotation databases
Ensembli | ENST00000336164.9; ENSP00000338130.4; ENSG00000134539.17 ENST00000350274.9; ENSP00000310929.7; ENSG00000134539.17 [Q13241-3] ENST00000381908.7; ENSP00000371333.4; ENSG00000134539.17 |
GeneIDi | 3824 |
KEGGi | hsa:3824 |
MANE-Selecti | ENST00000336164.9; ENSP00000338130.4; NM_002262.5; NP_002253.2 |
UCSCi | uc001qxw.5, human [Q13241-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Functional Glycomics Gateway - Glycan Binding CD94 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U30610 mRNA Translation: AAC50291.1 Y14287, Y14288 Genomic DNA Translation: CAA74663.1 AJ000673 Genomic DNA Translation: CAA04230.1 AJ000001 mRNA Translation: CAA03845.1 AB009597 mRNA Translation: BAA24450.1 AB010084 Genomic DNA Translation: BAA24451.1 AC022075 Genomic DNA No translation available. BC028009 mRNA Translation: AAH28009.1 |
CCDSi | CCDS8621.1 [Q13241-1] CCDS8622.1 [Q13241-3] |
RefSeqi | NP_001107868.1, NM_001114396.1 [Q13241-1] NP_002253.1, NM_002262.3 [Q13241-1] NP_031360.1, NM_007334.2 [Q13241-3] XP_016874780.1, XM_017019291.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1B6E | X-ray | 2.60 | A | 52-179 | [»] | |
3BDW | X-ray | 2.50 | A/C | 57-179 | [»] | |
3CDG | X-ray | 3.40 | E/J | 57-179 | [»] | |
3CII | X-ray | 4.41 | G/I | 59-179 | [»] | |
AlphaFoldDBi | Q13241 | |||||
SMRi | Q13241 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 110023, 132 interactors |
ComplexPortali | CPX-2502, CD94-NKG2A natural killer receptor complex CPX-5901, CD94-NKG2C natural killer receptor complex CPX-5903, CD94-NKG2E natural killer receptor complex |
IntActi | Q13241, 3 interactors |
STRINGi | 9606.ENSP00000371333 |
PTM databases
GlyGeni | Q13241, 2 sites |
iPTMneti | Q13241 |
PhosphoSitePlusi | Q13241 |
Genetic variation databases
BioMutai | KLRD1 |
DMDMi | 334302835 |
Proteomic databases
jPOSTi | Q13241 |
MassIVEi | Q13241 |
PaxDbi | Q13241 |
PeptideAtlasi | Q13241 |
PRIDEi | Q13241 |
ProteomicsDBi | 59243 [Q13241-1] 59244 [Q13241-2] 59245 [Q13241-3] |
Protocols and materials databases
Antibodypediai | 11712, 880 antibodies from 37 providers |
DNASUi | 3824 |
Genome annotation databases
Ensembli | ENST00000336164.9; ENSP00000338130.4; ENSG00000134539.17 ENST00000350274.9; ENSP00000310929.7; ENSG00000134539.17 [Q13241-3] ENST00000381908.7; ENSP00000371333.4; ENSG00000134539.17 |
GeneIDi | 3824 |
KEGGi | hsa:3824 |
MANE-Selecti | ENST00000336164.9; ENSP00000338130.4; NM_002262.5; NP_002253.2 |
UCSCi | uc001qxw.5, human [Q13241-1] |
Organism-specific databases
CTDi | 3824 |
DisGeNETi | 3824 |
GeneCardsi | KLRD1 |
HGNCi | HGNC:6378, KLRD1 |
HPAi | ENSG00000134539, Tissue enhanced (lymphoid) |
MIMi | 602894, gene |
neXtProti | NX_Q13241 |
OpenTargetsi | ENSG00000134539 |
PharmGKBi | PA30167 |
VEuPathDBi | HostDB:ENSG00000134539 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4297, Eukaryota |
GeneTreei | ENSGT00940000160107 |
InParanoidi | Q13241 |
OMAi | GWIGYQC |
TreeFami | TF336674 |
Enzyme and pathway databases
PathwayCommonsi | Q13241 |
Reactomei | R-HSA-198933, Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell R-HSA-2172127, DAP12 interactions R-HSA-2424491, DAP12 signaling |
SignaLinki | Q13241 |
Miscellaneous databases
BioGRID-ORCSi | 3824, 7 hits in 1061 CRISPR screens |
ChiTaRSi | KLRD1, human |
EvolutionaryTracei | Q13241 |
GeneWikii | KLRD1 |
GenomeRNAii | 3824 |
Pharosi | Q13241, Tbio |
PROi | PR:Q13241 |
RNActi | Q13241, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000134539, Expressed in granulocyte and 141 other tissues |
ExpressionAtlasi | Q13241, baseline and differential |
Genevisiblei | Q13241, HS |
Family and domain databases
CDDi | cd03593, CLECT_NK_receptors_like, 1 hit |
Gene3Di | 3.10.100.10, 1 hit |
InterProi | View protein in InterPro IPR001304, C-type_lectin-like IPR016186, C-type_lectin-like/link_sf IPR016187, CTDL_fold IPR033992, NKR-like_CTLD |
Pfami | View protein in Pfam PF00059, Lectin_C, 1 hit |
SMARTi | View protein in SMART SM00034, CLECT, 1 hit |
SUPFAMi | SSF56436, SSF56436, 1 hit |
PROSITEi | View protein in PROSITE PS50041, C_TYPE_LECTIN_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | KLRD1_HUMAN | |
Accessioni | Q13241Primary (citable) accession number: Q13241 Secondary accession number(s): O43321 Q9UEQ0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | May 31, 2011 | |
Last modified: | May 25, 2022 | |
This is version 187 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human cell differentiation molecules
CD nomenclature of surface proteins of human leucocytes and list of entries - Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references