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Protein

NKG2-D type II integral membrane protein

Gene

KLRK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Function as an activating and costimulatory receptor involved in immunosurveillance upon binding to various cellular stress-inducible ligands displayed at the surface of autologous tumor cells and virus-infected cells. Provides both stimulatory and costimulatory innate immune responses on activated killer (NK) cells, leading to cytotoxic activity. Acts as a costimulatory receptor for T-cell receptor (TCR) in CD8+ T-cell-mediated adaptive immune responses by amplifying T-cell activation. Stimulates perforin-mediated elimination of ligand-expressing tumor cells. Signaling involves calcium influx, culminating in the expression of TNF-alpha. Participates in NK cell-mediated bone marrow graft rejection. May play a regulatory role in differentiation and survival of NK cells. Binds to ligands belonging to various subfamilies of MHC class I-related glycoproteins including MICA, MICB, RAET1E, RAET1G, RAET1L/ULBP6, ULBP1, ULBP2, ULBP3 (ULBP2>ULBP1>ULBP3) and ULBP4.8 Publications

Miscellaneous

Is not capable of signal transduction by itself, but operates through the adapter protein HCST (PubMed:10426994 and PubMed:15894612). Some families of ligands for human and mouse KLRK1 receptors have been characterized being very similar in structure and highly likely to be orthologs. In humans, an additional distinct subfamily of ligands (MICA and MICB) differs structurally, having an extra MHC alpha 3-like domain (PubMed:23298206).1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionReceptor
Biological processAdaptive immunity, Differentiation, Immunity, Innate immunity
LigandLectin

Enzyme and pathway databases

ReactomeiR-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-2172127 DAP12 interactions
R-HSA-2424491 DAP12 signaling
SIGNORiP26718

Names & Taxonomyi

Protein namesi
Recommended name:
NKG2-D type II integral membrane protein
Alternative name(s):
Killer cell lectin-like receptor subfamily K member 1
NK cell receptor D
NKG2-D-activating NK receptor
CD_antigen: CD314
Gene namesi
Name:KLRK1
Synonyms:D12S2489E, NKG2D
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000213809.8
HGNCiHGNC:18788 KLRK1
MIMi611817 gene
neXtProtiNX_P26718

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 51CytoplasmicSequence analysisAdd BLAST51
Transmembranei52 – 72Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini73 – 216ExtracellularSequence analysisAdd BLAST144

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi66R → A: Inhibits association with the HCST signaling dimer. 1 Publication1

Organism-specific databases

DisGeNETi100528032
22914
PharmGKBiPA128394594

Polymorphism and mutation databases

BioMutaiKLRK1
DMDMi128370

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000466651 – 216NKG2-D type II integral membrane proteinAdd BLAST216

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi96 ↔ 105
Disulfide bondi99 ↔ 110
Disulfide bondi127 ↔ 211
Glycosylationi131N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi163N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi189 ↔ 203
Glycosylationi202N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP26718
PaxDbiP26718
PeptideAtlasiP26718
PRIDEiP26718

PTM databases

iPTMnetiP26718
PhosphoSitePlusiP26718

Expressioni

Tissue specificityi

Expressed in natural killer (NK) cells, CD8+ alpha-beta and gamma-delta T-cells. Expressed on essentially all CD56+CD3- NK cells from freshly isolated PBMC. Expressed in interferon-producing killer dendritic cells (IKDCs).3 Publications

Inductioni

Up-regulated by interleukin IL15 in primary NK cells.1 Publication

Gene expression databases

BgeeiENSG00000213809
CleanExiHS_KLRK1
ExpressionAtlasiP26718 baseline and differential
GenevisibleiP26718 HS

Organism-specific databases

HPAiCAB021896
HPA068877

Interactioni

Subunit structurei

Homodimer; disulfide-linked. Heterohexamer composed of two subunits of KLRK1 and four subunits of HCST/DAP10. Interacts (via transmembrane domain) with HCST/DAP10 (via transmembrane domain); the interaction is required for KLRK1 NK cell surface and induces NK cell-mediated cytotoxicity. Does not interact with TYROBP. Interacts with CEACAM1; recruits PTPN6 that dephosphorylates VAV1 (PubMed:23696226).7 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116576, 2 interactors
CORUMiP26718
DIPiDIP-31100N
IntActiP26718, 8 interactors
MINTiP26718
STRINGi9606.ENSP00000240618

Structurei

Secondary structure

1216
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi94 – 96Combined sources3
Beta strandi103 – 106Combined sources4
Beta strandi109 – 118Combined sources10
Helixi120 – 128Combined sources9
Turni129 – 131Combined sources3
Beta strandi133 – 135Combined sources3
Turni140 – 143Combined sources4
Helixi144 – 148Combined sources5
Beta strandi153 – 159Combined sources7
Turni161 – 163Combined sources3
Beta strandi166 – 168Combined sources3
Beta strandi176 – 178Combined sources3
Beta strandi180 – 182Combined sources3
Beta strandi185 – 193Combined sources9
Turni194 – 196Combined sources3
Beta strandi197 – 201Combined sources5
Beta strandi207 – 213Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1HYRX-ray2.70A/B80-216[»]
1KCGX-ray2.60A/B93-216[»]
1MPUX-ray2.50A80-216[»]
4PDCX-ray1.99A/B/C/D93-215[»]
4S0UX-ray2.35A/B90-215[»]
ProteinModelPortaliP26718
SMRiP26718
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP26718

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini98 – 213C-type lectinPROSITE-ProRule annotationAdd BLAST116

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4297 Eukaryota
ENOG410XPJ1 LUCA
HOGENOMiHOG000220925
HOVERGENiHBG052629
InParanoidiP26718
KOiK06728
OrthoDBiEOG091G0K9P
PhylomeDBiP26718
TreeFamiTF336674

Family and domain databases

CDDicd03593 CLECT_NK_receptors_like, 1 hit
Gene3Di3.10.100.10, 1 hit
InterProiView protein in InterPro
IPR001304 C-type_lectin-like
IPR016186 C-type_lectin-like/link_sf
IPR016187 CTDL_fold
IPR033992 NKR-like_CTLD
PfamiView protein in Pfam
PF00059 Lectin_C, 1 hit
SMARTiView protein in SMART
SM00034 CLECT, 1 hit
SUPFAMiSSF56436 SSF56436, 1 hit
PROSITEiView protein in PROSITE
PS50041 C_TYPE_LECTIN_2, 1 hit

Sequencei

Sequence statusi: Complete.

This entry describes 1 isoform i produced by alternative splicing. AlignAdd to basket

Note: A number of isoforms are produced.
Isoform 1 (identifier: P26718-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGWIRGRRSR HSWEMSEFHN YNLDLKKSDF STRWQKQRCP VVKSKCRENA
60 70 80 90 100
SPFFFCCFIA VAMGIRFIIM VAIWSAVFLN SLFNQEVQIP LTESYCGPCP
110 120 130 140 150
KNWICYKNNC YQFFDESKNW YESQASCMSQ NASLLKVYSK EDQDLLKLVK
160 170 180 190 200
SYHWMGLVHI PTNGSWQWED GSILSPNLLT IIEMQKGDCA LYASSFKGYI
210
ENCSTPNTYI CMQRTV
Length:216
Mass (Da):25,274
Last modified:August 1, 1992 - v1
Checksum:iC22F6BD533D7800E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti186K → R in BAF84709 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01329572A → T in allele NKG2-D*02. 4 PublicationsCorresponds to variant dbSNP:rs2255336Ensembl.1
Natural variantiVAR_030738177N → S. Corresponds to variant dbSNP:rs2306182Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54870 mRNA Translation: CAA38652.1
AJ001687, AJ001688, AJ001689 Genomic DNA Translation: CAA04925.1
AF461811 mRNA Translation: AAL65233.1
AF260135 mRNA Translation: AAF86973.1
AF260136 mRNA Translation: AAF86974.1
AK292059 mRNA Translation: BAF84748.1
AK292020 mRNA Translation: BAF84709.1
AC022075 Genomic DNA No translation available.
CH471094 Genomic DNA Translation: EAW96178.1
BC039836 mRNA Translation: AAH39836.1
CCDSiCCDS8623.1 [P26718-1]
PIRiPT0375
RefSeqiNP_001186734.1, NM_001199805.1
NP_031386.2, NM_007360.3
UniGeneiHs.387787

Genome annotation databases

EnsembliENST00000240618; ENSP00000240618; ENSG00000213809
ENST00000540818; ENSP00000446003; ENSG00000213809
GeneIDi100528032
22914
KEGGihsa:100528032
hsa:22914
UCSCiuc009zhj.4 human [P26718-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNKG2D_HUMAN
AccessioniPrimary (citable) accession number: P26718
Secondary accession number(s): A8K7K5, A8K7P4, Q9NR41
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: May 23, 2018
This is version 168 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

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