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Protein

NKG2-D type II integral membrane protein

Gene

Klrk1

Organism
Mus musculus (Mouse)
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 RAET1A, RAET1B, RAET1C, RAET1D, RAET1E, H60 and MULT1.14 Publications

Miscellaneous

Is not capable of signal transduction by itself; isoform 1 operates either through the signaling adapter protein HCST and isoform 2 through both HCST and TYROBP signaling adapter proteins (PubMed:12426564). Some families of ligands for mouse and human 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).2 Publications

GO - Molecular functioni

  • carbohydrate binding Source: UniProtKB-KW
  • kinase binding Source: UniProtKB
  • MHC class Ib receptor activity Source: MGI
  • MHC class I protein binding Source: MGI
  • protein homodimerization activity Source: MGI

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-MMU-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-MMU-2424491 DAP12 signaling

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:Nkg2d
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1196250 Klrk1

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 – 66CytoplasmicSequence analysisAdd BLAST66
Transmembranei67 – 89Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST23
Topological domaini90 – 232ExtracellularSequence analysisAdd BLAST143

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Involved in autoreactive CD8(+) T-cell-mediated development of autoimmune diabetes.1 Publication

Disruption phenotypei

Mice display no visible phenotype. According to PubMed:18394936, show normal development of NK cells, B and T cells but display enhanced formation of aggressive tumors. According to PubMed:19631564, exhibit developmental perturbation in size of NK cell subpopulations, increased proliferation, faster maturation and increased sensitivity to apoptosis of immature NK cells, and lower cytolytic response to KLRK1-sensitive tumor targets.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000466681 – 232NKG2-D type II integral membrane proteinAdd BLAST232

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi112 ↔ 121
Disulfide bondi115 ↔ 126
Glycosylationi137N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi143 ↔ 227
Glycosylationi147N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi179N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi205 ↔ 219

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO54709
PRIDEiO54709

PTM databases

iPTMnetiO54709
PhosphoSitePlusiO54709

Expressioni

Tissue specificityi

Expressed in natural killer (NK) cells, activated CD8+ alpha-beta and gamma-delta T-cells and natural killer T (NKT) cells (at protein level). May be expressed on dendritic cell (DC). Isoform 1 is strongly expressed in natural killer (NK) cells. Isoform 2 is weakly expressed in natural killer (NK) cells. Isoform 1 and isoform 2 are expressed in stimulated, but not in unstimulated, CD8+ T-cells and macrophages.4 Publications

Developmental stagei

Expressed in NK cells from the thymus at 15 dpc (at protein level).1 Publication

Inductioni

Up-regulated in activated CD8+ T-cells. Up-regulated upon lipopolysaccharide (LPS) and interferon treatments in macrophages. Up-regulated in CD8+ T-cell infiltring pancreatic islets of prediabetic nonobese diabetic (NOD) mice (at protein level). Isoform 1 and isoform 2 are up-regulated upon T-cell receptor (TCR) stimulation in CD8+ T-cells. Isoform 1 is modestly up-regulated upon lipopolysaccharide (LPS) in macrophages. Isoform 2 is up-regulated upon lipopolysaccharide (LPS) in macrophages. Isoform 2 is up-regulated upon poly(I:C) and interleukin IL2 in natural killer (NK) cells.2 Publications

Gene expression databases

BgeeiENSMUSG00000030149
ExpressionAtlasiO54709 baseline and differential
GenevisibleiO54709 MM

Interactioni

Subunit structurei

Homodimer; disulfide-linked. Heterohexamer composed of two subunits of KLRK1 and four subunits of HCST/DAP10 (By similarity). Isoform 1 (via transmembrane domain) interacts with HCST/DAP10; the interaction is required for KLRK1 cell surface expression on activated CD8+ T-cells, but is dispensable on activated TYROBP-expressing NK cells. Isoform 2 (via transmembrane domain) interacts with HCST/DAP10 (via transmembrane domain); the interaction is required for KLRK1 NK cell surface expression and induces NK cell-mediated cytotoxicity. Isoform 2 (via transmembrane domain) interacts with TYROBP (via transmembrane domain); the interaction is required for KLRK1 NK cell surface expression and induce NK cell-mediated cytotoxicity and cytokine secretion. Isoform 1 does not interact with TYROBP. Interacts with CEACAM1; recruits PTPN6 that dephosphorylates VAV1 (By similarity).By similarity4 Publications

GO - Molecular functioni

  • kinase binding Source: UniProtKB
  • MHC class I protein binding Source: MGI
  • protein homodimerization activity Source: MGI

Protein-protein interaction databases

BioGridi205095, 3 interactors
IntActiO54709, 1 interactor
STRINGi10090.ENSMUSP00000032252

Structurei

Secondary structure

1232
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi110 – 112Combined sources3
Beta strandi120 – 122Combined sources3
Beta strandi125 – 134Combined sources10
Helixi136 – 144Combined sources9
Turni145 – 147Combined sources3
Turni156 – 159Combined sources4
Helixi160 – 164Combined sources5
Beta strandi169 – 175Combined sources7
Turni177 – 179Combined sources3
Beta strandi182 – 184Combined sources3
Turni192 – 194Combined sources3
Beta strandi196 – 198Combined sources3
Beta strandi205 – 208Combined sources4
Beta strandi213 – 217Combined sources5
Beta strandi223 – 229Combined sources7

3D structure databases

ProteinModelPortaliO54709
SMRiO54709
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO54709

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini122 – 228C-type lectinPROSITE-ProRule annotationAdd BLAST107

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4297 Eukaryota
ENOG410XPJ1 LUCA
GeneTreeiENSGT00730000110282
HOGENOMiHOG000220925
HOVERGENiHBG052629
InParanoidiO54709
KOiK06728
OMAiESYCGPC
OrthoDBiEOG091G0K9P
PhylomeDBiO54709
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

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: A number of isoforms are produced.
Isoform 1 (identifier: O54709-1) [UniParc]FASTAAdd to basket
Also known as: NKG2D long, NKG2D-L

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
MALIRDRKSH HSEMSKCHNY DLKPAKWDTS QEQQKQRLAL TTSQPGENGI
60 70 80 90 100
IRGRYPIEKL KISPMFVVRV LAIALAIRFT LNTLMWLAIF KETFQPVLCN
110 120 130 140 150
KEVPVSSREG YCGPCPNNWI CHRNNCYQFF NEEKTWNQSQ ASCLSQNSSL
160 170 180 190 200
LKIYSKEEQD FLKLVKSYHW MGLVQIPANG SWQWEDGSSL SYNQLTLVEI
210 220 230
PKGSCAVYGS SFKAYTEDCA NLNTYICMKR AV
Length:232
Mass (Da):26,710
Last modified:May 1, 1999 - v2
Checksum:i050536EF8C23088A
GO
Isoform 2 (identifier: O54709-2) [UniParc]FASTAAdd to basket
Also known as: NKG2D short, NKG2D-S

The sequence of this isoform differs from the canonical sequence as follows:
     1-13: Missing.

Show »
Length:219
Mass (Da):25,148
Checksum:i01A3B539F9E24A6A
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0539451 – 13Missing in isoform 2. 1 PublicationAdd BLAST13

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF054819 mRNA Translation: AAC24356.1
AF039026 mRNA Translation: AAD02117.1
BC057147 mRNA Translation: AAH57147.1
AF030313 mRNA Translation: AAC28245.1
CCDSiCCDS39660.1 [O54709-1]
CCDS39661.1 [O54709-2]
RefSeqiNP_001076791.1, NM_001083322.2 [O54709-2]
NP_149069.1, NM_033078.4 [O54709-1]
UniGeneiMm.8217

Genome annotation databases

EnsembliENSMUST00000032252; ENSMUSP00000032252; ENSMUSG00000030149 [O54709-1]
ENSMUST00000095412; ENSMUSP00000093061; ENSMUSG00000030149 [O54709-2]
GeneIDi27007
KEGGimmu:27007
UCSCiuc009egf.2 mouse [O54709-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiNKG2D_MOUSE
AccessioniPrimary (citable) accession number: O54709
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: May 1, 1999
Last modified: June 20, 2018
This is version 146 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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