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Protein

NKG2-D type II integral membrane protein

Gene

Klrk1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Adaptive immunity, Differentiation, Immunity, Innate immunity

Keywords - Ligandi

Lectin

Enzyme and pathway databases

ReactomeiR-MMU-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
R-MMU-2172127. DAP12 interactions.
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1196250. Klrk1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 6666CytoplasmicSequence analysisAdd
BLAST
Transmembranei67 – 8923Helical; Signal-anchor for type II membrane proteinSequence analysisAdd
BLAST
Topological domaini90 – 232143ExtracellularSequence analysisAdd
BLAST

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • external side of plasma membrane Source: MGI
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

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

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)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 232232NKG2-D type II integral membrane proteinPRO_0000046668Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi112 ↔ 121
Disulfide bondi115 ↔ 126
Glycosylationi137 – 1371N-linked (GlcNAc...)Sequence analysis
Disulfide bondi143 ↔ 227
Glycosylationi147 – 1471N-linked (GlcNAc...)Sequence analysis
Glycosylationi179 – 1791N-linked (GlcNAc...)Sequence analysis
Disulfide bondi205 ↔ 219

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO54709.
PRIDEiO54709.

PTM databases

iPTMnetiO54709.
PhosphoSiteiO54709.

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.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 interactions.
IntActiO54709. 1 interaction.
STRINGi10090.ENSMUSP00000032252.

Structurei

Secondary structure

1
232
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi110 – 1123Combined sources
Beta strandi120 – 1223Combined sources
Beta strandi125 – 13410Combined sources
Helixi136 – 1449Combined sources
Turni145 – 1473Combined sources
Turni156 – 1594Combined sources
Helixi160 – 1645Combined sources
Beta strandi169 – 1757Combined sources
Turni177 – 1793Combined sources
Beta strandi182 – 1843Combined sources
Turni192 – 1943Combined sources
Beta strandi196 – 1983Combined sources
Beta strandi205 – 2084Combined sources
Beta strandi213 – 2175Combined sources
Beta strandi223 – 2297Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1HQ8X-ray1.95A110-232[»]
4PP8X-ray1.95A/B109-232[»]
ProteinModelPortaliO54709.
SMRiO54709. Positions 109-232.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO54709.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini122 – 228107C-type lectinPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 C-type lectin domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4297. Eukaryota.
ENOG410XPJ1. LUCA.
GeneTreeiENSGT00730000110282.
HOGENOMiHOG000220925.
HOVERGENiHBG052629.
InParanoidiO54709.
KOiK06728.
OMAiIRFIVMV.
OrthoDBiEOG091G0K9P.
PhylomeDBiO54709.
TreeFamiTF336674.

Family and domain databases

Gene3Di3.10.100.10. 1 hit.
InterProiIPR001304. C-type_lectin.
IPR016186. C-type_lectin-like.
IPR016187. C-type_lectin_fold.
[Graphical view]
PfamiPF00059. Lectin_C. 1 hit.
[Graphical view]
SMARTiSM00034. CLECT. 1 hit.
[Graphical view]
SUPFAMiSSF56436. SSF56436. 1 hit.
PROSITEiPS50041. C_TYPE_LECTIN_2. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1313Missing in isoform 2. 1 PublicationVSP_053945Add
BLAST

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

Cross-referencesi

Web resourcesi

Functional Glycomics Gateway - Glycan Binding

NKG2 D

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1HQ8X-ray1.95A110-232[»]
4PP8X-ray1.95A/B109-232[»]
ProteinModelPortaliO54709.
SMRiO54709. Positions 109-232.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi205095. 3 interactions.
IntActiO54709. 1 interaction.
STRINGi10090.ENSMUSP00000032252.

PTM databases

iPTMnetiO54709.
PhosphoSiteiO54709.

Proteomic databases

PaxDbiO54709.
PRIDEiO54709.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi22914.
MGIiMGI:1196250. Klrk1.

Phylogenomic databases

eggNOGiKOG4297. Eukaryota.
ENOG410XPJ1. LUCA.
GeneTreeiENSGT00730000110282.
HOGENOMiHOG000220925.
HOVERGENiHBG052629.
InParanoidiO54709.
KOiK06728.
OMAiIRFIVMV.
OrthoDBiEOG091G0K9P.
PhylomeDBiO54709.
TreeFamiTF336674.

Enzyme and pathway databases

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

Miscellaneous databases

EvolutionaryTraceiO54709.
PROiO54709.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000030149.
ExpressionAtlasiO54709. baseline and differential.
GenevisibleiO54709. MM.

Family and domain databases

Gene3Di3.10.100.10. 1 hit.
InterProiIPR001304. C-type_lectin.
IPR016186. C-type_lectin-like.
IPR016187. C-type_lectin_fold.
[Graphical view]
PfamiPF00059. Lectin_C. 1 hit.
[Graphical view]
SMARTiSM00034. CLECT. 1 hit.
[Graphical view]
SUPFAMiSSF56436. SSF56436. 1 hit.
PROSITEiPS50041. C_TYPE_LECTIN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNKG2D_MOUSE
AccessioniPrimary (citable) accession number: O54709
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: May 1, 1999
Last modified: September 7, 2016
This is version 134 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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

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
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.