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Protein

NKG2-D type II integral membrane protein

Gene

KLRK1

Organism
Homo sapiens (Human)
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 MICA, MICB, RAET1E, RAET1G, ULBP1, ULBP2, ULBP3 (ULBP2>ULBP1>ULBP3) and ULBP4.6 Publications

GO - Molecular functioni

  • carbohydrate binding Source: UniProtKB-KW
  • MHC class Ib receptor activity Source: Ensembl
  • receptor activity Source: ProtInc

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-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

HGNCiHGNC:18788. KLRK1.

Subcellular locationi

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

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • external side of plasma membrane Source: Ensembl
  • integral component of membrane Source: ProtInc
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

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...)Sequence analysis1
Glycosylationi163N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi189 ↔ 203
Glycosylationi202N-linked (GlcNAc...)Sequence 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.

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

WithEntry#Exp.IntActNotes
MICAQ299832EBI-458344,EBI-1031130

Protein-protein interaction databases

BioGridi116576. 2 interactors.
DIPiDIP-31100N.
IntActiP26718. 4 interactors.
MINTiMINT-8289618.
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

Sequence similaritiesi

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

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4297. Eukaryota.
ENOG410XPJ1. LUCA.
HOGENOMiHOG000220925.
HOVERGENiHBG052629.
InParanoidiP26718.
KOiK06728.
OrthoDBiEOG091G0K9P.
PhylomeDBiP26718.
TreeFamiTF336674.

Family and domain databases

Gene3Di3.10.100.10. 1 hit.
InterProiIPR001304. C-type_lectin-like.
IPR016186. C-type_lectin-like/link.
IPR016187. CTDL_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]

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 rs2255336dbSNPEnsembl.1
Natural variantiVAR_030738177N → S.Corresponds to variant rs2306182dbSNPEnsembl.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

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
Functional Glycomics Gateway - Glycan Binding

NKG-2D

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.

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...

Protein-protein interaction databases

BioGridi116576. 2 interactors.
DIPiDIP-31100N.
IntActiP26718. 4 interactors.
MINTiMINT-8289618.
STRINGi9606.ENSP00000240618.

PTM databases

iPTMnetiP26718.
PhosphoSitePlusiP26718.

Polymorphism and mutation databases

BioMutaiKLRK1.
DMDMi128370.

Proteomic databases

MaxQBiP26718.
PaxDbiP26718.
PeptideAtlasiP26718.
PRIDEiP26718.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi100528032.
22914.
DisGeNETi100528032.
22914.
GeneCardsiKLRK1.
H-InvDBHIX0020427.
HGNCiHGNC:18788. KLRK1.
HPAiCAB021896.
MIMi611817. gene.
neXtProtiNX_P26718.
PharmGKBiPA128394594.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4297. Eukaryota.
ENOG410XPJ1. LUCA.
HOGENOMiHOG000220925.
HOVERGENiHBG052629.
InParanoidiP26718.
KOiK06728.
OrthoDBiEOG091G0K9P.
PhylomeDBiP26718.
TreeFamiTF336674.

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.

Miscellaneous databases

EvolutionaryTraceiP26718.
GeneWikiiKLRK1.
PROiP26718.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000213809.
CleanExiHS_KLRK1.
ExpressionAtlasiP26718. baseline and differential.
GenevisibleiP26718. HS.

Family and domain databases

Gene3Di3.10.100.10. 1 hit.
InterProiIPR001304. C-type_lectin-like.
IPR016186. C-type_lectin-like/link.
IPR016187. CTDL_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_HUMAN
AccessioniPrimary (citable) accession number: P26718
Secondary accession number(s): A8K7K5, A8K7P4, Q9NR41
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: November 30, 2016
This is version 158 of the entry and version 1 of the sequence. [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

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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 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.