KLRK1 killer cell lectin-like receptor subfamily K, member 1 [Homo sapiens (human)] - Gene

Summary

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Official Symbol: KLRK1provided by HGNC
Official Full Name: killer cell lectin-like receptor subfamily K, member 1provided by HGNC
Primary source: HGNC:18788
See related: Ensembl:ENSG00000213809; HPRD:17240; MIM:611817; Vega:OTTHUMG00000168574
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: KLR; CD314; NKG2D; NKG2-D; D12S2489E
Summary: Natural killer (NK) cells are lymphocytes that can mediate lysis of certain tumor cells and virus-infected cells without previous activation. They can also regulate specific humoral and cell-mediated immunity. NK cells preferentially express several calcium-dependent (C-type) lectins, which have been implicated in the regulation of NK cell function. The NKG2 gene family is located within the NK complex, a region that contains several C-type lectin genes preferentially expressed in NK cells. This gene encodes a member of the NKG2 family. The encoded transmembrane protein is characterized by a type II membrane orientation (has an extracellular C terminus) and the presence of a C-type lectin domain. It binds to a diverse family of ligands that include MHC class I chain-related A and B proteins and UL-16 binding proteins, where ligand-receptor interactions can result in the activation of NK and T cells. The surface expression of these ligands is important for the recognition of stressed cells by the immune system, and thus this protein and its ligands are therapeutic targets for the treatment of immune diseases and cancers. Read-through transcription exists between this gene and the upstream KLRC4 (killer cell lectin-like receptor subfamily C, member 4) family member in the same cluster. [provided by RefSeq, Dec 2010]

Genomic context

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Location :: 12p13.2-p12.3

Sequence :: Chromosome: 12; NC_000012.11 (10524952..10542653, complement)

See KLRK1 in Epigenomics, MapViewer

Chromosome 12 - NC_000012.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

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Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Decreased number and reduced NKG2D expression of Vdelta1 gammadelta T cells are involved in the impaired function of Vdelta1 gammadelta T cells in the tissue of gastric cancer.
Title: Decreased number and reduced NKG2D expression of Vδ1 γδ T cells are involved in the impaired function of Vδ1 γδ T cells in the tissue of gastric cancer.
Simultaneous knockdown of multiple ligands (MICA/B, ULBP2, and ULBP3) significantly attenuated NK cell cytolysis against human NKG2D ligand-positive hepatocyte L-02 cells.
Title: Simultaneous knockdown of multiple ligands of innate receptor NKG2D prevents natural killer cell-mediated fulminant hepatitis in mice.
Here, the authors show that cowpox virus-encoded OMCP binds the NKG2D homodimer as a monomer and competitively blocks host ligand engagement.
Title: Crystal structure of the cowpox virus-encoded NKG2D ligand OMCP.
The ability to express NKG2D at the cell surface was primarily determined by the activation or differentiation status of the CD4(+) T-cells and not by the antigen presenting cells
Title: Regulation and gene expression profiling of NKG2D positive human cytomegalovirus-primed CD4+ T-cells.
studies may suggest that the women with cervical cancer bearing the NKG2D 72Thr gene variant might be protected against progression to advanced stages of this cancer
Title: Prevalence of the NKG2D Thr72Ala polymorphism in patients with cervical carcinoma.
NKG2D haplotypes are associated with the expression levels of NKG2D protein on NK and CD8 T cells, resulting in inter-individual variations in human cytotoxic response.
Title: Effects of NKG2D haplotypes on the cell-surface expression of NKG2D protein on natural killer and CD8 T cells of peripheral blood among atomic-bomb survivors.
TGF-beta1 secreted by multipotent mesenchymal stromal cells is responsible for impaired cytotoxic t-cells and natural killer function by down-modulating surface NKG2D expression.
Title: Immune protection function of multipotent mesenchymal stromal cells: role of transforming growth factor-β1.
Decreased expression of NKG2D in transgenic mice in response to IL-4 is associated with inhibition of NKG2D-dependent CD8 T cell activation.
Title: Negative regulation of NKG2D expression by IL-4 in memory CD8 T cells.
these results suggest that differential expression of NKG2D-ligands in cervical cancer cell lines might be associated with the down-modulation of NKG2D, as well as with changes in the cytotoxic activity of NKL cells after cell-cell contact with the tumor cells.
Title: Cervical cancer cell lines expressing NKG2D-ligands are able to down-modulate the NKG2D receptor on NKL cells with functional implications.
study describes that both N-WASp and WASp participate in the inhibition of NK-cell chemotaxis in response to NKG2D WASp engagement, and that this effect is not dependent on the regulation of F-actin dynamics
Title: Wiskott-Aldrich syndrome protein (WASp) and N-WASp are involved in the regulation of NK-cell migration upon NKG2D activation.

Submit: New GeneRIF Correction See all (188)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

HIV-1 protein interactions

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Protein	Gene	Interaction	Pubs
Nef, p27	nef	HIV-1 Nef-mediated downregulation of NKG2DL triggers decreased signals delivered via NKG2D, which results in a weaker activation of NK cells and in reduced lysis	PubMed
Vpu, p16	vpu	HIV-1 Vpu-mediated down modulation of NTB-A decreases NK cell activation via NKG2D, which results in protecting HIV-1 infected cells from lysis by NK cells	PubMed

Go to the HIV-1, Human Protein Interaction Database

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P26718	DAP10	HCST	HPRD	PubMed
P26718	P30460	HLA-B	HPRD	PubMed
P26718	P26718	KLRK1	HPRD	PubMed
P26718	MICB	MICB	HPRD	PubMed
P26718	Q8TD07	RAET1E	HPRD	PubMed
P26718	Q6H3X3	RAET1G	HPRD	PubMed
P26718	O43914	TYROBP	HPRD	PubMed
P26718	Q9BZM4	ULBP3	HPRD	PubMed
BioGRID:116576	BioGRID:116079	HCST	BioGRID	PubMed	Affinity Capture-Western
BioGRID:116576	BioGRID:114054	RAE1	BioGRID	PubMed	Reconstituted Complex

Pathways from BioSystems

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Adaptive Immune System, organism-specific biosystem (from REACTOME)
Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
DAP12 interactions, organism-specific biosystem (from REACTOME)
DAP12 interactions, organism-specific biosystemDNAX activation protein of 12kDa (DAP12) is an immunoreceptor tyrosine-based activation motif (ITAM)-bearing adapter molecule that transduces activating signals in natural killer (NK) and myeloid cel...
DAP12 signaling, organism-specific biosystem (from REACTOME)
DAP12 signaling, organism-specific biosystemIn response to receptor ligation, the tyrosine residues in DAP12's immunoreceptor tyrosine-based activation motif (ITAM) are phosphorylated by Src family kinases. These phosphotyrosines form the dock...
Immune System, organism-specific biosystem (from REACTOME)
Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell, organism-specific biosystem (from REACTOME)
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell, organism-specific biosystemA number of receptors and cell adhesion molecules play a key role in modifying the response of cells of lymphoid origin (such as B-, T- and NK cells) to self and tumor antigens, as well as to pathoge...
Innate Immune System, organism-specific biosystem (from REACTOME)
Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
Malaria, organism-specific biosystem (from KEGG)
Malaria, organism-specific biosystemPlasmodium protozoa are parasites that account for malaria infection. Sporozoite forms of the parasite are injected by mosquito bites under the skin and are carried to the liver where they develop in...
Malaria, conserved biosystem (from KEGG)
Malaria, conserved biosystemPlasmodium protozoa are parasites that account for malaria infection. Sporozoite forms of the parasite are injected by mosquito bites under the skin and are carried to the liver where they develop in...
Natural killer cell mediated cytotoxicity, organism-specific biosystem (from KEGG)
Natural killer cell mediated cytotoxicity, organism-specific biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
Natural killer cell mediated cytotoxicity, conserved biosystem (from KEGG)
Natural killer cell mediated cytotoxicity, conserved biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...

General gene information

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Readthrough KLRC4-KLRK1

Readthrough gene: KLRC4-KLRK1, Included gene: KLRC4

Homology

Homologs of the KLRK1 gene: The KLRK1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, and rat.
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

General protein information

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Preferred Names: NKG2-D type II integral membrane protein

Names: NKG2-D type II integral membrane protein; NK cell receptor D; NKG2-D-activating NK receptor

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_027762.1 RefSeqGene

Range

4988..22689

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_007360.3 → NP_031386.2 NKG2-D type II integral membrane protein

Status: REVIEWED

Source sequence(s)

AC022075, AK292059, CB241686, DA933271

Consensus CDS

CCDS8623.1

UniProtKB/Swiss-Prot

P26718

Related

ENSP00000240618, OTTHUMP00000239062, ENST00000240618, OTTHUMT00000400269

Conserved Domains (2) summary

cd03593
Location:99 – 213
Blast Score: 338

CLECT_NK_receptors_like; C-type lectin-like domain (CTLD) of the type found in natural killer cell receptors (NKRs)

PHA03097
Location:47 – 214
Blast Score: 125

PHA03097; C-type lectin-like protein; Provisional

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000012.11 Reference GRCh37.p10 Primary Assembly

Range

10524952..10542653, complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000144.1 Alternate HuRef

Range

10267379..10285074, complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018923.1 Alternate CHM1_1.0

Range

10397928..10415622, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01067805.1 (34363..52058)	None
genomic	AC022075.29 (10059..45472)	None
genomic	AJ001687.1	CAA04925.1
genomic	AMYH01004277.1 (66286..83980)	None
genomic	CH471094.1	EAW96178.1
		EAW96180.1
		EAW96182.1
genomic	DQ494172.1	ABF50044.1
mRNA	AF260135.1	AAF86973.1
mRNA	AF260136.1	AAF86974.1
mRNA	AK226161.1	None
mRNA	AK292059.1	BAF84748.1
mRNA	BC039836.1	AAH39836.1
mRNA	CB241686.1	None
mRNA	DA933271.1	None
mRNA	DA960048.1	None