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FLASH GENE

Symbol

KLRK1

contributors: mct/npt/pgu - updated : 26-06-2013

HGNC name	killer cell lectin-like receptor subfamily K, member 1
HGNC id	18788

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Lymphoid/Immune spleen       highly Reproductive female system uterus cervix   highly Respiratory lung       moderately Urinary kidney       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Lymphoid

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune activated B lymphocyte Homo sapiens Lymphoid/Immune natural killer Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

extracytoplasmic carbohydrate recognition domain homologous with the C type family member, group V

conjugated

GlycoP

mono polymer

homomer , dimer

HOMOLOGY

interspecies

homolog to murine D6h12s2489e

Homologene

FAMILY

NKG2 family

CATEGORY

receptor membrane

SUBCELLULAR LOCALIZATION	plasma membrane
text	type II membrane orientation
	located within the NK complex
	type 2 membrane protein

basic FUNCTION	playing a role in the inhibition and activation of NK cells
	playing a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T-cells
	playing an early role in controlling and shaping tumor formation
	having a role to stimulate the formation of the NK immunological synapse (NKIS), with recruitment of NKG2D to the center synapse
	contributes to anti-tumour and anti-viral immune responses
	killer lectin-like receptor on natural killer cells triggering cytotoxicity through binding of glycans on target cells including sialyl Lewis X antigen
	is thought to participate in anticancer immune responses
	important activating receptor on lymphocytes
	KLRK1-mediated promotion of tumor growth becomes effective concurrent with the failure of immune defense at advanced tumor stages
	cancer cells themselves express KLRK1 in complex with HCST signaling adaptor
	its stimulation modulated the cytokine secretion of T cells activated simultaneously through CD3 and CD28
	regulates effector T-cell cytokine production
	vital activating receptor, also expressed on subsets of T cells, whose ligands are up-regulated by cells in stress
	KLRK1 ligand expression on target cells not only allows for activating receptor recognition, but also actively reduces expression of the inhibitory ligand, MHC class I, leading to enhanced recognition and killing by NK cells

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

immunity/defense

text	antimicrobial humoral response

PATHWAY

metabolism

signaling

signal transduction

a component	can form disulfide-bonded heterodimer with CD94
	KLRK1 in complex with the HCST signaling adaptor is expressed on most natural killer (NK) cells and CD8 T cells

INTERACTION

DNA

RNA

small molecule

protein	CD94 receptor, UL16-binding protein
	MICA, and MICB, ligands of the KLRK1, which activates NK cells and costimulates effector T cells, are inducibly expressed under harmful conditions, such as malignancies and microbial infections
	interacting with HCST and TYROBP
	KLRK1 ligands include the MHC class I-related chains A and B (MIC, A and B), which are absent from the surface of most normal cells but are induced by generic responses to cellular stress in diseased cells such as epithelial tumor cells
	ligand for KLRK1/KLRC1, KLRC2 is leukocyte antigen (HLA)-E, which is constitutively expressed on human cells
	bind to heparin and sulfate-containing polysaccharides (this binding is interesting for natural immunity in cancer progression and metastasis)
	interacts with two groups of ligands: the major histocompatibility complex class I chain-related A/B (MICA/B) family and the (ULBP) family, also known as retinoic acid early transcript (RAET1)
	cognate receptor for MICA (MICA-KLRK1 played a role in disease pathogenesis in the majority of patients in our cohort of cases of large granular lymphocyte leukemia and further investigation into this signaling axis may provide potent therapeutic targets)
	HMBOX1 may act as a negative regulator of NK cell functions via suppressing the KLRK1/HCST signaling pathway
	ligation of KLRK1 leads to phosphorylation of the associated HCST adaptor protein, thereby activating immune cells (PMID;
	CEACAM1 dampens antitumor immunity by down-regulating KLRK1 ligand expression on tumor cells
	MICA is a ligand of KLRK1
	augmented co-stimulation through KLRK1 is effective in rescuing CD4-unhelped CD8(+) T cells from their pathophysiological fate
	IL4 downregulated in a STAT6-dependent manner the memory-specific expression of KLRK1, thereby increasing the activation threshold of memory CD8 T cells
	KLRK1-RAET1L interactions

cell & other

REGULATION

repressed by

MICA

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   of KLRK1 and KLRF1 ligands by Kaposi sarcoma-associated herpesvirus K5 protects against NK cell cytotoxicity

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS