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Symbol KLRK1 contributors: mct/npt/pgu - updated : 26-06-2013
HGNC name killer cell lectin-like receptor subfamily K, member 1
HGNC id 18788
Location 12p13.2      Physical location : 10.524.952 - 10.542.640
Synonym name
  • NKG2-D type II integral membrane protein
  • natural killer cell receptor G2D
  • DNA segment on chromosome 12 (unique) 2489 expressed sequence
  • CD314 antigen
  • Synonym symbol(s) KLR, KLRC4, NKG2D, D12S2489E, CD314, FLJ17759, FLJ75772
    TYPE functioning gene
    SPECIAL FEATURE overlapping, gene in gene
    text the first non-coding exon at the 5' end of the transcript is included in the 3' end of the KLRC4 transcript
    STRUCTURE 17.70 kb     8 Exon(s)
    motif repetitive sequence   long interspersed repetitive elements
    text structure two LINE elements
    MAPPING cloned Y linked N status confirmed
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 1593 - 216 - 2007 17923698
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunespleen   highly
    Reproductivefemale systemuteruscervix highly
    Respiratorylung   moderately
    Urinarykidney   moderately
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immuneactivated B lymphocyte Homo sapiens
    Lymphoid/Immunenatural killer Homo sapiens
    cell lineage
    cell lines
    at STAGE
  • extracytoplasmic carbohydrate recognition domain homologous with the C type family member, group V
  • conjugated GlycoP
    mono polymer homomer , dimer
    interspecies homolog to murine D6h12s2489e
  • NKG2 family
  • CATEGORY receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane
  • 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
    PHYSIOLOGICAL PROCESS immunity/defense
    text antimicrobial humoral response
    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
    small molecule
  • 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
    repressed by MICA
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    of KLRK1 and KLRF1 ligands by Kaposi sarcoma-associated herpesvirus K5 protects against NK cell cytotoxicity
    Variant & Polymorphism
    Candidate gene
    Therapy target