CD314 KLRK1 (killer cell lectin-like receptor subfamily K member 1), NKG2D
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 2 glycoprotein
NK Cell
T Cell
Macrophage
Myeloid Cell
42 / 42

Expression
CD314 is expressed on human NK cells, CD8+ T cells, a minor subset CD4+ T cells and , on some myeloid cells.  Expression is essentially all CD56+CD3-NK cells from freshly isolated PBMC and also detected in CD8-αβ T cells.  Mice express CD314 on NK cells, γ/δ and a subset of NK1.1 T cells as well as on activated macrophages.

Structure

MOLECULAR FAMILY NAME: Belongs to the C-type lectin family.

CD314 is a single-pass type-2 glycoprotein.  It contains an extracellular domain which contain a single C-type lectin domain linked to a membrane-proximal stalk and contains 3 potential N-glycosylation sites, a transmembrane region which contains an arginine amino acid and a 51 aa N-terminal cytoplasmic domain.  CD314 is a member of the NKG2 group which are expressed primarily in natural killer (NK) cells and encodes a family of transmembrane proteins.  CD314 exists in the membrane as a disulphide-linked homodimer and requires association with the adaptor molecules DAP10 for membrane expression.  DAP10 contains an aspartate amino acid in the transmembrane domain, which is thought to form a salt bridge to the argionine.  DAP10 also contains a YINM motif which is phosphorylated to initiate a signal cascade.   

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 1 isoform.  Murine CD314 has an isoform with a shorter cytoplasmic domain, generated by alternative RNA splicing.  This isoform can associate with either DAP10 or DAP12 (CD172b).  The latter has an ITAM activation motif.

POST-TRANSLATIONAL MODIFICATION: No information.



Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD314

CD314 binds strongly to at least 6 ligands in the human, all of which are related to MHC class I.  They are MICA, MICB, H60, ULBPs (1-3) and RAE-1.  MICA and MICB have been identified as ligands for CD314.  Binding of ligand to receptor activates NK cells and co-stimulates T cells.  Engagement activates cytolysis and cytokine production.  Mice have orthologs of the ULBP genes but lack MIC genes. 


Function
CD314 exists as a homodimer and interacts together with DAP10 which is required for cell surface expression.  The receptor for MICA, MICB and MLBP1-3 plays a role for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T cells and is involved in the immune surveillance exerted by T and B lymphocytes.  This protein may also play a role in regulating lymphocyte adhesion.  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 contain several C-type lectin genes, preferentially expressed on NK cells. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD314 IN INTACT ANIMAL

CD314 may play a role on integrin dependent morphology and motility functions and may participate in the regulation of neurite outgrowth and maintence of the neural network in the brain.  CD314 antibodies are used in studies of cytotoxocity particularly in relation to cancer.  CD314 recognizes transformed or virus-infected cells expressing CD314 ligands and thereby activated cell-mediating killing.


Comments
MOLECULAR INTERACTION-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD314: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD314: No information.

ADDITIONAL INSIGHTS

For further information see Rosen, D. B. et al (2004) J. Immunol. 173: 2470-2478.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene22914P26718
Antibodies

Revised June 25, 2008


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