CD337 NCR3 (natural cytotoxicity triggering receptor 3), NKp30 (natural killer cell p30-related protein),  Ly117, 1C7
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
NK Cell
30 / 30

Expression
CD337 is expressed selectively on all resting and activated NK cells and weakly in the spleen.

Structure
MOLECULAR FAMILY NAME: Belongs to  the immunuloglobulin gene family.

CD337 is a single-pass type-1 183 aa glycoprotein.  It contains an 18 aa signal sequence, a 117 aa extracellular domain which contains 1 Ig-like C2-type domain and 2 potential N-linked glycosylation sites, a 21 aa transmembrane domain which contains positively charged arginine that is predicted to associate with the CD3ζ chain (CD247) and a 45 aa intracellular cytoplasmic domain which has no known signaling motifs.  CD337 is a novel NK-specific molecule belonging to a group of receptors collectively termed the natural cytotoxicity receptors (NCR) within the Ig superfamily.

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 6 different isoforms.

POST-TRANSLATIONAL MODIFICATION

CD337 has 2 potential N-linked glycosylation sites.

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD337

CD337 interacts with CD3ζ.  CD337 is reported to bind membrane-associated heparan sulphate proteoglycans on tumor cells but a recent study found heparan sulphate are ligands to CD337.

Function
CD337 is a cytotoxicity-activating receptor and is a specific marker of NK cells that is partially responsible for NK-cell-mediated tumor cell lysis but the main receptor is involved in killing immature dendritic cells.  CD337-mediated NK cell interactions with immature dendritic cells does not alway end up in death.  Binding of NK cell CD337 with DC ligands promotes release of TNFα and IFNγ by NK cells which in turn promotes maturation of DC.  This function is controlled by HLA-specific inhibitory NK receptors.  The surface density of CD335, CD336 and CD337 correlates with the magnitude of NK cell cytolytic activity against target cells.  Variation in the surface density of these molecules occurs within and between individuals.  Prolactin can upregulate CD335 and CD337 expression of both NCRs.  Transforming growth factors β (TGFβ) downregulates the surface expression of NKp30 and inhibits NKp30 mediated killing of immature dendritic cells.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD337 IN INTACT ANIMAL

CD337 mediated cytotoxicity of tumor cells is suicidal for NK cells as CD337 engagement with tumor cell ligands leads to upregulation of FasL protein synthesis and release.  FasL ligation of Fas on the NK cell surface triggers caspase 3-dependent apoptosis.

Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD337: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD337: No information.

ADDITIONAL INSIGHTS

For further information see Moretta, A. et al (2001) Ann. Rev. Immunol. 19: 197-223.



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrez 259197O14931
Antibodies

Revised June 25, 2008


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