CD336 NCR2 (natural cytotoxicity triggering receptor 2), NKp44 (natural killer cell p44-related protein), LY95 (lymphocyte antigen 95 homolog), 
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
NK Cell
T Cell
44 / 44

Expression
CD336 is expressed selectively by IL-2 activated NK cells and in vitro a minor subset of γ/δ T cells.

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

CD336 is a single-pass type-1 255 aa transmembrane glycoprotein.  It contains an 171 aa extracellular domain which contains 1 Ig-like C2-type domain and 1 potential N-linked glycosylation site, a 21aa transmembrane domain and a 63 aa cytoplasmic domain.which has no known signaling motif.  CD336 has an exon encoding the 5-prime UTR and leader peptide.  A second exon encodes the Ig-like C2-type domain and a variable number of downstream exons encoding the stalk, transmembrane and cytoplasmic regions.  It is a novel NK-specific molecule belonging to a group of receptors collectively termed the natural cytotoxicity receptors (NCR) family within the Ig superfamily. 

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 3 different isoforms.

POST-TRANSLATIONAL MODIFICATION

CD336 has 2 potential N- and 1 O-linked glycosylation sites and has a molecular mass of 44 kDa.

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD336

CD336 interacts with TYROBP/DAP12.  CD336 binds the hemagglutinins of both influenza and Sendai viruses.

Function
CD336 belongs to a group of receptors collectively termed the natural cytotoxicity receptors (NCR).  This cytotoxicity-activating receptor that may contribute to the increased efficiency of activated NK cells to mediate cell lysis. of autologous virus-infected cells and tumor cells.  These receptors trigger NK cells activation upon recognition of non-MHC and HLA ligands promoting lysis of the tumor target cell.  CD336 is involved in viral hemagglutinins.  CD336 lacks any cytoplasmic signaling motifs but associates with DAP12/KARAP that bears an ITIM and delivers activating signals.  The surface density of CD335, CD336 and CD337 correlates with the magnitude of NK-cell cytolytic activity against target.  Variation in the surface density of these molecules within and between individuals.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD336 IN INTACT ANIMAL

CD336-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-
PROTEIN AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD336: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD336: No information.

ADDITIONAL INSIGHTS

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


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 9436O95944
Antibodies

Revised June 25, 2008


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