|CD244||NAIL (NK cell activation-inducing ligand), 2B4, Nmrk, NKR2B4 (natural killer receptor 2B4), SLAM4|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
Type 1 glycoprotein
|70 / 70|
|Human CD244 is expressed on the surface of resting and activated NK cells, g/d T cells, ~50% CD8+ T cells, some CD8+ thymocytes, a small % of CD4+ cells, monocytes and basophils. In mice, expression is on dendritic epidermal T cells and on all NK and T cells capable of non-MHC-restricted cytotoxicity. The latter include dendritic epidermal gd T cells and a subset of T cells cultured in IL-2. CD244 is not expressed on B cells. CD244 is expressed in spleen, PBL, lung, liver, testis and small intestine.|
|MOLECULAR FAMILY NAME: Belongs to the immunoglobulin gene superfamily.|
CD244 is a single-pass type-1 370 aa glycoprotein. It contains 21 aa leader sequence, a 208 aa extracellulardomain which contains an Ig-like V-type and an Ig-like C2-type and 8 potential N-linked glycosylation sites, a 21 aa transmembrane domain and a 120 aa long cytoplasmic tail with 4 tyrosine-based switch motifs (ITSMs, TxYxxV/I) capable of binding several SH2-domain containing proteins including both activating and inhibitory signaling molecules. The extracellular portion of this Ig domain-containing glycoprotein exhibits several structural features that place it within the CD2 family of the Ig (see CD2), which probably arose from a series of gene duplication events. In addition to CD2 and CD244 this family includes CD48, CD58, CD84 CD229, and CD150. The human CD244 exhibits about 66% identify with mouse CD244. The mouse CD244 gene is situated on mouse chromosome 1 near the gene for Ly-17, mouse CD32, placing it close to the CD229 and CD48 loci.
CD244 is phosphorylated by src family kinases like lck. Alternative splicing yields 4 different isoforms.
The membrane-proximal Ig domain is particularly highly glycosylated. There are 8 potential N-linked glycoylation sites in human CD244 and 7 in mouse CD244. About 35% of the Mr corresponds to glycosylation of the protein. Cytoplasmic tyrosine residues are phosphorylated upon NK cell activation by target cells that express CD4.
| LIGANDS AND MOLECULES ASSOCIATED WITH CD244|
|CD244 plays a role in non-MHC-restricted cytotoxic activity of NK cells and acts as a costimulatory ligand for both NK cell and T cells in vitro. Treatment with a CD244 mAb activates these cells which augments the non-MHC-restricted cytotoxicity. CD244 is a NK cell-cell surface receptor which recruits protein tyrosine phosphatase, SHP-2, and the adapter signaling protein, SAP. CD244 modulates NK cell cytokine production, cytolytic function and extravasation. It may modulate other receptor-ligand interactions to enhance leukocyte activation. During CD244-CD48 mediated homotypic interaction of T cells and NK cells or NK-T-cell interactions, CD244 signaling is proposed to induce optimal activation of T cells and NK cells and may serve to increase cell-cell adhesion. However interaction of CD244 on NK cells with other CD48+ target cells such as tumor cell can lead to inhibition of NK effector functions. CD244 knockout mice are phenotypically normal but have an increased capacity to clear CD48+ tumor cells in vivo. Consistent with this finding are the result of cytotoxicity assays performed with CD244-/- splenic NK cells, which demonstrated enhanced killing of CD48+ target cells. These findings are consistent with CD244 acting as an inhibitory receptor.|
BIOCHEMICAL ACTIVITY: No information.
DISEASE RELEVANCE AND FUNCTION OF CD244 IN INTACT ANIMAL
Defective signaling by CD244 and SAP may contribute to the X-linked lymphoproliferative (XLP) disorder that is triggered following EBV infection. XLP was identified as SLAM associated protein (SAP) and encodes a small SH2 domain containing protein. CD244 may play a role in autoimmune diseases such as rheumatoid arthritis. A proportion of CD244+CD8+ T cells in HIV infected individuals increases with disease progression.
|MOLECULAR INTERACTIONS -|
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD244: No information.
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD244
The Src-family kinases like lck or fyn can phosphorylate CD244.
CD244 may function as a co-receptor with NKp46, an activating receptor implicated in natural cytotoxicity. Inhibitory receptors on NK cells can block CD244-mediated NK cell activation and prevent tyrosine phosphorylation of CD244.
Database accession numbers
Revised June 25, 2008