|CD319||SLAMF7 (SLAM family member 7), CRACC, 19A24, 19A, CS1|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
Type 1 glycoprotein
|66 / 66|
|CD319 is expressed on NK cells, subsets of mature dendritic cells, activated B cells, cytotoxic lymphocytes but not in promyelocytic, B- or T-cell lines. Expression is high in spleen, lymph node, periperal blood leukocytes and lowest in bone marrow. Expression is in small intestine, stomach, appendix, lung and trachea. |
|MOLECULAR FAMILY NAME: Belongs to the immunoglobulin gene family.|
CD319 is a single-pass type-1 335 aa transmembrane glycoprotein. It contains a 22 aa signal sequence, a 225 aa extracellular domain which contains an Ig-like C2-type domain and 6 putative N-linked glycosylation sites, a 23 aa transmembrane domain and a 85 aa cytoplasmic tail which has 2 immunoreceptor tyrosine-based switch motifs (ITIMs). CD319 shows a 66 kDa protein with immunoprecipation and SDS-PAGE, and after deglycosylation, a 37 kDa protein. Immunoblot analysis showed that CD319 is tyrosine phosphorylated in activated NK cells and is associated with 19- and 39 kDa proteins. CD319 has a homology with the CD2 family of receptors within the Ig superfamily. Some of the CD2 members stimulate cytotoxicity through the CD319 associated protein.
Alternative splicing yields 3 different isoforms. Isoform 1 and 2 are observed in NK cells and mediate NK cell activation through a SAP-independent extracellular signal-related ERK-pathway. The long isoform is the functional molecule. Isoform 3 is the short isoform that lacks ITIM motifs and does not trigger any signaling pathways. Isoform 3 does not mediate any activation. SAP can bind the cytoplasmic tail of isoform 1 when phosphorylated in the presence of Fyn (in vitro). Isoform 3 is expressed at a much lower level.
CD319 has 6 putative N-linked glycosylation sites.
|LIGANDS AND MOLECULE ASSOCIATES WITH CD319|
CD319 displays homophilic binding.
|CD319 is thought to play a role in regulating T cell and NK cell functions. CD319 is thought to play a role in regulating T cell and NK cell functions. RT-PCR analysis detected CD319 expression in NK and CD8 positive cytotoxic cells. Flow cytometric analysis demonstrated expression on nearly all NK cells, a large subset of CD8 cells and a few CD4 and B cells. B cells were upregulated upon CD40 activation and expression on dendritic cells were upregulated by influenza virus, lipopolysaccharide and CD40L. Functional analysis indicated that CD319 mediates lysis that is in addition to that mediated by CD335 or CD16. Further analysis determined that unlike CD244, cytotoxicity mediated by CD319 or CD335 is CD319-associated protein independent and that CD319 triggers ERK activation. Unlike other members of the CD2 family, CD319 triggers NK cell-mediated cytotoxicity via the recruitment of extracellular signal-regulated kinases-1/2 instead of a SAP-dependent signaling pathway. Although CD319-mediated SAP-independent cytotoxicity occurs in NK cells, studies have found that SAP does associate with CD319 cytoplasmic tail and therefore may play a signaling role in other CD319-mediated effects. Ligation of CD319 was shown to induce proliferation, adhesion, cytokine secretion and cytotoxicity of T cells as well as NK cells. NK cell function is regulated by a balance between signaling inhibitory and activating receptors. Some members of the CD2 family of activating receptors (e.g. CD244) stimulate cytotoxicity through the CD319-associated protein. |
Unlike other members of the CD2 family, CD319 triggers NK cell-mediated cytotoxicity via the recruitment of extracellular signal-regulated kinases-1/2 instead of a SAP-dependent
BIOCHEMICAL ACTIVITY: No information.
DISEASE RELEVANCE AND FUNCTION OF CD319 IN INTACT ANIMAL
Mutations in the SH2 domain of CD319 cause deficiencies in other CD2 family proteins that transduce signals through CD319 and these deficiences lead to uncontrolled Epstein-Barr virus (EBV) infections, and ultimately, to X-linked lymphoprpliferative disease. It is proposed that CD319 may be important in controlling pathogens other than EBV. This protein may also play a role in regulating lymphocyte adhesion.
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD319: No information.
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD319: No information.
For further informationj see Murphy, J.J. et al (2002) Biochem. J. 361: 431-436.
Database accession numbers
Revised June 25, 2008