CD96 Tactile (T cell activation increased late expression)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
NK Cell
Leukemia cell
T Cell
160 / 160
180 / 180
240 / 240

Expression
CD96 is expressed at low levels on peripheral resting T and NK cells and expression is at higher levels when activated, both helper and cytotoxic, T and NK cells which is increased reaching a maximum at 6-9 days.  CD96 is not expressed on B cells or monocytes.  In studies, CD96 was expressed on 78% of T cell leukemia and on 29% acute myeloid leukemias.  It was not expressed on any non-hematopoietic cell lines tested.

Structure
MOLECULAR FAMILY NAME: Belongs to the immunoglobulin supergene family.

CD96 is a single-chain type-1 569 aa glycoprotein.  It contains a signal peptide, an extracellular domain which contains 1 Ig-like C2-type domain, 2 Ig-like V-type domains, 1 mucin-like domain, 15 N-linked glycosylation sites that can be sialylated and sulfated and a 132 aa serine/threonine/proline-rich stalk region which is probably O-glycosylated, a transmembrane domain and a 45 aa  proline-rich cytoplasmic domain with ITIM-like motifs however, no inhibitory signaling function has been attributed to these sequences.  CD96 can form disulphide-linked homodimers.

MOLECULAR MASS
Cell Type Unreduced Reduced
160, 180, 240 kDa 160 kDa

POST-TRANSCRIPTIONAL MODIFICATION

CD96 has several differentially spliced transcripts.  The 1st encodes a soluble form consisting only of the 3 Ig-like domains, while the 2nd encodes an insertion of 16 aa into the 2nd Ig domain.

POST-TRANSLATIONAL MODIFICATION

There is extensive N- and O-linked glycosylation, sialylated and sulfate.


Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD96: 

CD96 binds  the poliovirus receptor CD155 (PVR).

Function
CD96 plays a role in the adhesion of activated T and NK cells during the late phase of immune response.  It also plays a role in antigen presentation and/or lymphocyte activation.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD96 IN INTACT ANIMAL

CD96 is a useful marker for immunophenotyping of T-cell acute lymphoblastic leukemias as well as a subgroup of acute myeloid leukemias.  CD96 promotes T lymphocyte and NK cell adhesion to target cells expressing poliovirus receptor (PVR).  Strong adhesion between CD96 and PVR stimulates cytotoxicity of activated NK cells and promotes transfer of PVR from the target cell to the NK cell.  PVR is expressed at high levels in many tumors and the recognition of PVR via binding to CD96 may be important for NK-cell recognition of tumors.

Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD96: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD96: No information.

ADDITIONAL INSIGHTS

There is adhesion of activated T and NK cells during the late phase of the immune response.  The partial sequence of mouse CD96 from EST indicates that the transmembrane and cytoplasmic domains are highly conserved across species.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene10225Q5JPB3
Antibodies

Revised June 25, 2008


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