CD6 T12
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Peripheral blood
B Cell
Thymocyte
Neuron
T Cell
105 / 105
130 / 130

Expression
CD6 is expressed at low levels on immature thymocytes, and at high levels on mature medullary thymocytes. CD6 is also expressed on the majority of peripheral blood T cells, a subset of B cells CCL, and may be expressed on a subset of neurons.

Structure
MOLECULAR FAMILY NAME: Belongs to the scavanger receptor superfamily.

CD6 is a single-pass type-1 668 aa glycoprotein.  It contains an extracellular domain which contains 3 scavenger receptor cysteine-rich  (SRCR) domains which is similar to CD5, a short transmembrane-proximal stalk containing polysulfated O-linked oligosaccharides and a cytoplasmic domain containing potential SH2, SH3, PKC and casein kinase-2 binding sites and may be alternatively spliced. 

MOLECULAR MASS
Cell type Unreduced Reduced
Peripheral blood T cells 105 kDa or 130 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 5 different isoforms.  In humans, alternative splice variants have been isolated by RT-PCR from normal lymphocytes, which are predicted to result in molecules with different cytoplasmic tail regions - 244 aa long, 212 aa mid-length and 171 aa short.  There are 2 additional splice variants that have also been isolated from a patient with B cell chronic lymphocytic leukemia (B-CLL).

POST-TRANSLATIONAL MODIFICATION

CD6 is extensively glycosylated.  Phosphorylation of serine and threonine residues occur constitutively in phytohemagglutinin (PHA) blasts. Tyrosines on CD6 are phosphorylated and serines hyperphosphorylated upon stimulation through the TCR complex.

Ligands
The ligand for CD6 is CD166 or activated leukocyte cell adhesion molecule (ALCAM).  CD166 contains 5 IgSF domains and is present on thymic epithelial cells and activated lymphocytes, monocytes and neural cells.  The interaction involves the N-terminal domain of CD166 and the membrane-proximal scavenger receptor cysteine-rich domain of CD6.

LIGANDS AND MOLECULES ASSOCIATED WITH CD6
Molecule Comment
Activated leukocyte cell adhesion molecule (ALCAM, CD166) Divalent cation-independent ligand for CD6.  ALCAM binds the membrane proximal SRCR domain (domain 3)
gp90 Potential divalent cation-dependent ligans(s) for CD6, currently unidentified.
gp40 Potential divalent cation-dependent ligans(s) for CD6, currently unidentified.
 



Function
CD6 functions in T cell co-stimulation and adhesion and has a possible role in regulation of apoptosis of lymphocytes.  Through its interaction with CD166 in the thymus, CD6 has a role in T cell development. CD6 has a role in thymocyte resistance to apoptosis and positive selection.  It is important in mature T cell reponses to both alloantigen and self antigen.  CD6 is an adhesion molecule mediating the binding of developing thymocytes with thymic epithelial cells. MAbs to CD6 have been shown to either enhance or inhibit the autologous mixed leukocyte reactions (MLR). Coligation of CD3 and CD6 leads to Ca++ flux. There is evidence that CD6 ligation by mAbs directly stimulates T-cells in the presence of macrophages. CD6 is co-stimulatory with CD3 or PMA.  A role for CD6 in signal transduction is postulated based on stimulatory effects of mAbs. CD6 is hyperphosphorylated on serine and phosphorylated on tyrosine residues on activation

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD6 IN INTACT ANIMAL

CD6 may be involved in autoimmunity and graft vs. host disease (GVHD).  CD6 T cells are less autoreactive than CD6+ T cells and antibodies to CD6 (T12), have long been used to deplete T cells from bone marrow transplants to prevent graft versus host disease (GVHD).

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD6: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD6: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 923P30203
MouseU37543
Antibodies
BAQ82A   View Reactivity
BAQ83A   View Reactivity
BAQ91A   View Reactivity
CACT141A   View Reactivity
CC38   View Reactivity
LH43A   View Reactivity
LT10A   View Reactivity
M-T605   View Reactivity
MEM-98   View Reactivity
MIL8   View Reactivity
PG90A   View Reactivity

Revised June 25, 2008


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