CD253 TNFSF10 (tumor necrosis factor ligand superfamily, member 10), TL2 (TNF-like 2), TRAIL, APO-2L
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 2 glycoprotein
T Cell
B Cell
Monocyte
NK Cell
Spleen
Prostate
Lung
Thymus
Kidney
Dendritic Cell
Gut
33 / 33

Expression
CD253 is expressed on dendritic cells, NK cells, activated B, T cells and monocytes.  Expression is in lymphoid (spleen, thymus, gut-associated lympoid tissue) and non-lymphoid ( prostate, kidney and wide expression in lung) tissues.  

Structure
MOLECULE FAMILY NAME: Belongs to the tumor necrosis factor superfamily.

CD253 is a single-pass type-2 281 aa glycoprotein.  It contains an extracellular domain, a 21 aa hydrophobic transmembrane domain and a 17 aa N-terminal cytoplasmic domain but contains no signal sequence.  The extracellular domain shares a significant homology with that of other TNF family members such as FasL and TNF-α.  The extracellular domain is shed as a 19 kDa protein that forms dimers and trimers of 48 kDa and 66 kDa.  CD253 is also released in a vesicle-associated form.

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION: No information.

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD253

CD253 binds to five related receptors: DR4 (death receptor), DR5, DcR1 (decoy receptor), DcR2 and OPG (osteoprotegerin), all members of the TNF family.

Function
CD253 binds to several members of TNF receptor superfamily including CD261, CD262, CD263 and CD264 and possible also to TNFRSF11B.  The activity of this protein may be modulated by binding to the decoy receptors CD263, CD264 and TNFRSF11B that cannot induce apoptosis.  The multiplicity of receptors is unusal.  The principle activity of CD253 seems to induce apoptosis, but the physiological function may be more complex.  Apoptosis occurs in transformed and tumor cells, but does not appear to kill normal cells althought it is expressed at a significant level in normal tissues.  Spliced isoforms, which lack exons 3 or 2 and 3, have lost their pro-apoptotic activity.  Gene knockout studies suggest that CD253 plays a role in tumor surveillance by immune cells.  Blocking CD253 with antibody suggests that CD253 mediates IFN-γ-dependent NK cell function including killing of tumor cells and virus infected cells.  The binding of this protein to its receptors has been shown to trigger the activation of MAPK8/JNK, caspase 8, and caspase 3.  CD253 is also in control of CD8 T cell memory cells by CD4 cells. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD253 IN INTACT ANIMAL

Studies indictate that CD253 plays a role in tumor survillance by immune cells.  CD253 may mediate IFN-γ-dependent NK-cell function including killing tumor cells and virus-infected cells. 

Comments

MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH TRANSCRIPTION OF CD253: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD253: No information.

ADDITIONAL INSIGHTS

For further information see Wiley, S.R. et al (1995) Immunity 3: 673-682.



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 8743P50591
Antibodies

Revised June 25, 2008


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