CD254 TNFSF11 (tumor necrosis factor ligand superfamily member 11), TRANCE, RANKL,  hRANKL2
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 2 glycoprotein
T Cell
Lymphoid Cell
Osteoclast
Lymph Node
Osteoblast
Stromal Cell
35 / 35

Expression
CD254 is expressed on osteoblasts, osteclasts, bone marrow stromal cells, peripheral lymph nodes, secondary lymphoid tissues and activated T cells.  Expression is weak in spleen, peripheral blood leukocytes, bone marrow, heart, brain, placenta, skeletal muscle, stomach and thyroid. 

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

CD254 is a single-pass type-2 317 aa glycoprotein.  It contains an extracellular domain, a transmembrane domain and a cytoplasmic domain.  It is predicted to form a homotrimer in the membrane.

MOLECULE MASS

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yeilds 3 different isoforms.  One isoform lacks a membrane insertion region and a soluble form is derived from the membrane form by proteolysis.  Isoform 1 and 3 are glycoproteins and isoform 2 is secreted.  The cleavage may be catalyzed by ADAM17.

POST-TRANSLATIONAL MODIFICATION: No information.

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD254

CD254 binds CD265 and Osteoprotegerin.

Function
CD265, (TNFRSF11A/RANK) is a functional receptor, whereas CD254 (TNFRSF11A/OPG) acts as a decoy receptor.   CD254 enhances dendritic cells to stimulate naive T cell proliferation.  The gene which encodes CD254 is a ligand for osteoprotegerin and functions as a key factor for osteoclast differentiation and activation and bone development.  The protein was shown to be a dendritic cell survival factor and is involved in the regulation of T cell-dependent immune response.  CD254 may be involved in regulation of apoptosis.  T cell activation was reported to induce expression of this gene and lead to an increased of osteoclastogenesis and bone loss.  There may be an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.  The protein was also shown to activate antiapoptotic kinase AKT/PKB throught a signaling complex involving SRC kinase and tumor necrosis factor receptor-associated factor (TRAF) 6 which indicated this protein may have a role in the regulation of cell apoptosis.  Knockout mice lack osteoclasts and show severe osteoporosis as well as defective lymphocyte differentiation.  The deficient mice exhibited defects in early differentiation of T and B lymphocytes, and failed to form lobulo-alveolar mammary structures during pregnancy. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD254 IN INTACT ANIMAL:

CD254 has a role in bone and immune system suggesting that this molecule may be a potential diagnostic and therapeutic target.


Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD254: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD254: No information.

ADDITIONAL INSIGHTS

For further information see Bachmann, M. F. et al (1999) J. Exp. Med. 189: 1025-1031.



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 8600O14788
Antibodies

Revised June 25, 2008


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