|CD254||TNFSF11 (tumor necrosis factor ligand superfamily member 11), TRANCE, RANKL, hRANKL2|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
Type 2 glycoprotein
|35 / 35|
|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. |
|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.
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 AND MOLECULE ASSOCIATED WITH CD254|
CD254 binds CD265 and Osteoprotegerin.
|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.
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD254: No information.
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD254: No information.
For further information see Bachmann, M. F. et al (1999) J. Exp. Med. 189: 1025-1031.
Database accession numbers
Revised June 25, 2008