ODF; TRANCE; OPGL; TNFSF 11; CD254 Antibody – Rat Monoclonal

This gene encodes a member of the tumor necrosis factor (TNF) cytokine family which is a ligand for osteoprotegerin and functions as a key factor for osteoclast differentiation and activation. This protein was shown to be a dentritic cell survival factor and is involved in the regulation of T cell-dependent immune response. T cell activation was reported to induce expression of this gene and lead to an increase of osteoclastogenesis and bone loss. This protein was shown to activate antiapoptotic kinase AKT/PKB through 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. Targeted disruption of the related gene in mice led to severe osteopetrosis and a lack of osteoclasts. The deficient mice exhibited defects in early differentiation of T and B lymphocytes, and failed to form lobulo-alveolar mammary structures during pregnancy. Two alternatively spliced transcript variants have been found. [provided by RefSeq, Jul 2008]

TNFSF11: Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy. Homotrimer. Up-regulated by T-cell receptor stimulation. Highest in the peripheral lymph nodes, weak in spleen, peripheral blood Leukocytes, bone marrow, heart, placenta, skeletal muscle, stomach and thyroid. Belongs to the tumor necrosis factor family. 3 isoforms of the human protein are produced by alternative splicing.

Protein type: Membrane protein, integral

Chromosomal Location of Human Ortholog: 13q14

Cellular Component: cytoplasm; extracellular region; extracellular space; integral to plasma membrane; plasma membrane

Molecular Function: cytokine activity; tumor necrosis factor receptor binding; tumor necrosis factor receptor superfamily binding

Biological Process: activation of JNK activity; activation of NF-kappaB transcription factor; bone resorption; calcium ion homeostasis; cytokine and chemokine mediated signaling pathway; immune response; mammary gland epithelial cell proliferation; monocyte chemotaxis; organ morphogenesis; ossification; osteoclast differentiation; positive regulation of bone resorption; positive regulation of corticotropin-releasing hormone secretion; positive regulation of homotypic cell-cell adhesion; positive regulation of I-kappaB kinase/NF-kappaB cascade; positive regulation of MAP kinase activity; positive regulation of osteoclast differentiation; positive regulation of protein kinase B signaling cascade; positive regulation of T cell activation; positive regulation of transcription factor activity; positive regulation of transcription from RNA polymerase II promoter; protein homooligomerization; tumor necrosis factor-mediated signaling pathway

Disease: Osteopetrosis, Autosomal Recessive 2