Tnfsf11

Function

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 (By similarity). Induces osteoclastogenesis by activating multiple signaling pathways in osteoclast precursor cells, chief among which is induction of long lasting oscillations in the intracellular concentration of Ca (2+) resulting in the activation of NFATC1, which translocates to the nucleus and induces osteoclast-specific gene transcription to allow differentiation of osteoclasts (PubMed:24039232). During osteoclast differentiation, in a TMEM64 and ATP2A2-dependent manner induces activation of CREB1 and mitochondrial ROS generation necessary for proper osteoclast generation (PubMed:23395171, PubMed:26644563).

Involvement in disease

Deficiency in Tnfsf11 results in failure to form lobulo-alveolar mammary structures during pregnancy, resulting in death of newborns. Trance-deficient mice show severe osteopetrosis, with no osteoclasts, marrow spaces, or tooth eruption, and exhibit profound growth retardation at several skeletal sites, including the limbs, skull, and vertebrae and have marked chondrodysplasia, with thick, irregular growth plates and a relative increase in hypertrophic chondrocytes.

Post-translational modifications

N-glycosylated.

The soluble form of isoform 1 derives from the membrane form by proteolytic processing. The cleavage may be catalyzed by ADAM17. A further shorter soluble form was observed.

Sequence similarities

Belongs to the tumor necrosis factor family.

Tissue specificity

Highly expressed in thymus and lymph nodes, but not in non-lymphoid tissues and is abundantly expressed in T-cells but not in B-cells. A high level expression is also seen in the trabecular bone and lung.

Cellular localization

• Isoform 1
• Cell membrane
• Single-pass type II membrane protein
• Isoform 2
• Cell membrane
• Single-pass type II membrane protein
• Isoform 3
• Cytoplasm
• Tumor necrosis factor ligand superfamily member 11, soluble form
• Secreted

Alternative names

• Tumor necrosis factor ligand superfamily member 11
• Osteoclast differentiation factor
• Osteoprotegerin ligand
• Receptor activator of nuclear factor kappa-B ligand
• TNF-related activation-induced cytokine
• ODF
• OPGL
• RANKL
• TRANCE
• Rankl
• Opgl
• Trance
• Tnfsf11

Database links

• entrezGene:21943
• swissprot:O35235

Target type

Proteins

Primary research area

Immunology & Infectious Disease

Molecular weight

35003Da