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 (PubMed:22664871). 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. During osteoclast differentiation, in a TMEM64 and ATP2A2-dependent manner induces activation of CREB1 and mitochondrial ROS generation necessary for proper osteoclast generation (By similarity).
Involvement in disease
Osteopetrosis, autosomal recessive 2
OPTB2
A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. OPTB2 is characterized by paucity of osteoclasts, suggesting a molecular defect in osteoclast development.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
The soluble form of isoform 1 derives from the membrane form by proteolytic processing (By similarity). The cleavage may be catalyzed by ADAM17.
Sequence Similarities
Belongs to the tumor necrosis factor family.
Tissue Specificity
Highest in the peripheral lymph nodes, weak in spleen, peripheral blood Leukocytes, bone marrow, heart, placenta, skeletal muscle, stomach and thyroid.
Cellular localization
- Isoform 1
- Cell membrane
- Single-pass type II membrane protein
- Isoform 3
- Cell membrane
- Single-pass type II membrane protein
- Isoform 2
- Cytoplasm
- Tumor necrosis factor ligand superfamily member 11, soluble form
- Secreted
Alternative names
CD254, OPGL, RANKL, TRANCE, TNFSF11, 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