Homo sapiens TNFSF11
Tumor necrosis factor ligand superfamily member 11 |
Protein names
Tumor necrosis factor ligand superfamily member 11 |
Alternative names
Osteoclast differentiation factor, Osteoprotegerin ligand, Receptor activator of nuclear factor kappa-B ligand, TNF-related activation-induced cytokine |
Gene names
TNFSF11 |
Protein family
Belongs to the tumor necrosis factor family |
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) |
Subcellular location
Secreted |
Structure
Homotrimer (By similarity). Interacts with TNFRSF11B (PubMed:22664871). Interacts with TNFRSF11A. Interacts with FBN1 (via N-terminal domain) in a Ca(+2)-dependent manner (By similarity). Interacts with TNFAIP6 (via both Link and CUB domains) |
Post-translational modification
The soluble form of isoform 1 derives from the membrane form by proteolytic processing (By similarity). The cleavage may be catalyzed by ADAM17
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Involvement in disease
Osteopetrosis, autosomal recessive 2
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.
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Keywords
3D-structure, Alternative splicing, Cell membrane, Cytokine, Cytoplasm, Developmental protein, Differentiation, Disease variant, Glycoprotein, Membrane, Osteopetrosis, Proteomics identification, Receptor, Reference proteome, Secreted, Signal-anchor, Transmembrane, Transmembrane helix |
Sequence
MRRASRDYTKYLRGSEEMGGGPGAPHEGPLHAPPPPAPHQPPAASRSMFVALLGLGLGQV VCSVALFFYFRAQMDPNRISEDGTHCIYRILRLHENADFQDTTLESQDTKLIPDSCRRIK QAFQGAVQKELQHIVGSQHIRAEKAMVDGSWLDLAKRSKLEAQPFAHLTINATDIPSGSH KVSLSSWYHDRGWAKISNMTFSNGKLIVNQDGFYYLYANICFRHHETSGDLATEYLQLMV YVTKTSIKIPSSHTLMKGGSTKYWSGNSEFHFYSINVGGFFKLRSGEEISIEVSNPSLLD PDQDATYFGAFKVRDID |
| UniProt accession: O14788 |
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