TNFSF11

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 Gene(Protein Coding) TNF Superfamily Member 11

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).

Biological Process bone resorption Source:Ensembl
Biological Process calcium ion homeostasis Source:Ensembl
Biological Process calcium-mediated signaling Source:UniProtKB
Biological Process cellular response to leukemia inhibitory factor Source:Ensembl
Biological Process cytokine-mediated signaling pathway Source:BHF-UCL1 Publication
Biological Process ERK1 and ERK2 cascade Source:Ensembl
Biological Process I-kappaB kinase/NF-kappaB signaling Source:Ensembl
Biological Process immune response Source:UniProtKB1 Publication
Biological Process JNK cascade Source:Ensembl
Biological Process mammary gland alveolus development Source:Ensembl
Biological Process mammary gland epithelial cell proliferation Source:Ensembl
Biological Process monocyte chemotaxis Source:BHF-UCL1 Publication
Biological Process negative regulation of transcription by RNA polymerase II Source:Ensembl
Biological Process ossification Source:Ensembl
Biological Process osteoclast development Source:Ensembl
Biological Process osteoclast differentiation Source:BHF-UCL1 Publication
Biological Process osteoclast proliferation Source:Ensembl
Biological Process paracrine signaling Source:Ensembl
Biological Process positive regulation of bone resorption Source:UniProtKB1 Publication
Biological Process positive regulation of corticotropin-releasing hormone secretion Source:BHF-UCLBy Similarity
Biological Process positive regulation of DNA-binding transcription factor activity Source:BHF-UCLBy Similarity
Biological Process positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling Source:BHF-UCL1 Publication
Biological Process positive regulation of fever generation by positive regulation of prostaglandin secretion Source:BHF-UCLBy Similarity
Biological Process positive regulation of gene expression Source:Ensembl
Biological Process positive regulation of homotypic cell-cell adhesion Source:BHF-UCL1 Publication
Biological Process positive regulation of I-kappaB kinase/NF-kappaB signaling Source:Ensembl
Biological Process positive regulation of intracellular signal transduction Source:BHF-UCL1 Publication
Biological Process positive regulation of JNK cascade Source:Ensembl
Biological Process positive regulation of MAP kinase activity Source:BHF-UCL1 Publication
Biological Process positive regulation of NF-kappaB transcription factor activity Source:BHF-UCL1 Publication
Biological Process positive regulation of osteoclast development Source:Ensembl
Biological Process positive regulation of osteoclast differentiation Source:UniProtKB2 Publications
Biological Process positive regulation of protein kinase B signaling Source:Ensembl
Biological Process positive regulation of T cell activation Source:BHF-UCL1 Publication
Biological Process positive regulation of transcription by RNA polymerase II Source:BHF-UCL1 Publication
Biological Process protein kinase B signaling Source:Ensembl
Biological Process regulation of actin binding Source:Ensembl
Biological Process TNFSF11-mediated signaling pathway Source:BHF-UCL1 Publication
Biological Process tooth eruption Source:Ensembl
Biological Process tumor necrosis factor-mediated signaling pathway Source:BHF-UCLBy Similarity

Isoform 1
Cell membrane
Isoform 3
Cell membrane
Isoform 2
Cytoplasm
Tumor necrosis factor ligand superfamily member 11, soluble form
Secreted

steopetrosis, 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.

Cytoplasmic: 1-47
Helical: 48-68
Extracellular: 69-317

The soluble form of isoform 1 derives from the membrane form by proteolytic processing (By similarity).
The cleavage may be catalyzed by ADAM17.