TNFSF11
GeneName
TNFSF11
Summary
TNFSF11, also known as RANKL, sRANKL, or ODF, is a 35kDa cytokine that plays a vital role in bone metabolism and immune regulation. It is primarily expressed in the extracellular region and is secreted into the extracellular space. TNFSF11 is a key mediator in osteoclast differentiation and activation, promoting bone resorption through its interaction with the RANK receptor on osteoclast precursors. Additionally, it is involved in various signalling pathways, including the JNK cascade and NF-kappaB signalling, and has roles in immune responses and cellular processes such as monocyte chemotaxis and T cell activation.
Importance
TNFSF11 is relevant to: - Osteoporosis and other bone-related disorders due to its central role in osteoclast development and bone resorption - Immune system regulation, particularly in the context of inflammation and autoimmune diseases - Cancer research, as it is implicated in tumour microenvironment interactions and metastasis - Mammary gland development and function, influencing epithelial cell proliferation and differentiation
Top Products
For researchers investigating TNFSF11, we highly recommend the well-cited polyclonal antibody, Anti-RANKL antibody (ab9957). This antibody has garnered 78 citations, underscoring its reliability and trust within the scientific community. It is particularly effective for Western blotting (WB) and ELISA applications, making it a valuable tool for those studying the role of TNFSF11 in various biological processes. Its proven performance in these applications ensures that researchers can confidently utilise it in their experiments. The Recombinant human RANKL protein (Active) ELISA Kit (ab269158) is an excellent option for researchers looking to measure TNFSF11 with precision.
Abcam Product Citation Summary
The data indicates that the TNFSF11 target is being extensively studied in various human and rat cell contexts, particularly focusing on hypoxia, osteoblast differentiation, and pro-osteoclastic markers. The use of Western blotting is predominant, highlighting its importance in detecting this target in different biological scenarios, including giant cell tumors.
Abcam Product Citation Table
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