Tclin TNFSF11 Tumor necrosis factor ligand superfamily member 11

Protein Summary

Description

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). 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]

Uniprot Accession IDs

• O14788
• O14723
• Q96Q17
• Q9P2Q3

Gene Name

• TNFSF11

Ensembl ID

• ENST00000239849
• ENSP00000239849
• ENSG00000120659
• ENST00000358545
• ENSP00000351347
• ENST00000398795
• ENSP00000381775
• ENST00000405262
• ENSP00000384042
• ENST00000544862
• ENSP00000444913

Symbol

• OPGL
• RANKL
• TRANCE
• ODF
• OPGL
• sOdf
• CD254
• OPTB2
• RANKL
• TNLG6B
• TRANCE
• hRANKL2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
biological term	1
chemical	0.88
PubMedID	0.87
gene perturbation	0.83

Protein Classes

PANTHER Classes

Protein / Signaling Molecule / Cytokine / Tumor Necrosis Factor Family Member / Tumor Necrosis Factor Ligand Superfamily Member 11

DTO Classes

Protein / Signaling / Cytokine / Tumor Necrosis Factor Family Member / Tumor Necrosis Factor Ligand Superfamily Member 11

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 7453.06   (req: < 5)

Gene RIFs: 665   (req: <= 3)

Antibodies: 1061   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 7453.06   (req: >= 5)

Gene RIFs: 665   (req: > 3)

Antibodies: 1061   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 38

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 2

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 1