Molecule Information

General Information of the Molecule (ID: Mol01930)

• Name: TNF superfamily member 11 (TNFSF11) ,Homo sapiens
• Synonyms: TNFSF11; OPGL; RANKL; TRANCE
• Molecule Type: Protein
• Gene Name: TNFSF11
• Gene ID: 8600
• Location: chr13:42,562,736-42,608,013[+]
• Sequence:
  MRRASRDYTKYLRGSEEMGGGPGAPHEGPLHAPPPPAPHQPPAASRSMFVALLGLGLGQV
  VCSVALFFYFRAQMDPNRISEDGTHCIYRILRLHENADFQDTTLESQDTKLIPDSCRRIK
  QAFQGAVQKELQHIVGSQHIRAEKAMVDGSWLDLAKRSKLEAQPFAHLTINATDIPSGSH
  KVSLSSWYHDRGWAKISNMTFSNGKLIVNQDGFYYLYANICFRHHETSGDLATEYLQLMV
  YVTKTSIKIPSSHTLMKGGSTKYWSGNSEFHFYSINVGGFFKLRSGEEISIEVSNPSLLD
  PDQDATYFGAFKVRDID
• 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. 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.
• Uniprot ID: TNF11_HUMAN
• Ensembl ID: ENSG00000120659
• HGNC ID: HGNC:11926

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Matrine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Osteoporosis [1]

• Sensitive Disease: Osteoporosis [ICD-11: FB83.1]
• Sensitive Drug: Matrine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: NF-kappaB signaling pathway; Inhibition; hsa04064
• Cell Pathway Regulation: AKT signaling pathway; Inhibition; hsa04151
• Cell Pathway Regulation: MAPK signaling pathway; Inhibition; hsa04010
• In Vitro Model: RAW264.7 cells; Ascites; Mus musculus (Mouse); CVCL_0493
• In Vivo Model: C57BL/6 mice; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: TRAP staining assay
• Mechanism Description: The imbalance between the osteogenic effects of osteoblasts and the osteoclasts of osteoclasts is one of the pathogenesis of postmenopausal osteoporosis. Secretion of estrogen causes an increase in the level of proinflammatory cytokines. Inflammation-induced osteoclast hyperactivity plays a crucial role in the imbalance. Matrine can inhibit osteoclastogenesis, inhibit inflammation and alleviate osteoporosis by regulating the NF-kappa-B/AKT/MAPK pathway.

Disease Class: Osteoporosis [1]

• Sensitive Disease: Osteoporosis [ICD-11: FB83.1]
• Sensitive Drug: Matrine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: NF-kappaB signaling pathway; Inhibition; hsa04064
• Cell Pathway Regulation: AKT signaling pathway; Inhibition; hsa04151
• Cell Pathway Regulation: MAPK signaling pathway; Inhibition; hsa04010
• In Vitro Model: RAW264.7 cells; Ascites; Mus musculus (Mouse); CVCL_0493
• In Vivo Model: C57BL/6 mice; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: TRAP staining assay
• Mechanism Description: The imbalance between the osteogenic effects of osteoblasts and the osteoclasts of osteoclasts is one of the pathogenesis of postmenopausal osteoporosis. Secretion of estrogen causes an increase in the level of proinflammatory cytokines. Inflammation-induced osteoclast hyperactivity plays a crucial role in the imbalance. Matrine can inhibit osteoclastogenesis, inhibit inflammation and alleviate osteoporosis by regulating the NF-kappa-B/AKT/MAPK pathway.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 15

Osteoporosis [ICD-11: FB83]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Bone marrow
• The Specified Disease: Osteoporosis
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.42E-01; Fold-change: -1.61E-01; Z-score: -3.69E-01

References

• Ref 1: Matrine: A Promising Natural Product With Various Pharmacological Activities .Front Pharmacol. 2020 May 7;11:588. doi: 10.3389/fphar.2020.00588. eCollection 2020. 10.3389/fphar.2020.00588