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tumor necrosis factor receptor superfamily member 11B; osteoprotegerin; osteoclastogenesis inhibitory factor (TNFRSF11B OCIF OPG)

Function: - acts as decoy receptor for RANKL & thus neutralizes its function in osteoclastogenesis - regulation of osteoclast activity - inhibits activation of osteoclasts & promotes osteoclast apoptosis in vitro - bone homeostasis seems to depend on the local RANKL/OPG ratio - may also play a role in preventing arterial calcification - may act as decoy receptor for TRAIL & protect against apoptosis - TRAIL binding blocks the inhibition of osteoclastogenesis Structure: - homodimer - N-glycosylated - contains sialic acid residues - N-terminus is blocked - contains 2 death domains - contains 4 TNFR-Cys repeats Compartment: secreted Expression: - highly expressed in adult lung, heart, kidney, liver, spleen, thymus, prostate, ovary, small intestine, thyroid, lymph node, trachea, adrenal gland, testis, & bone marrow - detected at very low levels in brain, placenta & skeletal muscle - highly expressed in fetal kidney, liver & lung - up-regulated by increasing Ca+2-concentration in the medium & estrogens - down-regulated by glucocorticoids Pathology: - defects in TNFRSF11B are the cause of juvenile Paget's disease

General

glycoprotein secreted protein tumor necrosis factor [TNF] receptor family

Properties

SIZE: entity length = 401 aa MW = 46 kD COMPARTMENT: plasma membrane MOTIF: signal sequence {1-21} TNFR-Cys {24-62} MOTIF: cysteine residue {C41} MODIFICATION: cysteine residue {C54} cysteine residue {C44} MODIFICATION: cysteine residue {C62} cysteine residue {C54} MODIFICATION: cysteine residue {C41} cysteine residue {C62} MODIFICATION: cysteine residue {C44} TNFR-Cys {65-105} MOTIF: cysteine residue {C65} MODIFICATION: cysteine residue {C80} cysteine residue {C80} MODIFICATION: cysteine residue {C65} cysteine residue {C83} MODIFICATION: cysteine residue {C97} cysteine residue {C87} MODIFICATION: cysteine residue {C105} cysteine residue {C97} MODIFICATION: cysteine residue {C83} N-glycosylation site {N98} cysteine residue {C105} MODIFICATION: cysteine residue {C87} TNFR-Cys {107-142} MOTIF: cysteine residue {C107} MODIFICATION: cysteine residue {C118} cysteine residue {C118} MODIFICATION: cysteine residue {C107} cysteine residue {C124} MODIFICATION: cysteine residue {C142} cysteine residue {C142} MODIFICATION: cysteine residue {C124} TNFR-Cys {145-185} MOTIF: cysteine residue {C145} MODIFICATION: cysteine residue {C160} N-glycosylation site {N152} cysteine residue {C160} MODIFICATION: cysteine residue {C145} N-glycosylation site {N165} cysteine residue {C166} MODIFICATION: cysteine residue {C185} N-glycosylation site {N178} cysteine residue {C185} MODIFICATION: cysteine residue {C166} death domain NAME: death domain SITE: 198-269 death domain NAME: death domain SITE: 270-365 MOTIF: N-glycosylation site {N289} cysteine residue {400}

Database Correlations

OMIM correlations UniProt O00300 PFAM correlations Entrez Gene 4982 Kegg hsa:4982

References

  1. UniProt :accession O00300
  2. NIEHS-SNPs http://egp.gs.washington.edu/data/tnfrsf11b/
  3. Journal Watch vol 19, #24, pg 192-93 Dec 15, 1999
  4. Kong YY et al Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 402:304, 1999 PMID: 10580503