[1]
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NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Kidney;
DOI=10.1016/S0092-8674(00)80209-3; PubMed=9108485 [NCBI, ExPASy, EBI, Israel, Japan]
Simonet W.S.,
Lacey D.L.,
Dunstan C.R.,
Kelley M.,
Chang M.-S.,
Luethy R.,
Nguyen H.Q.,
Wooden S.,
Bennett L.,
Boone T.,
Shimamoto G.,
Derose M.,
Elliott R.,
Colombero A.,
Tan H.-L.,
Trail G.,
Sullivan J.,
Davy E.,
Bucay N., ![]()
Renshaw-Gegg L.,
Hughes T.M.,
Hill D.,
Pattison W.,
Campbell P.,
Sander S.,
Van G.,
Tarpley J.,
Derby P.,
Lee R.,
Suggs S.,
Boyle W.J.;
"Osteoprotegerin: a novel secreted protein involved in the regulation of bone density.";
Cell 89:309-319(1997).
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[2]
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NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Lung cancer;
DOI=10.1210/en.139.3.1329; PubMed=9492069 [NCBI, ExPASy, EBI, Israel, Japan]
Yasuda H.,
Shima N.,
Nakagawa N.,
Mochizuki S.,
Yano K.,
Fujise N.,
Sato Y.,
Goto M.,
Yamaguchi K.,
Kuriyama M.,
Kanno T.,
Murakami A.,
Tsuda E.,
Morinaga T.,
Higashio K.;
"Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro.";
Endocrinology 139:1329-1337(1998).
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[3]
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NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASN-3.
TISSUE=Placenta;
PubMed=9688283 [NCBI, ExPASy, EBI, Israel, Japan]
Morinaga T.,
Nakagawa N.,
Yasuda H.,
Tsuda E.,
Higashio K.;
"Cloning and characterization of the gene encoding human osteoprotegerin/osteoclastogenesis-inhibitory factor.";
Eur. J. Biochem. 254:685-691(1998).
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[4]
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NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-3.
TISSUE=Lung;
Suzuki Y.,
Sugano S.,
Totoki Y.,
Toyoda A.,
Takeda T.,
Sakaki Y.,
Tanaka A.,
Yokoyama S.;
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
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[5]
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NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASN-3 AND MET-104.
Livingston R.J.,
Rieder M.J.,
Chung M.-W.,
Ritchie T.K.,
Olson A.N.,
Nguyen C.P.,
Nguyen D.A.,
Poel C.L.,
Robertson P.D.,
Schackwitz W.S.,
Sherwood J.K.,
Sherwood A.M.,
Leithauser B.J.,
Nickerson D.A.;
"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
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[6]
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NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-3.
TISSUE=Eye;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
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[7]
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PROTEIN SEQUENCE OF 22-36 AND 378-401.
DOI=10.1006/bbrc.1998.8443; PubMed=9571159 [NCBI, ExPASy, EBI, Israel, Japan]
Tomoyasu A.,
Goto M.,
Fujise N.,
Mochizuki S.,
Yasuda H.,
Morinaga T.,
Tsuda E.,
Higashio K.;
"Characterization of monomeric and homodimeric forms of osteoclastogenesis inhibitory factor.";
Biochem. Biophys. Res. Commun. 245:382-387(1998).
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[8]
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PROTEIN SEQUENCE OF 22-36.
DOI=10.1110/ps.04682504; PubMed=15340161 [NCBI, ExPASy, EBI, Israel, Japan]
Zhang Z.,
Henzel W.J.;
"Signal peptide prediction based on analysis of experimentally verified cleavage sites.";
Protein Sci. 13:2819-2824(2004).
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[9]
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NUCLEOTIDE SEQUENCE [MRNA] OF 22-393.
TISSUE=Placenta;
PubMed=12110935 [NCBI, ExPASy, EBI, Israel, Japan]
He Z.-Y.,
Yang G.-Z.,
Zhang W.-J.,
Wu X.-F.;
"Cloning and expression of osteoprotegerin from Homo sapiens.";
Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao 31:680-684(1999).
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[10]
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PROTEIN SEQUENCE OF 242-255; 354-359 AND 369-378, AND FUNCTION.
DOI=10.1006/bbrc.1997.6603; PubMed=9168977 [NCBI, ExPASy, EBI, Israel, Japan]
Tsuda E.,
Goto M.,
Mochizuki S.,
Yano K.,
Kobayashi F.,
Morinaga T.,
Higashio K.;
"Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis.";
Biochem. Biophys. Res. Commun. 234:137-142(1997).
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[11]
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INTERACTION WITH TRAIL.
DOI=10.1074/jbc.273.23.14363; PubMed=9603945 [NCBI, ExPASy, EBI, Israel, Japan]
Emery J.G.,
McDonnell P.,
Burke M.B.,
Deen K.C.,
Lyn S.,
Silverman C.,
Dul E.,
Appelbaum E.R.,
Eichman C.,
DiPrinzio R.,
Dodds R.A.,
James I.E.,
Rosenberg M.,
Lee J.C.,
Young P.R.;
"Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL.";
J. Biol. Chem. 273:14363-14367(1998).
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[12]
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CHARACTERIZATION, AND MUTAGENESIS OF CYS-400.
DOI=10.1074/jbc.273.9.5117; PubMed=9478964 [NCBI, ExPASy, EBI, Israel, Japan]
Yamaguchi K.,
Kinosaki M.,
Goto M.,
Kobayashi F.,
Tsuda E.,
Morinaga T.,
Higashio K.;
"Characterization of structural domains of human osteoclastogenesis inhibitory factor.";
J. Biol. Chem. 273:5117-5123(1998).
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[13]
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REVIEW.
DOI=10.1002/1097-0142(20010801)92:3<460::AID-CNCR1344>3.0.CO;2-D; PubMed=11505389 [NCBI, ExPASy, EBI, Israel, Japan]
Hofbauer L.C.,
Neubauer A.,
Heufelder A.E.;
"Receptor activator of nuclear factor-kappaB ligand and osteoprotegerin: potential implications for the pathogenesis and treatment of malignant bone diseases.";
Cancer 92:460-470(2001).
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[14]
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VARIANT JPD ASP-182 DEL.
DOI=10.1093/hmg/11.18.2119; PubMed=12189164 [NCBI, ExPASy, EBI, Israel, Japan]
Cundy T.,
Hegde M.,
Naot D.,
Chong B.,
King A.,
Wallace R.,
Mulley J.,
Love D.R.,
Seidel J.,
Fawkner M.,
Banovic T.,
Callon K.E.,
Grey A.B.,
Reid I.R.,
Middleton-Hardie C.A.,
Cornish J.;
"A mutation in the gene TNFRSF11B encoding osteoprotegerin causes an idiopathic hyperphosphatasia phenotype.";
Hum. Mol. Genet. 11:2119-2127(2002).
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- FUNCTION: Acts as decoy receptor for RANKL and thereby neutralizes its function in osteoclastogenesis. Inhibits the activation of osteoclasts and 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 and protect against apoptosis. TRAIL binding blocks the inhibition of osteoclastogenesis.
- SUBUNIT: Homodimer.
- SUBCELLULAR LOCATION: Secreted.
- TISSUE SPECIFICITY: Highly expressed in adult lung, heart, kidney, liver, spleen, thymus, prostate, ovary, small intestine, thyroid, lymph node, trachea, adrenal gland, testis, and bone marrow. Detected at very low levels in brain, placenta and skeletal muscle. Highly expressed in fetal kidney, liver and lung.
- INDUCTION: Up-regulated by increasing calcium-concentration in the medium and estrogens. Down-regulated by glucocorticoids.
- PTM: N-glycosylated. Contains sialic acid residues.
- PTM: The N-terminus is blocked.
- DISEASE: Defects in TNFRSF11B are the cause of juvenile Paget disease (JPD) [MIM:239000]; also called hyperostosis corticalis deformans juvenilis or hereditary hyperphosphatasia or chronic congenital idiopathic hyperphosphatasia. JPD is a rare autosomal recessive osteopathy that presents in infancy or early childhood. The disorder is characterized by rapidly remodeling woven bone, osteopenia, debilitating fractures, and deformities due to a markedly accelerated rate of bone remodeling throughout the skeleton. Approximately 40 cases of JPD have been reported worldwide. Unless it is treated with drugs that block osteoclast-mediated skeletal resorption, the disease can be fatal.
- SIMILARITY: Contains 2 death domains.
- SIMILARITY: Contains 4 TNFR-Cys repeats.
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