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O00300 (TR11B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tumor necrosis factor receptor superfamily member 11B
Alternative name(s):
Osteoclastogenesis inhibitory factor
Osteoprotegerin
Gene names
Name:TNFRSF11B
Synonyms:OCIF, OPG
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length401 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Acts as decoy receptor for TNFSF11/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 ratio between TNFSF11 and TNFRSF11B. May also play a role in preventing arterial calcification. May act as decoy receptor for TNFSF10/TRAIL and protect against apoptosis. TNFSF10/TRAIL binding blocks the inhibition of osteoclastogenesis. Ref.12 Ref.16

Subunit structure

Homodimer. Interacts with TNFSF10 and TNFSF11. Ref.13 Ref.16

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.

Post-translational modification

N-glycosylated. Contains sialic acid residues. Ref.16

The N-terminus is blocked.

Involvement in disease

Juvenile Paget disease (JPD) [MIM:239000]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.17

Sequence similarities

Contains 2 death domains.

Contains 4 TNFR-Cys repeats.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainRepeat
Signal
   Molecular functionReceptor
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

extracellular matrix organization

Inferred from electronic annotation. Source: Ensembl

negative regulation of bone resorption

Inferred from electronic annotation. Source: Ensembl

negative regulation of odontogenesis of dentin-containing tooth

Inferred from electronic annotation. Source: Ensembl

response to arsenic-containing substance

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to estrogen

Inferred from electronic annotation. Source: Ensembl

response to magnesium ion

Inferred from electronic annotation. Source: Ensembl

response to nutrient

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement Ref.12. Source: ProtInc

skeletal system development

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentextracellular region

Traceable author statement Ref.1. Source: ProtInc

extracellular space

Inferred from direct assay PubMed 15516325. Source: BHF-UCL

proteinaceous extracellular matrix

Inferred from electronic annotation. Source: Ensembl

   Molecular_functioncytokine activity

Traceable author statement Ref.12. Source: ProtInc

receptor activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Ref.9 Ref.10
Chain22 – 401380Tumor necrosis factor receptor superfamily member 11B
PRO_0000034587

Regions

Repeat24 – 6239TNFR-Cys 1
Repeat65 – 10541TNFR-Cys 2
Repeat107 – 14236TNFR-Cys 3
Repeat145 – 18541TNFR-Cys 4
Domain198 – 26972Death 1
Domain270 – 36596Death 2

Sites

Site4001Involved in dimerization

Amino acid modifications

Glycosylation981N-linked (GlcNAc...) Potential
Glycosylation1521N-linked (GlcNAc...) Potential
Glycosylation1651N-linked (GlcNAc...) Potential
Glycosylation1781N-linked (GlcNAc...) Ref.16
Glycosylation2891N-linked (GlcNAc...) Potential
Disulfide bond41 ↔ 54 Ref.16
Disulfide bond44 ↔ 62 Ref.16
Disulfide bond65 ↔ 80 Ref.16
Disulfide bond83 ↔ 97 Ref.16
Disulfide bond87 ↔ 105 Ref.16
Disulfide bond107 ↔ 118 Ref.16
Disulfide bond124 ↔ 142 Ref.16
Disulfide bond145 ↔ 160 Ref.16
Disulfide bond166 ↔ 185 Ref.16

Natural variations

Natural variant31N → K. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6
Corresponds to variant rs2073618 [ dbSNP | Ensembl ].
VAR_013439
Natural variant1041V → M. Ref.6
Corresponds to variant rs11573906 [ dbSNP | Ensembl ].
VAR_018957
Natural variant1821Missing in JPD. Ref.17
VAR_019413

Experimental info

Mutagenesis78 – 792DE → AA: Decreases inhibition of osteoclast differentiation.
Mutagenesis1161E → A: Reduces affinity for TNFSF11. Decreases inhibition of osteoclast differentiation. Ref.16
Mutagenesis400 – 4012Missing: Abolishes dimerization. Ref.14
Mutagenesis4001C → S: Abolishes dimerization. Ref.14
Sequence conflict2631D → A in AAB53709. Ref.1

Secondary structure

................................. 401
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O00300 [UniParc].

Last modified February 8, 2011. Version 3.
Checksum: 2A23AC07BFA1E2DE

FASTA40146,026
        10         20         30         40         50         60 
MNNLLCCALV FLDISIKWTT QETFPPKYLH YDEETSHQLL CDKCPPGTYL KQHCTAKWKT 

        70         80         90        100        110        120 
VCAPCPDHYY TDSWHTSDEC LYCSPVCKEL QYVKQECNRT HNRVCECKEG RYLEIEFCLK 

       130        140        150        160        170        180 
HRSCPPGFGV VQAGTPERNT VCKRCPDGFF SNETSSKAPC RKHTNCSVFG LLLTQKGNAT 

       190        200        210        220        230        240 
HDNICSGNSE STQKCGIDVT LCEEAFFRFA VPTKFTPNWL SVLVDNLPGT KVNAESVERI 

       250        260        270        280        290        300 
KRQHSSQEQT FQLLKLWKHQ NKDQDIVKKI IQDIDLCENS VQRHIGHANL TFEQLRSLME 

       310        320        330        340        350        360 
SLPGKKVGAE DIEKTIKACK PSDQILKLLS LWRIKNGDQD TLKGLMHALK HSKTYHFPKT 

       370        380        390        400 
VTQSLKKTIR FLHSFTMYKL YQKLFLEMIG NQVQSVKISC L 

« Hide

References

« Hide 'large scale' references
[1]"Osteoprotegerin: a novel secreted protein involved in the regulation of bone density."
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. expand/collapse author list , 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.
Cell 89:309-319(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT LYS-3.
Tissue: Kidney.
[2]"Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro."
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.
Endocrinology 139:1329-1337(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT LYS-3.
Tissue: Lung cancer.
[3]"Cloning and characterization of the gene encoding human osteoprotegerin/osteoclastogenesis-inhibitory factor."
Morinaga T., Nakagawa N., Yasuda H., Tsuda E., Higashio K.
Eur. J. Biochem. 254:685-691(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LYS-3.
Tissue: Placenta.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LYS-3.
Tissue: Kidney.
[5]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
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[6]NIEHS SNPs program
Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LYS-3 AND MET-104.
[7]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Eye.
[9]"Characterization of monomeric and homodimeric forms of osteoclastogenesis inhibitory factor."
Tomoyasu A., Goto M., Fujise N., Mochizuki S., Yasuda H., Morinaga T., Tsuda E., Higashio K.
Biochem. Biophys. Res. Commun. 245:382-387(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 22-36 AND 378-401.
[10]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 22-36.
[11]"Cloning and expression of a novel mutated osteoprogerin/osteoclastogenesis inhibitory factor gene."
He Z.-Y., Yang G.-Z., Zhang W.-J., Wu X.-F.
Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao 31:680-684(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 22-393.
Tissue: Placenta.
[12]"Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis."
Tsuda E., Goto M., Mochizuki S., Yano K., Kobayashi F., Morinaga T., Higashio K.
Biochem. Biophys. Res. Commun. 234:137-142(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 242-255; 354-359 AND 369-378, FUNCTION.
[13]"Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL."
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.
J. Biol. Chem. 273:14363-14367(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TNFSF10.
[14]"Characterization of structural domains of human osteoclastogenesis inhibitory factor."
Yamaguchi K., Kinosaki M., Goto M., Kobayashi F., Tsuda E., Morinaga T., Higashio K.
J. Biol. Chem. 273:5117-5123(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION, MUTAGENESIS OF CYS-400.
[15]"Receptor activator of nuclear factor-kappaB ligand and osteoprotegerin: potential implications for the pathogenesis and treatment of malignant bone diseases."
Hofbauer L.C., Neubauer A., Heufelder A.E.
Cancer 92:460-470(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[16]"Crystal structure of human RANKL complexed with its decoy receptor osteoprotegerin."
Luan X., Lu Q., Jiang Y., Zhang S., Wang Q., Yuan H., Zhao W., Wang J., Wang X.
J. Immunol. 189:245-252(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 22-186 IN COMPLEX WITH TNFSF11, INTERACTION WITH TNFSF11, SUBUNIT, FUNCTION, MUTAGENESIS OF 78-ASP-GLU-79 AND GLU-116, GLYCOSYLATION AT ASN-178, DISULFIDE BONDS.
[17]"A mutation in the gene TNFRSF11B encoding osteoprotegerin causes an idiopathic hyperphosphatasia phenotype."
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.
Hum. Mol. Genet. 11:2119-2127(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT JPD ASP-182 DEL.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U94332 mRNA. Translation: AAB53709.1.
AB002146 mRNA. Translation: BAA25910.1.
AB008822 Genomic DNA. Translation: BAA32076.1.
AK313710 mRNA. Translation: BAG36455.1.
AK223155 mRNA. Translation: BAD96875.1.
AY466112 Genomic DNA. Translation: AAR23265.1.
AC107953 Genomic DNA. No translation available.
AP004283 Genomic DNA. No translation available.
BC030155 mRNA. Translation: AAH30155.1.
AF134187 mRNA. Translation: AAF20168.1.
RefSeqNP_002537.3. NM_002546.3.
UniGeneHs.81791.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3URFX-ray2.70Z22-186[»]
ProteinModelPortalO00300.
SMRO00300. Positions 26-186.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111028. 2 interactions.
STRING9606.ENSP00000297350.

PTM databases

PhosphoSiteO00300.

Proteomic databases

PaxDbO00300.
PRIDEO00300.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000297350; ENSP00000297350; ENSG00000164761.
GeneID4982.
KEGGhsa:4982.
UCSCuc003yon.4. human.

Organism-specific databases

CTD4982.
GeneCardsGC08M119935.
H-InvDBHIX0007748.
HGNCHGNC:11909. TNFRSF11B.
HPAHPA027013.
MIM239000. phenotype.
602643. gene.
neXtProtNX_O00300.
Orphanet2801. Juvenile Paget disease.
PharmGKBPA36602.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG80702.
HOGENOMHOG000273896.
HOVERGENHBG061495.
InParanoidO00300.
KOK05148.
OMADIDLCEN.
OrthoDBEOG786H2Q.
PhylomeDBO00300.
TreeFamTF331157.

Gene expression databases

ArrayExpressO00300.
BgeeO00300.
CleanExHS_TNFRSF11B.
GenevestigatorO00300.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
InterProIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR001368. TNFR/NGFR_Cys_rich_reg.
IPR022323. TNFR_11.
IPR017371. TNFR_11B.
[Graphical view]
PANTHERPTHR23097:SF36. PTHR23097:SF36. 1 hit.
PfamPF00531. Death. 1 hit.
PF00020. TNFR_c6. 2 hits.
[Graphical view]
PIRSFPIRSF038065. TNFR_11B. 1 hit.
PRINTSPR01961. TNFACTORR11.
PR01975. TNFACTORR11B.
SMARTSM00208. TNFR. 4 hits.
[Graphical view]
SUPFAMSSF47986. SSF47986. 2 hits.
PROSITEPS00652. TNFR_NGFR_1. 1 hit.
PS50050. TNFR_NGFR_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiOsteoprotegerin.
GenomeRNAi4982.
NextBio19182.
PROO00300.
SOURCESearch...

Entry information

Entry nameTR11B_HUMAN
AccessionPrimary (citable) accession number: O00300
Secondary accession number(s): B2R9A8 expand/collapse secondary AC list , O60236, Q53FX6, Q9UHP4
Entry history
Integrated into UniProtKB/Swiss-Prot: May 27, 2002
Last sequence update: February 8, 2011
Last modified: April 16, 2014
This is version 128 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM