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Reviewed, UniProtKB/Swiss-Prot O00300 (TR11B_HUMAN)

Last modified May 5, 2009. Version 84. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Tumor necrosis factor receptor superfamily member 11B
Alternative name(s):
    Osteoprotegerin
    Osteoclastogenesis inhibitory factor
Gene names
Name: TNFRSF11B
Synonyms: OCIF, OPG
OrganismHomo sapiens (Human)
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 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. Ref.11

Subunit structure

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.

Post-translational modification

N-glycosylated. Contains sialic acid residues.

The N-terminus is blocked.

Involvement in 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. Ref.15

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 termDirect protein sequencing
Gene Ontology (GO)
   Biological processapoptosis

Inferred from electronic annotation. Source: UniProtKB-KW

signal transduction Ref.11

Traceable author statement. Source: ProtInc

skeletal system development Ref.1

Traceable author statement. Source: ProtInc

   Molecular functioncytokine activity Ref.11

Traceable author statement. Source: ProtInc

receptor activity Ref.1

Traceable author statement. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Ref.8 Ref.9
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...) Potential
Glycosylation2891N-linked (GlcNAc...) Potential
Disulfide bond41 ↔ 54 By similarity
Disulfide bond44 ↔ 62 By similarity
Disulfide bond65 ↔ 80 By similarity
Disulfide bond83 ↔ 97 By similarity
Disulfide bond87 ↔ 105 By similarity
Disulfide bond107 ↔ 118 By similarity
Disulfide bond124 ↔ 142 By similarity
Disulfide bond145 ↔ 160 By similarity
Disulfide bond166 ↔ 185 By similarity

Natural variations

Natural variant31K → N: dbSNP rs2073618. Ref.3 Ref.5 Ref.6 Ref.7
VAR_013439
Natural variant1041V → M: dbSNP rs11573906. Ref.6
VAR_018957
Natural variant1821Missing in JPD. Ref.15
VAR_019413

Experimental info

Mutagenesis400 – 4012Missing: Abolishes dimerization. Ref.13
Mutagenesis4001C → S: Abolishes dimerization. Ref.13
Sequence conflict2631D → A in AAB53709. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O00300-1 [UniParc].

Last modified May 27, 2002. Version 2.
Checksum: EDF448B67D86C71E

FASTA40146,040
        10         20         30         40         50         60 
MNKLLCCALV 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: 9108485] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
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: 9492069] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
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: 9688283] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASN-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: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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], VARIANT ASN-3.
Tissue: Lung.
[6]NIEHS SNPs program
Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ASN-3 AND MET-104.
[7]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ASN-3.
Tissue: Eye.
[8]"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: 9571159] [Abstract]
Cited for: PROTEIN SEQUENCE OF 22-36 AND 378-401.
[9]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract]
Cited for: PROTEIN SEQUENCE OF 22-36.
[10]"Cloning and expression of osteoprotegerin from Homo sapiens."
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: 12110935] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 22-393.
Tissue: Placenta.
[11]"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: 9168977] [Abstract]
Cited for: PROTEIN SEQUENCE OF 242-255; 354-359 AND 369-378, FUNCTION.
[12]"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: 9603945] [Abstract]
Cited for: INTERACTION WITH TRAIL.
[13]"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: 9478964] [Abstract]
Cited for: CHARACTERIZATION, MUTAGENESIS OF CYS-400.
[14]"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: 11505389] [Abstract]
Cited for: REVIEW.
[15]"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: 12189164] [Abstract]
Cited for: VARIANT JPD ASP-182 DEL.
+Additional computationally mapped references.

Cross-references

Sequence databases

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.
BC030155 mRNA. Translation: AAH30155.1.
AF134187 mRNA. Translation: AAF20168.1.
IPIIPI00298362.
RefSeqNP_002537.3.
UniGeneHs.81791

3D structure databases

HSSPHSSP built from PDB template 1D0G based on UniProtKB O14763.
ModBaseSearch...

Proteomic databases

PRIDEO00300.

Genome annotation databases

EnsemblENSG00000164761. Homo sapiens. [Contig view]
GeneID4982.
KEGGhsa:4982.

Organism-specific databases

GeneCardsGC08M120004.
H-InvDBHIX0007748.
HGNCHGNC:11909. TNFRSF11B.
MIM239000. phenotype.
602643. gene.
Orphanet2801. Paget disease juvenile type.
PharmGKBPA36602.
GenAtlasSearch...

Phylogenomic databases

HOGENOMO00300.
HOVERGENO00300.

Gene expression databases

ArrayExpressO00300.
BgeeO00300.
CleanExHS_TNFRSF11B.
GermOnlineENSG00000164761. Homo sapiens.

Family and domain databases

InterProIPR000488. Death.
IPR017371. TNFR_11B.
IPR001368. TNFR_Cys_rich_reg.
[Graphical view]
PfamPF00531. Death. 1 hit.
PF00020. TNFR_c6. 3 hits.
[Graphical view]
PIRSFPIRSF038065. TNFR_11B. 1 hit.
SMARTSM00208. TNFR. 4 hits.
[Graphical view]
PROSITEPS50017. DEATH_DOMAIN. False negative.
PS00652. TNFR_NGFR_1. 1 hit.
PS50050. TNFR_NGFR_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio19182.
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: May 27, 2002
Last modified: May 5, 2009
This is version 84 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 8

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents