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Protein

Tumor necrosis factor receptor superfamily member 11B

Gene

TNFRSF11B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei400Involved in dimerization1

GO - Molecular functioni

  • cytokine activity Source: ProtInc
  • receptor activity Source: ProtInc
  • tumor necrosis factor-activated receptor activity Source: GO_Central

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

BioCyciZFISH:ENSG00000164761-MONOMER.
ReactomeiR-HSA-5669034. TNFs bind their physiological receptors.
SIGNORiO00300.

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor receptor superfamily member 11B
Alternative name(s):
Osteoclastogenesis inhibitory factor
Osteoprotegerin
Gene namesi
Name:TNFRSF11B
Synonyms:OCIF, OPG
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:11909. TNFRSF11B.

Subcellular locationi

GO - Cellular componenti

  • extracellular region Source: ProtInc
  • extracellular space Source: BHF-UCL
  • integral component of plasma membrane Source: GO_Central
  • plasma membrane Source: Reactome
  • proteinaceous extracellular matrix Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Paget disease of bone 5, juvenile-onset (PDB5)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive, juvenile-onset form of Paget disease, a disorder of bone remodeling characterized by increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Osteoclastic overactivity followed by compensatory osteoblastic activity leads to a structurally disorganized mosaic of bone (woven bone), which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone. PDB5 clinical manifestations include short stature, progressive long bone deformities, fractures, vertebral collapse, skull enlargement, and hyperostosis with progressive deafness.
See also OMIM:239000
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019413182Missing in PDB5. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi78 – 79DE → AA: Decreases inhibition of osteoclast differentiation. 1 Publication2
Mutagenesisi116E → A: Reduces affinity for TNFSF11. Decreases inhibition of osteoclast differentiation. 1 Publication1
Mutagenesisi400 – 401Missing : Abolishes dimerization. 2
Mutagenesisi400C → S: Abolishes dimerization. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi4982.
MalaCardsiTNFRSF11B.
MIMi239000. phenotype.
OpenTargetsiENSG00000164761.
Orphaneti2801. Juvenile Paget disease.
PharmGKBiPA36602.

Polymorphism and mutation databases

BioMutaiTNFRSF11B.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 212 PublicationsAdd BLAST21
ChainiPRO_000003458722 – 401Tumor necrosis factor receptor superfamily member 11BAdd BLAST380

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi41 ↔ 54PROSITE-ProRule annotation1 Publication
Disulfide bondi44 ↔ 62PROSITE-ProRule annotation1 Publication
Disulfide bondi65 ↔ 80PROSITE-ProRule annotation1 Publication
Disulfide bondi83 ↔ 97PROSITE-ProRule annotation1 Publication
Disulfide bondi87 ↔ 105PROSITE-ProRule annotation1 Publication
Glycosylationi98N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi107 ↔ 118PROSITE-ProRule annotation1 Publication
Disulfide bondi124 ↔ 142PROSITE-ProRule annotation1 Publication
Disulfide bondi145 ↔ 160PROSITE-ProRule annotation1 Publication
Glycosylationi152N-linked (GlcNAc...)Sequence analysis1
Glycosylationi165N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi166 ↔ 185PROSITE-ProRule annotation1 Publication
Glycosylationi178N-linked (GlcNAc...)1 Publication1
Glycosylationi289N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

N-glycosylated. Contains sialic acid residues.1 Publication
The N-terminus is blocked.

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO00300.
PeptideAtlasiO00300.
PRIDEiO00300.

PTM databases

iPTMnetiO00300.
PhosphoSitePlusiO00300.

Expressioni

Tissue specificityi

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.

Inductioni

Up-regulated by increasing calcium-concentration in the medium and estrogens. Down-regulated by glucocorticoids.

Gene expression databases

BgeeiENSG00000164761.
CleanExiHS_TNFRSF11B.
ExpressionAtlasiO00300. baseline and differential.
GenevisibleiO00300. HS.

Organism-specific databases

HPAiHPA027013.

Interactioni

Subunit structurei

Homodimer. Interacts with TNFSF10 and TNFSF11.2 Publications

GO - Molecular functioni

  • cytokine activity Source: ProtInc

Protein-protein interaction databases

BioGridi111028. 2 interactors.
STRINGi9606.ENSP00000297350.

Structurei

Secondary structure

1401
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi29 – 31Combined sources3
Beta strandi35 – 37Combined sources3
Beta strandi40 – 42Combined sources3
Beta strandi48 – 52Combined sources5
Beta strandi56 – 58Combined sources3
Beta strandi61 – 64Combined sources4
Beta strandi91 – 95Combined sources5
Beta strandi99 – 101Combined sources3
Beta strandi104 – 107Combined sources4
Beta strandi111 – 114Combined sources4
Beta strandi117 – 120Combined sources4
Beta strandi128 – 132Combined sources5
Beta strandi136 – 138Combined sources3
Beta strandi141 – 144Combined sources4
Beta strandi155 – 157Combined sources3
Beta strandi167 – 171Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3URFX-ray2.70Z22-186[»]
ProteinModelPortaliO00300.
SMRiO00300.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati24 – 62TNFR-Cys 1Add BLAST39
Repeati65 – 105TNFR-Cys 2Add BLAST41
Repeati107 – 142TNFR-Cys 3Add BLAST36
Repeati145 – 185TNFR-Cys 4Add BLAST41
Domaini198 – 269Death 1Add BLAST72
Domaini270 – 365Death 2Add BLAST96

Sequence similaritiesi

Contains 2 death domains.Curated
Contains 4 TNFR-Cys repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IFEM. Eukaryota.
ENOG4111PUQ. LUCA.
GeneTreeiENSGT00760000119204.
HOGENOMiHOG000273896.
HOVERGENiHBG061495.
InParanoidiO00300.
KOiK05148.
OMAiSRQLMCD.
OrthoDBiEOG091G03XW.
PhylomeDBiO00300.
TreeFamiTF331157.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR001368. TNFR/NGFR_Cys_rich_reg.
IPR022323. TNFR_11.
IPR017371. TNFR_11B.
IPR011641. Tyr-kin_ephrin_A/B_rcpt-like.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF00020. TNFR_c6. 3 hits.
[Graphical view]
PIRSFiPIRSF038065. TNFR_11B. 1 hit.
PRINTSiPR01961. TNFACTORR11.
PR01975. TNFACTORR11B.
SMARTiSM00005. DEATH. 1 hit.
SM01411. Ephrin_rec_like. 2 hits.
SM00208. TNFR. 4 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 2 hits.
PROSITEiPS00652. TNFR_NGFR_1. 1 hit.
PS50050. TNFR_NGFR_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O00300-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNNLLCCALV FLDISIKWTT QETFPPKYLH YDEETSHQLL CDKCPPGTYL
60 70 80 90 100
KQHCTAKWKT VCAPCPDHYY TDSWHTSDEC LYCSPVCKEL QYVKQECNRT
110 120 130 140 150
HNRVCECKEG RYLEIEFCLK HRSCPPGFGV VQAGTPERNT VCKRCPDGFF
160 170 180 190 200
SNETSSKAPC RKHTNCSVFG LLLTQKGNAT HDNICSGNSE STQKCGIDVT
210 220 230 240 250
LCEEAFFRFA VPTKFTPNWL SVLVDNLPGT KVNAESVERI KRQHSSQEQT
260 270 280 290 300
FQLLKLWKHQ NKDQDIVKKI IQDIDLCENS VQRHIGHANL TFEQLRSLME
310 320 330 340 350
SLPGKKVGAE DIEKTIKACK PSDQILKLLS LWRIKNGDQD TLKGLMHALK
360 370 380 390 400
HSKTYHFPKT VTQSLKKTIR FLHSFTMYKL YQKLFLEMIG NQVQSVKISC

L
Length:401
Mass (Da):46,026
Last modified:February 8, 2011 - v3
Checksum:i2A23AC07BFA1E2DE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti263D → A in AAB53709 (PubMed:9108485).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0134393N → K.5 PublicationsCorresponds to variant rs2073618dbSNPEnsembl.1
Natural variantiVAR_018957104V → M.1 PublicationCorresponds to variant rs11573906dbSNPEnsembl.1
Natural variantiVAR_019413182Missing in PDB5. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS6326.1.
RefSeqiNP_002537.3. NM_002546.3.
UniGeneiHs.81791.

Genome annotation databases

EnsembliENST00000297350; ENSP00000297350; ENSG00000164761.
GeneIDi4982.
KEGGihsa:4982.
UCSCiuc003yon.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS6326.1.
RefSeqiNP_002537.3. NM_002546.3.
UniGeneiHs.81791.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3URFX-ray2.70Z22-186[»]
ProteinModelPortaliO00300.
SMRiO00300.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111028. 2 interactors.
STRINGi9606.ENSP00000297350.

PTM databases

iPTMnetiO00300.
PhosphoSitePlusiO00300.

Polymorphism and mutation databases

BioMutaiTNFRSF11B.

Proteomic databases

PaxDbiO00300.
PeptideAtlasiO00300.
PRIDEiO00300.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000297350; ENSP00000297350; ENSG00000164761.
GeneIDi4982.
KEGGihsa:4982.
UCSCiuc003yon.5. human.

Organism-specific databases

CTDi4982.
DisGeNETi4982.
GeneCardsiTNFRSF11B.
H-InvDBHIX0007748.
HGNCiHGNC:11909. TNFRSF11B.
HPAiHPA027013.
MalaCardsiTNFRSF11B.
MIMi239000. phenotype.
602643. gene.
neXtProtiNX_O00300.
OpenTargetsiENSG00000164761.
Orphaneti2801. Juvenile Paget disease.
PharmGKBiPA36602.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFEM. Eukaryota.
ENOG4111PUQ. LUCA.
GeneTreeiENSGT00760000119204.
HOGENOMiHOG000273896.
HOVERGENiHBG061495.
InParanoidiO00300.
KOiK05148.
OMAiSRQLMCD.
OrthoDBiEOG091G03XW.
PhylomeDBiO00300.
TreeFamiTF331157.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000164761-MONOMER.
ReactomeiR-HSA-5669034. TNFs bind their physiological receptors.
SIGNORiO00300.

Miscellaneous databases

GeneWikiiOsteoprotegerin.
GenomeRNAii4982.
PROiO00300.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164761.
CleanExiHS_TNFRSF11B.
ExpressionAtlasiO00300. baseline and differential.
GenevisibleiO00300. HS.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR001368. TNFR/NGFR_Cys_rich_reg.
IPR022323. TNFR_11.
IPR017371. TNFR_11B.
IPR011641. Tyr-kin_ephrin_A/B_rcpt-like.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF00020. TNFR_c6. 3 hits.
[Graphical view]
PIRSFiPIRSF038065. TNFR_11B. 1 hit.
PRINTSiPR01961. TNFACTORR11.
PR01975. TNFACTORR11B.
SMARTiSM00005. DEATH. 1 hit.
SM01411. Ephrin_rec_like. 2 hits.
SM00208. TNFR. 4 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 2 hits.
PROSITEiPS00652. TNFR_NGFR_1. 1 hit.
PS50050. TNFR_NGFR_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTR11B_HUMAN
AccessioniPrimary (citable) accession number: O00300
Secondary accession number(s): B2R9A8
, O60236, Q53FX6, Q9UHP4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 27, 2002
Last sequence update: February 8, 2011
Last modified: November 2, 2016
This is version 146 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.