UniProtKB - O00300 (TR11B_HUMAN)
Protein
Tumor necrosis factor receptor superfamily member 11B
Gene
TNFRSF11B
Organism
Homo sapiens (Human)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 400 | Involved in dimerization | 1 |
GO - Molecular functioni
- cytokine activity Source: ProtInc
- signaling receptor activity Source: ProtInc
GO - Biological processi
- apoptotic process Source: UniProtKB-KW
- extracellular matrix organization Source: Ensembl
- negative regulation of bone resorption Source: Ensembl
- negative regulation of odontogenesis of dentin-containing tooth Source: Ensembl
- response to arsenic-containing substance Source: Ensembl
- response to drug Source: Ensembl
- response to estrogen Source: Ensembl
- response to magnesium ion Source: Ensembl
- response to nutrient Source: Ensembl
- signal transduction Source: ProtInc
- skeletal system development Source: ProtInc
- tumor necrosis factor-mediated signaling pathway Source: Reactome
Keywordsi
Molecular function | Receptor |
Biological process | Apoptosis |
Enzyme and pathway databases
PathwayCommonsi | O00300 |
Reactomei | R-HSA-5669034, TNFs bind their physiological receptors |
SIGNORi | O00300 |
Names & Taxonomyi
Protein namesi | Recommended name: Tumor necrosis factor receptor superfamily member 11BAlternative name(s): Osteoclastogenesis inhibitory factor Osteoprotegerin |
Gene namesi | Name:TNFRSF11B Synonyms:OCIF, OPG |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:11909, TNFRSF11B |
MIMi | 602643, gene |
neXtProti | NX_O00300 |
VEuPathDBi | HostDB:ENSG00000164761.8 |
Subcellular locationi
Extracellular region or secreted
Extracellular region or secreted
- extracellular matrix Source: Ensembl
- extracellular region Source: ProtInc
- extracellular space Source: BHF-UCL
Plasma Membrane
- plasma membrane Source: Reactome
Keywords - Cellular componenti
SecretedPathology & Biotechi
Involvement in diseasei
Paget disease of bone 5, juvenile-onset (PDB5)1 Publication
The disease is caused by variants 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_019413 | 182 | Missing in PDB5. 1 Publication | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 78 – 79 | DE → AA: Decreases inhibition of osteoclast differentiation. 1 Publication | 2 | |
Mutagenesisi | 116 | E → A: Reduces affinity for TNFSF11. Decreases inhibition of osteoclast differentiation. 1 Publication | 1 | |
Mutagenesisi | 400 – 401 | Missing : Abolishes dimerization. | 2 | |
Mutagenesisi | 400 | C → S: Abolishes dimerization. 1 Publication | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 4982 |
MalaCardsi | TNFRSF11B |
MIMi | 239000, phenotype |
OpenTargetsi | ENSG00000164761 |
Orphaneti | 1416, Familial calcium pyrophosphate deposition 2801, Juvenile Paget disease |
PharmGKBi | PA36602 |
Miscellaneous databases
Pharosi | O00300, Tbio |
Genetic variation databases
BioMutai | TNFRSF11B |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 21 | 2 PublicationsAdd BLAST | 21 | |
ChainiPRO_0000034587 | 22 – 401 | Tumor necrosis factor receptor superfamily member 11BAdd BLAST | 380 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 41 ↔ 54 | PROSITE-ProRule annotation1 Publication | ||
Disulfide bondi | 44 ↔ 62 | PROSITE-ProRule annotation1 Publication | ||
Disulfide bondi | 65 ↔ 80 | PROSITE-ProRule annotation1 Publication | ||
Disulfide bondi | 83 ↔ 97 | PROSITE-ProRule annotation1 Publication | ||
Disulfide bondi | 87 ↔ 105 | PROSITE-ProRule annotation1 Publication | ||
Glycosylationi | 98 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 107 ↔ 118 | PROSITE-ProRule annotation1 Publication | ||
Disulfide bondi | 124 ↔ 142 | PROSITE-ProRule annotation1 Publication | ||
Disulfide bondi | 145 ↔ 160 | PROSITE-ProRule annotation1 Publication | ||
Glycosylationi | 152 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 165 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 166 ↔ 185 | PROSITE-ProRule annotation1 Publication | ||
Glycosylationi | 178 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 289 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
N-glycosylated. Contains sialic acid residues.1 Publication
The N-terminus is blocked.
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
jPOSTi | O00300 |
MassIVEi | O00300 |
PaxDbi | O00300 |
PeptideAtlasi | O00300 |
PRIDEi | O00300 |
ProteomicsDBi | 47829 |
PTM databases
GlyGeni | O00300, 6 sites |
iPTMneti | O00300 |
PhosphoSitePlusi | O00300 |
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
Bgeei | ENSG00000164761, Expressed in tendon of biceps brachii and 169 other tissues |
ExpressionAtlasi | O00300, baseline and differential |
Genevisiblei | O00300, HS |
Organism-specific databases
HPAi | ENSG00000164761, Tissue enhanced (kidney, thyroid gland) |
Interactioni
Subunit structurei
Homodimer.
Interacts with TNFSF10 and TNFSF11.
2 PublicationsBinary interactionsi
Hide detailsO00300
With | #Exp. | IntAct |
---|---|---|
HTT [P42858] | 3 | EBI-15481185,EBI-466029 |
PSEN1 - isoform 2 [P49768-2] | 3 | EBI-15481185,EBI-11047108 |
TNFSF11 [O14788] | 3 | EBI-15481185,EBI-7404021 |
GO - Molecular functioni
- cytokine activity Source: ProtInc
Protein-protein interaction databases
BioGRIDi | 111028, 2 interactors |
ComplexPortali | CPX-4663, Osteoprotegerin complex |
IntActi | O00300, 4 interactors |
STRINGi | 9606.ENSP00000297350 |
Miscellaneous databases
RNActi | O00300, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | O00300 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 24 – 62 | TNFR-Cys 1Add BLAST | 39 | |
Repeati | 65 – 105 | TNFR-Cys 2Add BLAST | 41 | |
Repeati | 107 – 142 | TNFR-Cys 3Add BLAST | 36 | |
Repeati | 145 – 185 | TNFR-Cys 4Add BLAST | 41 | |
Domaini | 198 – 269 | Death 1Add BLAST | 72 | |
Domaini | 270 – 365 | Death 2Add BLAST | 96 |
Keywords - Domaini
Repeat, SignalPhylogenomic databases
eggNOGi | ENOG502QVRT, Eukaryota |
GeneTreei | ENSGT00940000155167 |
HOGENOMi | CLU_057708_0_0_1 |
InParanoidi | O00300 |
OMAi | KFLCCTL |
OrthoDBi | 358120at2759 |
PhylomeDBi | O00300 |
TreeFami | TF331157 |
Family and domain databases
InterProi | View protein in InterPro IPR011029, DEATH-like_dom_sf IPR000488, Death_domain IPR001368, TNFR/NGFR_Cys_rich_reg IPR022323, TNFR_11 IPR017371, TNFR_11B IPR011641, Tyr-kin_ephrin_A/B_rcpt-like |
Pfami | View protein in Pfam PF00531, Death, 1 hit PF00020, TNFR_c6, 3 hits |
PIRSFi | PIRSF038065, TNFR_11B, 1 hit |
PRINTSi | PR01961, TNFACTORR11 PR01975, TNFACTORR11B |
SMARTi | View protein in SMART SM00005, DEATH, 1 hit SM01411, Ephrin_rec_like, 2 hits SM00208, TNFR, 4 hits |
SUPFAMi | SSF47986, SSF47986, 2 hits |
PROSITEi | View protein in PROSITE PS00652, TNFR_NGFR_1, 1 hit PS50050, TNFR_NGFR_2, 2 hits |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
O00300-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketE5RFV7 | E5RFV7_HUMAN | Tumor necrosis factor receptor supe... | TNFRSF11B | 145 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 263 | D → A in AAB53709 (PubMed:9108485).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_013439 | 3 | N → K5 PublicationsCorresponds to variant dbSNP:rs2073618EnsemblClinVar. | 1 | |
Natural variantiVAR_018957 | 104 | V → M1 PublicationCorresponds to variant dbSNP:rs11573906EnsemblClinVar. | 1 | |
Natural variantiVAR_019413 | 182 | Missing in PDB5. 1 Publication | 1 |
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 |
CCDSi | CCDS6326.1 |
RefSeqi | NP_002537.3, NM_002546.3 |
Genome annotation databases
Ensembli | ENST00000297350; ENSP00000297350; ENSG00000164761 |
GeneIDi | 4982 |
KEGGi | hsa:4982 |
UCSCi | uc003yon.5, human |
Similar proteinsi
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 |
CCDSi | CCDS6326.1 |
RefSeqi | NP_002537.3, NM_002546.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3URF | X-ray | 2.70 | Z | 22-186 | [»] | |
SMRi | O00300 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 111028, 2 interactors |
ComplexPortali | CPX-4663, Osteoprotegerin complex |
IntActi | O00300, 4 interactors |
STRINGi | 9606.ENSP00000297350 |
PTM databases
GlyGeni | O00300, 6 sites |
iPTMneti | O00300 |
PhosphoSitePlusi | O00300 |
Genetic variation databases
BioMutai | TNFRSF11B |
Proteomic databases
jPOSTi | O00300 |
MassIVEi | O00300 |
PaxDbi | O00300 |
PeptideAtlasi | O00300 |
PRIDEi | O00300 |
ProteomicsDBi | 47829 |
Protocols and materials databases
Antibodypediai | 13632, 756 antibodies |
Genome annotation databases
Ensembli | ENST00000297350; ENSP00000297350; ENSG00000164761 |
GeneIDi | 4982 |
KEGGi | hsa:4982 |
UCSCi | uc003yon.5, human |
Organism-specific databases
CTDi | 4982 |
DisGeNETi | 4982 |
GeneCardsi | TNFRSF11B |
HGNCi | HGNC:11909, TNFRSF11B |
HPAi | ENSG00000164761, Tissue enhanced (kidney, thyroid gland) |
MalaCardsi | TNFRSF11B |
MIMi | 239000, phenotype 602643, gene |
neXtProti | NX_O00300 |
OpenTargetsi | ENSG00000164761 |
Orphaneti | 1416, Familial calcium pyrophosphate deposition 2801, Juvenile Paget disease |
PharmGKBi | PA36602 |
VEuPathDBi | HostDB:ENSG00000164761.8 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QVRT, Eukaryota |
GeneTreei | ENSGT00940000155167 |
HOGENOMi | CLU_057708_0_0_1 |
InParanoidi | O00300 |
OMAi | KFLCCTL |
OrthoDBi | 358120at2759 |
PhylomeDBi | O00300 |
TreeFami | TF331157 |
Enzyme and pathway databases
PathwayCommonsi | O00300 |
Reactomei | R-HSA-5669034, TNFs bind their physiological receptors |
SIGNORi | O00300 |
Miscellaneous databases
BioGRID-ORCSi | 4982, 3 hits in 877 CRISPR screens |
ChiTaRSi | TNFRSF11B, human |
GeneWikii | Osteoprotegerin |
GenomeRNAii | 4982 |
Pharosi | O00300, Tbio |
PROi | PR:O00300 |
RNActi | O00300, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000164761, Expressed in tendon of biceps brachii and 169 other tissues |
ExpressionAtlasi | O00300, baseline and differential |
Genevisiblei | O00300, HS |
Family and domain databases
InterProi | View protein in InterPro IPR011029, DEATH-like_dom_sf IPR000488, Death_domain IPR001368, TNFR/NGFR_Cys_rich_reg IPR022323, TNFR_11 IPR017371, TNFR_11B IPR011641, Tyr-kin_ephrin_A/B_rcpt-like |
Pfami | View protein in Pfam PF00531, Death, 1 hit PF00020, TNFR_c6, 3 hits |
PIRSFi | PIRSF038065, TNFR_11B, 1 hit |
PRINTSi | PR01961, TNFACTORR11 PR01975, TNFACTORR11B |
SMARTi | View protein in SMART SM00005, DEATH, 1 hit SM01411, Ephrin_rec_like, 2 hits SM00208, TNFR, 4 hits |
SUPFAMi | SSF47986, SSF47986, 2 hits |
PROSITEi | View protein in PROSITE PS00652, TNFR_NGFR_1, 1 hit PS50050, TNFR_NGFR_2, 2 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TR11B_HUMAN | |
Accessioni | O00300Primary (citable) accession number: O00300 Secondary accession number(s): B2R9A8 Q9UHP4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 27, 2002 |
Last sequence update: | February 8, 2011 | |
Last modified: | February 10, 2021 | |
This is version 174 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Direct protein sequencing, Reference proteomeDocuments
- Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - Human chromosome 8
Human chromosome 8: entries, gene names and cross-references to MIM