Q9Y6Q6 · TNR11_HUMAN

  • Protein
    Tumor necrosis factor receptor superfamily member 11A
  • Gene
    TNFRSF11A
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis (PubMed:9878548).
Its interaction with EEIG1 promotes osteoclastogenesis via facilitating the transcription of NFATC1 and activation of PLCG2 (By similarity).
Involved in the regulation of interactions between T-cells and dendritic cells (By similarity).

Features

Showing features for binding site.

161650100150200250300350400450500550600
TypeIDPosition(s)Description
Binding site133Na+ (UniProtKB | ChEBI)
Binding site134Na+ (UniProtKB | ChEBI)
Binding site160Na+ (UniProtKB | ChEBI)

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentcytosol
Cellular Componentexternal side of plasma membrane
Cellular Componentmembrane raft
Cellular Componentplasma membrane
Molecular Functioncytokine binding
Molecular Functionmetal ion binding
Molecular Functionsignaling receptor activity
Molecular Functiontransmembrane signaling receptor activity
Molecular Functiontumor necrosis factor receptor activity
Biological Processadaptive immune response
Biological Processcell-cell signaling
Biological Processcellular response to zinc ion starvation
Biological Processcircadian temperature homeostasis
Biological Processlymph node development
Biological Processmammary gland alveolus development
Biological Processmonocyte chemotaxis
Biological Processmultinuclear osteoclast differentiation
Biological Processossification
Biological Processosteoclast differentiation
Biological Processpositive regulation of bone resorption
Biological Processpositive regulation of cell population proliferation
Biological Processpositive regulation of DNA-binding transcription factor activity
Biological Processpositive regulation of ERK1 and ERK2 cascade
Biological Processpositive regulation of fever generation by positive regulation of prostaglandin secretion
Biological Processpositive regulation of JUN kinase activity
Biological Processpositive regulation of NF-kappaB transcription factor activity
Biological Processpositive regulation of osteoclast differentiation
Biological Processresponse to ethanol
Biological Processresponse to insulin
Biological Processresponse to interleukin-1
Biological Processresponse to lipopolysaccharide
Biological Processresponse to mechanical stimulus
Biological Processresponse to organic cyclic compound
Biological Processresponse to tumor necrosis factor
Biological Processsignal transduction
Biological Processtumor necrosis factor-mediated signaling pathway

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Tumor necrosis factor receptor superfamily member 11A
  • Alternative names
    • Osteoclast differentiation factor receptor (ODFR)
    • Receptor activator of NF-KB
  • CD Antigen Name
    • CD265

Gene names

    • Name
      TNFRSF11A
    • Synonyms
      RANK

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    Q9Y6Q6
  • Secondary accessions
    • I4EC36
    • I4EC38
    • I4EC39
    • I7JE63
    • N0GVH0
    • Q59EP9

Proteomes

Organism-specific databases

Subcellular Location

Isoform 1

Cell membrane
; Single-pass type I membrane protein
Membrane raft

Isoform RANK-e5a

Cell membrane
; Single-pass type I membrane protein

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain30-212Extracellular
Transmembrane213-233Helical
Topological domain234-616Cytoplasmic

Keywords

Disease & Variants

Involvement in disease

Familial expansile osteolysis (FEO)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    Rare autosomal dominant bone disorder characterized by focal areas of increased bone remodeling. The osteolytic lesions develop usually in the long bones during early adulthood. FEO is often associated with early-onset deafness and loss of dentition.
  • See also
    MIM:174810
Natural variants in FEO
Variant IDPosition(s)ChangeDescription
VAR_01151721L>LLLCALLin FEO

Paget disease of bone 2, early-onset (PDB2)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    A 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.
  • See also
    MIM:602080
Natural variants in PDB2
Variant IDPosition(s)ChangeDescription
VAR_01151621L>LALLLLCALLin PDB2

Osteopetrosis, autosomal recessive 7 (OPTB7)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. OPTB7 is characterized by paucity of osteoclasts, suggesting a molecular defect in osteoclast development. OPTB7 is associated with hypogammaglobulinemia.
  • See also
    MIM:612301
Natural variants in OPTB7
Variant IDPosition(s)ChangeDescription
VAR_04678853G>Rin OPTB7; two patients with osteoclast-poor osteopetrosis; dbSNP:rs121908659
VAR_046789129R>Cin OPTB7; a patient with osteoclast-poor osteopetrosis; dbSNP:rs121908657
VAR_046791170R>Gin OPTB7; two siblings with osteoclast-poor osteopetrosis; dbSNP:rs121908655
VAR_046792175C>Rin OPTB7; two patients with osteoclast-poor osteopetrosis; dbSNP:rs121908656
VAR_046793244A>Sin OPTB7; one patient with osteoclast-poor osteopetrosis; dbSNP:rs121908658

Features

Showing features for natural variant.

TypeIDPosition(s)Description
Natural variantVAR_01151621in PDB2
Natural variantVAR_01151721in FEO
Natural variantVAR_04678853in OPTB7; two patients with osteoclast-poor osteopetrosis; dbSNP:rs121908659
Natural variantVAR_046789129in OPTB7; a patient with osteoclast-poor osteopetrosis; dbSNP:rs121908657
Natural variantVAR_046790141in dbSNP:rs35211496
Natural variantVAR_046791170in OPTB7; two siblings with osteoclast-poor osteopetrosis; dbSNP:rs121908655
Natural variantVAR_046792175in OPTB7; two patients with osteoclast-poor osteopetrosis; dbSNP:rs121908656
Natural variantVAR_011518192in dbSNP:rs1805034
Natural variantVAR_046793244in OPTB7; one patient with osteoclast-poor osteopetrosis; dbSNP:rs121908658

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 742 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for signal, chain, disulfide bond, glycosylation, modified residue (large scale data), modified residue.

TypeIDPosition(s)SourceDescription
Signal1-29UniProt
ChainPRO_000003458530-616UniProtTumor necrosis factor receptor superfamily member 11A
Disulfide bond34↔46UniProt
Disulfide bond47↔60UniProt
Disulfide bond50↔68UniProt
Disulfide bond71↔86UniProt
Disulfide bond92↔112UniProt
Glycosylation105UniProtN-linked (GlcNAc...) asparagine
Disulfide bond114↔127UniProt
Disulfide bond124↔126UniProt
Disulfide bond133↔151UniProt
Disulfide bond154↔169UniProt
Glycosylation174UniProtN-linked (GlcNAc...) asparagine
Disulfide bond175↔194UniProt
Modified residue (large scale data)463PRIDEPhosphoserine
Modified residue580UniProtPhosphoserine
Modified residue (large scale data)580PRIDEPhosphoserine

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Ubiquitous expression with high levels in skeletal muscle, thymus, liver, colon, small intestine and adrenal gland.

Gene expression databases

Organism-specific databases

Interaction

Subunit

Binds to the clefts between the subunits of the TNFSF11 ligand trimer to form a heterohexamer (By similarity).
Part of a complex composed of EEIG1, TNFRSF11A/RANK, PLCG2, GAB2, TEC and BTK; complex formation increases in the presence of TNFSF11/RANKL (PubMed:23478294).
Interacts with TRAF1, TRAF2, TRAF3, TRAF5 and TRAF6 (PubMed:9774460).
Interacts (via cytoplasmic domain) with GAB2 (PubMed:15750601).
Interacts (via cytoplasmic domain); with EEIG1 (via N-terminus); when in the presence of TNFSF11/RANKL (By similarity).

Binary interactions

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for repeat, region, compositional bias.

TypeIDPosition(s)Description
Repeat34-68TNFR-Cys 1
Repeat71-112TNFR-Cys 2
Repeat114-151TNFR-Cys 3
Repeat154-194TNFR-Cys 4
Region468-536Disordered
Compositional bias483-497Basic and acidic residues
Compositional bias507-536Polar residues
Region544-549Required for interaction with EEIG1 and osteoclast differentiation
Region556-616Disordered

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (6)
  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.

This entry describes 6 isoforms produced by Alternative splicing.

Q9Y6Q6-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Length
    616
  • Mass (Da)
    66,034
  • Last updated
    1999-11-01 v1
  • Checksum
    E3DE9A7A08196F81
MAPRARRRRPLFALLLLCALLARLQVALQIAPPCTSEKHYEHLGRCCNKCEPGKYMSSKCTTTSDSVCLPCGPDEYLDSWNEEDKCLLHKVCDTGKALVAVVAGNSTTPRRCACTAGYHWSQDCECCRRNTECAPGLGAQHPLQLNKDTVCKPCLAGYFSDAFSSTDKCRPWTNCTFLGKRVEHHGTEKSDAVCSSSLPARKPPNEPHVYLPGLIILLLFASVALVAAIIFGVCYRKKGKALTANLWHWINEACGRLSGDKESSGDSCVSTHTANFGQQGACEGVLLLTLEEKTFPEDMCYPDQGGVCQGTCVGGGPYAQGEDARMLSLVSKTEIEEDSFRQMPTEDEYMDRPSQPTDQLLFLTEPGSKSTPPFSEPLEVGENDSLSQCFTGTQSTVGSESCNCTEPLCRTDWTPMSSENYLQKEVDSGHCPHWAASPSPNWADVCTGCRNPPGEDCEPLVGSPKRGPLPQCAYGMGLPPEEEASRTEARDQPEDGADGRLPSSARAGAGSGSSPGGQSPASGNVTGNSNSTFISSGQVMNFKGDIIVVYVSQTSQEGAAAAAEPMGRPVQEETLARRDSFAGNGPRFPDPCGGPEGLREPEKASRPVQEQGGAKA

Q9Y6Q6-2

  • Name
    2
  • Synonyms
    delta7,8,9
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q9Y6Q6-3

  • Name
    3
  • Synonyms
    delta8,9
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q9Y6Q6-4

  • Name
    4
  • Synonyms
    delta9
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q9Y6Q6-5

  • Name
    5
  • Synonyms
    exon9a
  • Note
    Reduced ability to bind RANKL and to activate NF-kappaB as compared to isoform 1.
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 523-616: GNVTGNSNSTFISSGQVMNFKGDIIVVYVSQTSQEGAAAAAEPMGRPVQEETLARRDSFAGNGPRFPDPCGGPEGLREPEKASRPVQEQGGAKA → D

Q9Y6Q6-6

  • Name
    RANK-e5a
  • Note
    Reduced ability to bind RANKL and to activate NF-kappaB as compared to isoform 1.
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Sequence caution

The sequence BAD92999.1 differs from that shown. Reason: Erroneous initiation Extended N-terminus.

Features

Showing features for alternative sequence, compositional bias.

TypeIDPosition(s)Description
Alternative sequenceVSP_054179143-157in isoform RANK-e5a
Alternative sequenceVSP_046901206-522in isoform 2
Alternative sequenceVSP_054180244-522in isoform 3
Alternative sequenceVSP_054181263in isoform 4
Alternative sequenceVSP_054182264-616in isoform 4
Compositional bias483-497Basic and acidic residues
Compositional bias507-536Polar residues
Alternative sequenceVSP_054183523-616in isoform 5

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF018253
EMBL· GenBank· DDBJ
AAB86809.1
EMBL· GenBank· DDBJ
mRNA
HF584702
EMBL· GenBank· DDBJ
CCQ44072.1
EMBL· GenBank· DDBJ
mRNA
HE647782
EMBL· GenBank· DDBJ
CCF23032.1
EMBL· GenBank· DDBJ
mRNA
HE649916
EMBL· GenBank· DDBJ
CCF55033.1
EMBL· GenBank· DDBJ
mRNA
HE649917
EMBL· GenBank· DDBJ
CCF55034.1
EMBL· GenBank· DDBJ
mRNA
HE659518
EMBL· GenBank· DDBJ
CCF77738.1
EMBL· GenBank· DDBJ
mRNA
AB209762
EMBL· GenBank· DDBJ
BAD92999.1
EMBL· GenBank· DDBJ
mRNA Different initiation

Genome annotation databases

Similar Proteins

Disclaimer

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