TNFRSF11A

Protein identityUniProt · HPA

UniProt accession

Q9Y6Q6

Gene

TNFRSF11A

Ensembl

ENSG00000141655

Chromosome

18

Canonical length

616 aa

Protein class

CD markers, Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Plasma membrane,Cytosol

Secretome location

Intracellular and membrane

OverviewNCBI Gene

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptors can interact with various TRAF family proteins, through which this receptor induces the activation of NF-kappa B and MAPK8/JNK. This receptor and its ligand are important regulators of the interaction between T cells and dendritic cells. This receptor is also an essential mediator for osteoclast and lymph node development. Mutations at this locus have been associated with familial expansile osteolysis, autosomal recessive osteopetrosis, and Paget disease of bone. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Aug 2012]

Canonical amino-acid sequenceUniProt

616 residues, UniProt reviewed canonical sequence.

>Q9Y6Q6|TNFRSF11A
     1  MAPRARRRRP LFALLLLCAL LARLQVALQI APPCTSEKHY EHLGRCCNKC EPGKYMSSKC
    61  TTTSDSVCLP CGPDEYLDSW NEEDKCLLHK VCDTGKALVA VVAGNSTTPR RCACTAGYHW
   121  SQDCECCRRN TECAPGLGAQ HPLQLNKDTV CKPCLAGYFS DAFSSTDKCR PWTNCTFLGK
   181  RVEHHGTEKS DAVCSSSLPA RKPPNEPHVY LPGLIILLLF ASVALVAAII FGVCYRKKGK
   241  ALTANLWHWI NEACGRLSGD KESSGDSCVS THTANFGQQG ACEGVLLLTL EEKTFPEDMC
   301  YPDQGGVCQG TCVGGGPYAQ GEDARMLSLV SKTEIEEDSF RQMPTEDEYM DRPSQPTDQL
   361  LFLTEPGSKS TPPFSEPLEV GENDSLSQCF TGTQSTVGSE SCNCTEPLCR TDWTPMSSEN
   421  YLQKEVDSGH CPHWAASPSP NWADVCTGCR NPPGEDCEPL VGSPKRGPLP QCAYGMGLPP
   481  EEEASRTEAR DQPEDGADGR LPSSARAGAG SGSSPGGQSP ASGNVTGNSN STFISSGQVM
   541  NFKGDIIVVY VSQTSQEGAA AAAEPMGRPV QEETLARRDS FAGNGPRFPD PCGGPEGLRE
   601  PEKASRPVQE QGGAKA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TNFRSF11A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.61

Highest tissue expression

29 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TNFRSF11A.

Disease | AllUniProt

Conditions TNFRSF11A is implicated in, by any mechanism.

• Familial expansile osteolysis (FEO) MIM:174810
• Paget disease of bone 2, early-onset (PDB2) MIM:602080
• Osteopetrosis, autosomal recessive 7 (OPTB7) MIM:612301

Disease | GeneticClinVar

33 pathogenic / likely-pathogenic of 791 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal recessive osteopetrosis 7
• Familial expansile osteolysis
• Paget disease of bone 2, early-onset
• Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.6

gnomAD pLI

0.01

gnomAD missense Z

1.29

DepMap mean gene effect

0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adaptive immune response
• cell-cell signaling
• cellular response to zinc ion starvation
• circadian temperature homeostasis
• lymph node development
• mammary gland alveolus development
• monocyte chemotaxis
• multinuclear osteoclast differentiation
• ossification
• osteoclast differentiation
• positive regulation of bone resorption
• positive regulation of canonical NF-kappaB signal transduction
• positive regulation of cell population proliferation
• positive regulation of ERK1 and ERK2 cascade
• positive regulation of fever generation by positive regulation of prostaglandin secretion
• positive regulation of JNK cascade
• positive regulation of non-canonical NF-kappaB signal transduction
• positive regulation of osteoclast differentiation
• response to ethanol
• response to insulin
• response to interleukin-1
• response to lipopolysaccharide
• response to mechanical stimulus
• response to tumor necrosis factor
• signal transduction
• tumor necrosis factor-mediated signaling pathway

Molecular functions

• cytokine binding
• metal ion binding
• signaling receptor activity
• transmembrane signaling receptor activity
• tumor necrosis factor receptor activity

Cellular components

• cytosol
• external side of plasma membrane
• membrane raft
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• TNFR/NGFR cysteine-rich region
• Tumour necrosis factor receptor 11
• TNFR/NGFR cysteine-rich region
• Tumour necrosis factor receptor 11A
• Tumor necrosis factor receptor 11A, N-terminal
• Rank, cysteine-rich repeat domain 2
• Tumor necrosis factor receptor superfamily member 11A
• Receptor activator of the NF-KB cysteine-rich repeat domain 2

KeywordsUniProt

• Cell membrane
• Deafness
• Disulfide bond
• Glycoprotein
• Membrane
• Metal-binding
• Osteopetrosis
• Phosphoprotein
• Receptor
• Repeat
• Signal
• Sodium
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of TNFRSF11A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• TRAF1
• TRAF2
• TRAF3
• TRAF5
• TRAF6
• GAB2
• TNFSF11