TNFSF11

Protein identityUniProt · HPA

UniProt accession

O14788

Gene

TNFSF11

Ensembl

ENSG00000120659

Chromosome

13

Canonical length

317 aa

Protein class

Cancer-related genes, CD markers, Disease related genes, FDA approved drug targets, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins, Predicted secreted proteins

Secretome location

Secreted to blood

Quaternary structure

Homotrimer

OverviewNCBI Gene

This gene encodes a member of the tumor necrosis factor (TNF) cytokine family which is a ligand for osteoprotegerin and functions as a key factor for osteoclast differentiation and activation. This protein was shown to be a dentritic cell survival factor and is involved in the regulation of T cell-dependent immune response. T cell activation was reported to induce expression of this gene and lead to an increase of osteoclastogenesis and bone loss. This protein was shown to activate antiapoptotic kinase AKT/PKB through a signaling complex involving SRC kinase and tumor necrosis factor receptor-associated factor (TRAF) 6, which indicated this protein may have a role in the regulation of cell apoptosis. Targeted disruption of the related gene in mice led to severe osteopetrosis and a lack of osteoclasts. The deficient mice exhibited defects in early differentiation of T and B lymphocytes, and failed to form lobulo-alveolar mammary structures during pregnancy. Two alternatively spliced transcript variants have been found. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

317 residues, UniProt reviewed canonical sequence.

>O14788|TNFSF11
     1  MRRASRDYTK YLRGSEEMGG GPGAPHEGPL HAPPPPAPHQ PPAASRSMFV ALLGLGLGQV
    61  VCSVALFFYF RAQMDPNRIS EDGTHCIYRI LRLHENADFQ DTTLESQDTK LIPDSCRRIK
   121  QAFQGAVQKE LQHIVGSQHI RAEKAMVDGS WLDLAKRSKL EAQPFAHLTI NATDIPSGSH
   181  KVSLSSWYHD RGWAKISNMT FSNGKLIVNQ DGFYYLYANI CFRHHETSGD LATEYLQLMV
   241  YVTKTSIKIP SSHTLMKGGS TKYWSGNSEF HFYSINVGGF FKLRSGEEIS IEVSNPSLLD
   301  PDQDATYFGA FKVRDID

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TNFSF11 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)

0.43

Highest tissue expression

12 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TNFSF11.

Disease | AllUniProt

Conditions TNFSF11 is implicated in, by any mechanism.

• Osteopetrosis, autosomal recessive 2 (OPTB2) MIM:259710

Disease | GeneticClinVar

5 pathogenic / likely-pathogenic of 264 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal recessive osteopetrosis 2

Disease | ImmuneIEDB

Conditions an epitope on TNFSF11 was assayed in.

• narcolepsy B cell
• multiple sclerosis B cell
• peripheral nervous system disease B cell

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)

0.85

gnomAD pLI

0

gnomAD missense Z

0.93

DepMap mean gene effect

0.12

DepMap dependency class

none

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

• bone resorption
• calcium ion homeostasis
• calcium-mediated signaling
• cell surface receptor signaling pathway
• cellular response to leukemia inhibitory factor
• cytokine-mediated signaling pathway
• immune response
• JNK cascade
• mammary gland alveolus development
• mammary gland epithelial cell proliferation
• monocyte chemotaxis
• negative regulation of transcription by RNA polymerase II
• ossification
• osteoclast development
• osteoclast differentiation
• osteoclast proliferation
• paracrine signaling
• phosphatidylinositol 3-kinase/protein kinase B signal transduction
• positive regulation of bone resorption
• positive regulation of canonical NF-kappaB signal transduction
• positive regulation of corticotropin-releasing hormone secretion
• positive regulation of ERK1 and ERK2 cascade
• positive regulation of extrinsic apoptotic signaling pathway
• positive regulation of fever generation by positive regulation of prostaglandin secretion
• positive regulation of gene expression
• positive regulation of homotypic cell-cell adhesion
• positive regulation of intracellular signal transduction
• positive regulation of JNK cascade
• positive regulation of MAPK cascade
• positive regulation of non-canonical NF-kappaB signal transduction
• positive regulation of osteoclast development
• positive regulation of osteoclast differentiation
• positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• positive regulation of T cell activation
• positive regulation of transcription by RNA polymerase II
• tooth eruption
• tumor necrosis factor-mediated signaling pathway

Molecular functions

• cytokine activity
• identical protein binding
• tumor necrosis factor receptor binding

Cellular components

• cytoplasm
• extracellular region
• extracellular space
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Tumour necrosis factor domain
• Tumour necrosis factor-like domain superfamily
• Tumour necrosis factor ligand 10/11
• TNF(Tumour Necrosis Factor) family

KeywordsUniProt

• Cell membrane
• Cytokine
• Cytoplasm
• Developmental protein
• Differentiation
• Glycoprotein
• Membrane
• Osteopetrosis
• Receptor
• Secreted
• Signal-anchor
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of TNFSF11 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• FBN1
• TNFAIP6
• TNFRSF11A
• TNFRSF11B