TNFSF10

Protein identityUniProt · HPA

UniProt accession

P50591

Gene

TNFSF10

Ensembl

ENSG00000121858

Chromosome

3

Canonical length

281 aa

Protein class

Cancer-related genes, CD markers, Predicted intracellular proteins, Predicted membrane proteins, Predicted secreted proteins, Transporters

Secretome location

Secreted to blood

Quaternary structure

Homotrimer

OverviewNCBI Gene

The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein preferentially induces apoptosis in transformed and tumor cells, but does not appear to kill normal cells although it is expressed at a significant level in most normal tissues. This protein binds to several members of TNF receptor superfamily including TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and possibly also to TNFRSF11B/OPG. The activity of this protein may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and TNFRSF11B/OPG that cannot induce apoptosis. The binding of this protein to its receptors has been shown to trigger the activation of MAPK8/JNK, caspase 8, and caspase 3. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

Canonical amino-acid sequenceUniProt

281 residues, UniProt reviewed canonical sequence.

>P50591|TNFSF10
     1  MAMMEVQGGP SLGQTCVLIV IFTVLLQSLC VAVTYVYFTN ELKQMQDKYS KSGIACFLKE
    61  DDSYWDPNDE ESMNSPCWQV KWQLRQLVRK MILRTSEETI STVQEKQQNI SPLVRERGPQ
   121  RVAAHITGTR GRSNTLSSPN SKNEKALGRK INSWESSRSG HSFLSNLHLR NGELVIHEKG
   181  FYYIYSQTYF RFQEEIKENT KNDKQMVQYI YKYTSYPDPI LLMKSARNSC WSKDAEYGLY
   241  SIYQGGIFEL KENDRIFVSV TNEHLIDMDH EASFFGAFLV G

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TNFSF10 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)

0.4

Highest tissue expression

195 nTPM

Expression across tissuesHPA

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)

0.64

gnomAD pLI

0.13

gnomAD missense Z

0.17

DepMap mean gene effect

0.03

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 10% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• apoptotic process
• cell surface receptor signaling pathway
• cell-cell signaling
• immune response
• positive regulation of apoptotic process
• positive regulation of canonical NF-kappaB signal transduction
• positive regulation of extrinsic apoptotic signaling pathway
• positive regulation of release of cytochrome c from mitochondria
• signal transduction
• TRAIL-activated apoptotic signaling pathway

Molecular functions

• cytokine activity
• identical protein binding
• signaling receptor binding
• TRAIL binding
• tumor necrosis factor receptor binding
• zinc ion binding

Cellular components

• extracellular exosome
• 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
• Tumour necrosis factor, conserved site
• TNF(Tumour Necrosis Factor) family

KeywordsUniProt

• Apoptosis
• Cell membrane
• Cytokine
• Membrane
• Metal-binding
• Phosphoprotein
• Secreted
• Signal-anchor
• Transmembrane
• Transmembrane helix
• Zinc

InteractionsUniProt · HPA

Protein binding partners of TNFSF10 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• TNFRSF11B
• TNFRSF10B