Q09H18 · Q09H18_MACMU

Function

function

Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance. Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6.
The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.

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 Componentextracellular space
Cellular Componentplasma membrane
Molecular Functioncytokine activity
Molecular Functiontumor necrosis factor receptor binding
Biological Processimmune response
Biological Processnecroptotic signaling pathway
Biological Processregulation of biological quality
Biological Processregulation of developmental process
Biological Processregulation of multicellular organismal process
Biological Processregulation of secretion
Biological Processvascular endothelial growth factor production

Keywords

  • Molecular function

Names & Taxonomy

Protein names

  • Recommended name
    Tumor necrosis factor
  • Short names
    TNF-a
  • Alternative names
    • Cachectin
    • TNF-alpha
    • Tumor necrosis factor ligand superfamily member 2
  • Cleaved into 5 chains

Gene names

    • Name
      TNF-alpha

Organism names

  • Taxonomic identifier
  • Strains
    • 95027
    • 95114
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Cercopithecidae > Cercopithecinae > Macaca

Accessions

  • Primary accession
    Q09H18

Subcellular Location

Cell membrane
; Single-pass type II membrane protein

C-domain 2

Secreted

Tumor necrosis factor, soluble form

Secreted

Tumor necrosis factor, membrane form

Membrane
; Single-pass type II membrane protein

C-domain 1

Secreted

Keywords

PTM/Processing

Features

Showing features for signal, chain.

Type
IDPosition(s)Description
Signal1-23
ChainPRO_501013358424-182Tumor necrosis factor

Post-translational modification

O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid.
The membrane form, but not the soluble form, is phosphorylated on serine residues. Dephosphorylation of the membrane form occurs by binding to soluble TNFRSF1A/TNFR1.
The soluble form derives from the membrane form by proteolytic processing. The membrane-bound form is further proteolytically processed by SPPL2A or SPPL2B through regulated intramembrane proteolysis producing TNF intracellular domains (ICD1 and ICD2) released in the cytosol and TNF C-domain 1 and C-domain 2 secreted into the extracellular space.

Keywords

Interaction

Subunit

Homotrimer. Interacts with SPPL2B.

Family & Domains

Features

Showing features for domain.

TypeIDPosition(s)Description
Domain54-182THD

Sequence similarities

Belongs to the tumor necrosis factor family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Fragment
  • Length
    182
  • Mass (Da)
    19,957
  • Last updated
    2006-10-17 v1
  • Checksum
    C0DDC5B18CA83FA8
FSFLLVAGATTLFCLLHFGVIGPQREEFPKDPSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELTDNQLVVPSEGLYLIYSQVLFKGQGCPSNHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRETPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINLPDY

Features

Showing features for non-terminal residue.

TypeIDPosition(s)Description
Non-terminal residue1
Non-terminal residue182

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
DQ902456
EMBL· GenBank· DDBJ
ABI63789.1
EMBL· GenBank· DDBJ
mRNA
DQ902462
EMBL· GenBank· DDBJ
ABI63795.1
EMBL· GenBank· DDBJ
mRNA

Similar Proteins

Disclaimer

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