Q1WM27 · TNFA_DASNO

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 (By similarity).
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 (By similarity).
Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6 (By similarity).
Promotes osteoclastogenesis and therefore mediates bone resorption (By similarity).
The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.

Features

Showing features for site.

123320406080100120140160180200220
TypeIDPosition(s)Description
Site33-34Cleavage; by SPPL2A or SPPL2B
Site38-39Cleavage; by SPPL2A or SPPL2B
Site48-49Cleavage; by SPPL2A or SPPL2B
Site50-51Cleavage; by SPPL2A or SPPL2B
Site77-78Cleavage; by ADAM17

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 Componentcell surface
Cellular Componentextracellular space
Cellular Componentplasma membrane
Molecular Functioncytokine activity
Molecular Functiontumor necrosis factor receptor binding
Biological Processextrinsic apoptotic signaling pathway via death domain receptors
Biological Processimmune response
Biological Processnecroptotic signaling pathway
Biological Processnegative regulation of protein-containing complex disassembly
Biological Processpositive regulation of apoptotic process
Biological Processpositive regulation of JUN kinase activity
Biological Processpositive regulation of MAP kinase activity
Biological Processpositive regulation of NF-kappaB transcription factor activity
Biological Processpositive regulation of protein phosphorylation
Biological Processpositive regulation of protein-containing complex disassembly
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processregulation of biological quality
Biological Processregulation of developmental process
Biological Processregulation of multicellular organismal process
Biological Processregulation of secretion
Biological Processtumor necrosis factor-mediated signaling pathway
Biological Processvascular endothelial growth factor production

Keywords

Names & Taxonomy

Protein names

Gene names

    • Name
      TNF
    • Synonyms
      TNFA, TNFSF2

Organism names

Accessions

  • Primary accession
    Q1WM27

Subcellular Location

Cell membrane
; Single-pass type II membrane protein

Tumor necrosis factor, membrane form

Membrane
; Single-pass type II membrane protein

Tumor necrosis factor, soluble form

Secreted

C-domain 1

Secreted

C-domain 2

Secreted

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-34Cytoplasmic
Transmembrane35-55Helical; Signal-anchor for type II membrane protein
Topological domain56-233Extracellular

Keywords

PTM/Processing

Features

Showing features for chain, modified residue, lipidation, glycosylation, disulfide bond.

TypeIDPosition(s)Description
ChainPRO_00004172161-34Intracellular domain 2
ChainPRO_00004172151-38Intracellular domain 1
ChainPRO_00002537531-233Tumor necrosis factor, membrane form
Modified residue2Phosphoserine; by CK1
Lipidation19N6-myristoyl lysine
Lipidation20N6-myristoyl lysine
ChainPRO_000041721749-?C-domain 1
ChainPRO_000041721851-?C-domain 2
ChainPRO_000025375478-233Tumor necrosis factor, soluble form
Glycosylation80O-linked (GalNAc...) serine; in soluble form
Disulfide bond145↔177

Post-translational modification

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 (By similarity).
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 (By similarity).
O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid.

Tumor necrosis factor, soluble form

The soluble form is demyristoylated by SIRT6, promoting its secretion.

Keywords

PTM databases

Interaction

Subunit

Homotrimer. Interacts with SPPL2B (By similarity).

Structure

Family & Domains

Features

Showing features for domain.

TypeIDPosition(s)Description
Domain88-233THD

Sequence similarities

Belongs to the tumor necrosis factor family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    233
  • Mass (Da)
    25,404
  • Last updated
    2006-05-02 v1
  • Checksum
    A5ABBC9E182329AD
MSTESMIRDVELAEEALPKKVGPQGSRRCWCLSLFSFLLVAGATALFCLLQFGVIGPQRDEQLPSGFHLNSPLAQTLRSSSRAPSDKPVAHVVADPEAEGRLRWLSRRTNTLLAYGAALTDNQLVVPADGLYLVYSQLLFTGQGCAPAQPLLTHTVSRFAASYQTKVNLLSAIKSPCPRETPEGAEAKPWYEPIYLGGVFQLDKGDRFSAETNLPAYLDFAEPGQVYFGLIAL

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
DQ096649
EMBL· GenBank· DDBJ
AAZ76592.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice.
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.
FeedbackHelp