Q1WM27 · TNFA_DASNO
- ProteinTumor necrosis factor
- GeneTNF
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids233 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 33-34 | Cleavage; by SPPL2A or SPPL2B | ||||
Sequence: SL | ||||||
Site | 38-39 | Cleavage; by SPPL2A or SPPL2B | ||||
Sequence: LL | ||||||
Site | 48-49 | Cleavage; by SPPL2A or SPPL2B | ||||
Sequence: CL | ||||||
Site | 50-51 | Cleavage; by SPPL2A or SPPL2B | ||||
Sequence: LQ | ||||||
Site | 77-78 | Cleavage; by ADAM17 | ||||
Sequence: LR |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Molecular function
Names & Taxonomy
Protein names
- Recommended nameTumor necrosis factor
- Alternative names
- Cleaved into 6 chains
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Xenarthra > Cingulata > Dasypodidae > Dasypus
Accessions
- Primary accessionQ1WM27
Subcellular Location
UniProt Annotation
GO Annotation
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
C-domain 1
C-domain 2
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-34 | Cytoplasmic | ||||
Sequence: MSTESMIRDVELAEEALPKKVGPQGSRRCWCLSL | ||||||
Transmembrane | 35-55 | Helical; Signal-anchor for type II membrane protein | ||||
Sequence: FSFLLVAGATALFCLLQFGVI | ||||||
Topological domain | 56-233 | Extracellular | ||||
Sequence: GPQRDEQLPSGFHLNSPLAQTLRSSSRAPSDKPVAHVVADPEAEGRLRWLSRRTNTLLAYGAALTDNQLVVPADGLYLVYSQLLFTGQGCAPAQPLLTHTVSRFAASYQTKVNLLSAIKSPCPRETPEGAEAKPWYEPIYLGGVFQLDKGDRFSAETNLPAYLDFAEPGQVYFGLIAL |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, modified residue, lipidation, glycosylation, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000417216 | 1-34 | Intracellular domain 2 | |||
Sequence: MSTESMIRDVELAEEALPKKVGPQGSRRCWCLSL | ||||||
Chain | PRO_0000417215 | 1-38 | Intracellular domain 1 | |||
Sequence: MSTESMIRDVELAEEALPKKVGPQGSRRCWCLSLFSFL | ||||||
Chain | PRO_0000253753 | 1-233 | Tumor necrosis factor, membrane form | |||
Sequence: MSTESMIRDVELAEEALPKKVGPQGSRRCWCLSLFSFLLVAGATALFCLLQFGVIGPQRDEQLPSGFHLNSPLAQTLRSSSRAPSDKPVAHVVADPEAEGRLRWLSRRTNTLLAYGAALTDNQLVVPADGLYLVYSQLLFTGQGCAPAQPLLTHTVSRFAASYQTKVNLLSAIKSPCPRETPEGAEAKPWYEPIYLGGVFQLDKGDRFSAETNLPAYLDFAEPGQVYFGLIAL | ||||||
Modified residue | 2 | Phosphoserine; by CK1 | ||||
Sequence: S | ||||||
Lipidation | 19 | N6-myristoyl lysine | ||||
Sequence: K | ||||||
Lipidation | 20 | N6-myristoyl lysine | ||||
Sequence: K | ||||||
Chain | PRO_0000417217 | 49-? | C-domain 1 | |||
Sequence: MSTESMIRDVELAEEALPKKVGPQGSRRCWCLSLFSFLLVAGATALFC | ||||||
Chain | PRO_0000417218 | 51-? | C-domain 2 | |||
Sequence: MSTESMIRDVELAEEALPKKVGPQGSRRCWCLSLFSFLLVAGATALFCLL | ||||||
Chain | PRO_0000253754 | 78-233 | Tumor necrosis factor, soluble form | |||
Sequence: RSSSRAPSDKPVAHVVADPEAEGRLRWLSRRTNTLLAYGAALTDNQLVVPADGLYLVYSQLLFTGQGCAPAQPLLTHTVSRFAASYQTKVNLLSAIKSPCPRETPEGAEAKPWYEPIYLGGVFQLDKGDRFSAETNLPAYLDFAEPGQVYFGLIAL | ||||||
Glycosylation | 80 | O-linked (GalNAc...) serine; in soluble form | ||||
Sequence: S | ||||||
Disulfide bond | 145↔177 | |||||
Sequence: CAPAQPLLTHTVSRFAASYQTKVNLLSAIKSPC |
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
PTM databases
Interaction
Subunit
Homotrimer. Interacts with SPPL2B (By similarity).
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 88-233 | THD | ||||
Sequence: PVAHVVADPEAEGRLRWLSRRTNTLLAYGAALTDNQLVVPADGLYLVYSQLLFTGQGCAPAQPLLTHTVSRFAASYQTKVNLLSAIKSPCPRETPEGAEAKPWYEPIYLGGVFQLDKGDRFSAETNLPAYLDFAEPGQVYFGLIAL |
Sequence similarities
Belongs to the tumor necrosis factor family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length233
- Mass (Da)25,404
- Last updated2006-05-02 v1
- ChecksumA5ABBC9E182329AD
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
DQ096649 EMBL· GenBank· DDBJ | AAZ76592.1 EMBL· GenBank· DDBJ | mRNA |