Detail Information for IndEnz0002013417
IED ID IndEnz0002013417
Enzyme Type ID protease013417
Protein Name Tumor necrosis factor
Cachectin
TNF-alpha
Tumor necrosis factor ligand superfamily member 2
TNF-a

Cleaved into: Tumor necrosis factor, membrane form
N-terminal fragment
NTF
; Intracellular domain 1
ICD1
; Intracellular domain 2
ICD2
; C-domain 1; C-domain 2; Tumor necrosis factor, soluble form
Gene Name Tnf Tnfa Tnfsf2
Organism Mus musculus (Mouse)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse)
Enzyme Sequence MSTESMIRDVELAEEALPQKMGGFQNSRRCLCLSLFSFLLVAGATTLFCLLNFGVIGPQRDEKFPNGLPLISSMAQTLTLRSSSQNSSDKPVAHVVANHQVEEQLEWLSQRANALLANGMDLKDNQLVVPADGLYLVYSQVLFKGQGCPDYVLLTHTVSRFAISYQEKVNLLSAVKSPCPKDTPEGAELKPWYEPIYLGGVFQLEKGDQLSAEVNLPKYLDFAESGQVYFGVIAL
Enzyme Length 235
Uniprot Accession Number P06804
Absorption
Active Site
Activity Regulation
Binding Site
Calcium Binding
catalytic Activity
DNA Binding
EC Number
Enzyme 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 (PubMed:25586176). Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6 (By similarity). {ECO:0000250|UniProtKB:P01375, ECO:0000269|PubMed:25586176}.; FUNCTION: The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells. {ECO:0000250|UniProtKB:P01375}.
Temperature Dependency
PH Dependency
Pathway
nucleotide Binding
Features Beta strand (12); Chain (6); Disulfide bond (1); Glycosylation (2); Helix (1); Lipidation (1); Modified residue (1); Natural variant (2); Sequence conflict (3); Site (5); Topological domain (2); Transmembrane (1); Turn (1)
Keywords 3D-structure;Cell membrane;Cytokine;Direct protein sequencing;Disulfide bond;Glycoprotein;Lipoprotein;Membrane;Myristate;Phosphoprotein;Reference proteome;Secreted;Signal-anchor;Transmembrane;Transmembrane helix
Interact With
Induction
Subcellular Location SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane protein.; SUBCELLULAR LOCATION: [Tumor necrosis factor, membrane form]: Membrane {ECO:0000250}; Single-pass type II membrane protein {ECO:0000250}.; SUBCELLULAR LOCATION: [Tumor necrosis factor, soluble form]: Secreted.; SUBCELLULAR LOCATION: [C-domain 1]: Secreted {ECO:0000250}.; SUBCELLULAR LOCATION: [C-domain 2]: Secreted {ECO:0000250}.
Modified Residue MOD_RES 2; /note=Phosphoserine; by CK1; /evidence=ECO:0000250
Post Translational Modification PTM: 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 soluble form derives from the membrane form by proteolytic processing. {ECO:0000250}.; PTM: 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). {ECO:0000250}.; PTM: O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid. {ECO:0000250}.
Signal Peptide
Structure 3D X-ray crystallography (3)
Cross Reference PDB 2TNF; 7KP7; 7KP8;
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Motif
Gene Encoded By
Mass 25,896
Kinetics
Metal Binding
Rhea ID
Cross Reference Brenda