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TNF-a (human)

Overview TNF-a 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. Homotrimer. Interacts with SPPL2B. Belongs to the tumor necrosis factor family. Note: This description may include information from UniProtKB. Protein type: Membrane protein, integral; Apoptosis; Cytokine; Motility/polarity/chemotaxis Cellular Component: extracellular space; recycling endosome; cell surface; integral to plasma membrane; plasma membrane; phagocytic cup; external side of plasma membrane; lipid raft Molecular Function: identical protein binding; protein binding; protease binding; cytokine activity; tumor necrosis factor receptor binding Biological Process: extracellular matrix organization and biogenesis; positive regulation of nitric oxide biosynthetic process; positive regulation of NFAT protein import into nucleus; activation of MAPK activity; positive regulation of osteoclast differentiation; positive regulation of apoptosis; positive regulation of transcription, DNA-dependent; response to glucocorticoid stimulus; positive regulation of NF-kappaB import into nucleus; osteoclast differentiation; positive regulation of translational initiation by iron; positive regulation of membrane protein ectodomain proteolysis; activation of NF-kappaB transcription factor; positive regulation of MAP kinase activity; tumor necrosis factor-mediated signaling pathway; negative regulation of interleukin-6 production; JNK cascade; negative regulation of osteoblast differentiation; embryonic gut development; regulation of immunoglobulin secretion; response to drug; positive regulation of cytokine production; positive regulation of heterotypic cell-cell adhesion; positive regulation of I-kappaB kinase/NF-kappaB cascade; positive regulation of mitosis; response to virus; glucose metabolic process; positive regulation of interleukin-6 production; positive regulation of interleukin-8 biosynthetic process; negative regulation of fat cell differentiation; positive regulation of chemokine production; negative regulation of cytokine secretion during immune response; positive regulation of protein transport; cell activation; defense response to Gram-positive bacterium; organ morphogenesis; induction of apoptosis via death domain receptors; response to mechanical stimulus; positive regulation of transcription factor activity; positive regulation of transcription from RNA polymerase II promoter; negative regulation of L-glutamate transport; response to activity; negative regulation of transcription, DNA-dependent; negative regulation of apoptosis; skeletal muscle contraction; sequestering of triacylglycerol; apoptosis; positive regulation of smooth muscle cell proliferation; positive regulation of JNK cascade; negative regulation of transcription from RNA polymerase II promoter; chronic inflammatory response to antigenic stimulus; response to salt stress; positive regulation of synaptic transmission; positive regulation of hair follicle development; negative regulation of cell proliferation; negative regulation of lipid catabolic process; positive regulation of neuron apoptosis; lipopolysaccharide-mediated signaling pathway; protein kinase B signaling cascade; positive regulation of chronic inflammatory response to antigenic stimulus; inflammatory response; regulation of I-kappaB kinase/NF-kappaB cascade; caspase activation; positive regulation of humoral immune response mediated by circulating immunoglobulin; positive regulation of protein complex disassembly; transformed cell apoptosis; MAPKKK cascade; calcium-mediated signaling; positive regulation of peptidyl-serine phosphorylation; humoral immune response; positive regulation of protein kinase B signaling cascade; negative regulation of glucose import; positive regulation of interferon-gamma production; positive regulation of programmed cell death; positive regulation of protein complex assembly; positive regulation of chemokine biosynthetic process; negative regulation of viral genome replication; protein import into nucleus, translocation; induction of apoptosis; response to hypoxia; positive regulation of fever; activation of MAPKKK activity; positive regulation of protein amino acid phosphorylation; receptor biosynthetic process; leukocyte tethering or rolling; regulation of insulin secretion; positive regulation of cytokine secretion Reference #:  P01375 (UniProtKB) Alt. Names/Synonyms: APC1 protein; Cachectin; DIF; TNF; TNF superfamily, member 2; TNF, macrophage-derived; TNF, monocyte-derived; TNF-a; TNF-alpha; TNFA; TNFSF2; Tumor necrosis factor; tumor necrosis factor (TNF superfamily, member 2); tumor necrosis factor alpha; Tumor necrosis factor ligand superfamily member 2; Tumor necrosis factor, membrane form; Tumor necrosis factor, soluble form Gene Symbols: TNF Molecular weight: 25,644 Da Basal Isoelectric point: 6.44  Predict pI for various phosphorylation states CST Pathways:  Death Receptor Signaling  |  Inhibition of Apoptosis  |  Insulin Receptor Signaling Protein-Specific Antibodies or siRNAs from Cell Signaling Technology®

Select Structure to View Below TNF-a 1A8M - A/C/B=77-233 (human) 1TNF - A/C/B=77-233 (human) 2AZ5 - A/D/C/B=86-233 (human) 2E7A - A/C/B=77-233 (human) 2TUN - F/A/D/C/E/B=77-233 (human) 2ZJC - A/C/B=77-233 (human) 2ZPX - A/C/B=77-233 (human) 3ALQ - F/A/D/C/E/B=77-233 (human) 3IT8 - H/A/C/I/G/B=82-233 (human) 3L9J - T=85-233 (human) 4G3Y - C=77-233 (human) 4TSV - A=84-233 (human) 5TSW - F/A/D/C/E/B=84-233 (human) 2TNF - A/C/B=80-235 (mouse)

STRING  |  Scansite  |  Phospho.ELM  |  Pfam  |  RCSB PDB 1A8M 1TNF 2AZ5 2E7A 2TUN 2ZJC 2ZPX 3ALQ 3IT8 3L9J 4G3Y 4TSV 5TSW  |  Phospho3D  |  DISEASE 157300 191160 248310 600807 611162  |  Source  |  UCSD-Nature  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene

	Modification Sites and Domains

	Modification Sites in Parent Protein, Orthologs, and Isoforms

SS  SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.	MS  MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.			human
0	1		S2	______MSTESMIRD
0	2		T3	_____MSTESMIRDV
0	2		S5	___MSTESMIRDVEL
0	1		S162-p	TISRIAVsYQTKVNL
0	1		S171-p	QTKVNLLsAIKSPCQ

	mouse
S2-p	______MstEsMIRD
T3-p	_____MstEsMIRDV
S5-p	___MstEsMIRDVEL
S164	TVSRFAISYQEKVNL
S173	QEKVNLLSAVKSPCP

	rat
S2	______MSTESMIRD
T3	_____MSTESMIRDV
S5	___MSTESMIRDVEL
S164	TVSRFAISYQEKVSL
S173	QEKVSLLSAIKSPCP

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