This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, and cancer. Knockout studies in mice also suggested the neuroprotective function of this cytokine. [provided by RefSeq, Jul 2008]

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.

Protein type: Membrane protein, integral; Apoptosis; Motility/polarity/chemotaxis; Cytokine

Chromosomal Location of Human Ortholog: 6p21.3

Cellular Component: extracellular space; recycling endosome; cell surface; integral to plasma membrane; extracellular region; plasma membrane; external side of plasma membrane; lipid raft; phagocytic cup

Molecular Function: identical protein binding; protein binding; protease binding; cytokine activity; tumor necrosis factor receptor binding

Biological Process: positive regulation of JNK activity; extracellular matrix organization and biogenesis; positive regulation of nitric oxide biosynthetic process; positive regulation of NFAT protein import into nucleus; positive regulation of apoptosis; activation of MAPK activity; positive regulation of osteoclast differentiation; positive regulation of transcription, DNA-dependent; response to glucocorticoid stimulus; positive regulation of caspase activity; 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; positive regulation of phagocytosis; negative regulation of interleukin-6 production; JNK cascade; negative regulation of osteoblast differentiation; positive regulation of action potential; regulation of immunoglobulin secretion; embryonic gut development; negative regulation of protein complex disassembly; response to drug; positive regulation of cytokine production; positive regulation of I-kappaB kinase/NF-kappaB cascade; positive regulation of heterotypic cell-cell adhesion; positive regulation of mitosis; response to virus; positive regulation of interleukin-6 production; positive regulation of interleukin-8 biosynthetic process; glucose metabolic 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; detection of mechanical stimulus involved in sensory perception of pain; defense response to Gram-positive bacterium; DNA damage response, signal transduction resulting in induction of apoptosis; induction of apoptosis via death domain receptors; positive regulation of transcription factor activity; positive regulation of transcription from RNA polymerase II promoter; response to activity; negative regulation of L-glutamate transport; negative regulation of transcription, DNA-dependent; skeletal muscle contraction; sequestering of triacylglycerol; positive regulation of smooth muscle cell proliferation; negative regulation of transcription from RNA polymerase II promoter; positive regulation of interleukin-18 production; chronic inflammatory response to antigenic stimulus; positive regulation of synaptic transmission; response to salt stress; positive regulation of hair follicle development; negative regulation of cell proliferation; response to radiation; 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; regulation of I-kappaB kinase/NF-kappaB cascade; inflammatory response; caspase activation; positive regulation of humoral immune response mediated by circulating immunoglobulin; positive regulation of protein complex disassembly; transformed cell apoptosis; calcium-mediated signaling; MAPKKK cascade; 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 programmed cell death; positive regulation of interferon-gamma production; positive regulation of protein complex assembly; positive regulation of chemokine biosynthetic process; negative regulation of viral genome replication; protein import into nucleus, translocation; positive regulation of protein kinase activity; activation of MAPKKK activity; response to hypoxia; positive regulation of fever; positive regulation of protein amino acid phosphorylation; receptor biosynthetic process; leukocyte tethering or rolling; negative regulation of myoblast differentiation; regulation of insulin secretion; positive regulation of cytokine secretion

Disease: Asthma, Susceptibility To; Migraine With Or Without Aura, Susceptibility To, 1; Malaria, Susceptibility To