TNF-alpha

Tumor necrosis factor alpha (TNF-alpha), also known as TNF, TNFA or TNFSF2, is the prototypic cytokine of the TNF superfamily, and is a multifunctional molecule involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. Two receptors, TNF-R1 (TNF receptor type 1; CD120a; p55/60) and TNF-R2 (TNF receptor type 2; CD120b; p75/80), bind to TNF-alpha. TNF-alpha protein is produced mainly by macrophages, and large amounts of this cytokine are released in response to lipopolysaccharide, other bacterial products, and Interleukin-1 (IL-1). TNF-alpha is involved in fighting against the tumorigenesis, thus, is regarded as a molecular insight in cancer treatment.

TNF-alpha Related Areas

Cancer>>Angiogenesis>>Cytokines/Chemokines in Angiogenesis>>TNF-alpha

Cancer>>Cancer Biomarkers>>TNF-alpha

Immunology>>Cytokine & Receptor>>TNF Superfamily>>TNF-alpha

TNF-alpha Alternative Names

TNF-alpha, TNF, TNFA, TNFSF2, DADB-70P7.1, DIF [Homo sapiens]
TNF-alpha, Tnf, Tnfa, TNFSF2, TNFalpha, Tnfsf1a, DIF, MGC151434 [Mus musculus]

Summaries for TNF-alpha

Entrez Gene summary for TNF-alpha:

Tumor necrosis factor (TNF) is a multifunctional proinflammatory cytokine secreted predominantly by monocytes/macrophages that has effects on lipid metabolism, coagulation, insulin resistance, and endothelial function. TNF was originally identified in mouse serum after injection with Mycobacterium bovis strain bacillus Calmette-Guerin (BCG) and endotoxin. Serum from such animals was cytotoxic or cytostatic to a number of mouse and human transformed cell lines and produced hemorrhagic necrosis and in some instances complete regression of certain transplanted tumors in mice

OMIM - description for TNF-alpha:

Probable role in regulating transcription of specific genes. May regulate through NFKB1 the expression of the CCL2/MCP-1 chemokine. May play a role in tumor necrosis factor alpha (TNF-alpha) gene expression.

Wikipedia summary for TNF-alpha:

Tumor necrosis factor (TNF, cachexin or cachectin formerly known as tumor necrosis factor-alpha or TNF-α) is a cytokine involved in systemic inflammation and is a member of a group of cytokines that stimulate the acute phase reaction. It is produced chiefly by activated macrophages, although it can be produced by other cell types as well.

Human TNF-alpha Protein General Information

 

• Protein names: Recommended name: Tumor necrosis factor
  Short Name: TNF-alpha
• Sequence length: 233 AA
• Domain: Signal-anchor Transmembrane Transmembrane helix
• Sequence similarities: Belongs to the tumor necrosis factor family.
• Post-translational modification: The soluble form derives from the membrane form by proteolytic processing. 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. O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid.
• Subunit structure: Homotrimer.
• Subcellular location: Cell membrane; Single-pass type II membrane protein.
• Involvement in disease: Genetic variations in TNF are a cause of susceptibility psoriatic arthritis (PSORAS) [MIM:607507]. PSORAS is an inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoidlike pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis).

General information above from UniProt

Function for TNF-alpha Protein

UniProtKB:

Probable role in regulating transcription of specific genes. May regulate through NFKB1 the expression of the CCL2/MCP-1 chemokine. May play a role in tumor necrosis factor alpha (TNF-alpha) gene expression.

Genatlas:

• TNF-alpha tumor necrosis factor family
• TNF-alpha potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion
• potent proinflammatory cytokine involved in the cachexia
• TNF-alpha enhancing insulin resistance in peripheral tissues of cancer patients
• TNF-alpha mediating neuronal death in injured brain (by inducing resistance to the protective effect of IGF1)
• TNF-alpha is involved in inflammatory and immune responses
• TNF-alpha stimulating the sphingomyelinase (SMPD1)
• TNFalpha-induced ROS, cause oxidation and inhibition of JNK-inactivating phosphatases
• critical cytokine mediating the downstream antiresorptive effects of TSH on the skeleton
• TNF-alpha inducing human follicular dendritic cells (FDC)proliferation by upregulated C8orf4 (TC1)
• TNF-alpha having a direct effect on small bowel iron transporter expression and function, leading to an inhibition of iron transport
• mediates tumor angiogenesis through dysregulated FRAP1 signaling caused by suppression of TSC1 by IKBKB (revealing a novel mechanism of inflammation-mediated tumor angiogenesis)
• TNF-alpha through the activation of RFK, enhances the incorporation of FAD in NADPH oxidase enzymes, a critical step for the assembly and activation of NADPH oxidase (Yazdanpanah 2009)

Homology for human TNF-alpha

• homolog to rattus Tnf (79.74 pc)
• homolog to murine Tnf (80.17 pc)

Phenotype Information for TNF-alpha

• Gene/Locus: TNF-alpha,TNFA,TNF
• Phenotype: Asthma, susceptibility to Dementia, vascular, susceptibility to Malaria, cerebral, susceptibility to Migraine without aura, susceptibility to Septic shock, susceptibility to

Phenotype Information for TNF-alpha from OMIM (Online Mendelian Inheritance in Man)

Drugs for TNF-alpha

Target	Drug Name	Disease	Drug Status
TNF-alpha	Pentoxifylline	Intermittent claudication	Approved
TNF-alpha	Etanercept	Rheumatoid arthritis	Approved
TNF-alpha	Infliximab	Psoriasis, Crohn's disease,TTDS00131 Drug(s) Infliximab DAP000107 Psoriasis, Crohn's disease,	Approved
TNF-alpha	Adalimumab	Rheumatoid arthritis	Approved
TNF-alpha	Thalidomide	Multiple myeloma	Approved
TNF-alpha	Lenalidomide	Multiple myeloma	Approved

Drugs for TNF-alpha from TTD (Therapeutic Targets Database)