GENERAL INFORMATIONi
Gene namei TNF
Synonyms DIF, TNF-alpha, TNFA, TNFSF2
Gene descriptioni Tumor necrosis factor
Protein classi Cancer-related genes
Candidate cardiovascular disease genes
Disease related genes
FDA approved drug targets
Human disease related genes
Plasma proteins
Predicted locationi Secreted, Intracellular
Protein evidence Evidence at protein level (all genes)
GENE INFORMATIONi
Chromosome 6
Cytoband p21.33
Chromosome location (bp) 31575565 - 31578336
Number of transcriptsi 2
Ensembl ENSG00000232810 (version 109)
Entrez gene 7124
HGNC HGNC:11892
UniProt P01375 (UniProt - Evidence at protein level)
neXtProt NX_P01375
GeneCards TNF
Antibodypedia TNF antibodies


PROTEIN FUNCTION
Protein function (UniProt)i 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. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Up-regulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective 1. Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line 2, 3, 4. 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 5. Promotes osteoclastogenesis and therefore mediates bone resorption (By similarity). show less
Molecular function (UniProt)i Cytokine
Gene summary (Entrez)i 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, psoriasis, rheumatoid arthritis ankylosing spondylitis, tuberculosis, autosomal dominant polycystic kidney disease, and cancer. Mutations in this gene affect susceptibility to cerebral malaria, septic shock, and Alzheimer disease. Knockout studies in mice also suggested the neuroprotective function of this cytokine. [provided by RefSeq, Aug 2020] show less
PROTEIN INFORMATIONi
Splice variant SwissProt TrEMBL Protein class Gene ontology Length & mass Signal peptide
(predicted)		 Transmembrane regions
(predicted)
TNF-208
ENSP00000398698
ENST00000449264
P01375
[Direct mapping] Tumor necrosis factor Tumor necrosis factor, membrane form Intracellular domain 1 Intracellular domain 2 C-domain 1 C-domain 2 Tumor necrosis factor, soluble form
Show all
Q5STB3
[Target identity:100%; Query identity:100%] Tumor necrosis factor Intracellular domain 1 Intracellular domain 2 C-domain 1 C-domain 2 Tumor necrosis factor, soluble form
Show all
   MEMSAT3 predicted membrane proteins
   MEMSAT-SVM predicted membrane proteins
   Phobius predicted membrane proteins
   SCAMPI predicted membrane proteins
   THUMBUP predicted membrane proteins
   TMHMM predicted membrane proteins
Predicted secreted proteins
   SPOCTOPUS predicted secreted proteins
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Plasma proteins
Cancer-related genes
   Candidate cancer biomarkers
   Mutated cancer genes
Candidate cardiovascular disease genes
Disease related genes
FDA approved drug targets
   Biotech drugs
   Small molecule drugs
Human disease related genes
   Immune system diseases
   Allergies and autoimmune diseases
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
   DeepTMHMM predicted membrane proteins
Show all
GO:0000122 [negative regulation of transcription by RNA polymerase II]
GO:0000165 [MAPK cascade]
GO:0000976 [transcription cis-regulatory region binding]
GO:0001666 [response to hypoxia]
GO:0001774 [microglial cell activation]
GO:0001775 [cell activation]
GO:0001819 [positive regulation of cytokine production]
GO:0001891 [phagocytic cup]
GO:0001932 [regulation of protein phosphorylation]
GO:0001934 [positive regulation of protein phosphorylation]
GO:0001937 [negative regulation of endothelial cell proliferation]
GO:0002020 [protease binding]
GO:0002037 [negative regulation of L-glutamate import across plasma membrane]
GO:0002281 [macrophage activation involved in immune response]
GO:0002439 [chronic inflammatory response to antigenic stimulus]
GO:0002523 [leukocyte migration involved in inflammatory response]
GO:0002526 [acute inflammatory response]
GO:0002637 [regulation of immunoglobulin production]
GO:0002719 [negative regulation of cytokine production involved in immune response]
GO:0002876 [positive regulation of chronic inflammatory response to antigenic stimulus]
GO:0002925 [positive regulation of humoral immune response mediated by circulating immunoglobulin]
GO:0003009 [skeletal muscle contraction]
GO:0003085 [negative regulation of systemic arterial blood pressure]
GO:0005102 [signaling receptor binding]
GO:0005125 [cytokine activity]
GO:0005164 [tumor necrosis factor receptor binding]
GO:0005515 [protein binding]
GO:0005576 [extracellular region]
GO:0005615 [extracellular space]
GO:0005737 [cytoplasm]
GO:0005886 [plasma membrane]
GO:0006006 [glucose metabolic process]
GO:0006357 [regulation of transcription by RNA polymerase II]
GO:0006915 [apoptotic process]
GO:0006919 [activation of cysteine-type endopeptidase activity involved in apoptotic process]
GO:0006952 [defense response]
GO:0006954 [inflammatory response]
GO:0006955 [immune response]
GO:0006959 [humoral immune response]
GO:0007154 [cell communication]
GO:0007165 [signal transduction]
GO:0007249 [I-kappaB kinase/NF-kappaB signaling]
GO:0007254 [JNK cascade]
GO:0007623 [circadian rhythm]
GO:0008285 [negative regulation of cell population proliferation]
GO:0008625 [extrinsic apoptotic signaling pathway via death domain receptors]
GO:0008630 [intrinsic apoptotic signaling pathway in response to DNA damage]
GO:0009314 [response to radiation]
GO:0009410 [response to xenobiotic stimulus]
GO:0009612 [response to mechanical stimulus]
GO:0009615 [response to virus]
GO:0009617 [response to bacterium]
GO:0009651 [response to salt stress]
GO:0009750 [response to fructose]
GO:0009887 [animal organ morphogenesis]
GO:0009897 [external side of plasma membrane]
GO:0009986 [cell surface]
GO:0010033 [response to organic substance]
GO:0010459 [negative regulation of heart rate]
GO:0010573 [vascular endothelial growth factor production]
GO:0010628 [positive regulation of gene expression]
GO:0010629 [negative regulation of gene expression]
GO:0010693 [negative regulation of alkaline phosphatase activity]
GO:0010888 [negative regulation of lipid storage]
GO:0014068 [positive regulation of phosphatidylinositol 3-kinase signaling]
GO:0014070 [response to organic cyclic compound]
GO:0014823 [response to activity]
GO:0016020 [membrane]
GO:0019722 [calcium-mediated signaling]
GO:0023052 [signaling]
GO:0030198 [extracellular matrix organization]
GO:0030316 [osteoclast differentiation]
GO:0030730 [sequestering of triglyceride]
GO:0030866 [cortical actin cytoskeleton organization]
GO:0031334 [positive regulation of protein-containing complex assembly]
GO:0031622 [positive regulation of fever generation]
GO:0031642 [negative regulation of myelination]
GO:0031663 [lipopolysaccharide-mediated signaling pathway]
GO:0031667 [response to nutrient levels]
GO:0032496 [response to lipopolysaccharide]
GO:0032715 [negative regulation of interleukin-6 production]
GO:0032722 [positive regulation of chemokine production]
GO:0032724 [positive regulation of fractalkine production]
GO:0032729 [positive regulation of interferon-gamma production]
GO:0032731 [positive regulation of interleukin-1 beta production]
GO:0032741 [positive regulation of interleukin-18 production]
GO:0032755 [positive regulation of interleukin-6 production]
GO:0032757 [positive regulation of interleukin-8 production]
GO:0033138 [positive regulation of peptidyl-serine phosphorylation]
GO:0033209 [tumor necrosis factor-mediated signaling pathway]
GO:0034116 [positive regulation of heterotypic cell-cell adhesion]
GO:0034138 [toll-like receptor 3 signaling pathway]
GO:0035509 [negative regulation of myosin-light-chain-phosphatase activity]
GO:0035900 [response to isolation stress]
GO:0036005 [response to macrophage colony-stimulating factor]
GO:0042127 [regulation of cell population proliferation]
GO:0042311 [vasodilation]
GO:0042531 [positive regulation of tyrosine phosphorylation of STAT protein]
GO:0042742 [defense response to bacterium]
GO:0042802 [identical protein binding]
GO:0043025 [neuronal cell body]
GO:0043065 [positive regulation of apoptotic process]
GO:0043066 [negative regulation of apoptotic process]
GO:0043068 [positive regulation of programmed cell death]
GO:0043122 [regulation of I-kappaB kinase/NF-kappaB signaling]
GO:0043123 [positive regulation of I-kappaB kinase/NF-kappaB signaling]
GO:0043154 [negative regulation of cysteine-type endopeptidase activity involved in apoptotic process]
GO:0043242 [negative regulation of protein-containing complex disassembly]
GO:0043243 [positive regulation of protein-containing complex disassembly]
GO:0043280 [positive regulation of cysteine-type endopeptidase activity involved in apoptotic process]
GO:0043406 [positive regulation of MAP kinase activity]
GO:0043410 [positive regulation of MAPK cascade]
GO:0043491 [protein kinase B signaling]
GO:0043507 [positive regulation of JUN kinase activity]
GO:0043525 [positive regulation of neuron apoptotic process]
GO:0043537 [negative regulation of blood vessel endothelial cell migration]
GO:0045071 [negative regulation of viral genome replication]
GO:0045121 [membrane raft]
GO:0045123 [cellular extravasation]
GO:0045429 [positive regulation of nitric oxide biosynthetic process]
GO:0045471 [response to ethanol]
GO:0045598 [regulation of fat cell differentiation]
GO:0045599 [negative regulation of fat cell differentiation]
GO:0045662 [negative regulation of myoblast differentiation]
GO:0045668 [negative regulation of osteoblast differentiation]
GO:0045670 [regulation of osteoclast differentiation]
GO:0045672 [positive regulation of osteoclast differentiation]
GO:0045732 [positive regulation of protein catabolic process]
GO:0045760 [positive regulation of action potential]
GO:0045785 [positive regulation of cell adhesion]
GO:0045840 [positive regulation of mitotic nuclear division]
GO:0045892 [negative regulation of DNA-templated transcription]
GO:0045893 [positive regulation of DNA-templated transcription]
GO:0045930 [negative regulation of mitotic cell cycle]
GO:0045944 [positive regulation of transcription by RNA polymerase II]
GO:0045994 [positive regulation of translational initiation by iron]
GO:0046325 [negative regulation of glucose import]
GO:0046330 [positive regulation of JNK cascade]
GO:0046427 [positive regulation of receptor signaling pathway via JAK-STAT]
GO:0048143 [astrocyte activation]
GO:0048566 [embryonic digestive tract development]
GO:0048661 [positive regulation of smooth muscle cell proliferation]
GO:0050708 [regulation of protein secretion]
GO:0050727 [regulation of inflammatory response]
GO:0050729 [positive regulation of inflammatory response]
GO:0050766 [positive regulation of phagocytosis]
GO:0050768 [negative regulation of neurogenesis]
GO:0050793 [regulation of developmental process]
GO:0050796 [regulation of insulin secretion]
GO:0050806 [positive regulation of synaptic transmission]
GO:0050807 [regulation of synapse organization]
GO:0050830 [defense response to Gram-positive bacterium]
GO:0050890 [cognition]
GO:0050900 [leukocyte migration]
GO:0050901 [leukocyte tethering or rolling]
GO:0050966 [detection of mechanical stimulus involved in sensory perception of pain]
GO:0050995 [negative regulation of lipid catabolic process]
GO:0051000 [positive regulation of nitric-oxide synthase activity]
GO:0051044 [positive regulation of membrane protein ectodomain proteolysis]
GO:0051046 [regulation of secretion]
GO:0051091 [positive regulation of DNA-binding transcription factor activity]
GO:0051092 [positive regulation of NF-kappaB transcription factor activity]
GO:0051173 [positive regulation of nitrogen compound metabolic process]
GO:0051222 [positive regulation of protein transport]
GO:0051239 [regulation of multicellular organismal process]
GO:0051384 [response to glucocorticoid]
GO:0051798 [positive regulation of hair follicle development]
GO:0051897 [positive regulation of protein kinase B signaling]
GO:0051966 [regulation of synaptic transmission, glutamatergic]
GO:0055037 [recycling endosome]
GO:0060252 [positive regulation of glial cell proliferation]
GO:0060557 [positive regulation of vitamin D biosynthetic process]
GO:0060559 [positive regulation of calcidiol 1-monooxygenase activity]
GO:0060664 [epithelial cell proliferation involved in salivary gland morphogenesis]
GO:0060693 [regulation of branching involved in salivary gland morphogenesis]
GO:0061044 [negative regulation of vascular wound healing]
GO:0061048 [negative regulation of branching involved in lung morphogenesis]
GO:0065008 [regulation of biological quality]
GO:0070374 [positive regulation of ERK1 and ERK2 cascade]
GO:0070886 [positive regulation of calcineurin-NFAT signaling cascade]
GO:0071219 [cellular response to molecule of bacterial origin]
GO:0071222 [cellular response to lipopolysaccharide]
GO:0071230 [cellular response to amino acid stimulus]
GO:0071300 [cellular response to retinoic acid]
GO:0071316 [cellular response to nicotine]
GO:0071346 [cellular response to interferon-gamma]
GO:0071407 [cellular response to organic cyclic compound]
GO:0071677 [positive regulation of mononuclear cell migration]
GO:0071803 [positive regulation of podosome assembly]
GO:0072577 [endothelial cell apoptotic process]
GO:0072659 [protein localization to plasma membrane]
GO:0090324 [negative regulation of oxidative phosphorylation]
GO:0097190 [apoptotic signaling pathway]
GO:0097191 [extrinsic apoptotic signaling pathway]
GO:0097237 [cellular response to toxic substance]
GO:0097421 [liver regeneration]
GO:0097527 [necroptotic signaling pathway]
GO:0120190 [negative regulation of bile acid secretion]
GO:0140460 [response to Gram-negative bacterium]
GO:0150078 [positive regulation of neuroinflammatory response]
GO:0150129 [positive regulation of interleukin-33 production]
GO:1900017 [positive regulation of cytokine production involved in inflammatory response]
GO:1900222 [negative regulation of amyloid-beta clearance]
GO:1901224 [positive regulation of NIK/NF-kappaB signaling]
GO:1901554 [response to paracetamol]
GO:1901647 [positive regulation of synoviocyte proliferation]
GO:1901671 [positive regulation of superoxide dismutase activity]
GO:1902004 [positive regulation of amyloid-beta formation]
GO:1902565 [positive regulation of neutrophil activation]
GO:1902895 [positive regulation of miRNA transcription]
GO:1903078 [positive regulation of protein localization to plasma membrane]
GO:1903140 [regulation of establishment of endothelial barrier]
GO:1903223 [positive regulation of oxidative stress-induced neuron death]
GO:1903347 [negative regulation of bicellular tight junction assembly]
GO:1903721 [positive regulation of I-kappaB phosphorylation]
GO:1904646 [cellular response to amyloid-beta]
GO:1904707 [positive regulation of vascular associated smooth muscle cell proliferation]
GO:1904996 [positive regulation of leukocyte adhesion to vascular endothelial cell]
GO:1904999 [positive regulation of leukocyte adhesion to arterial endothelial cell]
GO:1905242 [response to 3,3',5-triiodo-L-thyronine]
GO:1990268 [response to gold nanoparticle]
GO:2000010 [positive regulation of protein localization to cell surface]
GO:2000272 [negative regulation of signaling receptor activity]
GO:2000334 [positive regulation of blood microparticle formation]
GO:2000343 [positive regulation of chemokine (C-X-C motif) ligand 2 production]
GO:2000347 [positive regulation of hepatocyte proliferation]
GO:2000351 [regulation of endothelial cell apoptotic process]
GO:2000377 [regulation of reactive oxygen species metabolic process]
GO:2000573 [positive regulation of DNA biosynthetic process]
GO:2001234 [negative regulation of apoptotic signaling pathway]
GO:2001238 [positive regulation of extrinsic apoptotic signaling pathway]
GO:2001240 [negative regulation of extrinsic apoptotic signaling pathway in absence of ligand]
GO:2001272 [positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis]
Show all
 233 aa
25.6 kDa 		No 0
TNF-209
ENSP00000514308
ENST00000699334
   MEMSAT3 predicted membrane proteins
   MEMSAT-SVM predicted membrane proteins
   Phobius predicted membrane proteins
   SCAMPI predicted membrane proteins
   THUMBUP predicted membrane proteins
   TMHMM predicted membrane proteins
Predicted secreted proteins
   SPOCTOPUS predicted secreted proteins
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Cancer-related genes
   Mutated cancer genes
Human disease related genes
   Immune system diseases
   Allergies and autoimmune diseases
Protein evidence (Ezkurdia et al 2014)
   DeepTMHMM predicted membrane proteins
Show all
GO:0005164 [tumor necrosis factor receptor binding]
GO:0006955 [immune response]
GO:0016020 [membrane]
Show all
 73 aa
8.1 kDa 		No 0

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