GeDiPNet: Comprehensive Gene Data - OMIM, HGNC, Ensembl, UniProt, GO, Transcription Factors & miRNA

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TNF (tumor necrosis factor)

Gene

7124

Tumor necrosis factor

TNF

DIF, TNF-alpha, TNFA, TNFSF2, TNLG1F

6p21.33

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/Hide all(2)

SNP ID	Visualize variation	Clinical significance	Consequence
rs1800629	G>A	Drug-response	Upstream transcript variant
rs281865419	C>T	Pathogenic	Coding sequence variant, missense variant

Show/Hide all(14)

miRTarBase ID	miRNA	Experiments	Reference
MIRT006787	hsa-miR-19a-3p	Luciferase reporter assay	21271217
MIRT006787	hsa-miR-19a-3p	Immunohistochemistry, Luciferase reporter assay, qRT-PCR, Western blot	23795660
MIRT006787	hsa-miR-19a-3p	Luciferase reporter assay	26041742
MIRT006857	hsa-miR-203a-3p	Luciferase reporter assay	22917968
MIRT053456	hsa-miR-452-5p	Microarray	23807165
MIRT054325	hsa-miR-187-3p	Immunoblot, Luciferase reporter assay, qRT-PCR	23071313
MIRT054762	hsa-miR-130a-3p	Luciferase reporter assay, qRT-PCR, Western blotting	24885472
MIRT054762	hsa-miR-130a-3p	qRT-PCR, Western blot	26045761
MIRT054762	hsa-miR-130a-3p	ChIP, Luciferase reporter assay, qRT-PCR, Western blot	26435691
MIRT437418	hsa-miR-143-3p	Luciferase reporter assay, qRT-PCR	23804075
MIRT733472	hsa-miR-125b-5p	ChIP, Luciferase reporter assay, qRT-PCR, Western blot	26435691
MIRT733712	hsa-miR-24-3p	Microarray, qRT-PCR	28057018
MIRT733989	hsa-miR-34a-5p	PCR array	28097098
MIRT734730	hsa-miR-17-5p	Luciferase reporter assay	26041742

Transcription factors

Show/Hide all(24)

Transcription factor	Regulation	Reference
ATF2	Activation	10688670;10748079;10913190;20068037
CEBPB	Unknown	10629048;9566900
CEBPD	Unknown	10629048
E2F1	Unknown	17707233
EGR1	Activation	10913190;14767560
ETV4	Unknown	7896795
HDAC11	Repression	21239696
HDAC3	Unknown	15356147
HMGB2	Activation	18218727
HSF1	Unknown	18689673
IRF5	Unknown	20237317
JUN	Activation	10318823;10688670;10748079;10913190
JUN	Unknown	7896795;9566900
LRRFIP1	Repression	16199883
NFAT5	Unknown	11485737
NFKB1	Activation	10079106;10748079;11749970;12058956;12686724;15013838;16707469;16916598;17407192;18057724;20066113;7876168;8219230;8679226
NFKB1	Unknown	10551799;10837498;10963848;11297551;14960579;15812247;16040075;16433741;17442180;17707233;18285351;20237317;9916895
NR4A1	Repression	19213954
RELA	Activation	10079106;10748079;11749970;12058956;12686724;15013838;16707469;16916598;17407192;18057724;20066113;7876168;8219230;8679226
RELA	Unknown	10551799;10837498;10963848;11297551;14960579;15812247;16040075;16433741;17442180;17707233;18285351;20237317;9916895
SIRT1	Unknown	21245135
SP1	Activation	10688670;10913190
SP1	Repression	12759366
SPI1	Unknown	10748079

Show/Hide all(197)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IDA	1618860, 15345745
GO:0000165	Process	MAPK cascade	IMP	21147091
GO:0000185	Process	Activation of MAPKKK activity	IDA	15310755
GO:0000187	Process	Activation of MAPK activity	IDA	10748004
GO:0000976	Function	Transcription regulatory region sequence-specific DNA binding	IDA	17350185
GO:0001774	Process	Microglial cell activation	ISS
GO:0001774	Process	Microglial cell activation	NAS	26753638
GO:0001819	Process	Positive regulation of cytokine production	IDA	10443688, 17922812
GO:0001891	Component	Phagocytic cup	ISS
GO:0001934	Process	Positive regulation of protein phosphorylation	IDA	10748004, 16723520, 17389591
GO:0001937	Process	Negative regulation of endothelial cell proliferation	IEA
GO:0002020	Function	Protease binding	IPI	12777399
GO:0002439	Process	Chronic inflammatory response to antigenic stimulus	IMP	14512626
GO:0002637	Process	Regulation of immunoglobulin production	IEA
GO:0002719	Process	Negative regulation of cytokine production involved in immune response	IDA	10443688
GO:0002876	Process	Positive regulation of chronic inflammatory response to antigenic stimulus	IEA
GO:0002925	Process	Positive regulation of humoral immune response mediated by circulating immunoglobulin	IEA
GO:0005125	Function	Cytokine activity	IBA	21873635
GO:0005125	Function	Cytokine activity	IDA	10748004
GO:0005164	Function	Tumor necrosis factor receptor binding	IBA	21873635
GO:0005164	Function	Tumor necrosis factor receptor binding	IDA	14512626
GO:0005164	Function	Tumor necrosis factor receptor binding	IPI	9435233
GO:0005515	Function	Protein binding	IPI	2848815, 11878931, 12887920, 14743216, 17681535, 19838188, 20080539, 20103630, 21784977, 22028622, 23032186, 23104095, 23955153, 24070898, 25241761, 25911380, 26649818, 30561431, 32296183, 32814053
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA	21873635
GO:0005615	Component	Extracellular space	IDA	3932069, 10443688, 12594207, 18355445, 21323571
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	IDA	18355445
GO:0006006	Process	Glucose metabolic process	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	ISS
GO:0006919	Process	Activation of cysteine-type endopeptidase activity involved in apoptotic process	IDA	16723520
GO:0006954	Process	Inflammatory response	IDA	10748004, 21147091, 22267480
GO:0006959	Process	Humoral immune response	IEA
GO:0007249	Process	I-kappaB kinase/NF-kappaB signaling	TAS
GO:0007254	Process	JNK cascade	IEA
GO:0008625	Process	Extrinsic apoptotic signaling pathway via death domain receptors	IBA	21873635
GO:0008625	Process	Extrinsic apoptotic signaling pathway via death domain receptors	IDA	10521396, 18202225, 18676776
GO:0008625	Process	Extrinsic apoptotic signaling pathway via death domain receptors	NAS	21319131
GO:0008630	Process	Intrinsic apoptotic signaling pathway in response to DNA damage	IEA
GO:0009615	Process	Response to virus	IDA	10490959
GO:0009651	Process	Response to salt stress	TAS	18355445
GO:0009897	Component	External side of plasma membrane	ISS
GO:0009986	Component	Cell surface	IBA	21873635
GO:0009986	Component	Cell surface	IDA	18355445
GO:0010573	Process	Vascular endothelial growth factor production	IDA	12794819
GO:0010628	Process	Positive regulation of gene expression	IDA	11085990, 21559518, 22267480, 22952837, 23608026, 23817958, 24998411, 25327529, 26371161, 31124343, 31824476
GO:0010628	Process	Positive regulation of gene expression	IGI	24299952
GO:0010628	Process	Positive regulation of gene expression	IMP	16203728, 23892569
GO:0010628	Process	Positive regulation of gene expression	ISS
GO:0010629	Process	Negative regulation of gene expression	IDA	15345745, 20164187, 22267480, 22499991, 26371161, 31124343, 31824476
GO:0010629	Process	Negative regulation of gene expression	IGI	24299952
GO:0010693	Process	Negative regulation of alkaline phosphatase activity	IEA
GO:0010803	Process	Regulation of tumor necrosis factor-mediated signaling pathway	TAS
GO:0010888	Process	Negative regulation of lipid storage	NAS	16464856
GO:0014068	Process	Positive regulation of phosphatidylinositol 3-kinase signaling	ISS
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0030198	Process	Extracellular matrix organization	IEA
GO:0030316	Process	Osteoclast differentiation	IEA
GO:0030730	Process	Sequestering of triglyceride	IDA	19032770
GO:0030866	Process	Cortical actin cytoskeleton organization	IDA	25816133
GO:0031334	Process	Positive regulation of protein-containing complex assembly	IDA	12813029
GO:0031622	Process	Positive regulation of fever generation	ISS
GO:0031663	Process	Lipopolysaccharide-mediated signaling pathway	IDA	21147091
GO:0032715	Process	Negative regulation of interleukin-6 production	IDA	10443688
GO:0032722	Process	Positive regulation of chemokine production	IDA	10490959
GO:0032724	Process	Positive regulation of fractalkine production	ISS
GO:0032729	Process	Positive regulation of interferon-gamma production	IEA
GO:0032731	Process	Positive regulation of interleukin-1 beta production	IDA	31124343
GO:0032755	Process	Positive regulation of interleukin-6 production	IDA	24299952
GO:0032755	Process	Positive regulation of interleukin-6 production	ISS
GO:0032757	Process	Positive regulation of interleukin-8 production	IDA	20551324, 23608026, 31824476
GO:0032757	Process	Positive regulation of interleukin-8 production	IGI	23608026
GO:0032757	Process	Positive regulation of interleukin-8 production	IMP	24790089
GO:0033138	Process	Positive regulation of peptidyl-serine phosphorylation	IDA	17389591, 18440775
GO:0033138	Process	Positive regulation of peptidyl-serine phosphorylation	ISS
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	IBA	21873635
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	IDA	31824476
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	IMP	10748004
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	TAS
GO:0034116	Process	Positive regulation of heterotypic cell-cell adhesion	IDA	10604883, 20551324
GO:0035509	Process	Negative regulation of myosin-light-chain-phosphatase activity	IDA	25816133
GO:0042531	Process	Positive regulation of tyrosine phosphorylation of STAT protein	ISS
GO:0042802	Function	Identical protein binding	IDA	14512626
GO:0042802	Function	Identical protein binding	IPI	2922050, 19838188, 23815148
GO:0043065	Process	Positive regulation of apoptotic process	IDA	16723520, 17389591, 22173242
GO:0043065	Process	Positive regulation of apoptotic process	IMP	9343261
GO:0043068	Process	Positive regulation of programmed cell death	IDA	16611992
GO:0043122	Process	Regulation of I-kappaB kinase/NF-kappaB signaling	IDA	10748004
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IBA	21873635
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IDA	15310755, 17922812
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	ISS
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	TAS	29702085
GO:0043154	Process	Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process	IGI	31124343
GO:0043242	Process	Negative regulation of protein-containing complex disassembly	IDA	17389591
GO:0043243	Process	Positive regulation of protein-containing complex disassembly	IDA	12813029, 17389591
GO:0043280	Process	Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	IDA	11577081
GO:0043406	Process	Positive regulation of MAP kinase activity	IDA	12813029, 17389591, 18440775
GO:0043491	Process	Protein kinase B signaling	IMP	21147091
GO:0043507	Process	Positive regulation of JUN kinase activity	IDA	17389591
GO:0043525	Process	Positive regulation of neuron apoptotic process	ISS
GO:0043537	Process	Negative regulation of blood vessel endothelial cell migration	IDA	22499991
GO:0045071	Process	Negative regulation of viral genome replication	IDA	10490959
GO:0045121	Component	Membrane raft	IDA	17010968
GO:0045429	Process	Positive regulation of nitric oxide biosynthetic process	IDA	8383325
GO:0045598	Process	Regulation of fat cell differentiation	ISS
GO:0045599	Process	Negative regulation of fat cell differentiation	NAS	16464856
GO:0045662	Process	Negative regulation of myoblast differentiation	IEA
GO:0045668	Process	Negative regulation of osteoblast differentiation	IEA
GO:0045672	Process	Positive regulation of osteoclast differentiation	IDA	17888176
GO:0045732	Process	Positive regulation of protein catabolic process	IDA	18632959
GO:0045785	Process	Positive regulation of cell adhesion	IMP	23892569
GO:0045860	Process	Positive regulation of protein kinase activity	IDA	11821416
GO:0045892	Process	Negative regulation of transcription, DNA-templated	IDA	16895791, 17350185
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IDA	10748004, 14512626, 17350185
GO:0045930	Process	Negative regulation of mitotic cell cycle	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IBA	21873635
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	15345745, 20551324
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IGI	16803872
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	ISS
GO:0045994	Process	Positive regulation of translational initiation by iron	IEA
GO:0046325	Process	Negative regulation of glucose import	IEA
GO:0046330	Process	Positive regulation of JNK cascade	IEA
GO:0046427	Process	Positive regulation of receptor signaling pathway via JAK-STAT	ISS
GO:0048143	Process	Astrocyte activation	NAS	26753638
GO:0048566	Process	Embryonic digestive tract development	IEP	20875417
GO:0048661	Process	Positive regulation of smooth muscle cell proliferation	IDA	16518841
GO:0050729	Process	Positive regulation of inflammatory response	TAS	24966471
GO:0050766	Process	Positive regulation of phagocytosis	IMP	18201371
GO:0050768	Process	Negative regulation of neurogenesis	TAS	20018408
GO:0050796	Process	Regulation of insulin secretion	IDA	8383325
GO:0050806	Process	Positive regulation of synaptic transmission	ISS
GO:0050807	Process	Regulation of synapse organization	ISS
GO:0050830	Process	Defense response to Gram-positive bacterium	IEA
GO:0050890	Process	Cognition	TAS	22277195
GO:0050901	Process	Leukocyte tethering or rolling	IDA	10820279
GO:0050995	Process	Negative regulation of lipid catabolic process	IDA	19032770
GO:0051000	Process	Positive regulation of nitric-oxide synthase activity	IC	29702085
GO:0051044	Process	Positive regulation of membrane protein ectodomain proteolysis	IDA	18373975
GO:0051091	Process	Positive regulation of DNA-binding transcription factor activity	IDA	10748004
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IBA	21873635
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IDA	10383454, 11374864, 11821416, 15790681, 16280327, 16611992, 20551324, 25193116
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IMP	24790089
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	ISS
GO:0051173	Process	Positive regulation of nitrogen compound metabolic process	ISS
GO:0051222	Process	Positive regulation of protein transport	IDA	15310755
GO:0051384	Process	Response to glucocorticoid	IDA	10443688
GO:0051798	Process	Positive regulation of hair follicle development	IEA
GO:0051897	Process	Positive regulation of protein kinase B signaling	ISS
GO:0051966	Process	Regulation of synaptic transmission, glutamatergic	TAS	22277195
GO:0055037	Component	Recycling endosome	ISS
GO:0060252	Process	Positive regulation of glial cell proliferation	IDA	2104886
GO:0060252	Process	Positive regulation of glial cell proliferation	IGI	1752215
GO:0060557	Process	Positive regulation of vitamin D biosynthetic process	IDA	1690216
GO:0060559	Process	Positive regulation of calcidiol 1-monooxygenase activity	IDA	1690216
GO:0060664	Process	Epithelial cell proliferation involved in salivary gland morphogenesis	IEA
GO:0060693	Process	Regulation of branching involved in salivary gland morphogenesis	IEA
GO:0061044	Process	Negative regulation of vascular wound healing	IDA	22499991
GO:0061048	Process	Negative regulation of branching involved in lung morphogenesis	IDA	17350185
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	NAS	18606301
GO:0070886	Process	Positive regulation of calcineurin-NFAT signaling cascade	IDA	16803872
GO:0071230	Process	Cellular response to amino acid stimulus	IEA
GO:0071316	Process	Cellular response to nicotine	IDA	18676776
GO:0071407	Process	Cellular response to organic cyclic compound	IDA	21147091
GO:0071550	Process	Death-inducing signaling complex assembly	TAS
GO:0071677	Process	Positive regulation of mononuclear cell migration	NAS	21319131
GO:0071803	Process	Positive regulation of podosome assembly	IDA	15220135
GO:0072577	Process	Endothelial cell apoptotic process	IEA
GO:0072659	Process	Protein localization to plasma membrane	IDA	25816133
GO:0097191	Process	Extrinsic apoptotic signaling pathway	IDA	11577081, 16611992
GO:0097527	Process	Necroptotic signaling pathway	IDA	11101870, 22265413, 22265414, 22817896
GO:0150078	Process	Positive regulation of neuroinflammatory response	TAS	22277195, 26753638
GO:0150129	Process	Positive regulation of interleukin-33 production	IDA	31824476
GO:1900017	Process	Positive regulation of cytokine production involved in inflammatory response	IDA	31824476
GO:1900017	Process	Positive regulation of cytokine production involved in inflammatory response	IGI	23608026
GO:1900222	Process	Negative regulation of amyloid-beta clearance	ISS
GO:1901224	Process	Positive regulation of NIK/NF-kappaB signaling	IDA	17922812, 20041225, 31124343
GO:1901647	Process	Positive regulation of synoviocyte proliferation	IDA	31124343
GO:1901671	Process	Positive regulation of superoxide dismutase activity	IDA	22836756
GO:1902004	Process	Positive regulation of amyloid-beta formation	ISS
GO:1902895	Process	Positive regulation of pri-miRNA transcription by RNA polymerase II	IDA	22499991
GO:1903078	Process	Positive regulation of protein localization to plasma membrane	ISS
GO:1903140	Process	Regulation of establishment of endothelial barrier	IDA	25816133
GO:1903347	Process	Negative regulation of bicellular tight junction assembly	IDA	25816133
GO:1903721	Process	Positive regulation of I-kappaB phosphorylation	IDA	31124343
GO:1903799	Process	Negative regulation of production of miRNAs involved in gene silencing by miRNA	IDA	31124343, 31824476
GO:1904707	Process	Positive regulation of vascular associated smooth muscle cell proliferation	IEA
GO:1904996	Process	Positive regulation of leukocyte adhesion to vascular endothelial cell	IDA	26371161
GO:1904999	Process	Positive regulation of leukocyte adhesion to arterial endothelial cell	IDA	22267480
GO:2000010	Process	Positive regulation of protein localization to cell surface	IDA	19366699
GO:2000272	Process	Negative regulation of signaling receptor activity	IDA	10443688
GO:2000304	Process	Positive regulation of ceramide biosynthetic process	TAS
GO:2000334	Process	Positive regulation of blood microparticle formation	IDA	24998411
GO:2000343	Process	Positive regulation of chemokine (C-X-C motif) ligand 2 production	IDA	20551324
GO:2000351	Process	Regulation of endothelial cell apoptotic process	IMP	10843670
GO:2001234	Process	Negative regulation of apoptotic signaling pathway	IGI	31124343
GO:2001238	Process	Positive regulation of extrinsic apoptotic signaling pathway	IBA	21873635
GO:2001240	Process	Negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	IDA	10666185, 10748004

MIM	HGNC	e!Ensembl
191160	11892	ENSG00000232810

Protein

UniProt ID

P01375

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]

Protein 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. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates 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 (PubMed:23396208). 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 (PubMed:22517918, PubMed:16829952, PubMed:23396208). 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 (PubMed:12794819). ; The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.

PDB

1A8M , 1TNF , 2AZ5 , 2E7A , 2TUN , 2ZJC , 2ZPX , 3ALQ , 3IT8 , 3L9J , 3WD5 , 4G3Y , 4TSV , 4TWT , 4Y6O , 5M2I , 5M2J , 5M2M , 5MU8 , 5TSW , 5UUI , 5WUX , 5YOY , 6OOY , 6OOZ , 6OP0 , 6RMJ , 6X81 , 6X82 , 6X83 , 6X85 , 6X86 , 7ASY , 7AT7 , 7ATB , 7JRA , 7KP9 , 7KPA , 7KPB

Family and domains

Pfam

Accession	ID	Position in sequence	Description	Type
PF00229	TNF	102 → 233	TNF(Tumour Necrosis Factor) family	Domain

Sequence

MSTESMIRDVELAEEALPKKTGGPQGSRRCLFLSLFSFLIVAGATTLFCLLHFGVIGPQR
EEFPRDLSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELR
DNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRE
TPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRPDYLDFAESGQVYFGIIAL

Sequence length

233

Interactions

View interactions

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