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Aliases for TNF Gene

Aliases for TNF Gene

  • Tumor Necrosis Factor 2 3 3 5
  • Tumor Necrosis Factor Ligand Superfamily Member 2 3 4
  • Cachectin 3 4
  • TNF-Alpha 3 4
  • TNFSF2 3 4
  • TNF-A 3 4
  • TNFA 3 4
  • Tumor Necrosis Factor (TNF Superfamily, Member 2) 2
  • Tumor Necrosis Factor Ligand 1F 3
  • Tumor Necrosis Factor-Alpha 3
  • TNF Superfamily, Member 2 2
  • TNF, Macrophage-Derived 3
  • TNF, Monocyte-Derived 3
  • APC1 Protein 3
  • TNLG1F 3
  • DIF 3

External Ids for TNF Gene

Previous HGNC Symbols for TNF Gene

  • TNFA

Previous GeneCards Identifiers for TNF Gene

  • GC06P031606
  • GC06P031597
  • GC06P031314
  • GC06P031647
  • GC06P031652
  • GC06P031543
  • GC06P031330
  • GC06P031614
  • GC06P031622
  • GC06P031629
  • GC06P031640
  • GC06P031655
  • GC06P031668
  • GC06P031673
  • GC06P031996

Summaries for TNF Gene

Entrez Gene Summary for TNF Gene

  • 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]

GeneCards Summary for TNF Gene

TNF (Tumor Necrosis Factor) is a Protein Coding gene. Diseases associated with TNF include Malaria and Asthma. Among its related pathways are ERK Signaling and Akt Signaling. Gene Ontology (GO) annotations related to this gene include identical protein binding and cytokine activity. An important paralog of this gene is LTA.

UniProtKB/Swiss-Prot for TNF Gene

  • 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).

  • The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.

Tocris Summary for TNF Gene

  • NF-kappaB (nuclear factor-kappa B) is a rapidly acting primary transcription factor found in all cell types. It is involved in the cellular responses to stimuli such as cytokines and stress and plays a key role in regulating the immunological response to infections.

Gene Wiki entry for TNF Gene

Additional gene information for TNF Gene

No data available for CIViC summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TNF Gene

Genomics for TNF Gene

GeneHancer (GH) Regulatory Elements for TNF Gene

Promoters and enhancers for TNF Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH06J031567 Promoter/Enhancer 2.8 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 737.6 +2.9 2852 22.2 HDGF PKNOX1 SMAD1 MLX ZFP64 ARID4B SIN3A DMAP1 YBX1 ZNF2 TNF ATP6V1G2 LST1 GC06P032156 GC06P032157 GC06P032158 GC06P032160 GC06P032168 GC06P032170 GC06P032171
GH06J031563 Enhancer 1.4 FANTOM5 Ensembl ENCODE 31.2 -12.1 -12090 1.6 HDGF ATF1 ARNT NCOA2 TCF12 GATA2 E2F8 FOS NCOA1 MEF2D TNF MICB BAG6 CCHCR1 CSNK2B DHX16 ATP6V1G2 HLA-C HCG23 HLA-B
GH06J031562 Enhancer 0.8 FANTOM5 43 -13.3 -13327 0.4 EBF1 BATF ZFHX2 EED ATF7 ETV6 IKZF2 RUNX3 CREM EGR2 LTA TNF ATP6V1G2 STK19 HLA-B LST1 HSPA1B LOC100287329
GH06J031733 Promoter/Enhancer 2.7 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 3.5 +161.9 161888 8.5 CLOCK MLX ZFP64 YBX1 FEZF1 DMAP1 IRF4 YY1 SLC30A9 ZNF213 MSH5 CLIC1 MSH5-SAPCD1 DDX39B LY6G5B ATF6B LSM2 SKIV2L CSNK2B GPANK1
GH06J031813 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 2.3 +250.3 250309 25.6 CLOCK ZFP64 DMAP1 IRF4 YY1 SLC30A9 ZNF213 E2F8 ZNF143 SP3 C6orf48 HSPA1B HSPA1A HSPA1L GC06P032216 ATF6B DDX39B LY6G5B BAG6 LSM2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TNF on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the TNF gene promoter:
  • AP-1
  • p53
  • c-Fos
  • c-Jun
  • ATF-2

Genomic Locations for TNF Gene

Genomic Locations for TNF Gene
chr6:31,575,567-31,578,336
(GRCh38/hg38)
Size:
2,770 bases
Orientation:
Plus strand
chr6:31,543,344-31,546,113
(GRCh37/hg19)
Size:
2,770 bases
Orientation:
Plus strand

Genomic View for TNF Gene

Genes around TNF on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TNF Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TNF Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

Proteins for TNF Gene

  • Protein details for TNF Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P01375-TNFA_HUMAN
    Recommended name:
    Tumor necrosis factor
    Protein Accession:
    P01375
    Secondary Accessions:
    • O43647
    • Q9P1Q2
    • Q9UIV3

    Protein attributes for TNF Gene

    Size:
    233 amino acids
    Molecular mass:
    25644 Da
    Quaternary structure:
    • Homotrimer. Interacts with SPPL2B.
    SequenceCaution:
    • Sequence=AAF71992.1; Type=Frameshift; Positions=91, 157; Evidence={ECO:0000305}; Sequence=CAA75070.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for TNF Gene

neXtProt entry for TNF Gene

Post-translational modifications for TNF Gene

  • The soluble form derives from the membrane form by proteolytic processing. The membrane-bound form is further proteolytically processed by SPPL2A or SPPL2B through regulated intramembrane proteolysis producing TNF intracellular domains (ICD1 and ICD2) released in the cytosol and TNF C-domain 1 and C-domain 2 secreted into the extracellular space.
  • 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.
  • Glycosylation at posLast=8080
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • TNFA_HUMAN (609)

Other Protein References for TNF Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

Assay Products

No data available for DME Specific Peptides for TNF Gene

Domains & Families for TNF Gene

Gene Families for TNF Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Candidate cardiovascular disease genes
  • Disease related genes
  • FDA approved drug targets
  • Plasma proteins
  • Predicted intracellular proteins

Graphical View of Domain Structure for InterPro Entry

P01375

UniProtKB/Swiss-Prot:

TNFA_HUMAN :
  • Belongs to the tumor necrosis factor family.
Family:
  • Belongs to the tumor necrosis factor family.
genes like me logo Genes that share domains with TNF: view

Function for TNF Gene

Molecular function for TNF Gene

UniProtKB/Swiss-Prot 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).
UniProtKB/Swiss-Prot Function:
The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.
GENATLAS Biochemistry:
tumor necrosis factor,alpha (cachectin),potent proinflammatory cytokine,involved in inflammatory and immune responses,stimulating the sphingomyelinase (SMPD1),enhancing insulin resistance in peripheral tissues of cancer patients,susceptibility factor for narcolepsy and myasthenia gravis and cardiac sarcoidosis,with a common polymorphism in the promoter region (C->A) associated with reduced circulating levels of TNF,mediating neuronal death in injured brain (by inducing resistance to the protective effect of IGF1)

LifeMap Function Summary for TNF Gene

It affects the following cells:
TNF as growth factor is involved in stem cell differentiation protocols towards the derivation of the following cells:

Phenotypes From GWAS Catalog for TNF Gene

Gene Ontology (GO) - Molecular Function for TNF Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002020 protease binding IEA,IPI 12777399
GO:0005125 cytokine activity IDA 10748004
GO:0005164 tumor necrosis factor receptor binding IDA 14512626
GO:0005515 protein binding IPI 2848815
GO:0042802 identical protein binding IPI,IDA 2922050
genes like me logo Genes that share ontologies with TNF: view
genes like me logo Genes that share phenotypes with TNF: view

Animal Models for TNF Gene

MGI Knock Outs for TNF:

Clone Products

  • Addgene plasmids for TNF

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TNF Gene

Localization for TNF Gene

Subcellular locations from UniProtKB/Swiss-Prot for TNF Gene

Cell membrane; Single-pass type II membrane protein.
Tumor necrosis factor, membrane form: Membrane; Single-pass type II membrane protein.
Tumor necrosis factor, soluble form: Secreted.
C-domain 1: Secreted.
C-domain 2: Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TNF gene
Compartment Confidence
plasma membrane 5
extracellular 5
endosome 4
cytoskeleton 3
mitochondrion 3
peroxisome 3
nucleus 3
cytosol 3
endoplasmic reticulum 2
lysosome 2
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for TNF Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001891 phagocytic cup ISS,IEA --
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IDA 3932069
GO:0005622 intracellular IEA --
GO:0005886 plasma membrane TAS --
genes like me logo Genes that share ontologies with TNF: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for TNF Gene

Pathways & Interactions for TNF Gene

genes like me logo Genes that share pathways with TNF: view

Pathways by source for TNF Gene

SIGNOR curated interactions for TNF Gene

Activates:
Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for TNF Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000060 protein import into nucleus, translocation IDA 16280327
GO:0000122 negative regulation of transcription by RNA polymerase II IEA,IDA 1618860
GO:0000165 MAPK cascade IMP 21147091
GO:0000185 activation of MAPKKK activity IDA 15310755
GO:0000187 activation of MAPK activity IDA 10748004
genes like me logo Genes that share ontologies with TNF: view

Drugs & Compounds for TNF Gene

(200) Drugs for TNF Gene - From: DrugBank, PharmGKB, ClinicalTrials, DGIdb, FDA Approved Drugs, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adalimumab Approved Pharma antibody, Target 521
Etanercept Approved, Investigational Pharma antibody, Target 413
Infliximab Approved Pharma antibody, Target, inhibitor 407
Thalidomide Approved, Investigational, Withdrawn Pharma inhibitor, Target Immunomodulatory agent,sedative drug,angiogenesis inhibitor, Immunomodulatory agents, TNF-alpha synthesis inhibitor 1195
Certolizumab pegol Approved Pharma antibody, Target, neutralizer 131

(69) Additional Compounds for TNF Gene - From: Novoseek, HMDB, and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
cis,trans-5'-Hydroxythalidomide
  • 5'-OH-Thalidomide
SP 100030
154563-54-9

(3) Tocris Compounds for TNF Gene