TNF Gene (Protein Coding)

Tumor Necrosis Factor

GC06P047305
GIFtS:
51
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, ... See more...

Aliases for TNF Gene

Aliases for TNF Gene

  • Tumor Necrosis Factor 2 3 4 5
  • TNF-Alpha 2 3 4
  • TNFSF2 2 3 4
  • Tumor Necrosis Factor Ligand Superfamily Member 2 3 4
  • Cachectin 3 4
  • TNF-A 3 4
  • TNFA 3 4
  • DIF 2 3
  • 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
  • TNF 5

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
  • GC06P032311
  • GC06P032499
  • GC06P032604
  • GC06P033397
  • GC06P031629
  • GC06P031640
  • GC06P031655
  • GC06P031668
  • GC06P031673
  • GC06P031996
  • GC06P032174
  • GC06P032186

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 Asthma and Malaria. Among its related pathways are Apoptosis Modulation and Signaling and Monoamine Transport. Gene Ontology (GO) annotations related to this gene include identical protein binding and cytokine activity. An important paralog of this gene is LTB.

UniProtKB/Swiss-Prot Summary 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, 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).
  • 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 , Rfam classification and piRNA Summary for TNF Gene

Genomics for TNF Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for TNF Gene
- 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 the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TNF

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

Genomic Locations for TNF Gene

Genomic Locations for TNF Gene
chr6:31,575,565-31,578,336
(GRCh38/hg38)
Size:
2,772 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 Structure • Gene Density

Proteins for TNF Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • 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; 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

Protein Expression for TNF Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

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 Ser80
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • TNFA_HUMAN (609)

Other Protein References for TNF Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

Protein 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
  • Predicted secreted proteins

Protein Domains for TNF Gene

InterPro:
Blocks:
  • Tumor Necrosis Factor
  • Tumour necrosis factor family signature
  • Tumour necrosis factor alpha (cachectin) signature
ProtoNet:

Suggested Antigen Peptide Sequences for TNF Gene

GenScript: Design optimal peptide antigens:
  • Tumor necrosis factor (TNF superfamily, member 2) (B0V0H5_HUMAN)
  • Tumor necrosis factor alpha (B5BUQ6_HUMAN)
  • Tumor necrosis factor alpha (C1K3N5_HUMAN)
  • Tumor necrosis factor (Q5RT83_HUMAN)
  • cDNA, FLJ95875, Homo sapiens tumor necrosis factor (TNF superfamily, member 2)(TNF), mRNA (Q5STB3_HUMAN)

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

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  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

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, 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).
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:0000976 transcription regulatory region sequence-specific DNA binding IDA 17350185
GO:0002020 protease binding IEA,IPI 12777399
GO:0005125 cytokine activity IDA 10748004
GO:0005164 tumor necrosis factor receptor binding IPI 9435233
GO:0005515 protein binding IPI 2848815
genes like me logo Genes that share ontologies with TNF: view
genes like me logo Genes that share phenotypes with TNF: view

Human Phenotype Ontology for TNF Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TNF Gene

MGI Knock Outs for TNF:

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TNF

No data available for Enzyme Numbers (IUBMB) , 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
mitochondrion 4
nucleus 4
endosome 4
cytosol 4
cytoskeleton 3
peroxisome 3
endoplasmic reticulum 3
lysosome 3
golgi apparatus 2

Gene Ontology (GO) - Cellular Components for TNF Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001891 phagocytic cup IEA,ISS --
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IBA,IDA 3932069
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane IDA 18355445
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

PathCards logo

SuperPathways for TNF Gene

SuperPathway Contained pathways
1 TNFR1 Pathway
TNFR1 Pathway
.56
TNF Signaling
.55
Apoptosis and survival TNFR1 signaling pathway
.52
HIV-1 Nef- Negative effector of Fas and TNF-alpha
.46
Apoptotic Pathways Triggered By HIV1
.42
Apoptosis through Death Receptors
.42
Death Receptor Signaling
.36
TNF Signaling
.34
TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway
.34
TNF alpha Signaling Pathway
.30
2 PEDF Induced Signaling
MIF Mediated Glucocorticoid Regulation
.94
MIF Regulation of Innate Immune Cells
.94
PEDF Induced Signaling
.73
all-trans-Retinoic Acid Signaling in Brain
.71
RAR-Gamma-RXR-Alpha Degradation
.62
IL-6 Pathway
.61
STAT3 Pathway
.47
Endothelin-1 Signaling Pathway
.46
Cytokine-cytokine receptor interaction
.43
3 Allograft rejection
Allograft rejection
.65
Type I diabetes mellitus
.65
Graft-versus-host disease
.60
Allograft Rejection
.46
Asthma
.44
THC Differentiation Pathway
.39
Antigen processing and presentation
.35
4 TNF signaling
Death Receptor Signalling
.86
TNF signaling
.86
Regulation of TNFR1 signaling
.77
TNFR1-induced NFkappaB signaling pathway
.60
TNF receptor signaling pathway
.34
TNFR1-induced proapoptotic signaling
.01
TNFR1-mediated ceramide production
.01
5 Toll-like Receptor Signaling Pathway
Toll-like receptor signaling pathway
.92
Toll-like Receptor Signaling Pathway
.92
Regulation of toll-like receptor signaling pathway
.71
Hepatitis B
.37
Hepatitis C
.34
Chagas disease (American trypanosomiasis)
.31
genes like me logo Genes that share pathways with TNF: view

Pathways by source for TNF Gene

3 Sino Biological pathways for TNF Gene
15 GeneGo (Thomson Reuters) pathways for TNF Gene
  • Apoptosis and survival Anti-apoptotic TNFs/NF-kB/Bcl-2 pathway
  • Apoptosis and survival Anti-apoptotic TNFs/NF-kB/IAP pathway
  • Apoptosis and survival Apoptotic TNF-family pathways
  • Apoptosis and survival Caspase cascade
  • Apoptosis and survival TNFR1 signaling pathway
50 Qiagen pathways for TNF Gene
  • 14-3-3 and Regulation of BAD Activity
  • 14-3-3 Induced Apoptosis
  • 14-3-3 Induced Intracellular Signaling
  • Akt Signaling
  • all-trans-Retinoic Acid Signaling in Brain
2 Cell Signaling Technology pathways for TNF Gene
1 GeneTex pathway for TNF Gene

SIGNOR curated interactions for TNF Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for TNF Gene

GO ID Qualified GO term Evidence PubMed IDs
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
GO:0001774 microglial cell activation IEA,NAS 26753638
genes like me logo Genes that share ontologies with TNF: view

Drugs & Compounds for TNF Gene

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(210) Drugs for TNF Gene - From: DrugBank, PharmGKB, ClinicalTrials, ApexBio, DGIdb, HMDB, Tocris, and Novoseek