Mus musculus Gene: Tnf
Summary
InnateDB Gene IDBG-177358.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol Tnf
Gene Name tumor necrosis factor
Synonyms DIF; TNF-a; TNF-alpha; Tnfa; TNFalpha; Tnfsf1a; TNFSF2;
Species Mus musculus
Ensembl Gene ENSMUSG00000024401
Encoded Proteins
tumor necrosis factor
tumor necrosis factor
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
Tnf pre-treated macrophages exhibit endotoxin tolerance, i.e. less cytokine production, towards LPS challenge. Tnf-mediated cross-tolerization is mediated by suppression of LPS-induced signalling and chromatin remodelling.
Tnf is essential to mount an acute inflammatory response to dsDNA in the endothelium.
Mirlet7f and its target Tnfaip3 regulate immune responses to Mycobacterium tuberculosis and control bacterial burden by augmenting the production of Tnf and Il1b.
InnateDB Annotation from Orthologs
Summary
[Homo sapiens] TNF (TNF-alpha) is an important mediator of inflammation, apoptosis, and the development of secondary lymphoid structures and LRRFIP1 represses TNF expression.
[Homo sapiens] TNF pre-treated macrophages exhibit endotoxin tolerance, i.e. less cytokine production, towards LPS challenge. TNF-mediated cross-tolerization is mediated by suppression of LPS-induced signalling and chromatin remodelling.
[Homo sapiens] TNF is essential to mount an acute inflammatory response to dsDNA in the endothelium. (Demonstrated in murine model)
[Homo sapiens] IFN gamma creates a primed chromatin environment in macrophages to augment TLR-induced TNF transcription
[Homo sapiens] Secreted CCNA2 (CCN1) promotes anti-inflammatory cytokine IL10 release from epithelial cells via integrin αVβ6-PKC, and this subsequently suppresses TNF, CXCL2 and neutrophil infiltration in the lungs.
[Homo sapiens] DEFB103A and RNASE7 are induced in human umbilical endothelial cells (HUVECs) by classical inflammatory cytokines such as: IFNG, IL1B and TNF.
Entrez Gene
Summary This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. Members of this family are classified based on primary sequence, function, and structure. This protein is synthesized as a type-II transmembrane protein and is reported to be cleaved into products that exert distinct biological functions. It plays an important role in the innate immune response as well as regulating homeostasis but is also implicated in diseases of chronic inflammation. In mouse deficiency of this gene is associated with defects in response to bacterial infection, with defects in forming organized follicular dendritic cell networks and germinal centers, and with a lack of primary B cell follicles. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]
Gene Information
Type Protein coding
Genomic Location Chromosome 17:35199381-35202007
Strand Reverse strand
Band B1
Transcripts
ENSMUST00000025263 ENSMUSP00000025263
ENSMUST00000167924 ENSMUSP00000126122
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 61 experimentally validated interaction(s) in this database.
They are also associated with 76 interaction(s) predicted by orthology.
Experimentally validated
Total 61 [view]
Protein-Protein 17 [view]
Protein-DNA 27 [view]
Protein-RNA 17 [view]
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 76 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0002020 protease binding
GO:0005125 cytokine activity
GO:0005164 tumor necrosis factor receptor binding
GO:0005515 protein binding
GO:0042802 identical protein binding
GO:0044212 transcription regulatory region DNA binding
Biological Process
GO:0000060 protein import into nucleus, translocation
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0000165 MAPK cascade
GO:0000185 activation of MAPKKK activity
GO:0000187 activation of MAPK activity
GO:0001666 response to hypoxia
GO:0001775 cell activation
GO:0001819 positive regulation of cytokine production
GO:0001932 regulation of protein phosphorylation
GO:0001934 positive regulation of protein phosphorylation
GO:0002037 negative regulation of L-glutamate transport
GO:0002439 chronic inflammatory response to antigenic stimulus
GO:0002740 negative regulation of cytokine secretion 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:0006006 glucose metabolic process
GO:0006915 apoptotic process
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006927 transformed cell apoptotic process
GO:0006952 defense response
GO:0006954 inflammatory response
GO:0006955 immune response
GO:0006959 humoral immune response
GO:0007165 signal transduction
GO:0007254 JNK cascade
GO:0007275 multicellular organismal development
GO:0008283 cell proliferation
GO:0008284 positive regulation of cell proliferation
GO:0008285 negative regulation of cell 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:0009612 response to mechanical stimulus
GO:0009615 response to virus
GO:0009887 organ morphogenesis
GO:0010628 positive regulation of gene expression
GO:0010629 negative regulation of gene expression
GO:0010693 negative regulation of alkaline phosphatase activity
GO:0014823 response to activity
GO:0019722 calcium-mediated signaling
GO:0030198 extracellular matrix organization
GO:0030316 osteoclast differentiation
GO:0030730 sequestering of triglyceride
GO:0031334 positive regulation of protein complex assembly
GO:0031622 positive regulation of fever generation
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0032496 response to lipopolysaccharide
GO:0032715 negative regulation of interleukin-6 production
GO:0032722 positive regulation of chemokine production
GO:0032729 positive regulation of interferon-gamma production
GO:0032741 positive regulation of interleukin-18 production
GO:0032755 positive regulation of interleukin-6 production
GO:0032800 receptor biosynthetic process
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:0042127 regulation of cell proliferation
GO:0042346 positive regulation of NF-kappaB import into nucleus
GO:0042493 response to drug
GO:0042742 defense response to bacterium
GO:0043065 positive 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:0043242 negative regulation of protein complex disassembly
GO:0043243 positive regulation of protein complex disassembly
GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043406 positive regulation of MAP kinase activity
GO:0043491 protein kinase B signaling
GO:0043507 positive regulation of JUN kinase activity
GO:0043525 positive regulation of neuron apoptotic process
GO:0044130 negative regulation of growth of symbiont in host
GO:0045071 negative regulation of viral genome replication
GO:0045080 positive regulation of chemokine biosynthetic process
GO:0045087 innate immune response (InnateDB)
GO:0045123 cellular extravasation
GO:0045416 positive regulation of interleukin-8 biosynthetic process
GO:0045429 positive regulation of nitric oxide biosynthetic process
GO:0045668 negative regulation of osteoblast differentiation
GO:0045670 regulation of osteoclast differentiation
GO:0045672 positive regulation of osteoclast differentiation
GO:0045760 positive regulation of action potential
GO:0045840 positive regulation of mitosis
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0045994 positive regulation of translational initiation by iron
GO:0046325 negative regulation of glucose import
GO:0046330 positive regulation of JNK cascade
GO:0048566 embryonic digestive tract development
GO:0048661 positive regulation of smooth muscle cell proliferation
GO:0050708 regulation of protein secretion
GO:0050715 positive regulation of cytokine secretion
GO:0050729 positive regulation of inflammatory response
GO:0050796 regulation of insulin secretion
GO:0050806 positive regulation of synaptic transmission
GO:0050830 defense response to Gram-positive bacterium
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:0051023 regulation of immunoglobulin secretion
GO:0051044 positive regulation of membrane protein ectodomain proteolysis
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051222 positive regulation of protein transport
GO:0051384 response to glucocorticoid
GO:0051533 positive regulation of NFAT protein import into nucleus
GO:0051798 positive regulation of hair follicle development
GO:0051897 positive regulation of protein kinase B signaling
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:0061048 negative regulation of branching involved in lung morphogenesis
GO:0071222 cellular response to lipopolysaccharide
GO:0071230 cellular response to amino acid stimulus
GO:0071316 cellular response to nicotine
GO:0071407 cellular response to organic cyclic compound
GO:0071803 positive regulation of podosome assembly
GO:0097190 apoptotic signaling pathway
GO:0097191 extrinsic apoptotic signaling pathway
GO:0097527 necroptotic signaling pathway
GO:1990268 response to gold nanoparticle
GO:2000010 positive regulation of protein localization to cell surface
GO:2000343 positive regulation of chemokine (C-X-C motif) ligand 2 production
GO:2000377 regulation of reactive oxygen species metabolic process
GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
Cellular Component
GO:0001891 phagocytic cup
GO:0005615 extracellular space
GO:0005622 intracellular
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0009897 external side of plasma membrane
GO:0009986 cell surface
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030141 secretory granule
GO:0045121 membrane raft
GO:0055037 recycling endosome
Orthologs
Species
Homo sapiens
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
REACTOME
Transcriptional regulation of white adipocyte differentiation pathway
Apoptosis pathway
Mus musculus biological processes pathway
TNF signaling pathway
Death Receptor Signalling pathway
Developmental Biology pathway
Extrinsic Pathway for Apoptosis pathway
Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes pathway
KEGG
MAPK signaling pathway pathway
Cytokine-cytokine receptor interaction pathway
mTOR signaling pathway pathway
Apoptosis pathway
TGF-beta signaling pathway pathway
Osteoclast differentiation pathway
Antigen processing and presentation pathway
Toll-like receptor signaling pathway pathway
NOD-like receptor signaling pathway pathway
RIG-I-like receptor signaling pathway pathway
Hematopoietic cell lineage pathway
Natural killer cell mediated cytotoxicity pathway
T cell receptor signaling pathway pathway
Fc epsilon RI signaling pathway pathway
Adipocytokine signaling pathway pathway
Type II diabetes mellitus pathway
Type I diabetes mellitus pathway
Alzheimer's disease pathway
Amyotrophic lateral sclerosis (ALS) pathway
Leishmaniasis pathway
Chagas disease (American trypanosomiasis) pathway
African trypanosomiasis pathway
Malaria pathway
Toxoplasmosis pathway
Amoebiasis pathway
Hepatitis C pathway
Asthma pathway
Systemic lupus erythematosus pathway
Allograft rejection pathway
Graft-versus-host disease pathway
Hypertrophic cardiomyopathy (HCM) pathway
Dilated cardiomyopathy pathway
INOH
TNFR1 signaling pathway pathway
GPCR signaling pathway
JAK STAT pathway and regulation pathway
PID BIOCARTA
PID NCI
Pathway Predictions based on Human Orthology Data
NETPATH
TNFalpha pathway
TWEAK pathway
REACTOME
Developmental Biology pathway
Extrinsic Pathway for Apoptosis pathway
Apoptosis pathway
TNF signaling pathway
Transcriptional regulation of white adipocyte differentiation pathway
Death Receptor Signalling pathway
Extrinsic Pathway for Apoptosis pathway
TNF signaling pathway
Death Receptor Signalling pathway
Apoptosis pathway
KEGG
MAPK signaling pathway pathway
Cytokine-cytokine receptor interaction pathway
mTOR signaling pathway pathway
Apoptosis pathway
TGF-beta signaling pathway pathway
Osteoclast differentiation pathway
Antigen processing and presentation pathway
Toll-like receptor signaling pathway pathway
NOD-like receptor signaling pathway pathway
RIG-I-like receptor signaling pathway pathway
Hematopoietic cell lineage pathway
Natural killer cell mediated cytotoxicity pathway
T cell receptor signaling pathway pathway
Fc epsilon RI signaling pathway pathway
Adipocytokine signaling pathway pathway
Type II diabetes mellitus pathway
Type I diabetes mellitus pathway
Alzheimer's disease pathway
Amyotrophic lateral sclerosis (ALS) pathway
Leishmaniasis pathway
Chagas disease (American trypanosomiasis) pathway
African trypanosomiasis pathway
Malaria pathway
Toxoplasmosis pathway
Amoebiasis pathway
Hepatitis C pathway
Asthma pathway
Systemic lupus erythematosus pathway
Allograft rejection pathway
Graft-versus-host disease pathway
Hypertrophic cardiomyopathy (HCM) pathway
Dilated cardiomyopathy pathway
INOH
TNFR1 signaling pathway pathway
GPCR signaling pathway
JAK STAT pathway and regulation pathway
PID BIOCARTA
Mechanism of gene regulation by peroxisome proliferators via ppara [Biocarta view]
Nf-kb signaling pathway [Biocarta view]
Visceral fat deposits and the metabolic syndrome [Biocarta view]
Keratinocyte differentiation [Biocarta view]
Stress induction of hsp regulation [Biocarta view]
Tnfr1 signaling pathway [Biocarta view]
Nfat and hypertrophy of the heart [Biocarta view]
Signal transduction through il1r [Biocarta view]
Hiv-1 nef: negative effector of fas and tnf [Biocarta view]
Tnf/stress related signaling [Biocarta view]
Il-10 anti-inflammatory signaling pathway [Biocarta view]
Sodd/tnfr1 signaling pathway [Biocarta view]
Ceramide signaling pathway [Biocarta view]
Nfkb activation by nontypeable hemophilus influenzae [Biocarta view]
Cadmium induces dna synthesis and proliferation in macrophages [Biocarta view]
PID NCI
Ceramide signaling pathway
Caspase Cascade in Apoptosis
RXR and RAR heterodimerization with other nuclear receptor
Cellular roles of Anthrax toxin
IL27-mediated signaling events
TNF receptor signaling pathway
Downstream signaling in nave CD8+ T cells
Calcineurin-regulated NFAT-dependent transcription in lymphocytes
Signaling events mediated by HDAC Class I
Angiopoietin receptor Tie2-mediated signaling
IL23-mediated signaling events
Canonical NF-kappaB pathway
amb2 Integrin signaling
HIV-1 Nef: Negative effector of Fas and TNF-alpha
Cross-References
SwissProt P06804
TrEMBL Q0X0E6 Q3U593 Q6TDG3
UniProt Splice Variant
Entrez Gene 21926
UniGene Mm.1293
RefSeq NM_001278601 NM_013693
OMIM
CCDS CCDS28691 CCDS70801
HPRD
IMGT
MGI ID MGI:104798
MGI Symbol Tnf
EMBL AB039224 AB039225 AB039226 AB039227 AB039228 AB039229 AB039230 AB039231 AB039232 AB185894 AB185895 AB185896 AF109719 AK153319 AK153800 AK155964 AY423855 BC117057 BC137720 CH466666 D84196 D84199 M11731 M13049 M20155 M38296 U06950 U68414 X02611 Y00467
GenPept AAA18594 AAA40457 AAA40458 AAA40459 AAA40462 AAB65593 AAC82484 AAI17058 AAI37721 AAR00346 BAA19512 BAA19513 BAB68748 BAB68749 BAB68750 BAB68751 BAB68752 BAB68753 BAB68754 BAB68755 BAB68756 BAE31899 BAE32187 BAE33525 BAF02298 BAF02299 BAF02300 CAA26457 CAA68530 EDL26632
RNA Seq Atlas 21926