Tnf Gene Summary [Mouse]
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]
Details
| Type | Protein Coding |
| Official Symbol | Tnf |
| Official Name | tumor necrosis factor [Source:MGI Symbol;Acc:MGI:104798] |
| Ensembl ID | ENSMUSG00000024401 |
| Bio databases IDs | |
| Aliases | tumor necrosis factor |
| Synonyms | AT-TNF, DIF, IMD127, LOC103694380, RATTNF, TMTNF, TNF-a, TNF-alpha, Tnfsf1a, TNFSF2, TNF-α, TNLG1F, tumor necrosis factor, Tumor Necrosis Factor α, tumor necrosis factor, α, tumour necrosis factor, tumour Necrosis Factor Alpha, tumour necrosis factor, alpha, tumour Necrosis Factor α, tumour necrosis factor, α |
| Species | Mouse, Mus musculus |
| Orthologies |
Protein Domains
A protein domain is a distinct structural or functional region within a protein that can evolve, function, and exist independently of the rest of the protein chain. These domains in mouse Tnf often fold into stable, three-dimensional structures and are associated with specific biological functions, such as binding to DNA, other proteins, or small molecules.
- lectin-like domain
- TNF homology domain
- tumor necrosis factor receptor binding
- protease binding
- nucleic acid binding
- TNF
- protein binding
- cytokine
- cleavage site
- sequence-specific DNA binding
- identical protein binding
- double-stranded DNA binding
- receptor agonist activity
- membrane-proximal domain
Pathways
Biological processes and signaling networks where the Tnf gene in mouse plays a role, providing insight into its function and relevance in health or disease.
- 14-3-3-mediated Signaling
- Activation of IRF by Cytosolic Pattern Recognition Receptors
- Acute Phase Response Signaling
- Adipogenesis pathway
- Adrenomedullin signaling pathway
- Agranulocyte Adhesion and Diapedesis
- Airway Pathology in Chronic Obstructive Pulmonary Disease
- Allograft Rejection Signaling
- Altered T Cell and B Cell Signaling in Rheumatoid Arthritis
- Antioxidant Action of Vitamin C
- Apelin Liver Signaling Pathway
- Apoptosis Signaling
- Aryl Hydrocarbon Receptor Signaling
- Atherosclerosis Signaling
- Autophagy
- Ceramide Signaling
- Cholecystokinin/Gastrin-mediated Signaling
- Colorectal Cancer Metastasis Signaling
- Communication between Innate and Adaptive Immune Cells
- Crosstalk between Dendritic Cells and Natural Killer Cells
- Glucocorticoid Receptor Signaling
- LXR/RXR Activation
- PAK Signaling
Top Findings
The most significant associations for this gene, including commonly observed domains, pathway involvement, and functional highlights based on current data.
disease
- cognitive impairment
- hypertension
- depressive disorder
- acute myeloid leukemia
- neoplasia
- cardiac hypertrophy
- psoriasis
- active rheumatoid arthritis
- psoriatic arthritis
- polyarticular juvenile rheumatoid arthritis
phenotypes
- abnormal CD4-positive alpha-beta T cell physiology
- abnormal CD8-positive alpha beta T cell morphology
- abnormal Peyer's patch T cell area morphology
- abnormal Peyer's patch follicle morphology
- abnormal Peyer's patch germinal center morphology
- abnormal Peyer's patch morphology
- abnormal T cell physiology
- abnormal T cell subpopulation ratio
- abnormal T-helper 17 cell physiology
- abnormal alpha-beta intraepithelial T cell morphology
- abnormal aorta bulb morphology
- abnormal aortic valve flow
- abnormal aortic valve morphology
- abnormal cerebral cortex morphology
- abnormal chemokine secretion
- abnormal circulating chemokine level
- abnormal circulating leptin level
- abnormal class switch recombination
- abnormal cytokine level
- abnormal cytokine secretion
- abnormal cytotoxic T cell physiology
- abnormal fat pad morphology
- abnormal female reproductive system physiology
- abnormal follicular dendritic cell physiology
- abnormal food intake
- abnormal gamma-delta T cell morphology
- abnormal glucose homeostasis
- abnormal humoral immune response
- abnormal immune system physiology
- abnormal inflammatory response
- abnormal intestine physiology
- abnormal joint morphology
- abnormal limb morphology
- abnormal lipid homeostasis
- abnormal liver physiology
- abnormal long term spatial reference memory
- abnormal lung morphology
- abnormal lymph node B cell domain morphology
- abnormal lymph node cell ratio
- abnormal lymph node primary follicle morphology
- abnormal lymphocyte physiology
- abnormal macrophage physiology
- abnormal mesenteric lymph node morphology
- abnormal metallophilic macrophage morphology
- abnormal motor coordination/ balance
- abnormal myelopoiesis
- abnormal neutrophil physiology
- abnormal response to transplant
- abnormal rib joint morphology
- abnormal sleep pattern
- abnormal spermatogenesis
- abnormal spermiation
- abnormal spine curvature
- abnormal spleen B cell follicle morphology
- abnormal spleen follicular dendritic cell network
- abnormal spleen marginal sinus morphology
- abnormal spleen marginal zone morphology
- abnormal spleen morphology
- abnormal spleen primary B follicle morphology
- abnormal spleen white pulp morphology
- abnormal testes secretion
- abnormal testis physiology
- abnormal thoracic vertebrae morphology
- abnormal trabecular bone morphology
- abnormal vagina weight
- abnormal wrist joint morphology
- absent Peyer's patches
- absent axillary lymph nodes
- absent brachial lymph nodes
- absent cervical lymph nodes
- absent follicular dendritic cells
- absent germinal center B cells
- absent inguinal lymph nodes
- absent lymph node germinal center
- absent lymph nodes
- absent mesenteric lymph nodes
- absent peripheral lymph nodes
- absent popliteal lymph nodes
- absent spleen germinal center
- absent spleen marginal zone
- accelerated temporomandibular joint osteoarthritis
- alopecia
- altered susceptibility to infection
- alveolar process atrophy
- aortic aneurysm
- aortic valve stenosis
- arthritis
- autoimmune response
- cardiac fibrosis
- cardiac valve regurgitation
- decreased IgA level
- decreased IgG level
- decreased IgG1 level
- decreased IgG2a level
- decreased IgG3 level
- decreased Peyer's patch number
- decreased T cell number
- decreased apoptosis
- decreased body weight
- decreased cardiac output
- decreased circulating glucose level
- decreased circulating insulin level
- decreased circulating interferon-gamma level
- decreased circulating interleukin-1 alpha level
- decreased circulating interleukin-1 beta level
- decreased circulating interleukin-6 level
- decreased circulating leptin level
- decreased circulating triglyceride level
- decreased circulating tumor necrosis factor level
- decreased coping response
- decreased follicular dendritic cell number
- decreased grip strength
- decreased heart rate
- decreased immunoglobulin level
- decreased incidence of tumors by chemical induction
- decreased inflammatory response
- decreased interferon-gamma secretion
- decreased keratinocyte proliferation
- decreased liver free fatty acids level
- decreased macrophage cytokine production
- decreased percent body fat/body weight
- decreased sensitivity to induced morbidity/mortality
- decreased spleen germinal center number
- decreased spleen germinal center size
- decreased spleen white pulp amount
- decreased susceptibility to autoimmune disorder
- decreased susceptibility to bacterial infection
- decreased susceptibility to diet-induced obesity
- decreased susceptibility to endotoxin shock
- decreased susceptibility to experimental autoimmune encephalomyelitis
- decreased susceptibility to induced arthritis
- decreased susceptibility to parasitic infection
- decreased susceptibility to type IV hypersensitivity reaction
- decreased testis weight
- decreased tumor necrosis factor secretion
- decreased ventricle muscle contractility
- decreased vertical activity
- enhanced wound healing
- enlarged liver
- enlarged spleen
- heart inflammation
- hepatic steatosis
- hindlimb paralysis
- hypoactivity
- ileum inflammation
- impaired coordination
- impaired macrophage phagocytosis
- increased B cell number
- increased CD4-positive alpha beta T cell number
- increased CD4-positive alpha-beta memory T cell number
- increased CD8-positive alpha-beta T cell number
- increased IgM level
- increased anxiety-related response
- increased apoptosis
- increased body length
- increased body mass index
- increased body weight
- increased bone mineral density
- increased cell migration
- increased cell proliferation
- increased circulating tumor necrosis factor level
- increased dendritic cell number
- increased fibroblast cell migration
- increased fibroblast proliferation
- increased grooming behavior
- increased heart weight
- increased interferon-gamma secretion
- increased interleukin-2 secretion
- increased leukocyte cell number
- increased liver weight
- increased lymphocyte cell number
- increased neutrophil cell number
- increased osteoblast cell number
- increased sensitivity to induced morbidity/mortality
- increased serotonin level
- increased spleen weight
- increased susceptibility to Poxviridae infection
- increased susceptibility to Riboviria infection
- increased susceptibility to bacterial infection
- increased susceptibility to bacterial infection induced morbidity/mortality
- increased susceptibility to diet-induced obesity
- increased susceptibility to endotoxin shock
- increased susceptibility to fungal infection
- increased susceptibility to injury
- increased susceptibility to parasitic infection
- increased tumor necrosis factor secretion
- intermingled spleen red and white pulp
- intestinal inflammation
- joint dislocation
- kyphosis
- limb paralysis
- long tibia
- lung inflammation
- lymph node hypoplasia
- oligozoospermia
- premature death
- prolonged QT interval
- prolonged estrus
- rheumatoid arthritis
- skin inflammation
- skin lesions
- small Peyer's patches
- small intestinal inflammation
- steatorrhea
- thick aortic valve
- thick mitral valve
- thymus hypoplasia
role in cell
- lipolysis in
- accumulation in
- expression in
- differentiation
- cellular infiltration by
- activation in
- proliferation
- mitochondrial respiration in
- respiration
- shedding in
Subcellular Expression
Locations within the cell where the protein is known or predicted to be active, providing insight into its function and cellular context.
- Extracellular Space
- Cytoplasm
- cell surface
- intracellular space
- apical compartment
- membrane surface
- cellular membrane
- Nucleus
- Plasma Membrane
- Golgi Apparatus
- granules
- apical cell surfaces
- plasma membrane extracellular face
- microdomains
- Golgi buds
- mast cell secretory granules
- recycling endosomes
- secretory granules
- membrane rafts
- perikaryon
- exosomes
- plasma
- phagocytic cups
Gene Ontology Annotations
Describes the biological processes, cellular components, and molecular functions associated with the mouse Tnf gene, providing context for its role in the cell.
Biological Process
Functions and activities the gene product is involved in
- positive regulation of JUN kinase activity
- positive regulation of programmed cell death
- JNK cascade
- positive regulation of tyrosine phosphorylation of STAT protein
- induction of apoptosis via death domain receptors
- positive regulation of sequence-specific DNA binding transcription factor activity
- positive regulation of NF-kappaB transcription factor activity
- positive regulation of cytokine production involved in inflammatory response
- regulation of insulin secretion
- inflammatory response
- positive regulation of fractalkine production
- response to hypoxia
- positive regulation of chronic inflammatory response to antigenic stimulus
- negative regulation of transcription, DNA-dependent
- positive regulation of transcription, DNA-dependent
- regulation of immunoglobulin production
- positive regulation of interferon-gamma production
- humoral immune response
- response to macrophage colony-stimulating factor stimulus
- positive regulation of chemokine production
- defense response to Gram-positive bacterium
- positive regulation of peptidyl-serine phosphorylation
- negative regulation of branching involved in lung morphogenesis
- positive regulation of protein localization at cell surface
- negative regulation of vascular wound healing
- positive regulation of inflammatory response
- negative regulation of mitotic cell cycle
- DNA damage response, signal transduction resulting in induction of apoptosis
- negative regulation of interleukin-6 production
- leukocyte migration involved in inflammatory response
- negative regulation of myoblast differentiation
- negative regulation of protein complex disassembly
- positive regulation of humoral immune response mediated by circulating immunoglobulin
- detection of mechanical stimulus involved in sensory perception of pain
- endothelial cell apoptotic process
- positive regulation of fever generation
- positive regulation of podosome assembly
- positive regulation of protein kinase B signaling cascade
- positive regulation of MAP kinase activity
- positive regulation of nitric oxide biosynthetic process
- response to salt stress
- extrinsic apoptotic signaling pathway
- positive regulation of I-kappaB kinase/NF-kappaB cascade
- regulation of I-kappaB kinase/NF-kappaB cascade
- positive regulation of protein complex disassembly
- vasodilation
- positive regulation of cell adhesion
- response to xenobiotic stimulus
- epithelial cell proliferation involved in salivary gland morphogenesis
- positive regulation of transcription from RNA polymerase II promoter
- positive regulation of neuron apoptotic process
- negative regulation of osteoblast differentiation
- positive regulation of smooth muscle cell proliferation
- astrocyte activation
- protein kinase B signaling cascade
- positive regulation of osteoclast differentiation
- response to glucocorticoid stimulus
- positive regulation of mononuclear cell migration
- regulation of reactive oxygen species metabolic process
- regulation of metabolic process
- positive regulation of protein complex assembly
- cellular response to nicotine
- negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
- negative regulation of blood vessel endothelial cell migration
- negative regulation of oxidative phosphorylation
- negative regulation of receptor activity
- positive regulation of glial cell proliferation
- positive regulation of MAPK cascade
- microglial cell activation
- cellular response to retinoic acid
- cellular response to toxin
- positive regulation of protein phosphorylation
- extracellular matrix organization
- positive regulation of extrinsic apoptotic signaling pathway
- negative regulation of lipid storage
- negative regulation of endothelial cell proliferation
- leukocyte tethering or rolling
- positive regulation of cytokine production
- positive regulation of hair follicle development
- negative regulation of apoptotic signaling pathway
- response to fructose stimulus
- macrophage activation involved in immune response
- positive regulation of mitosis
- glucose metabolic process
- negative regulation of L-glutamate transport
- cortical actin cytoskeleton organization
- embryonic digestive tract development
- positive regulation of membrane protein ectodomain proteolysis
- skeletal muscle contraction
- chronic inflammatory response to antigenic stimulus
- negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
- positive regulation of calcineurin-NFAT signaling cascade
- negative regulation of heart rate
- negative regulation of cytokine production involved in immune response
- activation of cysteine-type endopeptidase activity involved in apoptotic process
- calcium-mediated signaling
- vascular endothelial growth factor production
- regulation of synaptic transmission, glutamatergic
- negative regulation of lipid catabolic process
- regulation of synapse organization
- positive regulation of synaptic transmission
- positive regulation of calcidiol 1-monooxygenase activity
- negative regulation of beta-amyloid clearance
- positive regulation of protein catabolic process
- circadian rhythm
- positive regulation of JAK-STAT cascade
- positive regulation of vitamin D biosynthetic process
- positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
- negative regulation of gene expression
- positive regulation of interleukin-8 production
- tumor necrosis factor-mediated signaling pathway
- negative regulation of myosin-light-chain-phosphatase activity
- positive regulation of gene expression
- toll-like receptor 3 signaling pathway
- response to isolation stress
- negative regulation of neurogenesis
- response to activity
- sequestering of triglyceride
- positive regulation of interleukin-6 production
- response to nutrient levels
- protein localization in plasma membrane
- response to virus
- negative regulation of transcription from RNA polymerase II promoter
- cellular response to amino acid stimulus
- response to ethanol
- positive regulation of protein transport
- cognition
- cellular response to ionizing radiation
- positive regulation of interleukin-18 production
- negative regulation of viral genome replication
- positive regulation of DNA biosynthetic process
- positive regulation of blood microparticle formation
- regulation of branching involved in salivary gland morphogenesis
- regulation of endothelial cell apoptotic process
- negative regulation of glucose import
- negative regulation of systemic arterial blood pressure
- negative regulation of fat cell differentiation
- positive regulation of translational initiation by iron
- regulation of fat cell differentiation
- osteoclast differentiation
- cellular response to lipopolysaccharide
- positive regulation of action potential
- positive regulation of JNK cascade
- positive regulation of ERK1 and ERK2 cascade
- positive regulation of apoptotic process
- positive regulation of heterotypic cell-cell adhesion
- positive regulation of chemokine (C-X-C motif) ligand 2 production
- cellular response to interferon-gamma
- positive regulation of hepatocyte proliferation
- negative regulation of myelination
- positive regulation of interleukin-1 beta production
Cellular Component
Where in the cell the gene product is active
- extracellular space
- membrane raft
- external side of plasma membrane
- recycling endosome
- neuronal cell body
- extracellular region
- phagocytic cup
- plasma membrane
- cell surface
Molecular Function
What the gene product does at the molecular level
- identical protein binding
- protein binding
- tumor necrosis factor receptor binding
- transcription regulatory region sequence-specific DNA binding
- protease binding
- cytokine activity