The TNF gene and its putative association with human ageing

HGNC symbol

TNF

Aliases

TNFSF2; DIF; TNF-alpha; TNFA

Common name

tumor necrosis factor

Main reason for selection

Entry selected based on indirect or inconclusive evidence linking the gene product to ageing in humans or in one or more model systems

Description

A cytokine involved in the immune response, TNF can induce cell death in some tumour cells. It can also induce cellular proliferation and differentiation [493].

TNF-deficient mice develop normally but are more susceptible to some infectious agents [493]. Other results from mice suggest that TNF may protect neurons by stimulating antioxidant pathways [492]. There is an association between TNF levels and age [715], though human polymorphisms in TNF have not been associated with longevity [221]. Although TNF may be associated with human age-related diseases, such as dementia [1168], more studies are necessary to establish what is TNF's involvement in human ageing.

Cytogenetic band

6p21.3

Location

2,917,465 bp to 2,920,233 bp

Orientation

Plus strand

Gene Ontology

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:0001819; positive regulation of cytokine production
GO:0001934; positive regulation of protein phosphorylation
GO:0001937; negative regulation of endothelial cell proliferation
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:0006006; glucose metabolic process
GO:0006919; activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006954; inflammatory response
GO:0006959; humoral immune response
GO:0007249; I-kappaB kinase/NF-kappaB signaling
GO:0007254; JNK cascade
GO:0008625; extrinsic apoptotic signaling pathway via death domain receptors
GO:0008630; intrinsic apoptotic signaling pathway in response to DNA damage
GO:0009615; response to virus
GO:0009651; response to salt stress
GO:0010628; positive regulation of gene expression
GO:0010629; negative regulation of gene expression
GO:0010693; negative regulation of alkaline phosphatase activity
GO:0010803; regulation of tumor necrosis factor-mediated signaling pathway
GO:0010888; negative regulation of lipid storage
GO:0030198; extracellular matrix organization
GO:0030316; osteoclast differentiation
GO:0030730; sequestering of triglyceride
GO:0030866; cortical actin cytoskeleton organization
GO:0031334; positive regulation of protein complex assembly
GO:0031622; positive regulation of fever generation
GO:0031663; lipopolysaccharide-mediated signaling pathway
GO:0032715; negative regulation of interleukin-6 production
GO:0032722; positive regulation of chemokine production
GO:0032729; positive regulation of interferon-gamma production
GO:0032755; positive regulation of interleukin-6 production
GO:0032757; positive regulation of interleukin-8 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:0035509; negative regulation of myosin-light-chain-phosphatase activity
GO:0042346; positive regulation of NF-kappaB import into nucleus
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: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:0045416; positive regulation of interleukin-8 biosynthetic process
GO:0045429; positive regulation of nitric oxide biosynthetic process
GO:0045599; negative regulation of fat cell differentiation
GO:0045662; negative regulation of myoblast differentiation
GO:0045668; negative regulation of osteoblast differentiation
GO:0045672; positive regulation of osteoclast differentiation
GO:0045785; positive regulation of cell adhesion
GO:0045860; positive regulation of protein kinase activity
GO:0045892; negative regulation of transcription, DNA-templated
GO:0045893; positive regulation of transcription, DNA-templated
GO:0045930; negative regulation of mitotic cell cycle
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:0048566; embryonic digestive tract development
GO:0048661; positive regulation of smooth muscle cell proliferation
GO:0050715; positive regulation of cytokine secretion
GO:0050766; positive regulation of phagocytosis
GO:0050796; regulation of insulin secretion
GO:0050830; defense response to Gram-positive bacterium
GO:0050901; leukocyte tethering or rolling
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:0070374; positive regulation of ERK1 and ERK2 cascade
GO:0071230; cellular response to amino acid stimulus
GO:0071316; cellular response to nicotine
GO:0071407; cellular response to organic cyclic compound
GO:0071550; death-inducing signaling complex assembly
GO:0071677; positive regulation of mononuclear cell migration
GO:0071803; positive regulation of podosome assembly
GO:0072577; endothelial cell apoptotic process
GO:0090002; establishment of protein localization to plasma membrane
GO:0097191; extrinsic apoptotic signaling pathway
GO:0097527; necroptotic signaling pathway
GO:1901224; positive regulation of NIK/NF-kappaB signaling
GO:1901671; positive regulation of superoxide dismutase activity
GO:1903140; regulation of establishment of endothelial barrier
GO:1903347; negative regulation of bicellular tight junction assembly
GO:1904707; positive regulation of vascular smooth muscle cell proliferation
GO:1904996; positive regulation of leukocyte adhesion to vascular endothelial cell
GO:1904999; positive regulation of leukocyte adhesion to arterial endothelial cell
GO:2000010; positive regulation of protein localization to cell surface
GO:2000304; positive regulation of ceramide biosynthetic process
GO:2000334; positive regulation of blood microparticle formation
GO:2000343; positive regulation of chemokine (C-X-C motif) ligand 2 production
GO:2001240; negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

Cellular component:

GO:0001891; phagocytic cup
GO:0005576; extracellular region
GO:0005615; extracellular space
GO:0005886; plasma membrane
GO:0005887; integral component of plasma membrane
GO:0009897; external side of plasma membrane
GO:0009986; cell surface
GO:0045121; membrane raft
GO:0055037; recycling endosome

Function:

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

Hide GO terms

Protein-protein interacting partners in GenAge

TNF, FAS, NFKBIA, CLU, CDC42, IKBKB

STRING interaction network