InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Tnf

Summary

InnateDB Protein

IDBP-628146.3

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Tnf

Protein Name

tumor necrosis factor

Synonyms

DIF; TNF-a; TNF-alpha; Tnfa; TNFalpha; Tnfsf1a; TNFSF2;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000126122

InnateDB Gene

IDBG-177358 (Tnf)

Protein Structure

UniProt Annotation

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.The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells. {ECO:0000250}.

Subcellular Localization

Cell membrane; Single-pass type II membrane protein.Tumor necrosis factor, membrane form: Membrane {ECO:0000250}; Single-pass type II membrane protein {ECO:0000250}.Tumor necrosis factor, soluble form: Secreted.C-domain 1: Secreted {ECO:0000250}.C-domain 2: Secreted {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

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:0000185	activation of MAPKKK activity
GO:0000187	activation of MAPK activity
GO:0001666	response to hypoxia
GO:0001775	cell activation
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: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: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:0009612	response to mechanical stimulus
GO:0009615	response to virus
GO:0009887	organ morphogenesis
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:0031622	positive regulation of fever generation
GO:0031663	lipopolysaccharide-mediated signaling pathway
GO:0032715	negative regulation of interleukin-6 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: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: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:0045840	positive regulation of mitosis
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: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:0050995	negative regulation of lipid catabolic process
GO:0051023	regulation of immunoglobulin secretion
GO:0051044	positive regulation of membrane protein ectodomain proteolysis
GO:0051092	positive regulation of NF-kappaB transcription factor activity
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:0071803	positive regulation of podosome assembly
GO:0097190	apoptotic signaling pathway
GO:0097191	extrinsic apoptotic signaling pathway
GO:0097527	necroptotic signaling pathway
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:0016020	membrane
GO:0030141	secretory granule
GO:0045121	membrane raft
GO:0055037	recycling endosome

Protein Structure and Domains

PDB ID

MGI:104798

InterPro

IPR002959 Tumour necrosis factor alpha
IPR006052 Tumour necrosis factor domain
IPR006053 Tumour necrosis factor
IPR008983 Tumour necrosis factor-like domain

PFAM

PF00229

PRINTS

PR01235
PR01234

PIRSF

SMART

SM00207

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt