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Protein

Tumor necrosis factor

Gene

Tnf

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.By similarity

GO - Molecular functioni

  • cytokine activity Source: MGI
  • identical protein binding Source: MGI
  • protease binding Source: BHF-UCL
  • transcription regulatory region DNA binding Source: MGI
  • tumor necrosis factor receptor binding Source: MGI

GO - Biological processi

Keywordsi

Molecular functionCytokine

Enzyme and pathway databases

ReactomeiR-MMU-5357786 TNFR1-induced proapoptotic signaling
R-MMU-5357905 Regulation of TNFR1 signaling
R-MMU-5357956 TNFR1-induced NFkappaB signaling pathway
R-MMU-5626978 TNFR1-mediated ceramide production
R-MMU-5668541 TNFR2 non-canonical NF-kB pathway
R-MMU-75893 TNF signaling

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor
Alternative name(s):
Cachectin
TNF-alpha
Tumor necrosis factor ligand superfamily member 2
Short name:
TNF-a
Cleaved into the following 6 chains:
Gene namesi
Name:Tnf
Synonyms:Tnfa, Tnfsf2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:104798 Tnf

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 35CytoplasmicSequence analysisAdd BLAST35
Transmembranei36 – 56Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini57 – 235ExtracellularSequence analysisAdd BLAST179

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL4984

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000344351 – 235Tumor necrosis factor, membrane formAdd BLAST235
ChainiPRO_00004172551 – 39Intracellular domain 1By similarityAdd BLAST39
ChainiPRO_00004172561 – 35Intracellular domain 2By similarityAdd BLAST35
ChainiPRO_000041725750 – ?C-domain 1By similarity
ChainiPRO_000041725852 – ?C-domain 2By similarity
ChainiPRO_000003443680 – 235Tumor necrosis factor, soluble formAdd BLAST156

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2Phosphoserine; by CK1By similarity1
Lipidationi20N6-myristoyl lysineBy similarity1
Glycosylationi83O-linked (GalNAc...) serine; in soluble formBy similarity1
Glycosylationi86N-linked (GlcNAc...) asparagine1
Disulfide bondi148 ↔ 179

Post-translational modificationi

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 (By similarity). The soluble form derives from the membrane form by proteolytic processing.By similarity
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 (By similarity).By similarity
O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei34 – 35Cleavage; by SPPL2A or SPPL2BBy similarity2
Sitei39 – 40Cleavage; by SPPL2A or SPPL2BBy similarity2
Sitei49 – 50Cleavage; by SPPL2A or SPPL2BBy similarity2
Sitei51 – 52Cleavage; by SPPL2A or SPPL2BBy similarity2
Sitei79 – 80Cleavage; by ADAM17By similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

EPDiP06804
PaxDbiP06804
PRIDEiP06804

PTM databases

iPTMnetiP06804
PhosphoSitePlusiP06804
SwissPalmiP06804

Miscellaneous databases

PMAP-CutDBiP06804

Expressioni

Gene expression databases

BgeeiENSMUSG00000024401 Expressed in 74 organ(s), highest expression level in epididymal fat pad
CleanExiMM_TNF
ExpressionAtlasiP06804 baseline and differential
GenevisibleiP06804 MM

Interactioni

Subunit structurei

Interacts with SPPL2B (By similarity). Homotrimer.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204240, 13 interactors
DIPiDIP-40029N
IntActiP06804, 2 interactors
STRINGi10090.ENSMUSP00000025263

Structurei

Secondary structure

1235
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP06804
SMRiP06804
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP06804

Family & Domainsi

Sequence similaritiesi

Belongs to the tumor necrosis factor family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410ISAN Eukaryota
ENOG410YQC4 LUCA
GeneTreeiENSGT00530000062992
HOGENOMiHOG000048729
HOVERGENiHBG012516
InParanoidiP06804
KOiK03156
OMAiPWYEPIY
OrthoDBiEOG091G0HIG
PhylomeDBiP06804
TreeFamiTF332169

Family and domain databases

CDDicd00184 TNF, 1 hit
Gene3Di2.60.120.40, 1 hit
InterProiView protein in InterPro
IPR006053 TNF
IPR002959 TNF_alpha
IPR021184 TNF_CS
IPR006052 TNF_dom
IPR008983 Tumour_necrosis_fac-like_dom
PANTHERiPTHR11471:SF23 PTHR11471:SF23, 1 hit
PfamiView protein in Pfam
PF00229 TNF, 1 hit
PRINTSiPR01234 TNECROSISFCT
PR01235 TNFALPHA
SMARTiView protein in SMART
SM00207 TNF, 1 hit
SUPFAMiSSF49842 SSF49842, 1 hit
PROSITEiView protein in PROSITE
PS00251 TNF_1, 1 hit
PS50049 TNF_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.iShow all

P06804-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSTESMIRDV ELAEEALPQK MGGFQNSRRC LCLSLFSFLL VAGATTLFCL
60 70 80 90 100
LNFGVIGPQR DEKFPNGLPL ISSMAQTLTL RSSSQNSSDK PVAHVVANHQ
110 120 130 140 150
VEEQLEWLSQ RANALLANGM DLKDNQLVVP ADGLYLVYSQ VLFKGQGCPD
160 170 180 190 200
YVLLTHTVSR FAISYQEKVN LLSAVKSPCP KDTPEGAELK PWYEPIYLGG
210 220 230
VFQLEKGDQL SAEVNLPKYL DFAESGQVYF GVIAL
Length:235
Mass (Da):25,896
Last modified:July 1, 1989 - v2
Checksum:i16DD2A9676D68C5D
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0R4J210A0A0R4J210_MOUSE
Tumor necrosis factor
Tnf mCG_15911
219Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti79 – 81Missing in AAB65593 (PubMed:9089109).Curated3
Sequence conflicti231G → R (PubMed:2419912).Curated1
Sequence conflicti231G → R (PubMed:2989794).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti7I → T in strain: BALB/c and C57BL/6. 1 Publication1
Natural varianti77T → A in strain: BALB/c and C57BL/6. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M20155 Genomic DNA Translation: AAA40462.1 Sequence problems.
M11731 mRNA Translation: AAA40458.1
M13049 mRNA Translation: AAA40457.1
X02611 mRNA Translation: CAA26457.1
M38296 Genomic DNA Translation: AAA40459.1
Y00467 Genomic DNA Translation: CAA68530.1
U06950 Unassigned DNA Translation: AAA18594.1
D84196 Genomic DNA Translation: BAA19512.1
D84199 Genomic DNA Translation: BAA19513.1
U68414 Genomic DNA Translation: AAB65593.1
AF109719 Genomic DNA Translation: AAC82484.1
AB039224 Genomic DNA Translation: BAB68748.1 Sequence problems.
AB039225 Genomic DNA Translation: BAB68749.1 Sequence problems.
AB039226 Genomic DNA Translation: BAB68750.1 Sequence problems.
AB039227 Genomic DNA Translation: BAB68751.1 Sequence problems.
AB039228 Genomic DNA Translation: BAB68752.1 Sequence problems.
AB039229 Genomic DNA Translation: BAB68753.1 Sequence problems.
AB039230 Genomic DNA Translation: BAB68754.1 Sequence problems.
AB039231 Genomic DNA Translation: BAB68755.1 Sequence problems.
AB039232 Genomic DNA Translation: BAB68756.1 Sequence problems.
CCDSiCCDS28691.1
PIRiA22908 QWMSN
RefSeqiNP_001265530.1, NM_001278601.1
NP_038721.1, NM_013693.3
UniGeneiMm.1293

Genome annotation databases

EnsembliENSMUST00000025263; ENSMUSP00000025263; ENSMUSG00000024401
GeneIDi21926
KEGGimmu:21926
UCSCiuc008cgr.2 mouse

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTNFA_MOUSE
AccessioniPrimary (citable) accession number: P06804
Secondary accession number(s): O35853, Q62326, Q91VF3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: July 1, 1989
Last modified: September 12, 2018
This is version 198 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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