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Protein

Tumor necrosis factor

Gene

TNF

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: -Experimental evidence at transcript 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

GO - Biological processi

Keywordsi

Molecular functionCytokine

Enzyme and pathway databases

ReactomeiR-BTA-5357786 TNFR1-induced proapoptotic signaling
R-BTA-5357905 Regulation of TNFR1 signaling
R-BTA-5357956 TNFR1-induced NFkappaB signaling pathway
R-BTA-5626978 TNFR1-mediated ceramide production
R-BTA-5668541 TNFR2 non-canonical NF-kB pathway
R-BTA-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
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 23

Organism-specific databases

VGNCiVGNC:36153 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 – 234ExtracellularSequence analysisAdd BLAST178

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000344031 – 234Tumor necrosis factor, membrane formAdd BLAST234
ChainiPRO_00004171791 – 39Intracellular domain 1By similarityAdd BLAST39
ChainiPRO_00004171801 – 35Intracellular domain 2By similarityAdd BLAST35
ChainiPRO_000041718150 – ?C-domain 1By similarity
ChainiPRO_000041718252 – ?C-domain 2By similarity
ChainiPRO_000003440478 – 234Tumor necrosis factor, soluble formAdd BLAST157

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2Phosphoserine; by CK1By similarity1
Lipidationi20N6-myristoyl lysineBy similarity1
Glycosylationi81O-linked (GalNAc...) serine; in soluble formBy similarity1
Disulfide bondi146 ↔ 178By similarity

Post-translational modificationi

The soluble form derives from the membrane form by proteolytic processing. 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).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
Sitei77 – 78Cleavage; by ADAM17By similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

PaxDbiQ06599
PRIDEiQ06599

Expressioni

Gene expression databases

BgeeiENSBTAG00000025471

Interactioni

Subunit structurei

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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000035682

Structurei

3D structure databases

ProteinModelPortaliQ06599
SMRiQ06599
ModBaseiSearch...
MobiDBiSearch...

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
InParanoidiQ06599
KOiK03156
OMAiPWYEPIY
OrthoDBiEOG091G0HIG
TreeFamiTF332169

Family and domain databases

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

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q06599-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSTKSMIRDV ELAEEVLSEK AGGPQGSRSC LCLSLFSFLL VAGATTLFCL
60 70 80 90 100
LHFGVIGPQR EEQSPGGPSI NSPLVQTLRS SSQASSNKPV AHVVADINSP
110 120 130 140 150
GQLRWWDSYA NALMANGVKL EDNQLVVPAD GLYLIYSQVL FRGQGCPSTP
160 170 180 190 200
LFLTHTISRI AVSYQTKVNI LSAIKSPCHR ETPEWAEAKP WYEPIYQGGV
210 220 230
FQLEKGDRLS AEINLPDYLD YAESGQVYFG IIAL
Length:234
Mass (Da):25,567
Last modified:June 26, 2007 - v2
Checksum:iBAE4D0CD3797F491
GO
Isoform 2 (identifier: Q06599-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     63-63: Missing.

Note: No experimental confirmation available.
Show »
Length:233
Mass (Da):25,439
Checksum:i8AF55C002A9763B0
GO

Sequence cautioni

The sequence AAA19573 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti114M → V in AAN76506 (Ref. 3) Curated1
Sequence conflicti167K → R in AAN76506 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti48F → C in strain: N'Dama. 1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_02619863Missing in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z14137 Genomic DNA Translation: CAA78511.1
AF011926 Genomic DNA Translation: AAB84086.1
AF011927 Genomic DNA Translation: AAB84087.1
AF348421 mRNA Translation: AAN76506.1
EU276079 mRNA Translation: ABX72077.1
BC134755 mRNA Translation: AAI34756.1
Z48808 mRNA Translation: CAA88743.1
U11040 Genomic DNA Translation: AAA19573.1 Sequence problems.
PIRiI46047 S24642
RefSeqiNP_776391.2, NM_173966.3 [Q06599-1]
UniGeneiBt.12756

Genome annotation databases

EnsembliENSBTAT00000035815; ENSBTAP00000035682; ENSBTAG00000025471 [Q06599-1]
GeneIDi280943
KEGGibta:280943

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTNFA_BOVIN
AccessioniPrimary (citable) accession number: Q06599
Secondary accession number(s): A4IFT5
, A9QWR7, O18779, Q27978
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 26, 2007
Last modified: May 23, 2018
This is version 151 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

Complete proteome, Reference proteome

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