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Protein

Tumor necrosis factor

Gene

TNF

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Complete GO annotation...

Keywords - Molecular functioni

Cytokine

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

Subcellular locationi

C-domain 1 :
C-domain 2 :

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

GO - Cellular componenti

Complete GO annotation...

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...); 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

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000035682.

Structurei

3D structure databases

ProteinModelPortaliQ06599.
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.
InterProiIPR006053. TNF.
IPR002959. TNF_alpha.
IPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PANTHERiPTHR11471:SF23. PTHR11471:SF23. 1 hit.
PfamiPF00229. TNF. 1 hit.
[Graphical view]
PRINTSiPR01234. TNECROSISFCT.
PR01235. TNFALPHA.
SMARTiSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMiSSF49842. SSF49842. 1 hit.
PROSITEiPS00251. TNF_1. 1 hit.
PS50049. TNF_2. 1 hit.
[Graphical view]

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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ06599.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000035682.

Proteomic databases

PaxDbiQ06599.
PRIDEiQ06599.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7124.

Phylogenomic databases

eggNOGiENOG410ISAN. Eukaryota.
ENOG410YQC4. LUCA.
GeneTreeiENSGT00530000062992.
HOGENOMiHOG000048729.
HOVERGENiHBG012516.
InParanoidiQ06599.
KOiK03156.
OMAiPWYEPIY.
OrthoDBiEOG091G0HIG.
TreeFamiTF332169.

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.

Gene expression databases

BgeeiENSBTAG00000025471.

Family and domain databases

Gene3Di2.60.120.40. 1 hit.
InterProiIPR006053. TNF.
IPR002959. TNF_alpha.
IPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PANTHERiPTHR11471:SF23. PTHR11471:SF23. 1 hit.
PfamiPF00229. TNF. 1 hit.
[Graphical view]
PRINTSiPR01234. TNECROSISFCT.
PR01235. TNFALPHA.
SMARTiSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMiSSF49842. SSF49842. 1 hit.
PROSITEiPS00251. TNF_1. 1 hit.
PS50049. TNF_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTNFA_BOVIN
AccessioniPrimary (citable) accession number: Q06599
Secondary accession number(s): A4IFT5
, A9QWR7, O18779, Q27978
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 26, 2007
Last modified: November 2, 2016
This is version 144 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.