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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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3535CytoplasmicSequence analysisAdd
BLAST
Transmembranei36 – 5621Helical; Signal-anchor for type II membrane proteinSequence analysisAdd
BLAST
Topological domaini57 – 234178ExtracellularSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 234234Tumor necrosis factor, membrane formPRO_0000034403Add
BLAST
Chaini1 – 3939Intracellular domain 1By similarityPRO_0000417179Add
BLAST
Chaini1 – 3535Intracellular domain 2By similarityPRO_0000417180Add
BLAST
Chaini50 – ?C-domain 1By similarityPRO_0000417181
Chaini52 – ?C-domain 2By similarityPRO_0000417182
Chaini78 – 234157Tumor necrosis factor, soluble formPRO_0000034404Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21Phosphoserine; by CK1By similarity
Lipidationi20 – 201N6-myristoyl lysineBy similarity
Glycosylationi81 – 811O-linked (GalNAc...); in soluble formBy similarity
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)LengthDescriptionGraphical viewFeature identifierActions
Sitei34 – 352Cleavage; by SPPL2A or SPPL2BBy similarity
Sitei39 – 402Cleavage; by SPPL2A or SPPL2BBy similarity
Sitei49 – 502Cleavage; by SPPL2A or SPPL2BBy similarity
Sitei51 – 522Cleavage; by SPPL2A or SPPL2BBy similarity
Sitei77 – 782Cleavage; by ADAM17By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

PaxDbiQ06599.
PRIDEiQ06599.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000035682.

Structurei

3D structure databases

ProteinModelPortaliQ06599.
SMRiQ06599. Positions 83-234.
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.
OrthoDBiEOG7V4B0Q.
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 AAA19573.1 differs from that shown. Reason: Erroneous gene model prediction. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti114 – 1141M → V in AAN76506 (Ref. 3) Curated
Sequence conflicti167 – 1671K → R in AAN76506 (Ref. 3) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti48 – 481F → C in strain: N'Dama.

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei63 – 631Missing in isoform 2. 1 PublicationVSP_026198

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.
SMRiQ06599. Positions 83-234.
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.
OrthoDBiEOG7V4B0Q.
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.

Miscellaneous databases

NextBioi20805057.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and characterization of the tandemly arranged bovine lymphotoxin and tumour necrosis factor-alpha genes."
    Cludts I., Cleuter Y., Kettmann R., Burny A., Droogmans L.
    Cytokine 5:336-341(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
  2. "Bovine TNF-alpha gene."
    Iraqi F.
    Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
    Strain: Boran and N'Dama.
  3. Ahn J.
    Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  4. "U.S. veterinary immune reagent network: expressed bovine gene sequences."
    U.S. Veterinary Immune Reagent Network
    Hudgens T., Tompkins D., Baldwin C.L.
    Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Strain: Belted Galloway.
    Tissue: Peripheral blood.
  5. NIH - Mammalian Gene Collection (MGC) project
    Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: Hereford.
    Tissue: Thymus.
  6. "Cloning of two members of the TNF-superfamily in cattle: CD40 ligand and tumor necrosis factor alpha."
    Mertens B.E.L.C., Muriuki M., Gaidulis L.
    Immunogenetics 42:430-431(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 50-233 (ISOFORM 1).
    Tissue: Blood.
  7. "Rapid communication: single strand conformational polymorphism (SSCP) of bovine tumor necrosis factor alpha."
    Dietz A.B., Neibergs H.L., Womack J.E., Kehrli M.E. Jr.
    J. Anim. Sci. 75:2567-2567(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 91-193.
    Strain: Holstein.

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: May 11, 2016
This is version 140 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.