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Protein

Tumor necrosis factor

Gene

Tnf

Organism
Rattus norvegicus (Rat)
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

  • cytokine activity Source: RGD
  • tumor necrosis factor receptor binding Source: RGD

GO - Biological processi

  • acute inflammatory response Source: RGD
  • apoptotic process Source: RGD
  • calcium-mediated signaling Source: RGD
  • cell activation Source: RGD
  • detection of mechanical stimulus involved in sensory perception of pain Source: RGD
  • immune response Source: InterPro
  • inflammatory response Source: RGD
  • necroptotic signaling pathway Source: UniProtKB
  • negative regulation of cell proliferation Source: RGD
  • negative regulation of glucose import Source: RGD
  • negative regulation of L-glutamate transport Source: RGD
  • negative regulation of myelination Source: RGD
  • positive regulation of action potential Source: RGD
  • positive regulation of apoptotic process Source: RGD
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: RGD
  • positive regulation of inflammatory response Source: RGD
  • positive regulation of interleukin-18 production Source: RGD
  • positive regulation of mitotic nuclear division Source: RGD
  • positive regulation of neuron apoptotic process Source: RGD
  • positive regulation of protein transport Source: RGD
  • positive regulation of synaptic transmission Source: RGD
  • response to activity Source: RGD
  • response to drug Source: RGD
  • response to gold nanoparticle Source: RGD
  • response to hypoxia Source: RGD
  • response to lipopolysaccharide Source: UniProtKB
  • response to mechanical stimulus Source: RGD
  • response to radiation Source: RGD
  • signal transduction Source: RGD
  • skeletal muscle contraction Source: RGD
  • toll-like receptor 3 signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Enzyme and pathway databases

ReactomeiR-RNO-5357786. TNFR1-induced proapoptotic signaling.
R-RNO-5357905. Regulation of TNFR1 signaling.
R-RNO-5357956. TNFR1-induced NFkappaB signaling pathway.
R-RNO-5626978. TNFR1-mediated ceramide production.
R-RNO-5668541. TNFR2 non-canonical NF-kB pathway.
R-RNO-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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 20

Organism-specific databases

RGDi3876. Tnf.

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 – 235ExtracellularSequence analysisAdd BLAST179

GO - Cellular componenti

  • extracellular space Source: RGD
  • integral component of membrane Source: RGD
  • intracellular Source: GOC
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000344511 – 235Tumor necrosis factor, membrane formAdd BLAST235
ChainiPRO_00004172871 – 39Intracellular domain 1By similarityAdd BLAST39
ChainiPRO_00004172881 – 35Intracellular domain 2By similarityAdd BLAST35
ChainiPRO_000041728950 – ?C-domain 1By similarity
ChainiPRO_000041729052 – ?C-domain 2By similarity
ChainiPRO_000003445280 – 235Tumor necrosis factor, soluble formAdd BLAST156

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2Phosphoserine; by CK1By similarity1
Lipidationi19N6-myristoyl lysineBy similarity1
Lipidationi20N6-myristoyl lysineBy similarity1
Glycosylationi83O-linked (GalNAc...); in soluble formBy similarity1
Glycosylationi86N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi148 ↔ 179By 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
Sitei79 – 80Cleavage; by ADAM17By similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

PaxDbiP16599.
PRIDEiP16599.

PTM databases

PhosphoSitePlusiP16599.

Expressioni

Gene expression databases

BgeeiENSRNOG00000000837.
GenevisibleiP16599. RN.

Interactioni

Subunit structurei

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

GO - Molecular functioni

  • cytokine activity Source: RGD
  • tumor necrosis factor receptor binding Source: RGD

Protein-protein interaction databases

DIPiDIP-39461N.
IntActiP16599. 70 interactors.
STRINGi10116.ENSRNOP00000001110.

Chemistry databases

BindingDBiP16599.

Structurei

3D structure databases

ProteinModelPortaliP16599.
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.
InParanoidiP16599.
KOiK03156.
OMAiPWYEPIY.
OrthoDBiEOG091G0HIG.
PhylomeDBiP16599.
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]

Sequencei

Sequence statusi: Complete.

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

P16599-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTESMIRDV ELAEEALPKK MGGLQNSRRC LCLSLFSFLL VAGATTLFCL
60 70 80 90 100
LNFGVIGPNK EEKFPNGLPL ISSMAQTLTL RSSSQNSSDK PVAHVVANHQ
110 120 130 140 150
AEEQLEWLSQ RANALLANGM DLKDNQLVVP ADGLYLIYSQ VLFKGQGCPD
160 170 180 190 200
YVLLTHTVSR FAISYQEKVS LLSAIKSPCP KDTPEGAELK PWYEPMYLGG
210 220 230
VFQLEKGDLL SAEVNLPKYL DITESGQVYF GVIAL
Length:235
Mass (Da):25,806
Last modified:August 1, 1990 - v1
Checksum:iB808EC6D049C2F3B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti39L → P in CAA05290 (PubMed:1627266).Curated1
Sequence conflicti39L → P in CAA47146 (PubMed:1627266).Curated1
Sequence conflicti163I → T in CAA05290 (PubMed:1627266).Curated1
Sequence conflicti163I → T in CAA47146 (PubMed:1627266).Curated1
Sequence conflicti202F → S in CAA05290 (PubMed:1627266).Curated1
Sequence conflicti202F → S in CAA47146 (PubMed:1627266).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti122L → P.1 Publication1
Natural varianti190K → E.1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D00475 Genomic DNA. Translation: BAA00367.1.
X66539 mRNA. Translation: CAA47146.1.
AJ002278 mRNA. Translation: CAA05290.1.
L00981 Genomic DNA. Translation: AAA16275.1.
AF329982 Genomic DNA. Translation: AAK53568.1.
AF329983 Genomic DNA. Translation: AAK53569.1.
AF329984 Genomic DNA. Translation: AAK53570.1.
AF329985 Genomic DNA. Translation: AAK53571.1.
AF329986 Genomic DNA. Translation: AAK53572.1.
AF329987 Genomic DNA. Translation: AAK53573.1.
AF269159 mRNA. Translation: AAF82567.1.
AF269160 mRNA. Translation: AAF82568.1.
AY427673 Genomic DNA. Translation: AAR91624.1.
AY427674 Genomic DNA. Translation: AAR91625.1.
AY427675 Genomic DNA. Translation: AAR91626.1.
BX883046 Genomic DNA. Translation: CAE84003.1.
BC107671 mRNA. Translation: AAI07672.1.
L19123 Genomic DNA. Translation: AAA42255.1.
PIRiJU0029.
RefSeqiNP_036807.1. NM_012675.3.
XP_008770997.1. XM_008772775.2.
UniGeneiRn.2275.

Genome annotation databases

EnsembliENSRNOT00000001110; ENSRNOP00000001110; ENSRNOG00000000837.
ENSRNOT00000079677; ENSRNOP00000074520; ENSRNOG00000055156.
GeneIDi103694380.
24835.
KEGGirno:103694380.
rno:24835.
UCSCiRGD:3876. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D00475 Genomic DNA. Translation: BAA00367.1.
X66539 mRNA. Translation: CAA47146.1.
AJ002278 mRNA. Translation: CAA05290.1.
L00981 Genomic DNA. Translation: AAA16275.1.
AF329982 Genomic DNA. Translation: AAK53568.1.
AF329983 Genomic DNA. Translation: AAK53569.1.
AF329984 Genomic DNA. Translation: AAK53570.1.
AF329985 Genomic DNA. Translation: AAK53571.1.
AF329986 Genomic DNA. Translation: AAK53572.1.
AF329987 Genomic DNA. Translation: AAK53573.1.
AF269159 mRNA. Translation: AAF82567.1.
AF269160 mRNA. Translation: AAF82568.1.
AY427673 Genomic DNA. Translation: AAR91624.1.
AY427674 Genomic DNA. Translation: AAR91625.1.
AY427675 Genomic DNA. Translation: AAR91626.1.
BX883046 Genomic DNA. Translation: CAE84003.1.
BC107671 mRNA. Translation: AAI07672.1.
L19123 Genomic DNA. Translation: AAA42255.1.
PIRiJU0029.
RefSeqiNP_036807.1. NM_012675.3.
XP_008770997.1. XM_008772775.2.
UniGeneiRn.2275.

3D structure databases

ProteinModelPortaliP16599.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-39461N.
IntActiP16599. 70 interactors.
STRINGi10116.ENSRNOP00000001110.

Chemistry databases

BindingDBiP16599.

PTM databases

PhosphoSitePlusiP16599.

Proteomic databases

PaxDbiP16599.
PRIDEiP16599.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000001110; ENSRNOP00000001110; ENSRNOG00000000837.
ENSRNOT00000079677; ENSRNOP00000074520; ENSRNOG00000055156.
GeneIDi103694380.
24835.
KEGGirno:103694380.
rno:24835.
UCSCiRGD:3876. rat.

Organism-specific databases

CTDi7124.
RGDi3876. Tnf.

Phylogenomic databases

eggNOGiENOG410ISAN. Eukaryota.
ENOG410YQC4. LUCA.
GeneTreeiENSGT00530000062992.
HOGENOMiHOG000048729.
HOVERGENiHBG012516.
InParanoidiP16599.
KOiK03156.
OMAiPWYEPIY.
OrthoDBiEOG091G0HIG.
PhylomeDBiP16599.
TreeFamiTF332169.

Enzyme and pathway databases

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

Miscellaneous databases

PROiP16599.

Gene expression databases

BgeeiENSRNOG00000000837.
GenevisibleiP16599. RN.

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_RAT
AccessioniPrimary (citable) accession number: P16599
Secondary accession number(s): Q6EE11, Q9JI26, Q9JI27
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: November 2, 2016
This is version 155 of the entry and version 1 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.