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Protein

Tumor necrosis factor

Gene

TNF

Organism
Canis lupus familiaris (Dog) (Canis familiaris)
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-CFA-5357786. TNFR1-induced proapoptotic signaling.
R-CFA-5357905. Regulation of TNFR1 signaling.
R-CFA-5357956. TNFR1-induced NFkappaB signaling pathway.
R-CFA-5626978. TNFR1-mediated ceramide production.
R-CFA-5668541. TNFR2 non-canonical NF-kB pathway.
R-CFA-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
OrganismiCanis lupus familiaris (Dog) (Canis familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
Proteomesi
  • UP000002254 Componenti: Chromosome 12

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 – 233ExtracellularSequence analysisAdd BLAST177

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000344091 – 233Tumor necrosis factor, membrane formAdd BLAST233
ChainiPRO_00004171991 – 39Intracellular domain 1By similarityAdd BLAST39
ChainiPRO_00004172001 – 35Intracellular domain 2By similarityAdd BLAST35
ChainiPRO_000041720150 – ?C-domain 1By similarity
ChainiPRO_000041720252 – ?C-domain 2By similarity
ChainiPRO_000003441077 – 233Tumor necrosis factor, soluble formAdd BLAST157

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2Phosphoserine; by CK1By similarity1
Lipidationi19N6-myristoyl lysineBy similarity1
Lipidationi20N6-myristoyl lysineBy similarity1
Glycosylationi80O-linked (GalNAc...); in soluble formBy similarity1
Disulfide bondi145 ↔ 177By 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
Sitei76 – 77Cleavage; by ADAM17By similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

PaxDbiP51742.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000000739.

Structurei

3D structure databases

ProteinModelPortaliP51742.
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.
InParanoidiP51742.
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]

Sequencei

Sequence statusi: Complete.

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

P51742-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTESMIRDV ELAEEPLPKK AGGPPGSRRC FCLSLFSFLL VAGATTLFCL
60 70 80 90 100
LHFGVIGPQR EELPNGLQLI SPLAQTVKSS SRTPSDKPVA HVVANPEAEG
110 120 130 140 150
QLQWLSRRAN ALLANGVELT DNQLIVPSDG LYLIYSQVLF KGQGCPSTHV
160 170 180 190 200
LLTHTISRFA VSYQTKVNLL SAIKSPCQRE TPEGTEAKPW YEPIYLGGVF
210 220 230
QLEKGDRLSA EINLPNYLDF AESGQVYFGI IAL
Length:233
Mass (Da):25,447
Last modified:October 1, 1996 - v1
Checksum:i7B2588FBC8B25340
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti59 – 60QR → PE in AAB32391 (Ref. 2) Curated2
Sequence conflicti66G → C in AAB32391 (Ref. 2) Curated1
Sequence conflicti74A → V in CAA93908 (Ref. 5) Curated1
Sequence conflicti111A → D in AAB32391 (Ref. 2) Curated1
Sequence conflicti116G → D in AAB32391 (Ref. 2) Curated1
Sequence conflicti134 – 135IY → DS in AAB32391 (Ref. 2) Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X94932 Genomic DNA. Translation: CAA64403.1.
S74068 mRNA. Translation: AAB32391.1.
AY423389 Genomic DNA. Translation: AAR27885.1.
DQ923808 mRNA. Translation: ABJ51909.1.
Z70046 mRNA. Translation: CAA93908.1.
RefSeqiNP_001003244.4. NM_001003244.4.
UniGeneiCfa.54.

Genome annotation databases

EnsembliENSCAFT00000000804; ENSCAFP00000000739; ENSCAFG00000000517.
GeneIDi403922.
KEGGicfa:403922.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X94932 Genomic DNA. Translation: CAA64403.1.
S74068 mRNA. Translation: AAB32391.1.
AY423389 Genomic DNA. Translation: AAR27885.1.
DQ923808 mRNA. Translation: ABJ51909.1.
Z70046 mRNA. Translation: CAA93908.1.
RefSeqiNP_001003244.4. NM_001003244.4.
UniGeneiCfa.54.

3D structure databases

ProteinModelPortaliP51742.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000000739.

Proteomic databases

PaxDbiP51742.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSCAFT00000000804; ENSCAFP00000000739; ENSCAFG00000000517.
GeneIDi403922.
KEGGicfa:403922.

Organism-specific databases

CTDi7124.

Phylogenomic databases

eggNOGiENOG410ISAN. Eukaryota.
ENOG410YQC4. LUCA.
GeneTreeiENSGT00530000062992.
HOGENOMiHOG000048729.
HOVERGENiHBG012516.
InParanoidiP51742.
KOiK03156.
OMAiPWYEPIY.
OrthoDBiEOG091G0HIG.
TreeFamiTF332169.

Enzyme and pathway databases

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

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_CANLF
AccessioniPrimary (citable) accession number: P51742
Secondary accession number(s): Q006K5, Q28339
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 2, 2016
This is version 127 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.