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Protein

Tumor necrosis factor

Gene

TNF

Organism
Sus scrofa (Pig)
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-SSC-5357786. TNFR1-induced proapoptotic signaling.
R-SSC-5357905. Regulation of TNFR1 signaling.
R-SSC-5357956. TNFR1-induced NFkappaB signaling pathway.
R-SSC-5626978. TNFR1-mediated ceramide production.
R-SSC-5668541. TNFR2 non-canonical NF-kB pathway.
R-SSC-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
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi
  • UP000008227 Componenti: Chromosome 7

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 – 232ExtracellularSequence analysisAdd BLAST176

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000344451 – 232Tumor necrosis factor, membrane formAdd BLAST232
ChainiPRO_00004172751 – 39Intracellular domain 1By similarityAdd BLAST39
ChainiPRO_00004172761 – 35Intracellular domain 2By similarityAdd BLAST35
ChainiPRO_000041727750 – ?C-domain 1By similarity
ChainiPRO_000041727852 – ?C-domain 2By similarity
ChainiPRO_000003444677 – 232Tumor 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
Glycosylationi80O-linked (GalNAc...); in soluble formBy similarity1
Disulfide bondi144 ↔ 176By 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

PaxDbiP23563.

Expressioni

Gene expression databases

BgeeiENSSSCG00000001404.
GenevisibleiP23563. SS.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000001491.

Structurei

3D structure databases

ProteinModelPortaliP23563.
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.
InParanoidiP23563.
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.

P23563-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTESMIRDV ELAEEALAKK AGGPQGSRRC LCLSLFSFLL VAGATTLFCL
60 70 80 90 100
LHFEVIGPQK EEFPAGPLSI NPLAQGLRSS SQTSDKPVAH VVANVKAEGQ
110 120 130 140 150
LQWQSGYANA LLANGVKLKD NQLVVPTDGL YLIYSQVLFR GQGCPSTNVF
160 170 180 190 200
LTHTISRIAV SYQTKVNLLS AIKSPCQRET PEGAEAKPWY EPIYLGGVFQ
210 220 230
LEKDDRLSAE INLPDYLDFA ESGQVYFGII AL
Length:232
Mass (Da):25,254
Last modified:November 1, 1991 - v1
Checksum:i65B28F702D99C8BE
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54001 Genomic DNA. Translation: CAA37949.1.
X54859 Genomic DNA. Translation: CAA38639.1.
X57321 mRNA. Translation: CAA40591.1.
AJ251914 Genomic DNA. Translation: CAB63852.1.
BX548169 Genomic DNA. Translation: CAN59689.1.
M29079 mRNA. Translation: AAA31128.1.
PIRiS12606.
RefSeqiNP_999187.1. NM_214022.1.
UniGeneiSsc.100.

Genome annotation databases

EnsembliENSSSCT00000001533; ENSSSCP00000001491; ENSSSCG00000001404.
GeneIDi397086.
KEGGissc:397086.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54001 Genomic DNA. Translation: CAA37949.1.
X54859 Genomic DNA. Translation: CAA38639.1.
X57321 mRNA. Translation: CAA40591.1.
AJ251914 Genomic DNA. Translation: CAB63852.1.
BX548169 Genomic DNA. Translation: CAN59689.1.
M29079 mRNA. Translation: AAA31128.1.
PIRiS12606.
RefSeqiNP_999187.1. NM_214022.1.
UniGeneiSsc.100.

3D structure databases

ProteinModelPortaliP23563.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000001491.

Proteomic databases

PaxDbiP23563.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSSSCT00000001533; ENSSSCP00000001491; ENSSSCG00000001404.
GeneIDi397086.
KEGGissc:397086.

Organism-specific databases

CTDi7124.

Phylogenomic databases

eggNOGiENOG410ISAN. Eukaryota.
ENOG410YQC4. LUCA.
GeneTreeiENSGT00530000062992.
HOGENOMiHOG000048729.
HOVERGENiHBG012516.
InParanoidiP23563.
KOiK03156.
OMAiPWYEPIY.
OrthoDBiEOG091G0HIG.
TreeFamiTF332169.

Enzyme and pathway databases

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

Gene expression databases

BgeeiENSSSCG00000001404.
GenevisibleiP23563. SS.

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_PIG
AccessioniPrimary (citable) accession number: P23563
Secondary accession number(s): A5D9N8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: November 2, 2016
This is version 130 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.