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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

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
Sitei76 – 772Cleavage; by ADAM17By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Enzyme and pathway databases

ReactomeiREACT_333034. TNF signaling.
REACT_358192. TNFR1-mediated proapoptotic 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
ProteomesiUP000008227 Componenti: Chromosome 7

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 – 232176ExtracellularSequence 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 – 232232Tumor necrosis factor, membrane formPRO_0000034445Add
BLAST
Chaini1 – 3939Intracellular domain 1By similarityPRO_0000417275Add
BLAST
Chaini1 – 3535Intracellular domain 2By similarityPRO_0000417276Add
BLAST
Chaini50 – ?C-domain 1By similarityPRO_0000417277
Chaini52 – ?C-domain 2By similarityPRO_0000417278
Chaini77 – 232156Tumor necrosis factor, soluble formPRO_0000034446Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21Phosphoserine; by CK1By similarity
Lipidationi19 – 191N6-myristoyl lysineBy similarity
Lipidationi20 – 201N6-myristoyl lysineBy similarity
Glycosylationi80 – 801O-linked (GalNAc...); in soluble formBy similarity
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

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Myristate, Phosphoprotein

Expressioni

Gene expression databases

GenevisibleiP23563. SS.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000001491.

Structurei

3D structure databases

ProteinModelPortaliP23563.
SMRiP23563. Positions 84-232.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the tumor necrosis factor family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG40413.
GeneTreeiENSGT00530000062992.
HOGENOMiHOG000048729.
HOVERGENiHBG012516.
InParanoidiP23563.
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]
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.
SMRiP23563. Positions 84-232.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000001491.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7124.

Phylogenomic databases

eggNOGiNOG40413.
GeneTreeiENSGT00530000062992.
HOGENOMiHOG000048729.
HOVERGENiHBG012516.
InParanoidiP23563.
KOiK03156.
OMAiPWYEPIY.
OrthoDBiEOG7V4B0Q.
TreeFamiTF332169.

Enzyme and pathway databases

ReactomeiREACT_333034. TNF signaling.
REACT_358192. TNFR1-mediated proapoptotic signaling.

Gene expression databases

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]
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. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "The porcine tumor necrosis factor-encoding genes: sequence and comparative analysis."
    Kuhnert P., Wuethrich C., Peterhans E., Pauli U.
    Gene 102:171-178(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Tissue: Liver.
  3. "Complete nucleotide sequence of a cDNA encoding porcine tumor necrosis factor-alpha."
    Choi C.S., Molitor T.W., Lin G.F., Murtaugh M.P.
    Anim. Biotechnol. 2:97-105(1991)
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Macrophage.
  4. "Sequence of the swine major histocompatibility complex region containing all non-classical class I genes."
    Chardon P., Rogel-Gaillard C., Cattolico L., Duprat S., Vaiman M., Renard C.
    Tissue Antigens 57:55-65(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Large white.
    Tissue: Fibroblast.
  5. Porcine genome sequencing project
    Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "Porcine tumor necrosis factor alpha: cloning with the polymerase chain reaction and determination of the nucleotide sequence."
    Pauli U., Beutler B., Peterhans E.
    Gene 81:185-191(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 44-232.

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: June 24, 2015
This is version 120 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

External Data

Dasty 3

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 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.