Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Tumor necrosis factor

Gene

TNF

Organism
Papio anubis (Olive baboon)
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 (By similarity).By similarity
The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
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 - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cytokine

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
OrganismiPapio anubis (Olive baboon)
Taxonomic identifieri9555 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaePapio
ProteomesiUP000028761 Componenti: Unplaced

Subcellular locationi

Chain C-domain 1 :
Chain C-domain 2 :

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3434CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei35 – 5723Helical; Signal-anchor for type II membrane proteinBy similarityAdd
BLAST
Topological domaini58 – 233176ExtracellularSequence 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 – 233233Tumor necrosis factor, membrane formPRO_0000034439Add
BLAST
Chaini1 – 3939Intracellular domain 1By similarityPRO_0000417263Add
BLAST
Chaini1 – 3535Intracellular domain 2By similarityPRO_0000417264Add
BLAST
Chaini50 – ?C-domain 1By similarityPRO_0000417265
Chaini52 – ?C-domain 2By similarityPRO_0000417266
Chaini77 – 233157Tumor necrosis factor, soluble formBy similarityPRO_0000034440Add
BLAST

Amino acid modifications

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Myristate, Phosphoprotein

Interactioni

Subunit structurei

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

Structurei

3D structure databases

ProteinModelPortaliP59695.
SMRiP59695. Positions 82-233.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the tumor necrosis factor family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

HOVERGENiHBG012516.

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.

P59695-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTESMIRDV ELAEEALPRK TAGPQGSRRR WFLRLFSFLL VAGATTLFCL
60 70 80 90 100
LHFGVIGPQR EEFPKDPSLI SPLAQAVRSS SRTPSDKPVA HVVANPQAEG
110 120 130 140 150
QLQWLNRRAN ALLANGVEPT DNQLVVPSEG LYLIYSQVLF KGQGCPSNHV
160 170 180 190 200
LLTHTISRIA VSYQTKVNLL SAIKSPCQRE TPEGAEAKPW YEPIYLGGVF
210 220 230
QLEKGDRLSA EINLPDYLDF AESGQVYFGI IAL
Length:233
Mass (Da):25,736
Last modified:May 23, 2003 - v1
Checksum:i0C477F9EB6CC9909
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY234222 mRNA. Translation: AAO85335.1.
RefSeqiNP_001106118.1. NM_001112648.1.
UniGeneiPan.11103.

Genome annotation databases

GeneIDi100126739.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY234222 mRNA. Translation: AAO85335.1.
RefSeqiNP_001106118.1. NM_001112648.1.
UniGeneiPan.11103.

3D structure databases

ProteinModelPortaliP59695.
SMRiP59695. Positions 82-233.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100126739.

Organism-specific databases

CTDi7124.

Phylogenomic databases

HOVERGENiHBG012516.

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

  1. "Cloning, sequencing, and homology analysis of nonhuman primate Fas/Fas-ligand and co-stimulatory molecules."
    Villinger F.J., Bostik P., Mayne A.E., King C.L., Genain C.P., Weiss W.R., Ansari A.A.
    Immunogenetics 53:315-328(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Entry informationi

Entry nameiTNFA_PAPAN
AccessioniPrimary (citable) accession number: P59695
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 23, 2003
Last sequence update: May 23, 2003
Last modified: March 4, 2015
This is version 84 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.