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P59695 (TNFA_PAPAN) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 80. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended 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:

  1. Tumor necrosis factor, membrane form
    Alternative name(s):
    N-terminal fragment
    Short name=NTF
  2. Intracellular domain 1
    Short name=ICD1
  3. Intracellular domain 2
    Short name=ICD2
  4. C-domain 1
  5. C-domain 2
  6. Tumor necrosis factor, soluble form
Gene names
Name:TNF
Synonyms:TNFA, TNFSF2
OrganismPapio anubis (Olive baboon)
Taxonomic identifier9555 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaePapio

Protein attributes

Sequence length233 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells By similarity.

Subunit structure

Homotrimer. Interacts with SPPL2B By similarity.

Subcellular location

Cell membrane; Single-pass type II membrane protein By similarity.

Tumor necrosis factor, membrane form: Membrane; Single-pass type II membrane protein By similarity.

Tumor necrosis factor, soluble form: Secreted By similarity.

C-domain 1: Secreted By similarity.

C-domain 2: Secreted By similarity.

Post-translational modification

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.

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.

O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid By similarity.

Sequence similarities

Belongs to the tumor necrosis factor family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 233233Tumor necrosis factor, membrane form
PRO_0000034439
Chain1 – 3939Intracellular domain 1 By similarity
PRO_0000417263
Chain1 – 3535Intracellular domain 2 By similarity
PRO_0000417264
Chain50 – ?C-domain 1 By similarityPRO_0000417265
Chain52 – ?C-domain 2 By similarityPRO_0000417266
Chain77 – 233157Tumor necrosis factor, soluble form By similarity
PRO_0000034440

Regions

Topological domain1 – 3434Cytoplasmic Potential
Transmembrane35 – 5723Helical; Signal-anchor for type II membrane protein; By similarity
Topological domain58 – 233176Extracellular Potential

Sites

Site39 – 402Cleavage; by SPPL2A or SPPL2B By similarity
Site49 – 502Cleavage; by SPPL2A or SPPL2B By similarity
Site51 – 522Cleavage; by SPPL2A or SPPL2B By similarity
Site76 – 772Cleavage; by ADAM17 By similarity

Amino acid modifications

Modified residue21Phosphoserine; by CK1 By similarity
Lipidation201N6-myristoyl lysine By similarity
Glycosylation801O-linked (GalNAc...); in soluble form By similarity
Disulfide bond145 ↔ 177 By similarity

Sequences

Sequence LengthMass (Da)Tools
P59695 [UniParc].

Last modified May 23, 2003. Version 1.
Checksum: 0C477F9EB6CC9909

FASTA23325,736
        10         20         30         40         50         60 
MSTESMIRDV ELAEEALPRK TAGPQGSRRR WFLRLFSFLL VAGATTLFCL LHFGVIGPQR 

        70         80         90        100        110        120 
EEFPKDPSLI SPLAQAVRSS SRTPSDKPVA HVVANPQAEG QLQWLNRRAN ALLANGVEPT 

       130        140        150        160        170        180 
DNQLVVPSEG LYLIYSQVLF KGQGCPSNHV LLTHTISRIA VSYQTKVNLL SAIKSPCQRE 

       190        200        210        220        230 
TPEGAEAKPW YEPIYLGGVF QLEKGDRLSA EINLPDYLDF AESGQVYFGI IAL 

« Hide

References

[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].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY234222 mRNA. Translation: AAO85335.1.
RefSeqNP_001106118.1. NM_001112648.1.
UniGenePan.11103.

3D structure databases

ProteinModelPortalP59695.
SMRP59695. Positions 82-233.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID100126739.

Organism-specific databases

CTD7124.

Phylogenomic databases

HOVERGENHBG012516.

Family and domain databases

Gene3D2.60.120.40. 1 hit.
InterProIPR006053. TNF.
IPR002959. TNF_alpha.
IPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamPF00229. TNF. 1 hit.
[Graphical view]
PRINTSPR01234. TNECROSISFCT.
PR01235. TNFALPHA.
SMARTSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMSSF49842. SSF49842. 1 hit.
PROSITEPS00251. TNF_1. 1 hit.
PS50049. TNF_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameTNFA_PAPAN
AccessionPrimary (citable) accession number: P59695
Entry history
Integrated into UniProtKB/Swiss-Prot: May 23, 2003
Last sequence update: May 23, 2003
Last modified: June 11, 2014
This is version 80 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families