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Protein

Tumor necrosis factor

Gene

TNF

Organism
Macropus eugenii (Tammar wallaby)
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

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
OrganismiMacropus eugenii (Tammar wallaby)
Taxonomic identifieri9315 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaMetatheriaDiprotodontiaMacropodidaeMacropus

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 – 233177ExtracellularSequence 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_0000034427Add
BLAST
Chaini1 – 3939Intracellular domain 1By similarityPRO_0000417239Add
BLAST
Chaini1 – 3535Intracellular domain 2By similarityPRO_0000417240Add
BLAST
Chaini50 – ?C-domain 1By similarityPRO_0000417241
Chaini52 – ?C-domain 2By similarityPRO_0000417242
Chaini78 – 233156Tumor necrosis factor, soluble formPRO_0000034428Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21Phosphoserine; by CK1By similarity
Lipidationi20 – 201N6-myristoyl lysineBy 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

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
Sitei77 – 782Cleavage; by ADAM17Sequence analysis

Keywords - PTMi

Disulfide bond, Lipoprotein, Myristate, Phosphoprotein

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi9315.ENSMEUP00000007583.

Structurei

3D structure databases

ProteinModelPortaliO77764.
SMRiO77764. 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

eggNOGiENOG410ISAN. Eukaryota.
ENOG410YQC4. LUCA.
HOGENOMiHOG000048729.
HOVERGENiHBG012516.
OrthoDBiEOG091G0HIG.

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.

O77764-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTENMIRDV ELAEEELQRK ARGPQGPGRC LCLILTFFLL LAGATLLFCL
60 70 80 90 100
LHFGVIGPQN EEASTDAFLG MKPVTQRVRS CQTESNKPVA HVIADPLAEG
110 120 130 140 150
KLQWLKRRAN VLLSNGMDLV DNQLVVPSTG LYLVYSQLLF KGEDCANEPL
160 170 180 190 200
LLTHTVSRVA LSYQSKVNLL SAIKSPCQKT VKGAREASPW YEPIYLGGVF
210 220 230
QLEKGDKLSA DTNYPNYLDF AESGQVYFGV IAL
Length:233
Mass (Da):25,697
Last modified:November 1, 1998 - v1
Checksum:i90AFFD137AF4E348
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF055915 mRNA. Translation: AAC61491.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF055915 mRNA. Translation: AAC61491.1.

3D structure databases

ProteinModelPortaliO77764.
SMRiO77764. Positions 82-233.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9315.ENSMEUP00000007583.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

eggNOGiENOG410ISAN. Eukaryota.
ENOG410YQC4. LUCA.
HOGENOMiHOG000048729.
HOVERGENiHBG012516.
OrthoDBiEOG091G0HIG.

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_MACEU
AccessioniPrimary (citable) accession number: O77764
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1998
Last modified: September 7, 2016
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.