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Protein

Tumor necrosis factor

Gene

TNF

Organism
Papio sp. (Baboon)
Status
Reviewed-Annotation score: -Protein inferred from homologyi

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

Keywordsi

Molecular functionCytokine

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 sp. (Baboon)
Taxonomic identifieri61183 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaePapio

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 35CytoplasmicSequence analysisAdd BLAST35
Transmembranei36 – 56Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini57 – 233ExtracellularSequence analysisAdd BLAST177

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000344431 – 233Tumor necrosis factor, membrane formAdd BLAST233
ChainiPRO_00004172711 – 39Intracellular domain 1By similarityAdd BLAST39
ChainiPRO_00004172721 – 35Intracellular domain 2By similarityAdd BLAST35
ChainiPRO_000041727350 – ?C-domain 1By similarity
ChainiPRO_000041727452 – ?C-domain 2By similarity
ChainiPRO_000003444477 – 233Tumor necrosis factor, soluble formAdd BLAST157

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2Phosphoserine; by CK1By similarity1
Lipidationi19N6-myristoyl lysineBy similarity1
Lipidationi20N6-myristoyl lysineBy similarity1
Glycosylationi80O-linked (GalNAc...) serine; in soluble formBy similarity1
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)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

Interactioni

Subunit structurei

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

GO - Molecular functioni

Structurei

3D structure databases

ProteinModelPortaliP33620
SMRiP33620
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
InterProiView protein in InterPro
IPR006053 TNF
IPR002959 TNF_alpha
IPR021184 TNF_CS
IPR006052 TNF_dom
IPR008983 Tumour_necrosis_fac-like_dom
PANTHERiPTHR11471:SF23 PTHR11471:SF23, 1 hit
PfamiView protein in Pfam
PF00229 TNF, 1 hit
PRINTSiPR01234 TNECROSISFCT
PR01235 TNFALPHA
SMARTiView protein in SMART
SM00207 TNF, 1 hit
SUPFAMiSSF49842 SSF49842, 1 hit
PROSITEiView protein in PROSITE
PS00251 TNF_1, 1 hit
PS50049 TNF_2, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P33620-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTESMIRDV ELAEEALPKK TGGPQGSRRC LFLSLFSFLL VAGATTLFCL
60 70 80 90 100
LHFGVIGPQR EEFPKDPSLI SPLAQAVRSS SRTPSDKPVA HVVANPQAEG
110 120 130 140 150
QLQWLNRRAN ALLANGVELR DNQLVVPSEG LYLIYSQVLF KGQGCPSTHV
160 170 180 190 200
LLTHTISRIA VSYQTKVNLL SAIKSPCQRE TPEGAEAKPW YEPIYLGGVF
210 220 230
QLEKGDRLSA EINLPDYLDF AESGQVYFGI IAL
Length:233
Mass (Da):25,557
Last modified:February 1, 1994 - v1
Checksum:i455360B48DC74173
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X62141 Genomic DNA Translation: CAA44068.1
PIRiS22052

Similar proteinsi

Entry informationi

Entry nameiTNFA_PAPSP
AccessioniPrimary (citable) accession number: P33620
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: October 25, 2017
This is version 98 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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