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Protein

Tumor necrosis factor

Gene

TNF

Organism
Pan troglodytes (Chimpanzee)
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 (By similarity).By similarity
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
OrganismiPan troglodytes (Chimpanzee)
Taxonomic identifieri9598 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePan
Proteomesi
  • UP000002277 Componenti: Unplaced

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 – 34CytoplasmicSequence analysisAdd BLAST34
Transmembranei35 – 57Helical; Signal-anchor for type II membrane proteinBy similarityAdd BLAST23
Topological domaini58 – 232ExtracellularSequence analysisAdd BLAST175

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000344371 – 232Tumor necrosis factor, membrane formAdd BLAST232
ChainiPRO_00004172591 – 39Intracellular domain 1By similarityAdd BLAST39
ChainiPRO_00004172601 – 35Intracellular domain 2By similarityAdd BLAST35
ChainiPRO_000041726150 – ?C-domain 1By similarity
ChainiPRO_000041726252 – ?C-domain 2By similarity
ChainiPRO_000003443877 – 232Tumor necrosis factor, soluble formBy similarityAdd BLAST156

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2Phosphoserine; by CK1By similarity1
Lipidationi19N6-myristoyl lysineBy similarity1
Lipidationi20N6-myristoyl lysineBy similarity1
Glycosylationi79O-linked (GalNAc...) serine; in soluble formBy similarity1
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

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

Proteomic databases

PaxDbiQ8HZD9

Expressioni

Gene expression databases

BgeeiENSPTRG00000017965

Interactioni

Subunit structurei

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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9598.ENSPTRP00000054518

Structurei

3D structure databases

ProteinModelPortaliQ8HZD9
SMRiQ8HZD9
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
InParanoidiQ8HZD9
KOiK03156
OMAiPWYEPIY
OrthoDBiEOG091G0HIG
TreeFamiTF332169

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.

Q8HZD9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTESMIRDV ELAEEALPKK TGGPQGSRRC LFLSLFSFLI VAGATTLFCL
60 70 80 90 100
LHFGVIGPQR EEFPRDLSLI SPLAQAGSSS RTPSDKPVAH VVANPQAEGQ
110 120 130 140 150
LQWLNRRANA LLANGVELRD NQLVVPSEGL YLIYSQVLFK GQGCPSTHVL
160 170 180 190 200
LTHTISRIAV SYQTKVNLLS AIKSPCQRET PEGAEAKPWY EPIYLGGVFQ
210 220 230
LEKGDRLSAE INRPDYLDFA ESGQVYFGII AL
Length:232
Mass (Da):25,446
Last modified:May 23, 2003 - v2
Checksum:iE4D71B19C6AE0D03
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti77G → VR (PubMed:16702430).Curated1
Sequence conflicti77G → VR (Ref. 4) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB054536 Genomic DNA Translation: BAB83882.1
BA000041 Genomic DNA Translation: BAC78157.1
AB210165 Genomic DNA Translation: BAE92772.1
AB210166 Genomic DNA Translation: BAE92774.1
AY091964 Genomic DNA Translation: AAM76582.1
RefSeqiNP_001038976.1, NM_001045511.1
XP_016810226.1, XM_016954737.1
UniGeneiPtr.6340

Genome annotation databases

GeneIDi494186
KEGGiptr:494186

Similar proteinsi

Entry informationi

Entry nameiTNFA_PANTR
AccessioniPrimary (citable) accession number: Q8HZD9
Secondary accession number(s): Q1XHZ6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 23, 2003
Last sequence update: May 23, 2003
Last modified: March 28, 2018
This is version 121 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health