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Protein

Tumor necrosis factor

Gene

TNF

Organism
Callithrix jacchus (White-tufted-ear marmoset)
Status
Reviewed-Annotation score: -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 - 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
OrganismiCallithrix jacchus (White-tufted-ear marmoset)
Taxonomic identifieri9483 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniPlatyrrhiniCebidaeCallitrichinaeCallithrixCallithrix
Proteomesi
  • UP000008225 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 – 55Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini56 – 232ExtracellularSequence analysisAdd BLAST177

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002629131 – 232Tumor necrosis factor, membrane formAdd BLAST232
ChainiPRO_00004171911 – 38Intracellular domain 1By similarityAdd BLAST38
ChainiPRO_00004171921 – 34Intracellular domain 2By similarityAdd BLAST34
ChainiPRO_000041719349 – ?C-domain 1By similarity
ChainiPRO_000041719451 – ?C-domain 2By similarity
ChainiPRO_000026291475 – 232Tumor necrosis factor, soluble formAdd BLAST158

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2Phosphoserine; by CK1By similarity1
Lipidationi19N6-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
Sitei33 – 34Cleavage; by SPPL2A or SPPL2BBy similarity2
Sitei38 – 39Cleavage; by SPPL2A or SPPL2BBy similarity2
Sitei48 – 49Cleavage; by SPPL2A or SPPL2BBy similarity2
Sitei50 – 51Cleavage; by SPPL2A or SPPL2BBy similarity2
Sitei75 – 76Cleavage; by ADAM17By similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

PRIDEiQ19LH4

Interactioni

Subunit structurei

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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9483.ENSCJAP00000005672

Structurei

3D structure databases

ProteinModelPortaliQ19LH4
SMRiQ19LH4
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
GeneTreeiENSGT00530000062992
HOGENOMiHOG000048729
HOVERGENiHBG012516
InParanoidiQ19LH4
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.

Q19LH4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTETMIQDV ELAEEALPKT RGPQGSKRRL FLSLFSFLLV AGATALFCLL
60 70 80 90 100
HFGVIGPQKD ELSKDFSLIS PLALAVRSSS RIPSDKPVAH VVANPQAEGQ
110 120 130 140 150
LQWLNRRANA LLANGVELRD NQLVVPSEGL YLVYSQVLFK GQGCPSNFML
160 170 180 190 200
LTHSISRIAV SYQAKVNLLS AIKSPCQRET PQGAKTNPWY EPIYLGGVFQ
210 220 230
LEKGDRLSAE INLPDYLDLA ESGQVYFGII GL
Length:232
Mass (Da):25,433
Last modified:July 11, 2006 - v1
Checksum:i67386DA9B9C685FA
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ520835 mRNA Translation: ABF67511.1
RefSeqiNP_001244190.1, NM_001257261.1

Genome annotation databases

EnsembliENSCJAT00000082686; ENSCJAP00000053053; ENSCJAG00000040100
GeneIDi100397484
KEGGicjc:100397484

Similar proteinsi

Entry informationi

Entry nameiTNFA_CALJA
AccessioniPrimary (citable) accession number: Q19LH4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: July 11, 2006
Last modified: June 20, 2018
This is version 83 of the entry and version 1 of the sequence. See 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

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