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Protein

Tumor necrosis factor

Gene

TNF

Organism
Pan troglodytes (Chimpanzee)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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
OrganismiPan troglodytes (Chimpanzee)
Taxonomic identifieri9598 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePan
Proteomesi
  • UP000002277 Componenti: Chromosome 6

Subcellular locationi

C-domain 1 :
C-domain 2 :

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3434CytoplasmicSequence analysisAdd
BLAST
Transmembranei35 – 5723Helical; Signal-anchor for type II membrane proteinBy similarityAdd
BLAST
Topological domaini58 – 232175ExtracellularSequence 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 – 232232Tumor necrosis factor, membrane formPRO_0000034437Add
BLAST
Chaini1 – 3939Intracellular domain 1By similarityPRO_0000417259Add
BLAST
Chaini1 – 3535Intracellular domain 2By similarityPRO_0000417260Add
BLAST
Chaini50 – ?C-domain 1By similarityPRO_0000417261
Chaini52 – ?C-domain 2By similarityPRO_0000417262
Chaini77 – 232156Tumor necrosis factor, soluble formBy similarityPRO_0000034438Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21Phosphoserine; by CK1By similarity
Lipidationi19 – 191N6-myristoyl lysineBy similarity
Lipidationi20 – 201N6-myristoyl lysineBy similarity
Glycosylationi79 – 791O-linked (GalNAc...); in soluble formBy similarity
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)LengthDescriptionGraphical viewFeature identifierActions
Sitei34 – 352Cleavage; by SPPL2A or SPPL2BBy similarity
Sitei39 – 402Cleavage; by SPPL2A or SPPL2BBy similarity
Sitei49 – 502Cleavage; by SPPL2A or SPPL2BBy similarity
Sitei51 – 522Cleavage; by SPPL2A or SPPL2BBy similarity
Sitei76 – 772Cleavage; by ADAM17By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

PaxDbiQ8HZD9.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi9598.ENSPTRP00000054518.

Structurei

3D structure databases

ProteinModelPortaliQ8HZD9.
SMRiQ8HZD9. Positions 81-232.
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.
InParanoidiQ8HZD9.
KOiK03156.
OMAiPWYEPIY.
OrthoDBiEOG7V4B0Q.
TreeFamiTF332169.

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.

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti77 – 771G → VR (PubMed:16702430).Curated
Sequence conflicti77 – 771G → VR (Ref. 4) Curated

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_009449140.1. XM_009450865.1.
UniGeneiPtr.6340.

Genome annotation databases

EnsembliENSPTRT00000061970; ENSPTRP00000054518; ENSPTRG00000017965.
GeneIDi494186.
KEGGiptr:494186.

Cross-referencesi

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_009449140.1. XM_009450865.1.
UniGeneiPtr.6340.

3D structure databases

ProteinModelPortaliQ8HZD9.
SMRiQ8HZD9. Positions 81-232.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9598.ENSPTRP00000054518.

Proteomic databases

PaxDbiQ8HZD9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSPTRT00000061970; ENSPTRP00000054518; ENSPTRG00000017965.
GeneIDi494186.
KEGGiptr:494186.

Organism-specific databases

CTDi7124.

Phylogenomic databases

eggNOGiENOG410ISAN. Eukaryota.
ENOG410YQC4. LUCA.
GeneTreeiENSGT00530000062992.
HOGENOMiHOG000048729.
HOVERGENiHBG012516.
InParanoidiQ8HZD9.
KOiK03156.
OMAiPWYEPIY.
OrthoDBiEOG7V4B0Q.
TreeFamiTF332169.

Miscellaneous databases

NextBioi20865667.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Comparative genomic analysis of the MHC: the evolution of class I duplication blocks, diversity and complexity from shark to man."
    Kulski J.K., Shiina T., Anzai T., Kohara S., Inoko H.
    Immunol. Rev. 190:95-122(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "Comparative sequencing of human and chimpanzee MHC class I regions unveils insertions/deletions as the major path to genomic divergence."
    Anzai T., Shiina T., Kimura N., Yanagiya K., Kohara S., Shigenari A., Yamagata T., Kulski J.K., Naruse T.K., Fujimori Y., Fukuzumi Y., Yamazaki M., Tashiro H., Iwamoto C., Umehara Y., Imanishi T., Meyer A., Ikeo K.
    , Gojobori T., Bahram S., Inoko H.
    Proc. Natl. Acad. Sci. U.S.A. 100:7708-7713(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "Rapid evolution of major histocompatibility complex class I genes in primates generates new disease alleles in humans via hitchhiking diversity."
    Shiina T., Ota M., Shimizu S., Katsuyama Y., Hashimoto N., Takasu M., Anzai T., Kulski J.K., Kikkawa E., Naruse T., Kimura N., Yanagiya K., Watanabe A., Hosomichi K., Kohara S., Iwamoto C., Umehara Y., Meyer A.
    , Wanner V., Sano K., Macquin C., Ikeo K., Tokunaga K., Gojobori T., Inoko H., Bahram S.
    Genetics 173:1555-1570(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "Molecular evolution in higher primates; gene specific and organism specific characteristics."
    O'Huigin C., Tichy H., Klein J.
    Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 33-186.

Entry informationi

Entry nameiTNFA_PANTR
AccessioniPrimary (citable) accession number: Q8HZD9
Secondary accession number(s): Q1XHZ6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 23, 2003
Last sequence update: May 23, 2003
Last modified: May 11, 2016
This is version 109 of the entry and version 2 of the sequence. [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

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.