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UniProtKB/Swiss-Prot entry P01375


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name TNFA_HUMAN
Primary accession number P01375
Secondary accession numbers O43647 Q9P1Q2 Q9UIV3
Integrated into Swiss-Prot on July 21, 1986
Sequence was last modified on July 21, 1986 (Sequence version 1)
Annotations were last modified on    June 16, 2009 (Entry version 137)
Name and origin of the protein
Protein name Tumor necrosis factor [Precursor]
Synonyms TNF-alpha
Tumor necrosis factor ligand superfamily member 2
TNF-a
Cachectin
Contains Tumor necrosis factor, membrane form
Tumor necrosis factor, soluble form
Gene name
Name: TNF
Synonyms: TNFA, TNFSF2
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=3555974 [NCBI, ExPASy, EBI, Israel, Japan]
Nedospasov S.A., Shakhov A.N., Turetskaya R.L., Mett V.A., Azizov M.M., Georgiev G.P., Korobko V.G., Dobrynin V.N., Filippov S.A., Bystrov N.S., Boldyreva E.F., Chuvpilo S.A., Chumakov A.M., Shingarova L.N., Ovchinnikov Y.A.;
"Tandem arrangement of genes coding for tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta) in the human genome.";
Cold Spring Harb. Symp. Quant. Biol. 51:611-624(1986).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
DOI=10.1038/312724a0; PubMed=6392892 [NCBI, ExPASy, EBI, Israel, Japan]
Pennica D., Nedwin G.E., Hayflick J.S., Seeburg P.H., Derynck R., Palladino M.A., Kohr W.J., Aggarwal B.B., Goeddel D.V.;
"Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin.";
Nature 312:724-729(1984).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
DOI=10.1038/313803a0; PubMed=3883195 [NCBI, ExPASy, EBI, Israel, Japan]
Shirai T., Yamaguchi H., Ito H., Todd C.W., Wallace R.B.;
"Cloning and expression in Escherichia coli of the gene for human tumour necrosis factor.";
Nature 313:803-806(1985).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
DOI=10.1093/nar/13.17.6361; PubMed=2995927 [NCBI, ExPASy, EBI, Israel, Japan]
Nedwin G.E., Naylor S.L., Sakaguchi A.Y., Smith D.H., Jarrett-Nedwin J., Pennica D., Goeddel D.V., Gray P.W.;
"Human lymphotoxin and tumor necrosis factor genes: structure, homology and chromosomal localization.";
Nucleic Acids Res. 13:6361-6373(1985).
[5]
NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1126/science.3856324; PubMed=3856324 [NCBI, ExPASy, EBI, Israel, Japan]
Wang A.M., Creasey A.A., Ladner M.B., Lin L.S., Strickler J., van Arsdell J.N., Yamamoto R., Mark D.F.;
"Molecular cloning of the complementary DNA for human tumor necrosis factor.";
Science 228:149-154(1985).
[6]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
DOI=10.1111/j.1432-1033.1985.tb09226.x; PubMed=3932069 [NCBI, ExPASy, EBI, Israel, Japan]
Marmenout A., Fransen L., Tavernier J., van der Heyden J., Tizard R., Kawashima E., Shaw A., Johnson M.J., Semon D., Mueller R., Ruysschaert M.-R., van Vliet A., Fiers W.;
"Molecular cloning and expression of human tumor necrosis factor and comparison with mouse tumor necrosis factor.";
Eur. J. Biochem. 152:515-522(1985).
[7]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
DOI=10.1038/ng0293-137; PubMed=8499947 [NCBI, ExPASy, EBI, Israel, Japan]
Iris F.J.M., Bougueleret L., Prieur S., Caterina D., Primas G., Perrot V., Jurka J., Rodriguez-Tome P., Claverie J.-M., Dausset J., Cohen D.;
"Dense Alu clustering and a potential new member of the NF kappa B family within a 90 kilobase HLA class III segment.";
Nat. Genet. 3:137-145(1993).
[8]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=10202016 [NCBI, ExPASy, EBI, Israel, Japan]
Neville M.J., Campbell R.D.;
"A new member of the Ig superfamily and a V-ATPase G subunit are among the predicted products of novel genes close to the TNF locus in the human MHC.";
J. Immunol. 162:4745-4754(1999).
[9]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1101/gr.1736803; PubMed=14656967 [NCBI, ExPASy, EBI, Israel, Japan]
Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D., Hood L.;
"Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse.";
Genome Res. 13:2621-2636(2003).
[10]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Shiina S., Tamiya G., Oka A., Inoko H.;
"Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region.";
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
[11]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Shiina T., Ota M., Katsuyama Y., Hashimoto N., Inoko H.;
"Genome diversity in HLA: a new strategy for detection of genetic polymorphisms in expressed genes within the HLA class III and class I regions.";
Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
[12]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
SeattleSNPs variation discovery resource;
Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
[13]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-84.
NIEHS SNPs program;
Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
[14]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Blood;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[15]
PROTEIN SEQUENCE OF 77-99, AND GLYCOSYLATION AT SER-80.
DOI=10.1111/j.1432-1033.1996.00431.x; PubMed=8631363 [NCBI, ExPASy, EBI, Israel, Japan]
Takakura-Yamamoto R., Yamamoto S., Fukuda S., Kurimoto M.;
"O-glycosylated species of natural human tumor-necrosis factor-alpha.";
Eur. J. Biochem. 235:431-437(1996).
[16]
NUCLEOTIDE SEQUENCE [MRNA] OF 77-233.
Jang J.S., Kim B.E.;
Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
[17]
NUCLEOTIDE SEQUENCE [MRNA] OF 84-214.
TISSUE=Prostatic carcinoma;
Shao C., Yan W., Zhu F., Yue W., Chai Y., Zhao Z., Wang C.;
Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
[18]
PHOSPHORYLATION (MEMBRANE FORM).
PubMed=8597870 [NCBI, ExPASy, EBI, Israel, Japan]
Pocsik E., Duda E., Wallach D.;
"Phosphorylation of the 26 kDa TNF precursor in monocytic cells and in transfected HeLa cells.";
J. Inflamm. 45:152-160(1995).
[19]
PHOSPHORYLATION BY CK1, AND DEPHOSPHORYLATION.
DOI=10.1093/emboj/18.8.2119; PubMed=10205166 [NCBI, ExPASy, EBI, Israel, Japan]
Watts A.D., Hunt N.H., Wanigasekara Y., Bloomfield G., Wallach D., Roufogalis B.D., Chaudhri G.;
"A casein kinase I motif present in the cytoplasmic domain of members of the tumour necrosis factor ligand family is implicated in 'reverse signalling'.";
EMBO J. 18:2119-2126(1999).
[20]
MUTAGENESIS.
PubMed=2009860 [NCBI, ExPASy, EBI, Israel, Japan]
Ostade X.V., Tavernier J., Prange T., Fiers W.;
"Localization of the active site of human tumour necrosis factor (hTNF) by mutational analysis.";
EMBO J. 10:827-836(1991).
[21]
MYRISTOYLATION AT LYS-19 AND LYS-20.
DOI=10.1084/jem.176.4.1053; PubMed=1402651 [NCBI, ExPASy, EBI, Israel, Japan]
Stevenson F.T., Bursten S.L., Locksley R.M., Lovett D.H.;
"Myristyl acylation of the tumor necrosis factor alpha precursor on specific lysine residues.";
J. Exp. Med. 176:1053-1062(1992).
[22]
CLEAVAGE BY ADAM17.
DOI=10.1038/385733a0; PubMed=9034191 [NCBI, ExPASy, EBI, Israel, Japan]
Moss M.L., Jin S.-L.C., Milla M.E., Burkhart W., Carter H.L., Chen W.-J., Clay W.C., Didsbury J.R., Hassler D., Hoffman C.R., Kost T.A., Lambert M.H., Leesnitzer M.A., McCauley P., McGeehan G., Mitchell J., Moyer M., Pahel G., Rocque W., Overton L.K., Schoenen F., Seaton T., Su J.-L., Warner J., Willard D., Becherer J.D.;
"Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha.";
Nature 385:733-736(1997).
[23]
X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
DOI=10.1038/338225a0; PubMed=2922050 [NCBI, ExPASy, EBI, Israel, Japan]
Jones E.Y., Stuart D.I., Walker N.P.;
"Structure of tumour necrosis factor.";
Nature 338:225-228(1989).
[24]
X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
PubMed=1964681 [NCBI, ExPASy, EBI, Israel, Japan]
Jones E.Y., Stuart D.I., Walker N.P.;
"The structure of tumour necrosis factor -- implications for biological function.";
J. Cell Sci. Suppl. 13:11-18(1990).
[25]
X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
PubMed=2551905 [NCBI, ExPASy, EBI, Israel, Japan]
Eck M.J., Sprang S.R.;
"The structure of tumor necrosis factor-alpha at 2.6-A resolution. Implications for receptor binding.";
J. Biol. Chem. 264:17595-17605(1989).
[26]
X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT ARG-107.
DOI=10.1093/protein/10.10.1101; PubMed=9488135 [NCBI, ExPASy, EBI, Israel, Japan]
Reed C., Fu Z.Q., Wu J., Xue Y.N., Harrison R.W., Chen M.J., Weber I.T.;
"Crystal structure of TNF-alpha mutant R31D with greater affinity for receptor R1 compared with R2.";
Protein Eng. 10:1101-1107(1997).
[27]
X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF MUTANT SER-3.
DOI=10.1074/jbc.273.4.2153; PubMed=9442056 [NCBI, ExPASy, EBI, Israel, Japan]
Cha S.S., Kim J.S., Cho H.S., Shin N.K., Jeong W., Shin H.C., Kim Y.J., Hahn J.H., Oh B.H.;
"High resolution crystal structure of a human tumor necrosis factor-alpha mutant with low systemic toxicity.";
J. Biol. Chem. 273:2153-2160(1998).
[28]
INVOLVEMENT IN PSORIATIC ARTHRITIS SUSCEPTIBILITY.
DOI=10.1002/art.10935; PubMed=12746914 [NCBI, ExPASy, EBI, Israel, Japan]
Balding J., Kane D., Livingstone W., Mynett-Johnson L., Bresnihan B., Smith O., FitzGerald O.;
"Cytokine gene polymorphisms: association with psoriatic arthritis susceptibility and severity.";
Arthritis Rheum. 48:1408-1413(2003).
[29]
INVOLVEMENT IN SUSCEPTIBILITY TO HBV INFECTION.
DOI=10.1093/hmg/ddg262; PubMed=12915457 [NCBI, ExPASy, EBI, Israel, Japan]
Kim Y.J., Lee H.-S., Yoon J.-H., Kim C.Y., Park M.H., Kim L.H., Park B.L., Shin H.D.;
"Association of TNF-alpha promoter polymorphisms with the clearance of hepatitis B virus infection.";
Hum. Mol. Genet. 12:2541-2546(2003).
Comments
  • FUNCTION: 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.
  • SUBUNIT: Homotrimer.
  • INTERACTION:
    P19438:TNFRSF1A; NbExp=1; IntAct=EBI-359977, EBI-299451;
  • SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane protein.
  • SUBCELLULAR LOCATION: Tumor necrosis factor, soluble form: Secreted.
  • PTM: The soluble form derives from the membrane form by proteolytic processing.
  • PTM: 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.
  • PTM: O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid.
  • DISEASE: Cachexia accompanies a variety of diseases, including cancer and infection, and is characterized by general ill health and malnutrition.
  • DISEASE: Genetic variations in TNF are associated with susceptibility to psoriatic arthritis [MIM:607507]. Psoriasis is a chronic inflammatory dermatosis that affects approximately 2% of the population. It is characterized by red, scaly skin lesions that are usually found on the scalp, elbows, and knees, and may be associated with severe arthritis. Psoriatic arthritis has been defined as an inflammatory arthritis usually without any rheumatoid factor in serum (seronegative arthritis) associated with psoriasis.
  • DISEASE: Genetic variations in TNF are associated with susceptibility to hepatitis B virus infection (HBV infection) [MIM:610424]. Approximately one third of all cases of cirrhosis and half of all cases of hepatocellular carcinoma can be attributed to chronic HBV infection. HBV infection may result in subclinical or asymptomatic infection, acute self-limited hepatitis, or fulminant hepatitis requiring liver transplantation.
  • SIMILARITY: Belongs to the tumor necrosis factor family.
  • SEQUENCE CAUTION:
    • Sequence=AAF71992.1; Type=Frameshift; Positions=91, 157;
    • Sequence=CAA75070.1; Type=Erroneous gene model prediction;
  • WEB RESOURCE: Name=Wikipedia; Note=Tumor necrosis factor alpha entry; URL="http://en.wikipedia.org/wiki/Tumor_necrosis_factor-alpha";.
  • WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/TNFaID319.html";.
  • WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/tnf/";.
  • WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/tnf/";.
  • WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=TNF";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
M16441; AAA61200.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X02910; CAA26669.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X01394; CAA25650.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M10988; AAA61198.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26331; AAA36758.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
Z15026; CAA78745.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
Y14768; CAA75070.1; ALT_SEQ; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF129756; AAD18091.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BA000025; BAB63396.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB088112; BAC54944.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AY066019; AAL47581.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AY214167; AAO21132.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC028148; AAH28148.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF043342; AAC03542.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF098751; AAF71992.1; ALT_FRAME; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00001671; -.
PIR A93585; QWHUN.
RefSeq NP_000585.2; -.
UniGene Hs.241570
3D structure databases
PDB
1A8M; X-ray; 2.30 A; A/B/C=77-233.[ExPASy / RCSB / EBI]
1TNF; X-ray; 2.60 A; A/B/C=77-233.[ExPASy / RCSB / EBI]
2AZ5; X-ray; 2.10 A; A/B/C/D=86-233.[ExPASy / RCSB / EBI]
2E7A; X-ray; 1.80 A; A/B/C=77-233.[ExPASy / RCSB / EBI]
2TUN; X-ray; 3.10 A; A/B/C/D/E/F=77-233.[ExPASy / RCSB / EBI]
2ZJC; X-ray; 2.50 A; A/B/C=77-233.[ExPASy / RCSB / EBI]
2ZPX; X-ray; 2.83 A; A/B/C=77-233.[ExPASy / RCSB / EBI]
4TSV; X-ray; 1.80 A; A=84-233.[ExPASy / RCSB / EBI]
5TSW; X-ray; 2.50 A; A/B/C/D/E/F=84-233.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1A8M; -.
1TNF; -.
2AZ5; -.
2E7A; -.
2TUN; -.
2ZJC; -.
2ZPX; -.
4TSV; -.
5TSW; -.
ModBase P01375.
Protein-protein interaction databases
DIP DIP:2895N; -.
IntAct P01375; 6.
PTM databases
GlycoSuiteDB P01375; -.
Enzyme and pathway databases
Pathway_Interaction_DB amb2_neutrophils_pathway; amb2 Integrin signaling.
angiopoietinreceptor_pathway; Angiopoietin receptor Tie2-mediated signaling.
nfat_tfpathway; Calcineurin-regulated NFAT-dependent transcription in lymphocytes.
nfkappabcanonicalpathway; Canonical NF-kappaB pathway.
caspase_pathway; Caspase cascade in apoptosis.
anthraxpathway; Cellular roles of Anthrax toxin.
ceramidepathway; Ceramide signaling pathway.
cd8tcrdownstreampathway; Downstream signaling in naive CD8+ T cells.
hivnefpathway; HIV-1 Nef: Negative effector of Fas and TNF-alpha.
il23pathway; IL23-mediated signaling events.
il27pathway; IL27-mediated signaling events.
rxr_vdr_pathway; RXR and RAR hetrodimerization with other nuclear receptor.
hdac_classi_pathway; Signaling events mediated by HDAC Class I.
tnfpathway; TNF receptor signaling pathway.
Reactome REACT_578; Apoptosis.
Organism-specific databases
GeneCards GC06P031652; -.
H-InvDB HIX0005719; -.
HIX0057958; -.
HIX0058135; -.
HGNC HGNC:11892; TNF.
GenAtlas TNF.
MIM 191160; gene. [NCBI / EBI]
607507; phenotype. [NCBI / EBI]
610424; phenotype. [NCBI / EBI]
Orphanet 40050; Psoriatic arthritis, adult form.
PharmGKB PA435; -.
Gene expression databases
ArrayExpress P01375; -.
Bgee P01375; -.
CleanEx HS_TNF; -.
GermOnline ENSG00000204490; Homo sapiens.
Ontologies
GO
GO:0009897; Cellular component: external side of plasma membrane (inferred from sequence or structural similarity from UniProtKB).
GO:0005615; Cellular component: extracellular space (inferred from direct assay from UniProtKB).
GO:0005887; Cellular component: integral to plasma membrane (inferred from direct assay from UniProtKB).
GO:0045121; Cellular component: membrane raft (inferred from direct assay from UniProtKB).
GO:0001891; Cellular component: phagocytic cup (inferred from sequence or structural similarity from UniProtKB).
GO:0055037; Cellular component: recycling endosome (inferred from sequence or structural similarity from UniProtKB).
GO:0005125; Molecular function: cytokine activity (inferred from direct assay from UniProtKB).
GO:0042802; Molecular function: identical protein binding (inferred from direct assay from UniProtKB).
GO:0005164; Molecular function: tumor necrosis factor receptor binding (inferred from direct assay from UniProtKB).
GO:0006919; Biological process: activation of caspase activity (inferred from direct assay from UniProtKB).
GO:0000187; Biological process: activation of MAPK activity (inferred from direct assay from UniProtKB).
GO:0006916; Biological process: anti-apoptosis (inferred from direct assay from UniProtKB).
GO:0002439; Biological process: chronic inflammatory response to antigenic stimulus (inferred from mutant phenotype from UniProtKB).
GO:0050901; Biological process: leukocyte tethering or rolling (inferred from direct assay from UniProtKB).
GO:0070265; Biological process: necrotic cell death (inferred from direct assay from UniProtKB).
GO:0002740; Biological process: negative regulation of cytokine secretion during immune response (inferred from direct assay from UniProtKB).
GO:0032715; Biological process: negative regulation of interleukin-6 production (inferred from direct assay from UniProtKB).
GO:0050995; Biological process: negative regulation of lipid catabolic process (inferred from direct assay from UniProtKB).
GO:0045071; Biological process: negative regulation of viral genome replication (inferred from direct assay from UniProtKB).
GO:0060559; Biological process: positive regulation of calcidiol 1-monooxygenase activity (inferred from direct assay from UniProtKB).
GO:0045080; Biological process: positive regulation of chemokine biosynthetic process (inferred from direct assay from UniProtKB).
GO:0032722; Biological process: positive regulation of chemokine production (inferred from direct assay from UniProtKB).
GO:0050715; Biological process: positive regulation of cytokine secretion (inferred from direct assay from UniProtKB).
GO:0043193; Biological process: positive regulation of gene-specific transcription (inferred from direct assay from UniProtKB).
GO:0034116; Biological process: positive regulation of heterotypic cell-cell adhesion (inferred from direct assay from UniProtKB).
GO:0043123; Biological process: positive regulation of I-kappaB kinase/NF-kappaB cascade (inferred from direct assay from UniProtKB).
GO:0051044; Biological process: positive regulation of membrane protein ectodomain proteolysis (inferred from direct assay from UniProtKB).
GO:0010940; Biological process: positive regulation of necrotic cell death (traceable author statement from UniProtKB).
GO:0042346; Biological process: positive regulation of NF-kappaB import into nucleus (inferred from direct assay from UniProtKB).
GO:0051092; Biological process: positive regulation of NF-kappaB transcription factor activity (inferred from direct assay from UniProtKB).
GO:0045429; Biological process: positive regulation of nitric oxide biosynthetic process (inferred from direct assay from UniProtKB).
GO:0001934; Biological process: positive regulation of protein amino acid phosphorylation (inferred from direct assay from UniProtKB).
GO:0048661; Biological process: positive regulation of smooth muscle cell proliferation (inferred from direct assay from UniProtKB).
GO:0060557; Biological process: positive regulation of vitamin D biosynthetic process (inferred from direct assay from UniProtKB).
GO:0000060; Biological process: protein import into nucleus, translocation (inferred from direct assay from UniProtKB).
GO:0032800; Biological process: receptor biosynthetic process (inferred from direct assay from UniProtKB).
GO:0050796; Biological process: regulation of insulin secretion (inferred from direct assay from UniProtKB).
GO:0051384; Biological process: response to glucocorticoid stimulus (inferred from direct assay from UniProtKB).
GO:0009651; Biological process: response to salt stress (traceable author statement from UniProtKB).
GO:0009615; Biological process: response to virus (inferred from direct assay from UniProtKB).
GO:0030730; Biological process: sequestering of triglyceride (inferred from direct assay from UniProtKB).
GO:0006927; Biological process: transformed cell apoptosis (inferred from direct assay from UniProtKB).
GO:0033209; Biological process: tumor necrosis factor-mediated signaling pathway (inferred from mutant phenotype from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR006053; TNF_abc.
IPR002959; TNF_alpha.
IPR006052; TNF_family.
IPR008983; Tumour_necrosis_fac-like.
Graphical view of domain structure.
Gene3D G3DSA:2.60.120.40; Tumour_necrosis_fac-like; 1.
Pfam PF00229; TNF; 1.
Pfam graphical view of domain structure.
PRINTS PR01234; TNECROSISFCT.
PR01235; TNFALPHA.
ProDom PD002012; TNF_subf; 1.
[Domain structure / List of seq. sharing at least 1 domain]
SMART SM00207; TNF; 1.
SMART graphical view of domain structure.
PROSITE PS00251; TNF_1; 1.
PS50049; TNF_2; 1.
PROSITE graphical view of domain structure (profiles).
Other
SWISS-3DIMAGE P01375.
Proteomic databases
PRIDE P01375; -.
Genome annotation databases
Ensembl ENSG00000204490; Homo sapiens. [Contig view]
ENSG00000206328; Homo sapiens. [Contig view]
ENSG00000206439; Homo sapiens. [Contig view]
GeneID 7124; -.
KEGG hsa:7124; -.
Phylogenomic databases
HOGENOM P01375; -.
HOVERGEN P01375; -.
OMA P01375; KAGGPQG.
Other
DrugBank DB00051; Adalimumab.
DB00640; Adenosine.
DB01427; Amrinone.
DB01076; Atorvastatin.
DB00608; Chloroquine.
DB01407; Clenbuterol.
DB00005; Etanercept.
DB01296; Glucosamine.
DB00065; Infliximab.
DB00704; Naltrexone.
DB01411; Pranlukast.
DB01366; Procaterol.
DB01232; Saquinavir.
DB00641; Simvastatin.
DB01041; Thalidomide.
NextBio 27879; -.
PMAP-CutDB P01375; -.
SOURCE TNF; Homo sapiens.
ProtoNet P01375.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Cell membrane; Cytokine; Direct protein sequencing; Disulfide bond; Glycoprotein; Lipoprotein; Membrane; Myristate; Phosphoprotein; Polymorphism; Secreted; Signal-anchor; Transmembrane.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   233  233     Tumor necrosis factor, membrane form. PRO_0000034423
CHAIN   77   233  157     Tumor necrosis factor, soluble form. PRO_0000034424
TOPO_DOM   1    35  35     Cytoplasmic (Potential). 
TRANSMEM   36    56  21     Signal-anchor for type II membrane protein (Potential). 
TOPO_DOM   57   233  177     Extracellular (Potential). 
SITE   76    77  2     Cleavage; by ADAM17. 
MOD_RES   2     2        Phosphoserine; by CK1. 
LIPID   19    19        N6-myristoyl lysine. 
LIPID   20    20        N6-myristoyl lysine. 
CARBOHYD   80    80        O-linked (GalNAc...); in soluble form. 
DISULFID   145   177         
VARIANT   84    84  1     P -> L (in dbSNP:rs4645843 [NCBI]). VAR_019378 [3D]
VARIANT   94    94  1     A -> T (in dbSNP:rs1800620 [NCBI]). VAR_011927 [3D]
MUTAGEN   105   105        L->S: Low activity. 
MUTAGEN   108   108        R->W: Biologically inactive. 
MUTAGEN   112   112        L->F: Biologically inactive. 
MUTAGEN   160   160        A->V: Biologically inactive. 
MUTAGEN   162   162        S->F: Biologically inactive. 
MUTAGEN   167   167        V->A,D: Biologically inactive. 
MUTAGEN   222   222        E->K: Biologically inactive. 
CONFLICT   63    63        F -> S (in Ref. 5; AAA61198). 
CONFLICT   84    86        PSD -> VNR (in Ref. 17). 
CONFLICT   183   183        E -> R (in Ref. 16; AAC03542). 
STRAND   106   108  3      
STRAND   121   125  5      
STRAND   130   144  15      
STRAND   152   159  8      
STRAND   161   163  3      
STRAND   167   174  8      
STRAND   177   179  3      
STRAND   183   185  3      
STRAND   189   202  14      
STRAND   207   213  7      
HELIX   215   217  3      
STRAND   223   229  7      
Sequence information
Length: 233 AA [This is the length of the unprocessed precursor] Molecular weight: 25644 Da [This is the MW of the unprocessed precursor] CRC64: 3DF90F96C9031FFE [This is a checksum on the sequence]
        10         20         30         40         50         60 
MSTESMIRDV ELAEEALPKK TGGPQGSRRC LFLSLFSFLI VAGATTLFCL LHFGVIGPQR 

        70         80         90        100        110        120 
EEFPRDLSLI SPLAQAVRSS SRTPSDKPVA HVVANPQAEG QLQWLNRRAN ALLANGVELR 

       130        140        150        160        170        180 
DNQLVVPSEG LYLIYSQVLF KGQGCPSTHV LLTHTISRIA VSYQTKVNLL SAIKSPCQRE 

       190        200        210        220        230 
TPEGAEAKPW YEPIYLGGVF QLEKGDRLSA EINRPDYLDF AESGQVYFGI IAL 

P01375 in FASTA format

View entry in raw text format (no links)
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BLAST logo BLAST submission on ExPASy/SIB
or at NCBI (USA)
Tools Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
PROSITE logo ScanProsite, MotifScan SWISS-MODEL Submit a homology modeling request to SWISS-MODEL
NPSA logo NPSA Sequence analysis tools

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