ID   TNFA_HUMAN              Reviewed;         233 AA.
AC   P01375; O43647; Q9P1Q2; Q9UIV3;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   05-APR-2011, entry version 159.
DE   RecName: Full=Tumor necrosis factor;
DE   AltName: Full=Cachectin;
DE   AltName: Full=TNF-alpha;
DE   AltName: Full=Tumor necrosis factor ligand superfamily member 2;
DE            Short=TNF-a;
DE   Contains:
DE     RecName: Full=Tumor necrosis factor, membrane form;
DE   Contains:
DE     RecName: Full=Tumor necrosis factor, soluble form;
DE   Flags: Precursor;
GN   Name=TNF; Synonyms=TNFA, TNFSF2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=87217060; PubMed=3555974;
RA   Nedospasov S.A., Shakhov A.N., Turetskaya R.L., Mett V.A.,
RA   Azizov M.M., Georgiev G.P., Korobko V.G., Dobrynin V.N.,
RA   Filippov S.A., Bystrov N.S., Boldyreva E.F., Chuvpilo S.A.,
RA   Chumakov A.M., Shingarova L.N., Ovchinnikov Y.A.;
RT   "Tandem arrangement of genes coding for tumor necrosis factor (TNF-
RT   alpha) and lymphotoxin (TNF-beta) in the human genome.";
RL   Cold Spring Harb. Symp. Quant. Biol. 51:611-624(1986).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX   MEDLINE=85086244; PubMed=6392892; DOI=10.1038/312724a0;
RA   Pennica D., Nedwin G.E., Hayflick J.S., Seeburg P.H., Derynck R.,
RA   Palladino M.A., Kohr W.J., Aggarwal B.B., Goeddel D.V.;
RT   "Human tumour necrosis factor: precursor structure, expression and
RT   homology to lymphotoxin.";
RL   Nature 312:724-729(1984).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX   MEDLINE=85137898; PubMed=3883195; DOI=10.1038/313803a0;
RA   Shirai T., Yamaguchi H., Ito H., Todd C.W., Wallace R.B.;
RT   "Cloning and expression in Escherichia coli of the gene for human
RT   tumour necrosis factor.";
RL   Nature 313:803-806(1985).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX   MEDLINE=86016093; PubMed=2995927; DOI=10.1093/nar/13.17.6361;
RA   Nedwin G.E., Naylor S.L., Sakaguchi A.Y., Smith D.H.,
RA   Jarrett-Nedwin J., Pennica D., Goeddel D.V., Gray P.W.;
RT   "Human lymphotoxin and tumor necrosis factor genes: structure,
RT   homology and chromosomal localization.";
RL   Nucleic Acids Res. 13:6361-6373(1985).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=85142190; PubMed=3856324; DOI=10.1126/science.3856324;
RA   Wang A.M., Creasey A.A., Ladner M.B., Lin L.S., Strickler J.,
RA   van Arsdell J.N., Yamamoto R., Mark D.F.;
RT   "Molecular cloning of the complementary DNA for human tumor necrosis
RT   factor.";
RL   Science 228:149-154(1985).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=86030296; PubMed=3932069;
RX   DOI=10.1111/j.1432-1033.1985.tb09226.x;
RA   Marmenout A., Fransen L., Tavernier J., van der Heyden J., Tizard R.,
RA   Kawashima E., Shaw A., Johnson M.J., Semon D., Mueller R.,
RA   Ruysschaert M.-R., van Vliet A., Fiers W.;
RT   "Molecular cloning and expression of human tumor necrosis factor and
RT   comparison with mouse tumor necrosis factor.";
RL   Eur. J. Biochem. 152:515-522(1985).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=93272029; PubMed=8499947; DOI=10.1038/ng0293-137;
RA   Iris F.J.M., Bougueleret L., Prieur S., Caterina D., Primas G.,
RA   Perrot V., Jurka J., Rodriguez-Tome P., Claverie J.-M., Dausset J.,
RA   Cohen D.;
RT   "Dense Alu clustering and a potential new member of the NF kappa B
RT   family within a 90 kilobase HLA class III segment.";
RL   Nat. Genet. 3:137-145(1993).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=99218514; PubMed=10202016;
RA   Neville M.J., Campbell R.D.;
RT   "A new member of the Ig superfamily and a V-ATPase G subunit are among
RT   the predicted products of novel genes close to the TNF locus in the
RT   human MHC.";
RL   J. Immunol. 162:4745-4754(1999).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=14656967; DOI=10.1101/gr.1736803;
RA   Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S.,
RA   Campbell R.D., Hood L.;
RT   "Analysis of the gene-dense major histocompatibility complex class III
RT   region and its comparison to mouse.";
RL   Genome Res. 13:2621-2636(2003).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Shiina S., Tamiya G., Oka A., Inoko H.;
RT   "Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region.";
RL   Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN   [11]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Shiina T., Ota M., Katsuyama Y., Hashimoto N., Inoko H.;
RT   "Genome diversity in HLA: a new strategy for detection of genetic
RT   polymorphisms in expressed genes within the HLA class III and class I
RT   regions.";
RL   Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN   [12]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG   SeattleSNPs variation discovery resource;
RL   Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN   [13]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-84.
RG   NIEHS SNPs program;
RL   Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN   [14]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Blood;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [15]
RP   PROTEIN SEQUENCE OF 77-99, AND GLYCOSYLATION AT SER-80.
RX   PubMed=8631363; DOI=10.1111/j.1432-1033.1996.00431.x;
RA   Takakura-Yamamoto R., Yamamoto S., Fukuda S., Kurimoto M.;
RT   "O-glycosylated species of natural human tumor-necrosis factor-
RT   alpha.";
RL   Eur. J. Biochem. 235:431-437(1996).
RN   [16]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 77-233.
RA   Jang J.S., Kim B.E.;
RL   Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN   [17]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 84-214.
RC   TISSUE=Prostatic carcinoma;
RA   Shao C., Yan W., Zhu F., Yue W., Chai Y., Zhao Z., Wang C.;
RL   Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN   [18]
RP   PHOSPHORYLATION (MEMBRANE FORM).
RX   MEDLINE=96170872; PubMed=8597870;
RA   Pocsik E., Duda E., Wallach D.;
RT   "Phosphorylation of the 26 kDa TNF precursor in monocytic cells and in
RT   transfected HeLa cells.";
RL   J. Inflamm. 45:152-160(1995).
RN   [19]
RP   PHOSPHORYLATION BY CK1, AND DEPHOSPHORYLATION.
RX   MEDLINE=99221647; PubMed=10205166; DOI=10.1093/emboj/18.8.2119;
RA   Watts A.D., Hunt N.H., Wanigasekara Y., Bloomfield G., Wallach D.,
RA   Roufogalis B.D., Chaudhri G.;
RT   "A casein kinase I motif present in the cytoplasmic domain of members
RT   of the tumour necrosis factor ligand family is implicated in 'reverse
RT   signalling'.";
RL   EMBO J. 18:2119-2126(1999).
RN   [20]
RP   MUTAGENESIS.
RX   MEDLINE=91184128; PubMed=2009860;
RA   Ostade X.V., Tavernier J., Prange T., Fiers W.;
RT   "Localization of the active site of human tumour necrosis factor
RT   (hTNF) by mutational analysis.";
RL   EMBO J. 10:827-836(1991).
RN   [21]
RP   MYRISTOYLATION AT LYS-19 AND LYS-20.
RX   MEDLINE=93018820; PubMed=1402651; DOI=10.1084/jem.176.4.1053;
RA   Stevenson F.T., Bursten S.L., Locksley R.M., Lovett D.H.;
RT   "Myristyl acylation of the tumor necrosis factor alpha precursor on
RT   specific lysine residues.";
RL   J. Exp. Med. 176:1053-1062(1992).
RN   [22]
RP   CLEAVAGE BY ADAM17.
RX   MEDLINE=97186575; PubMed=9034191; DOI=10.1038/385733a0;
RA   Moss M.L., Jin S.-L.C., Milla M.E., Burkhart W., Carter H.L.,
RA   Chen W.-J., Clay W.C., Didsbury J.R., Hassler D., Hoffman C.R.,
RA   Kost T.A., Lambert M.H., Leesnitzer M.A., McCauley P., McGeehan G.,
RA   Mitchell J., Moyer M., Pahel G., Rocque W., Overton L.K., Schoenen F.,
RA   Seaton T., Su J.-L., Warner J., Willard D., Becherer J.D.;
RT   "Cloning of a disintegrin metalloproteinase that processes precursor
RT   tumour-necrosis factor-alpha.";
RL   Nature 385:733-736(1997).
RN   [23]
RP   X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
RX   MEDLINE=89159409; PubMed=2922050; DOI=10.1038/338225a0;
RA   Jones E.Y., Stuart D.I., Walker N.P.;
RT   "Structure of tumour necrosis factor.";
RL   Nature 338:225-228(1989).
RN   [24]
RP   X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
RX   MEDLINE=91193276; PubMed=1964681;
RA   Jones E.Y., Stuart D.I., Walker N.P.;
RT   "The structure of tumour necrosis factor -- implications for
RT   biological function.";
RL   J. Cell Sci. Suppl. 13:11-18(1990).
RN   [25]
RP   X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
RX   MEDLINE=90008932; PubMed=2551905;
RA   Eck M.J., Sprang S.R.;
RT   "The structure of tumor necrosis factor-alpha at 2.6-A resolution.
RT   Implications for receptor binding.";
RL   J. Biol. Chem. 264:17595-17605(1989).
RN   [26]
RP   X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT ARG-107.
RX   MEDLINE=98147459; PubMed=9488135; DOI=10.1093/protein/10.10.1101;
RA   Reed C., Fu Z.Q., Wu J., Xue Y.N., Harrison R.W., Chen M.J.,
RA   Weber I.T.;
RT   "Crystal structure of TNF-alpha mutant R31D with greater affinity for
RT   receptor R1 compared with R2.";
RL   Protein Eng. 10:1101-1107(1997).
RN   [27]
RP   X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF MUTANT SER-3.
RX   MEDLINE=98113178; PubMed=9442056; DOI=10.1074/jbc.273.4.2153;
RA   Cha S.S., Kim J.S., Cho H.S., Shin N.K., Jeong W., Shin H.C.,
RA   Kim Y.J., Hahn J.H., Oh B.H.;
RT   "High resolution crystal structure of a human tumor necrosis factor-
RT   alpha mutant with low systemic toxicity.";
RL   J. Biol. Chem. 273:2153-2160(1998).
RN   [28]
RP   INVOLVEMENT IN PSORIATIC ARTHRITIS SUSCEPTIBILITY.
RX   PubMed=12746914; DOI=10.1002/art.10935;
RA   Balding J., Kane D., Livingstone W., Mynett-Johnson L., Bresnihan B.,
RA   Smith O., FitzGerald O.;
RT   "Cytokine gene polymorphisms: association with psoriatic arthritis
RT   susceptibility and severity.";
RL   Arthritis Rheum. 48:1408-1413(2003).
RN   [29]
RP   INVOLVEMENT IN SUSCEPTIBILITY TO HBV INFECTION.
RX   PubMed=12915457; DOI=10.1093/hmg/ddg262;
RA   Kim Y.J., Lee H.-S., Yoon J.-H., Kim C.Y., Park M.H., Kim L.H.,
RA   Park B.L., Shin H.D.;
RT   "Association of TNF-alpha promoter polymorphisms with the clearance of
RT   hepatitis B virus infection.";
RL   Hum. Mol. Genet. 12:2541-2546(2003).
CC   -!- FUNCTION: Cytokine that binds to TNFRSF1A/TNFR1 and
CC       TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can
CC       induce cell death of certain tumor cell lines. It is potent
CC       pyrogen causing fever by direct action or by stimulation of
CC       interleukin-1 secretion and is implicated in the induction of
CC       cachexia, Under certain conditions it can stimulate cell
CC       proliferation and induce cell differentiation.
CC   -!- SUBUNIT: Homotrimer.
CC   -!- INTERACTION:
CC       P19438:TNFRSF1A; NbExp=1; IntAct=EBI-359977, EBI-299451;
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane
CC       protein.
CC   -!- SUBCELLULAR LOCATION: Tumor necrosis factor, soluble form:
CC       Secreted.
CC   -!- PTM: The soluble form derives from the membrane form by
CC       proteolytic processing.
CC   -!- PTM: The membrane form, but not the soluble form, is
CC       phosphorylated on serine residues. Dephosphorylation of the
CC       membrane form occurs by binding to soluble TNFRSF1A/TNFR1.
CC   -!- PTM: O-glycosylated; glycans contain galactose, N-
CC       acetylgalactosamine and N-acetylneuraminic acid.
CC   -!- POLYMORPHISM: Genetic variations in TNF influence susceptibility
CC       to hepatitis B virus (HBV) infection [MIM:610424].
CC   -!- DISEASE: Genetic variations in TNF are a cause of susceptibility
CC       psoriatic arthritis (PSORAS) [MIM:607507]. PSORAS is an
CC       inflammatory, seronegative arthritis associated with psoriasis. It
CC       is a heterogeneous disorder ranging from a mild, non-destructive
CC       disease to a severe, progressive, erosive arthropathy. Five types
CC       of psoriatic arthritis have been defined: asymmetrical
CC       oligoarthritis characterized by primary involvement of the small
CC       joints of the fingers or toes; asymmetrical arthritis which
CC       involves the joints of the extremities; symmetrical polyarthritis
CC       characterized by a rheumatoidlike pattern that can involve hands,
CC       wrists, ankles, and feet; arthritis mutilans, which is a rare but
CC       deforming and destructive condition; arthritis of the sacroiliac
CC       joints and spine (psoriatic spondylitis).
CC   -!- SIMILARITY: Belongs to the tumor necrosis factor family.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAF71992.1; Type=Frameshift; Positions=91, 157;
CC       Sequence=CAA75070.1; Type=Erroneous gene model prediction;
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Tumor necrosis factor alpha
CC       entry;
CC       URL="http://en.wikipedia.org/wiki/Tumor_necrosis_factor-alpha";
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC       and Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/TNFaID319.html";
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/tnf/";
CC   -!- WEB RESOURCE: Name=SeattleSNPs;
CC       URL="http://pga.gs.washington.edu/data/tnf/";
CC   -!- WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and
CC       polymorphism database;
CC       URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=TNF";
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DR   EMBL; M16441; AAA61200.1; -; Genomic_DNA.
DR   EMBL; X02910; CAA26669.1; -; Genomic_DNA.
DR   EMBL; X01394; CAA25650.1; -; mRNA.
DR   EMBL; M10988; AAA61198.1; -; mRNA.
DR   EMBL; M26331; AAA36758.1; -; Genomic_DNA.
DR   EMBL; Z15026; CAA78745.1; -; Genomic_DNA.
DR   EMBL; Y14768; CAA75070.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; AF129756; AAD18091.1; -; Genomic_DNA.
DR   EMBL; BA000025; BAB63396.1; -; Genomic_DNA.
DR   EMBL; AB088112; BAC54944.1; -; Genomic_DNA.
DR   EMBL; AY066019; AAL47581.1; -; Genomic_DNA.
DR   EMBL; AY214167; AAO21132.1; -; Genomic_DNA.
DR   EMBL; BC028148; AAH28148.1; -; mRNA.
DR   EMBL; AF043342; AAC03542.1; -; mRNA.
DR   EMBL; AF098751; AAF71992.1; ALT_FRAME; mRNA.
DR   IPI; IPI00001671; -.
DR   PIR; A93585; QWHUN.
DR   RefSeq; NP_000585.2; NM_000594.2.
DR   UniGene; Hs.241570; -.
DR   PDB; 1A8M; X-ray; 2.30 A; A/B/C=77-233.
DR   PDB; 1TNF; X-ray; 2.60 A; A/B/C=77-233.
DR   PDB; 2AZ5; X-ray; 2.10 A; A/B/C/D=86-233.
DR   PDB; 2E7A; X-ray; 1.80 A; A/B/C=77-233.
DR   PDB; 2TUN; X-ray; 3.10 A; A/B/C/D/E/F=77-233.
DR   PDB; 2ZJC; X-ray; 2.50 A; A/B/C=77-233.
DR   PDB; 2ZPX; X-ray; 2.83 A; A/B/C=77-233.
DR   PDB; 3ALQ; X-ray; 3.00 A; A/B/C/D/E/F=77-233.
DR   PDB; 3IT8; X-ray; 2.80 A; A/B/C/G/H/I=82-233.
DR   PDB; 3L9J; X-ray; 2.10 A; T=85-233.
DR   PDB; 4TSV; X-ray; 1.80 A; A=84-233.
DR   PDB; 5TSW; X-ray; 2.50 A; A/B/C/D/E/F=84-233.
DR   PDBsum; 1A8M; -.
DR   PDBsum; 1TNF; -.
DR   PDBsum; 2AZ5; -.
DR   PDBsum; 2E7A; -.
DR   PDBsum; 2TUN; -.
DR   PDBsum; 2ZJC; -.
DR   PDBsum; 2ZPX; -.
DR   PDBsum; 3ALQ; -.
DR   PDBsum; 3IT8; -.
DR   PDBsum; 3L9J; -.
DR   PDBsum; 4TSV; -.
DR   PDBsum; 5TSW; -.
DR   ProteinModelPortal; P01375; -.
DR   SMR; P01375; 85-233.
DR   DIP; DIP-2895N; -.
DR   IntAct; P01375; 32.
DR   MINT; MINT-1131842; -.
DR   STRING; P01375; -.
DR   GlycoSuiteDB; P01375; -.
DR   PRIDE; P01375; -.
DR   Ensembl; ENST00000376122; ENSP00000365290; ENSG00000204490.
DR   Ensembl; ENST00000383496; ENSP00000372988; ENSG00000206439.
DR   Ensembl; ENST00000412275; ENSP00000392858; ENSG00000228321.
DR   Ensembl; ENST00000420425; ENSP00000410668; ENSG00000228849.
DR   Ensembl; ENST00000443707; ENSP00000389492; ENSG00000230108.
DR   Ensembl; ENST00000448781; ENSP00000389490; ENSG00000223952.
DR   Ensembl; ENST00000449264; ENSP00000398698; ENSG00000232810.
DR   GeneID; 7124; -.
DR   KEGG; hsa:7124; -.
DR   UCSC; uc003nui.1; human.
DR   CTD; 7124; -.
DR   GeneCards; GC06P031330; -.
DR   HGNC; HGNC:11892; TNF.
DR   MIM; 191160; gene.
DR   MIM; 607507; phenotype.
DR   MIM; 610424; phenotype.
DR   neXtProt; NX_P01375; -.
DR   Orphanet; 40050; Adult psoriatic arthritis.
DR   eggNOG; prNOG05738; -.
DR   HOGENOM; HBG125617; -.
DR   HOVERGEN; HBG012516; -.
DR   InParanoid; P01375; -.
DR   OMA; KAGGPQG; -.
DR   OrthoDB; EOG4JWVFT; -.
DR   PhylomeDB; P01375; -.
DR   Pathway_Interaction_DB; amb2_neutrophils_pathway; amb2 Integrin signaling.
DR   Pathway_Interaction_DB; angiopoietinreceptor_pathway; Angiopoietin receptor Tie2-mediated signaling.
DR   Pathway_Interaction_DB; nfat_tfpathway; Calcineurin-regulated NFAT-dependent transcription in lymphocytes.
DR   Pathway_Interaction_DB; nfkappabcanonicalpathway; Canonical NF-kappaB pathway.
DR   Pathway_Interaction_DB; caspase_pathway; Caspase cascade in apoptosis.
DR   Pathway_Interaction_DB; anthraxpathway; Cellular roles of Anthrax toxin.
DR   Pathway_Interaction_DB; ceramidepathway; Ceramide signaling pathway.
DR   Pathway_Interaction_DB; cd8tcrdownstreampathway; Downstream signaling in naive CD8+ T cells.
DR   Pathway_Interaction_DB; hivnefpathway; HIV-1 Nef: Negative effector of Fas and TNF-alpha.
DR   Pathway_Interaction_DB; il23pathway; IL23-mediated signaling events.
DR   Pathway_Interaction_DB; il27pathway; IL27-mediated signaling events.
DR   Pathway_Interaction_DB; rxr_vdr_pathway; RXR and RAR hetrodimerization with other nuclear receptor.
DR   Pathway_Interaction_DB; hdac_classi_pathway; Signaling events mediated by HDAC Class I.
DR   Pathway_Interaction_DB; tnfpathway; TNF receptor signaling pathway.
DR   Reactome; REACT_578; Apoptosis.
DR   DrugBank; DB00051; Adalimumab.
DR   DrugBank; DB00640; Adenosine.
DR   DrugBank; DB01427; Amrinone.
DR   DrugBank; DB01076; Atorvastatin.
DR   DrugBank; DB00608; Chloroquine.
DR   DrugBank; DB01407; Clenbuterol.
DR   DrugBank; DB00005; Etanercept.
DR   DrugBank; DB01296; Glucosamine.
DR   DrugBank; DB00065; Infliximab.
DR   DrugBank; DB00704; Naltrexone.
DR   DrugBank; DB01411; Pranlukast.
DR   DrugBank; DB01366; Procaterol.
DR   DrugBank; DB01232; Saquinavir.
DR   DrugBank; DB00641; Simvastatin.
DR   DrugBank; DB01041; Thalidomide.
DR   NextBio; 27879; -.
DR   PMAP-CutDB; P01375; -.
DR   CleanEx; HS_TNF; -.
DR   Genevestigator; P01375; -.
DR   GermOnline; ENSG00000204490; Homo sapiens.
DR   GO; GO:0009897; C:external side of plasma membrane; ISS:BHF-UCL.
DR   GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR   GO; GO:0005887; C:integral to plasma membrane; IDA:BHF-UCL.
DR   GO; GO:0045121; C:membrane raft; IDA:BHF-UCL.
DR   GO; GO:0001891; C:phagocytic cup; ISS:BHF-UCL.
DR   GO; GO:0055037; C:recycling endosome; ISS:BHF-UCL.
DR   GO; GO:0005125; F:cytokine activity; IDA:BHF-UCL.
DR   GO; GO:0042802; F:identical protein binding; IDA:BHF-UCL.
DR   GO; GO:0010843; F:promoter binding; IDA:UniProtKB.
DR   GO; GO:0016563; F:transcription activator activity; IDA:UniProtKB.
DR   GO; GO:0016564; F:transcription repressor activity; IDA:UniProtKB.
DR   GO; GO:0005164; F:tumor necrosis factor receptor binding; IDA:BHF-UCL.
DR   GO; GO:0006919; P:activation of caspase activity; IDA:BHF-UCL.
DR   GO; GO:0000187; P:activation of MAPK activity; IDA:BHF-UCL.
DR   GO; GO:0000185; P:activation of MAPKKK activity; IDA:BHF-UCL.
DR   GO; GO:0006916; P:anti-apoptosis; IDA:BHF-UCL.
DR   GO; GO:0002439; P:chronic inflammatory response to antigenic stimulus; IMP:BHF-UCL.
DR   GO; GO:0060555; P:induction of necroptosis by extracellular signals; IDA:BHF-UCL.
DR   GO; GO:0050901; P:leukocyte tethering or rolling; IDA:BHF-UCL.
DR   GO; GO:0070265; P:necrotic cell death; IDA:BHF-UCL.
DR   GO; GO:0061048; P:negative regulation of branching involved in lung morphogenesis; IDA:UniProtKB.
DR   GO; GO:0002740; P:negative regulation of cytokine secretion involved in immune response; IDA:BHF-UCL.
DR   GO; GO:0045599; P:negative regulation of fat cell differentiation; NAS:BHF-UCL.
DR   GO; GO:0032582; P:negative regulation of gene-specific transcription; IDA:UniProtKB.
DR   GO; GO:0032715; P:negative regulation of interleukin-6 production; IDA:BHF-UCL.
DR   GO; GO:0050995; P:negative regulation of lipid catabolic process; IDA:BHF-UCL.
DR   GO; GO:0010888; P:negative regulation of lipid storage; NAS:BHF-UCL.
DR   GO; GO:0045071; P:negative regulation of viral genome replication; IDA:BHF-UCL.
DR   GO; GO:0060559; P:positive regulation of calcidiol 1-monooxygenase activity; IDA:BHF-UCL.
DR   GO; GO:0045080; P:positive regulation of chemokine biosynthetic process; IDA:BHF-UCL.
DR   GO; GO:0032722; P:positive regulation of chemokine production; IDA:BHF-UCL.
DR   GO; GO:0050715; P:positive regulation of cytokine secretion; IDA:BHF-UCL.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; NAS:BHF-UCL.
DR   GO; GO:0031622; P:positive regulation of fever generation; ISS:BHF-UCL.
DR   GO; GO:0043193; P:positive regulation of gene-specific transcription; IDA:UniProtKB.
DR   GO; GO:0034116; P:positive regulation of heterotypic cell-cell adhesion; IDA:BHF-UCL.
DR   GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IDA:BHF-UCL.
DR   GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IDA:BHF-UCL.
DR   GO; GO:0042346; P:positive regulation of NF-kappaB import into nucleus; IDA:BHF-UCL.
DR   GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR   GO; GO:0051533; P:positive regulation of NFAT protein import into nucleus; IDA:MGI.
DR   GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IDA:BHF-UCL.
DR   GO; GO:0045672; P:positive regulation of osteoclast differentiation; IDA:BHF-UCL.
DR   GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR   GO; GO:0031334; P:positive regulation of protein complex assembly; IDA:BHF-UCL.
DR   GO; GO:0043243; P:positive regulation of protein complex disassembly; IDA:BHF-UCL.
DR   GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IDA:BHF-UCL.
DR   GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IGI:MGI.
DR   GO; GO:0060557; P:positive regulation of vitamin D biosynthetic process; IDA:BHF-UCL.
DR   GO; GO:0000060; P:protein import into nucleus, translocation; IDA:UniProtKB.
DR   GO; GO:0032800; P:receptor biosynthetic process; IDA:BHF-UCL.
DR   GO; GO:0050796; P:regulation of insulin secretion; IDA:BHF-UCL.
DR   GO; GO:0051384; P:response to glucocorticoid stimulus; IDA:BHF-UCL.
DR   GO; GO:0009651; P:response to salt stress; TAS:BHF-UCL.
DR   GO; GO:0009615; P:response to virus; IDA:BHF-UCL.
DR   GO; GO:0030730; P:sequestering of triglyceride; IDA:BHF-UCL.
DR   GO; GO:0006927; P:transformed cell apoptosis; IDA:BHF-UCL.
DR   GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IMP:BHF-UCL.
DR   InterPro; IPR006053; TNF_a/b/c.
DR   InterPro; IPR002959; TNF_alpha.
DR   InterPro; IPR021184; TNF_CS.
DR   InterPro; IPR006052; TNF_family.
DR   InterPro; IPR008983; Tumour_necrosis_fac-like.
DR   Gene3D; G3DSA:2.60.120.40; Tumour_necrosis_fac-like; 1.
DR   Pfam; PF00229; TNF; 1.
DR   PRINTS; PR01234; TNECROSISFCT.
DR   PRINTS; PR01235; TNFALPHA.
DR   SMART; SM00207; TNF; 1.
DR   SUPFAM; SSF49842; TNF_like; 1.
DR   PROSITE; PS00251; TNF_1; 1.
DR   PROSITE; PS50049; TNF_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; Complete proteome; Cytokine;
KW   Direct protein sequencing; Disulfide bond; Glycoprotein; Lipoprotein;
KW   Membrane; Myristate; Phosphoprotein; Polymorphism; Secreted;
KW   Signal-anchor; Transmembrane; Transmembrane helix.
FT   CHAIN         1    233       Tumor necrosis factor, membrane form.
FT                                /FTId=PRO_0000034423.
FT   CHAIN        77    233       Tumor necrosis factor, soluble form.
FT                                /FTId=PRO_0000034424.
FT   TOPO_DOM      1     35       Cytoplasmic (Potential).
FT   TRANSMEM     36     56       Helical; Signal-anchor for type II
FT                                membrane protein; (Potential).
FT   TOPO_DOM     57    233       Extracellular (Potential).
FT   SITE         76     77       Cleavage; by ADAM17.
FT   MOD_RES       2      2       Phosphoserine; by CK1.
FT   LIPID        19     19       N6-myristoyl lysine.
FT   LIPID        20     20       N6-myristoyl lysine.
FT   CARBOHYD     80     80       O-linked (GalNAc...); in soluble form.
FT   DISULFID    145    177
FT   VARIANT      84     84       P -> L (in dbSNP:rs4645843).
FT                                /FTId=VAR_019378.
FT   VARIANT      94     94       A -> T (in dbSNP:rs1800620).
FT                                /FTId=VAR_011927.
FT   MUTAGEN     105    105       L->S: Low activity.
FT   MUTAGEN     108    108       R->W: Biologically inactive.
FT   MUTAGEN     112    112       L->F: Biologically inactive.
FT   MUTAGEN     160    160       A->V: Biologically inactive.
FT   MUTAGEN     162    162       S->F: Biologically inactive.
FT   MUTAGEN     167    167       V->A,D: Biologically inactive.
FT   MUTAGEN     222    222       E->K: Biologically inactive.
FT   CONFLICT     63     63       F -> S (in Ref. 5; AAA61198).
FT   CONFLICT     84     86       PSD -> VNR (in Ref. 17).
FT   CONFLICT    183    183       E -> R (in Ref. 16; AAC03542).
FT   STRAND      106    108
FT   STRAND      121    125
FT   STRAND      130    144
FT   STRAND      152    159
FT   STRAND      161    163
FT   STRAND      167    174
FT   STRAND      177    179
FT   STRAND      183    185
FT   STRAND      189    202
FT   STRAND      207    213
FT   HELIX       215    217
FT   STRAND      223    229
SQ   SEQUENCE   233 AA;  25644 MW;  3DF90F96C9031FFE CRC64;
     MSTESMIRDV ELAEEALPKK TGGPQGSRRC LFLSLFSFLI VAGATTLFCL LHFGVIGPQR
     EEFPRDLSLI SPLAQAVRSS SRTPSDKPVA HVVANPQAEG QLQWLNRRAN ALLANGVELR
     DNQLVVPSEG LYLIYSQVLF KGQGCPSTHV LLTHTISRIA VSYQTKVNLL SAIKSPCQRE
     TPEGAEAKPW YEPIYLGGVF QLEKGDRLSA EINRPDYLDF AESGQVYFGI IAL
//
