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Identification
HMDB Protein ID HMDBP02070
Secondary Accession Numbers
  • 7551
Name Tumor necrosis factor
Synonyms
  1. Cachectin
  2. TNF-a
  3. TNF-alpha
  4. Tumor necrosis factor ligand superfamily member 2
  5. Tumor necrosis factor, membrane form
  6. Tumor necrosis factor, soluble form
Gene Name TNF
Protein Type Enzyme
Biological Properties
General Function Involved in tumor necrosis factor receptor binding
Specific 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
Pathways
  • Fc Epsilon Receptor I Signaling in Mast Cells
Reactions Not Available
GO Classification
Component
membrane
cell part
Function
binding
cytokine receptor binding
tumor necrosis factor receptor superfamily binding
tumor necrosis factor receptor binding
protein binding
receptor binding
Process
immune system process
immune response
Cellular Location
  1. Tumor necrosis factor
  2. soluble form:Secreted
Gene Properties
Chromosome Location Chromosome:6
Locus 6p21.3
SNPs TNF
Gene Sequence
>702 bp
ATGAGCACTGAAAGCATGATCCGGGACGTGGAGCTGGCCGAGGAGGCGCTCCCCAAGAAG
ACAGGGGGGCCCCAGGGCTCCAGGCGGTGCTTGTTCCTCAGCCTCTTCTCCTTCCTGATC
GTGGCAGGCGCCACCACGCTCTTCTGCCTGCTGCACTTTGGAGTGATCGGCCCCCAGAGG
GAAGAGTTCCCCAGGGACCTCTCTCTAATCAGCCCTCTGGCCCAGGCAGTCAGATCATCT
TCTCGAACCCCGAGTGACAAGCCTGTAGCCCATGTTGTAGCAAACCCTCAAGCTGAGGGG
CAGCTCCAGTGGCTGAACCGCCGGGCCAATGCCCTCCTGGCCAATGGCGTGGAGCTGAGA
GATAACCAGCTGGTGGTGCCATCAGAGGGCCTGTACCTCATCTACTCCCAGGTCCTCTTC
AAGGGCCAAGGCTGCCCCTCCACCCATGTGCTCCTCACCCACACCATCAGCCGCATCGCC
GTCTCCTACCAGACCAAGGTCAACCTCCTCTCTGCCATCAAGAGCCCCTGCCAGAGGGAG
ACCCCAGAGGGGGCTGAGGCCAAGCCCTGGTATGAGCCCATCTATCTGGGAGGGGTCTTC
CAGCTGGAGAAGGGTGACCGACTCAGCGCTGAGATCAATCGGCCCGACTATCTCGACTTT
GCCGAGTCTGGGCAGGTCTACTTTGGGATCATTGCCCTGTGA
Protein Properties
Number of Residues 233
Molecular Weight 25644.1
Theoretical pI 6.92
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 36-56
Protein Sequence
>Tumor necrosis factor
MSTESMIRDVELAEEALPKKTGGPQGSRRCLFLSLFSFLIVAGATTLFCLLHFGVIGPQR
EEFPRDLSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELR
DNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRE
TPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRPDYLDFAESGQVYFGIIAL
GenBank ID Protein 37220
UniProtKB/Swiss-Prot ID P01375
UniProtKB/Swiss-Prot Entry Name TNFA_HUMAN
PDB IDs
GenBank Gene ID X01394
GeneCard ID TNF
GenAtlas ID TNF
HGNC ID HGNC:11892
References
General References
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  2. Xie T, Rowen L, Aguado B, Ahearn ME, Madan A, Qin S, Campbell RD, Hood L: Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse. Genome Res. 2003 Dec;13(12):2621-36. [PubMed:14656967 ]
  3. Neville MJ, Campbell RD: 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. 1999 Apr 15;162(8):4745-54. [PubMed:10202016 ]
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  5. Pennica D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R, Palladino MA, Kohr WJ, Aggarwal BB, Goeddel DV: Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature. 1984 Dec 20-1985 Jan 2;312(5996):724-9. [PubMed:6392892 ]
  6. Shirai T, Yamaguchi H, Ito H, Todd CW, Wallace RB: Cloning and expression in Escherichia coli of the gene for human tumour necrosis factor. Nature. 1985 Feb 28-Mar 6;313(6005):803-6. [PubMed:3883195 ]
  7. Nedwin GE, Naylor SL, Sakaguchi AY, Smith D, Jarrett-Nedwin J, Pennica D, Goeddel DV, Gray PW: Human lymphotoxin and tumor necrosis factor genes: structure, homology and chromosomal localization. Nucleic Acids Res. 1985 Sep 11;13(17):6361-73. [PubMed:2995927 ]
  8. Wang AM, Creasey AA, Ladner MB, Lin LS, Strickler J, Van Arsdell JN, Yamamoto R, Mark DF: Molecular cloning of the complementary DNA for human tumor necrosis factor. Science. 1985 Apr 12;228(4696):149-54. [PubMed:3856324 ]
  9. Marmenout A, Fransen L, Tavernier J, Van der Heyden J, Tizard R, Kawashima E, Shaw A, Johnson MJ, Semon D, Muller R, et al.: Molecular cloning and expression of human tumor necrosis factor and comparison with mouse tumor necrosis factor. Eur J Biochem. 1985 Nov 4;152(3):515-22. [PubMed:3932069 ]
  10. Iris FJ, Bougueleret L, Prieur S, Caterina D, Primas G, Perrot V, Jurka J, Rodriguez-Tome P, Claverie JM, Dausset J, et al.: Dense Alu clustering and a potential new member of the NF kappa B family within a 90 kilobase HLA class III segment. Nat Genet. 1993 Feb;3(2):137-45. [PubMed:8499947 ]
  11. Takakura-Yamamoto R, Yamamoto S, Fukuda S, Kurimoto M: O-glycosylated species of natural human tumor-necrosis factor-alpha. Eur J Biochem. 1996 Jan 15;235(1-2):431-7. [PubMed:8631363 ]
  12. Pocsik E, Duda E, Wallach D: Phosphorylation of the 26 kDa TNF precursor in monocytic cells and in transfected HeLa cells. J Inflamm. 1995;45(3):152-60. [PubMed:8597870 ]
  13. Watts AD, Hunt NH, Wanigasekara Y, Bloomfield G, Wallach D, Roufogalis BD, 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. 1999 Apr 15;18(8):2119-26. [PubMed:10205166 ]
  14. Van Ostade X, Tavernier J, Prange T, Fiers W: Localization of the active site of human tumour necrosis factor (hTNF) by mutational analysis. EMBO J. 1991 Apr;10(4):827-36. [PubMed:2009860 ]
  15. Stevenson FT, Bursten SL, Locksley RM, Lovett DH: Myristyl acylation of the tumor necrosis factor alpha precursor on specific lysine residues. J Exp Med. 1992 Oct 1;176(4):1053-62. [PubMed:1402651 ]
  16. Moss ML, Jin SL, Milla ME, Bickett DM, Burkhart W, Carter HL, Chen WJ, Clay WC, Didsbury JR, Hassler D, Hoffman CR, Kost TA, Lambert MH, Leesnitzer MA, McCauley P, McGeehan G, Mitchell J, Moyer M, Pahel G, Rocque W, Overton LK, Schoenen F, Seaton T, Su JL, Becherer JD, et al.: Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Nature. 1997 Feb 20;385(6618):733-6. [PubMed:9034191 ]
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  18. Jones EY, Stuart DI, Walker NP: The structure of tumour necrosis factor--implications for biological function. J Cell Sci Suppl. 1990;13:11-8. [PubMed:1964681 ]
  19. Eck MJ, Sprang SR: The structure of tumor necrosis factor-alpha at 2.6 A resolution. Implications for receptor binding. J Biol Chem. 1989 Oct 15;264(29):17595-605. [PubMed:2551905 ]
  20. Reed C, Fu ZQ, Wu J, Xue YN, Harrison RW, Chen MJ, Weber IT: Crystal structure of TNF-alpha mutant R31D with greater affinity for receptor R1 compared with R2. Protein Eng. 1997 Oct;10(10):1101-7. [PubMed:9488135 ]
  21. Cha SS, Kim JS, Cho HS, Shin NK, Jeong W, Shin HC, Kim YJ, Hahn JH, Oh BH: High resolution crystal structure of a human tumor necrosis factor-alpha mutant with low systemic toxicity. J Biol Chem. 1998 Jan 23;273(4):2153-60. [PubMed:9442056 ]
  22. 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. 2003 May;48(5):1408-13. [PubMed:12746914 ]
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