Tumor necrosis factor superfamily

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Tumor necrosis factor superfamily
Mouse Tumor Necrosis Factor Alpha.png
Trimeric structure of TNF alpha, produced by Mus musculus, based on PDB structure 2TNF (1.4 Å Resolution). Different colors represent different monomers. Baeyens, KJ et al. (1999).[1] Figure rendered using FirstGlance Jmol.
OPM superfamily292
OPM protein2hew
Available protein structures:
Pfam  structures / ECOD  
PDBsumstructure summary
PDB 1du3 EBI.jpg
crystal structure of trail-sdr5
Pfam clanCL0100
Available protein structures:
Pfam  structures / ECOD  
PDBsumstructure summary

The tumor necrosis factor (TNF) superfamily is a protein superfamily of type II transmembrane proteins containing TNF homology domain and forming trimers. Members of this superfamily can be released from the cell membrane by extracellular proteolytic cleavage and function as a cytokine. These proteins are expressed predominantly by immune cells and they regulate diverse cell functions, including immune response and inflammation, but also proliferation, differentiation, apoptosis and embryogenesis.[2][3]

The superfamily contains 19 members that bind to 29 members of TNF receptor superfamily.[4] An occurrence of orthologs in invertebrates hints at ancient origin of this superfamily in evolution.[2]

The PROSITE pattern of this superfamily is located in a beta sheet in the central section of the protein that is conserved across all members.


There are 19 family members, numerically classified as TNFSF#, where # denotes the member number, sometimes followed by a letter.[4][2]

TNFSF# Name Synonyms Gene Function
1 Lymphotoxin alpha TNFβ, TNFSF1B LTA Induction of inflammation and antiviral response, development of secondary lymphoid organs, role in tumorigenesis
2 Tumor necrosis factor TNFα, Dif, Necrosin, TNFSF1A, ... TNF Regulation of immune cells, induction of fever, cachexia, inflammation and apoptosis, inhibition of tumorigenesis and viral replication and response to sepsis
3 Lymphotoxin beta TNFγ LTB Induction of inflammation and antiviral response, development of secondary lymphoid organs, role in tumorigenesis
4 OX40 ligand CD252, Gp34, CD134L TNFSF4 Activation of T cell immune response by T cell costimulation
5 CD40 ligand CD154, TRAP, Gp39, T-BAM CD40LG Regulation of adaptive immune response by activating antigen-presenting cell
6 Fas ligand CD178, APTL, CD95L FASLG Regulation of T cell homeostasis by induction of apoptosis
7 CD27 ligand CD70 CD70 Regulation of B cell activation and T cell homeostasis
8 CD30 ligand CD153 TNFSF8 Induction of apoptosis of T cells and B cells, prevention of autoimmunity
9 CD137 ligand 4-1 BBL TNFSF9
10 TNF-related apoptosis-inducing ligand CD253, APO-2L TNFSF10 Inhibition of tumorigenesis, induction of apoptosis
11 Receptor activator of nuclear factor kappa-Β ligand CD254, OPGL, TRANCE, ODF TNFSF11 Tissue growth (particularly bone regeneration and remodeling), dendritic cell maturation
12 TNF-related weak inducer of apoptosis APO-3L, DR3L TNFSF12 Regulation of angiogenesis, induction of apoptosis
13 A proliferation-inducing ligand CD256, TALL-2, TRDL1 TNFSF13 Regulation of B cell development and plasma cell survival
13B B-cell activating factor CD257, BLyS, TALL-1, TNFSF20, ... TNFSF13B Stimulation of B cell proliferation and differentiation
14 LIGHT CD258, HVEML TNFSF14 Stimulation of T cell proliferation, apoptosis regulation
15 Vascular endothelial growth inhibitor TL1, TL-1A TNFSF15 Inhibition of angiogenesis
18 TNF superfamily member 18 GITRL, AITRL, TL-6 TNFSF18 Regulation of T cell survival
19 Ectodysplasin A ED1-A1, ED1-A2 EDA Development of ectodermal tissues


  1. ^ Baeyens KJ, De Bondt HL, Raeymaekers A, Fiers W, De Ranter CJ (April 1999). "The structure of mouse tumour-necrosis factor at 1.4 A resolution: towards modulation of its selectivity and trimerization". Acta Crystallographica Section D. 55 (Pt 4): 772–8. doi:10.1107/s0907444998018435. PMID 10089307.
  2. ^ a b c The evolution of the immune system: conservation and diversification. Amsterdam: Elsevier. 2016. ISBN 978-0-12-801975-7. OCLC 950694824.
  3. ^ Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology (Ninth ed.). Philadelphia, PA. ISBN 978-0-323-47978-3. OCLC 973917896.
  4. ^ a b Aggarwal BB, Gupta SC, Kim JH (January 2012). "Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey". Blood. 119 (3): 651–65. doi:10.1182/blood-2011-04-325225. PMC 3265196. PMID 22053109.
This article incorporates text from the public domain Pfam and InterPro: IPR006052

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