Summary: TNF(Tumour Necrosis Factor) family
This is the Wikipedia entry entitled "Tumor necrosis factors". More...
Does Pfam agree with the content of the Wikipedia entry ?
Editing Wikipedia articles
Before you edit for the first time
You should take a few minutes to view the following pages:
How your contribution will be recorded
Tumor necrosis factors Edit Wikipedia article
|TNF (Tumor Necrosis Factor) family|
crystal structure of trail-sdr5
- Tumor necrosis factor (TNF), formerly known as TNFÎ± or TNF alpha, is the best-known member of this class. TNF is a monocyte-derived cytotoxin that has been implicated in tumor regression, septic shock, and cachexia. The protein is synthesized as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine. A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers. Both the mature protein and a partially processed form of the hormone can be secreted after cleavage of the propeptide.
- Lymphotoxin-alpha, formerly known as Tumor necrosis factor-beta (TNF-Î²), is a cytokine that is inhibited by interleukin 10.
- Tumor Necrosis Factor (TNF) (also known as cachectin  or TNF alpha) is a cytokine that has a wide variety of functions. It can cause cytolysis of certain tumor cell lines; it is involved in the induction of cachexia; it is a potent pyrogen, causing fever by direct action or by stimulation of interleukin-1 secretion; it can stimulate cell proliferation and induce cell differentiation under certain conditions.
- Lymphotoxin-alpha (LT-alpha) and lymphotoxin-beta (LT-beta), two related cytokines produced by lymphocytes that are cytotoxic for a wide range of tumor cells in vitro and in vivo.
- T cell antigen gp39 (CD40L), a cytokine that seems to be important in B-cell development and activation.
- CD27L, a cytokine that plays a role in T-cell activation. It induces the proliferation of co-stimulated T cells and enhances the generation of cytolytic T cells.
- CD30L, a cytokine that induces proliferation of T cells.
- FASL, a cell surface protein involved in cell death.
- 4-1BBL, an inducible T cell surface molecule that contributes to T-cell stimulation.
- OX40L, a cell surface protein that co-stimulates T cell proliferation and cytokine production.
- TNF-related apoptosis inducing ligand (TRAIL), a cytokine that induces apoptosis.
All these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognized by their specific receptors. Strong hydrogen bonds between the monomers stabilize the tertiary structure. One such example is the Asn34-Arg82 hydrogen bond in the M. musculus TNF alpha. The PROSITE pattern for this family is located in a beta-strand in the central section of the protein that is conserved across all members.
All members of the TNF family, with the exception of the secreted lymphotoxin and a proliferation-inducing ligand (APRIL), are type II transmembrane proteins that protrude from immune cells. Such membrane-bound TNF ligands frequently signal back to the immune cells when they contact and bind their cognate receptors on other cells.
Human proteins containing this domain include:
- CD40LG (TNFSF5); CD70 (TNFSF7); EDA; FASLG (TNFSF6); LTA (TNFSF1); LTB (TNFSF3);
- TNFSF4 (OX40L); TNFSF8 (CD153); TNFSF9; TNFSF10 (TRAIL); TNFSF11 (RANKL); TNFSF12 (TWEAK); TNFSF13; TNFSF13B; TNFSF14; TNFSF15; TNFSF18;
Notes and references
- Baeyens KJ, De Bondt HL, Raeymaekers A, Fiers W, De Ranter CJ (April 1999). "The structure of mouse tumour-necrosis factor at 1.4 Ã… resolution: towards modulation of its selectivity and trimerization". Acta Crystallogr. D Biol. Crystallogr. 55 (Pt 4): 772â€“8. doi:10.1107/s0907444998018435. PMID 10089307.
- Fransen L, MÃ¼ller R, Marmenout A, Tavernier J, Van der Heyden J, Kawashima E, Chollet A, Tizard R, Van Heuverswyn H, Van Vliet A (June 1985). "Molecular cloning of mouse tumour necrosis factor cDNA and its eukaryotic expression". Nucleic Acids Res. 13 (12): 4417â€“29. doi:10.1093/nar/13.12.4417. PMC 321797. PMID 2989794.
- Kriegler M, Perez C, DeFay K, Albert I, Lu SD (April 1988). "A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF". Cell 53 (1): 45â€“53. doi:10.1016/0092-8674(88)90486-2. PMID 3349526.
- Sherry B, Jue DM, Zentella A, Cerami A (December 1990). "Characterization of high molecular weight glycosylated forms of murine tumor necrosis factor". Biochem. Biophys. Res. Commun. 173 (3): 1072â€“8. doi:10.1016/S0006-291X(05)80895-2. PMID 2268312.
- Cseh K, Beutler B (September 1989). "Alternative cleavage of the cachectin/tumor necrosis factor propeptide results in a larger, inactive form of secreted protein". J. Biol. Chem. 264 (27): 16256â€“60. PMID 2777790.
- Waltenbaugh C, Doan T, Melvold R, Viselli S (2008). Immunology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 68. ISBN 0-7817-9543-5.
- Sun M, Fink PJ (2007). "A new class of reverse signaling costimulators belongs to the TNF family". J Immunol. 179 (7): 4307â€“12. doi:10.4049/jimmunol.179.7.4307. PMID 17878324.
- Peitsch MC, Jongeneel CV (February 1993). "A 3-D model for the CD40 ligand predicts that it is a compact trimer similar to the tumor necrosis factors". Int. Immunol. 5 (2): 233â€“8. doi:10.1093/intimm/5.2.233. PMID 8095800.
- Farrah T, Smith CA (July 1992). "Emerging cytokine family". Nature 358 (6381): 26. doi:10.1038/358026b0. PMID 1377364.
- Bazan JF (September 1993). "Emerging families of cytokines and receptors". Curr. Biol. 3 (9): 603â€“6. doi:10.1016/0960-9822(93)90009-D. PMID 15335677.
- D. CAPUT, et al., Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators, Proc. Natl. Acad. Sci. USA 83:1670-1674 Biochemistry, 1986 and references cited)
- Beutler B, Cerami A (October 1988). "The history, properties, and biological effects of cachectin". Biochemistry 27 (20): 7575â€“82. doi:10.1021/bi00420a001. PMID 3061461.
- Vilcek J, Lee TH (April 1991). "Tumor necrosis factor. New insights into the molecular mechanisms of its multiple actions". J. Biol. Chem. 266 (12): 7313â€“6. PMID 1850405.
- Browning JL, Ngam-ek A, Lawton P, DeMarinis J, Tizard R, Chow EP, Hession C, O'Brine-Greco B, Foley SF, Ware CF (March 1993). "Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface". Cell 72 (6): 847â€“56. doi:10.1016/0092-8674(93)90574-A. PMID 7916655.
- Suda T, Takahashi T, Golstein P, Nagata S (December 1993). "Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family". Cell 75 (6): 1169â€“78. doi:10.1016/0092-8674(93)90326-L. PMID 7505205.
- Baum PR, Gayle RB, Ramsdell F, Srinivasan S, Sorensen RA, Watson ML, Seldin MF, Baker E, Sutherland GR, Clifford KN (September 1994). "Molecular characterization of murine and human OX40/OX40 ligand systems: identification of a human OX40 ligand as the HTLV-1-regulated protein gp34". EMBO J. 13 (17): 3992â€“4001. PMC 395319. PMID 8076595.
- Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA (December 1995). "Identification and characterization of a new member of the TNF family that induces apoptosis". Immunity 3 (6): 673â€“82. doi:10.1016/1074-7613(95)90057-8. PMID 8777713.
- Tumor Necrosis Factors at the US National Library of Medicine Medical Subject Headings (MeSH)
- pex1 tumor necrosis factor gene
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
TNF(Tumour Necrosis Factor) family Provide feedback
No Pfam abstract.
Internal database links
|SCOOP:||C1q DUF553 Bact_transglu_N|
|Similarity to PfamA using HHSearch:||C1q|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR006052
Cytokines can be grouped into a family on the basis of sequence, functional and structural similarities [PUBMED:8095800, PUBMED:1377364, PUBMED:15335677]. Tumor necrosis factor (TNF) (also known as TNF-alpha or cachectin) is a monocyte-derived cytotoxin that has been implicated in tumour regression, septic shock and cachexia [PUBMED:2989794, PUBMED:3349526]. The protein is synthesised as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine [PUBMED:2268312]. A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers [PUBMED:2777790]. Both the mature protein and a partially-processed form of the hormone are secreted after cleavage of the propeptide [PUBMED:2777790].
There are a number of different families of TNF, but all these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognised by their specific receptors.
- Tumor Necrosis Factor (TNF) (also known as cachectin or TNF-alpha) [PUBMED:3061461, PUBMED:1850405] is a cytokine which has a wide variety of functions. It can cause cytolysis of certain tumor cell lines; it is involved in the induction of cachexia; it is a potent pyrogen, causing fever by direct action or by stimulation of interleukin-1 secretion; finally, it can stimulate cell proliferation and induce cell differentiation under certain conditions.
- Lymphotoxin-alpha (LT-alpha) and lymphotoxin-beta (LT-beta), two related cytokines produced by lymphocytes and which are cytotoxic for a wide range of tumor cells in vitro and in vivo [PUBMED:7916655].
- T cell antigen gp39 (CD40L), a cytokine which seems to be important in B-cell development and activation.
- CD27L, a cytokine which plays a role in T-cell activation. It induces the proliferation of costimulated T cells and enhances the generation of cytolytic T cells.
- CD30L, a cytokine which induces proliferation of T cells.
- FASL, a cytokine involved in cell death [PUBMED:7505205].
- 4-1BBL, a inducible T cell surface molecule that contributes to T-cell stimulation.
- OX40L, a cytokine that co-stimulates T cell proliferation and cytokine production [PUBMED:8076595].
- TNF-related apoptosis inducing ligand (TRAIL), a cytokine that induces apoptosis [PUBMED:8777713].
- TNF-alpha is synthesised as a type II membrane protein which then undergoes post-translational cleavage liberating the extracellular domain. CD27L, CD30L, CD40L, FASL, LT-beta, 4-1BBL and TRAIL also appear to be type II membrane proteins. LT-alpha is a secreted protein.
All these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognised by their specific receptors. The PROSITE pattern for this family is located in a beta-strand in the central section of the protein which is conserved across all members.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||membrane (GO:0016020)|
|Molecular function||tumor necrosis factor receptor binding (GO:0005164)|
|Biological process||immune response (GO:0006955)|
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Loading domain graphics...
The members of the C1q and TNF superfamily are involved in a diverse set of functions, which include: defense, inflammation, apoptosis, autoimmunity differentiation, organogenesis, hibernation and insulin-resistant obesity . Both C1q and TNF domains form a compact jelly-roll beta- sandwich. The core of these structures are conserved between the two families and corresponds to the detectable sequence similarity. Proteins containing both of these domains, form trimers before they are active. However, the surfaces of the domains are quite different and this difference is thought to give rise to the function difference between the clan members.
The clan contains the following 2 members:C1q TNF
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- Pfam viewer
- an HTML-based viewer that uses DAS to retrieve alignment fragments on request
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
If you find these logos useful in your own work, please consider citing the following article:
Note: You can also download the data file for the tree.
Curation and family details
|Number in seed:||28|
|Number in full:||1497|
|Average length of the domain:||121.60 aa|
|Average identity of full alignment:||23 %|
|Average coverage of the sequence by the domain:||48.95 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||14|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
How the sunburst is generated
Colouring and labels
Anomalies in the taxonomy tree
Missing taxonomic levels
Unmapped species names
Too many species/sequences
The tree shows the occurrence of this domain across different species. More...
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
There are 8 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the TNF domain has been found. There are 224 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
Loading structure mapping...