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438  structures 307  species 0  interactions 3723  sequences 26  architectures

Family: TNF (PF00229)

Summary: TNF(Tumour Necrosis Factor) family

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This is the Wikipedia entry entitled "Tumor necrosis factors". More...

Tumor necrosis factors Edit Wikipedia article

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TNF(Tumour Necrosis Factor) family Provide feedback

No Pfam abstract.

Literature references

  1. Copley RR; , J Mol Med 1999;77:361-363.: The gene for X-linked anhidrotic ectodermal dysplasia encodes a TNF- like domain. PUBMED:10353440 EPMC:10353440

Internal database links

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.

The following 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 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.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan C1q_TNF (CL0100), which has the following description:

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 [1]. 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[1].

The clan contains the following 7 members:

BclA_C C1q Chlam_vir DUF1860 DUF3845 Phage_tail_NK TNF


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

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Representative proteomes UniProt

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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

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HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD
Number in seed: 27
Number in full: 3723
Average length of the domain: 122.90 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 46.34 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.4 21.4
Trusted cut-off 21.4 21.5
Noise cut-off 21.3 21.3
Model length: 127
Family (HMM) version: 20
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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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 438 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 sequence.

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