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56  structures 1188  species 0  interactions 11320  sequences 246  architectures

Family: MATH (PF00917)

Summary: MATH domain

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MATH domain Provide feedback

This motif has been called the Meprin And TRAF-Homology (MATH) domain. This domain is hugely expanded in the nematode C. elegans [3].

Literature references

  1. Uren AG, Vaux DL; , Trends Biochem Sci 1996;21:244-245.: TRAF proteins and meprins share a conserved domain. PUBMED:8755243 EPMC:8755243

  2. McWhirter SM, Pullen SS, Holton JM, Crute JJ, Kehry MR, Alber T; , Proc Natl Acad Sci U S A 1999;96:8408-8413.: Crystallographic analysis of CD40 recognition and signaling by human TRAF2. PUBMED:10411888 EPMC:10411888

  3. Chervitz SA, Aravind L, Sherlock G, Ball CA, Koonin EV, Dwight SS, Harris MA, Dolinski K, Mohr S, Smith T, Weng S, Cherry JM, Botstein D; , Science 1998;282:2022-2028.: Comparison of the complete protein sets of worm and yeast: orthology and divergence. PUBMED:9851918 EPMC:9851918

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002083

Although apparently functionally unrelated, intracellular TRAFs and extracellular meprins share a conserved region of about 180 residues, the meprin and TRAF homology (MATH) domain [ PUBMED:12387856 ]. Meprins are mammalian tissue-specific metalloendopeptidases of the astacin family implicated in developmental, normal and pathological processes by hydrolysing a variety of proteins. Various growth factors, cytokines, and extracellular matrix proteins are substrates for meprins. They are composed of five structural domains: an N-terminal endopeptidase domain, a MAM domain (see PROSITEDOC ), a MATH domain, an EGF-like domain (see PROSITEDOC ) and a C-terminal transmembrane region. Meprin A and B form membrane bound homotetramer whereas homooligomers of meprin A are secreted. A proteolitic site adjacent to the MATH domain, only present in meprin A, allows the release of the protein from the membrane [ PUBMED:7890660 ].

TRAF proteins were first isolated by their ability to interact with TNF receptors [ PUBMED:8069916 ]. They promote cell survival by the activation of downstream protein kinases and, finally, transcription factors of the NF-kB and AP-1 family. The TRAF proteins are composed of 3 structural domains: a RING finger (see PROSITEDOC ) in the N-terminal part of the protein, one to seven TRAF zinc fingers (see PROSITEDOC ) in the middle and the MATH domain in the C-terminal part [ PUBMED:12387856 ]. The MATH domain is necessary and sufficient for self-association and receptor interaction. From the structural analysis two consensus sequence recognised by the TRAF domain have been defined: a major one, [PSAT]x[QE]E and a minor one, PxQxxD [ PUBMED:10518213 ].

The structure of the TRAF2 protein reveals a trimeric self-association of the MATH domain [ PUBMED:10206649 ]. The domain forms a new, light-stranded antiparallel beta sandwich structure. A coiled-coil region adjacent to the MATH domain is also important for the trimerisation. The oligomerisation is essential for establishing appropriate connections to form signalling complexes with TNF receptor-1. The ligand binding surface of TRAF proteins is located in beta-strands 6 and 7 [ PUBMED:10518213 ].

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 TRAF (CL0389), which has the following description:

Superfamily has a circularly permuted immunoglobulin-fold topology with extra an extra beta-strand. Families include the Math and the SIAH, or Seven in absentia, members.

The clan contains the following 8 members:

AvrL567-A MATH Sina Toxin_ToxA TRAF6_Z2 zf-ACC zf-TRAF zf-TRAF_2


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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.

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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: Pfam-B_1602 (release 3.0)
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 33
Number in full: 11320
Average length of the domain: 118.90 aa
Average identity of full alignment: 21 %
Average coverage of the sequence by the domain: 21.13 %

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 21.2 13.7
Trusted cut-off 21.2 13.7
Noise cut-off 21.1 13.6
Model length: 113
Family (HMM) version: 28
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
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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 MATH domain has been found. There are 56 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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