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PROSITE documentation PDOC50144

MATH/TRAF domain profile


Although apparently functionally unrelated, intracellular TRAFs and extracellular meprins share a conserved region of about 180 residues, the meprin and TRAF homology (MATH) domain [1].

Meprins are mammalian tissue-specific metalloendopeptidases of the astacin family implicated in developmental, normal and pathological processes by hydrolyzing 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 <PDOC00604>), a MATH domain, an EGF-like domain (see <PDOC00021>) 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 [2].

TRAF proteins were first isolated by their ability to interact with TNF receptors [3]. 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 <PDOC00449>) in the N-terminal part of the protein, one to seven TRAF zinc fingers (see <PDOC50145>) in the middle and the MATH domain in the C-terminal part [1]. The MATH domain is necessary and sufficient for self-association and receptor interaction. From the structural analysis two consensus sequence recognized by the TRAF domain have been defined: a major one, [PSAT]x[QE]E and a minor one, PxQxxD [4].

The structure of the TRAF2 protein reveals a trimeric self-association of the MATH domain (see <PDB:1CA4>) [5]. The domain forms a new, eight-stranded antiparallel β 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 signaling complexes with TNF receptor-1. The ligand binding surface of TRAF proteins is located in β-strands 6 and 7 [4].

The profile we developed covers the whole MATH domain.

Last update:

June 2003 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

MATH, PS50144; MATH/TRAF domain profile  (MATRIX)


1AuthorsSunnerhagen M. Pursglove S. Fladvad M.
TitleThe new MATH: homology suggests shared binding surfaces in meprin tetramers and TRAF trimers.
SourceFEBS Lett. 530:1-3(2002).
PubMed ID12387856

2AuthorsMarchand P. Tang J. Johnson G.D. Bond J.S.
TitleCOOH-terminal proteolytic processing of secreted and membrane forms of the alpha subunit of the metalloprotease meprin A. Requirement of the I domain for processing in the endoplasmic reticulum.
SourceJ. Biol. Chem. 270:5449-5456(1995).
PubMed ID7890660

3AuthorsRothe M. Wong S.C. Henzel W.J. Goeddel D.V.
TitleA novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor.
SourceCell 78:681-692(1994).
PubMed ID8069916

4AuthorsYe H. Park Y.C. Kreishman M. Kieff E. Wu H.
TitleThe structural basis for the recognition of diverse receptor sequences by TRAF2.
SourceMol. Cell 4:321-330(1999).
PubMed ID10518213

5AuthorsPark Y.C. Burkitt V. Villa A.R. Tong L. Wu H.
TitleStructural basis for self-association and receptor recognition of human TRAF2.
SourceNature 398:533-538(1999).
PubMed ID10206649

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