|PROSITE documentation PDOC50144|
Although apparently functionally unrelated, intracellular TRAFs and extracellular meprins share a conserved region of about 180 residues, the meprin and TRAF homology (MATH) domain .
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 .
TRAF proteins were first isolated by their ability to interact with TNF receptors . 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 . 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 .
The structure of the TRAF2 protein reveals a trimeric self-association of the MATH domain (see <PDB:1CA4>) . 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 .
The profile we developed covers the whole MATH domain.Last update:
June 2003 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Sunnerhagen M. Pursglove S. Fladvad M.|
|Title||The new MATH: homology suggests shared binding surfaces in meprin tetramers and TRAF trimers.|
|Source||FEBS Lett. 530:1-3(2002).|
|2||Authors||Marchand P. Tang J. Johnson G.D. Bond J.S.|
|Title||COOH-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.|
|Source||J. Biol. Chem. 270:5449-5456(1995).|
|3||Authors||Rothe M. Wong S.C. Henzel W.J. Goeddel D.V.|
|Title||A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor.|
|4||Authors||Ye H. Park Y.C. Kreishman M. Kieff E. Wu H.|
|Title||The structural basis for the recognition of diverse receptor sequences by TRAF2.|
|Source||Mol. Cell 4:321-330(1999).|
|5||Authors||Park Y.C. Burkitt V. Villa A.R. Tong L. Wu H.|
|Title||Structural basis for self-association and receptor recognition of human TRAF2.|