PROSITE documentation PDOC50144MATH/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.
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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). | |
| PubMed ID | 12387856 |
| 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). | |
| PubMed ID | 7890660 |
| 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. | |
| Source | Cell 78:681-692(1994). | |
| PubMed ID | 8069916 |
| 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). | |
| PubMed ID | 10518213 |
| 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. | |
| Source | Nature 398:533-538(1999). | |
| PubMed ID | 10206649 | |
| DOI | 10.1038/19110 |
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