{PDOC50144}
{PS50144; MATH}
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* MATH/TRAF domain profile *
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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  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 signaling complexes
with TNF receptor-1. The ligand binding surface of TRAF proteins is located in
beta-strands 6 and 7 [4].

The profile we developed covers the whole MATH domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: June 2003 / First entry.

[ 1] Sunnerhagen M., Pursglove S., Fladvad M.
     "The new MATH: homology suggests shared binding surfaces in meprin
     tetramers and TRAF trimers."
     FEBS Lett. 530:1-3(2002).
     PubMed=12387856
[ 2] Marchand P., Tang J., Johnson G.D., Bond J.S.
     "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."
     J. Biol. Chem. 270:5449-5456(1995).
     PubMed=7890660
[ 3] Rothe M., Wong S.C., Henzel W.J., Goeddel D.V.
     "A novel family of putative signal transducers associated with the
     cytoplasmic domain of the 75 kDa tumor necrosis factor receptor."
     Cell 78:681-692(1994).
     PubMed=8069916
[ 4] Ye H., Park Y.C., Kreishman M., Kieff E., Wu H.
     "The structural basis for the recognition of diverse receptor
     sequences by TRAF2."
     Mol. Cell 4:321-330(1999).
     PubMed=10518213
[ 5] Park Y.C., Burkitt V., Villa A.R., Tong L., Wu H.
     "Structural basis for self-association and receptor recognition of
     human TRAF2."
     Nature 398:533-538(1999).
     PubMed=10206649; DOI=10.1038/19110

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