MATH (meprin and TRAF-C homology) domain; an independent folding unit with an eight-stranded beta-sandwich structure found in meprins, TRAFs and other proteins. Meprins comprise a class of extracellular metalloproteases which are anchored to the membrane and are capable of cleaving growth factors, extracellular matrix proteins, and biologically active peptides. TRAF molecules serve as adapter proteins that link cell surface receptors of the Tumor Necrosis Factor and 1nterleukin-1/Toll-like families to downstream kinase cascades, which results in the activation of transcription factors and the regulation of cell survival, proliferation and stress responses in the immune and inflammatory systems. Other members include the ubiquitin ligases, TRIM37 and SPOP, and the ubiquitin-specific proteases, HAUSP and Ubp21p. A large number of uncharacterized members mostly from lineage-specific expansions in C. elegans and rice contain MATH and BTB domains, similar to SPOP. The MATH domain has been shown to bind peptide/protein substrates in TRAFs and HAUSP. It is possible that the MATH domain in other members of this superfamily also interacts with various protein substrates. The TRAF domain may also be involved in the trimerization of TRAFs. Based on homology, it is postulated that the MATH domain in meprins may be involved in its tetramer assembly and that the MATH domain, in general, may take part in diverse modular arrangements defined by adjacent multimerization domains.
Feature 1:putative substrate binding site [chemical binding site]
Evidence:
Comment:Based on the substrate binding site of TRAFs and HAUSP. The binding site residues involved in the binding of TRAFs to TNFRs and of HAUSP to p53/MDM2 partially overlap, but are not conserved. The substrate binding pocket located in the MATH domain for members of this superfamily may be in the same location, but the specific interactions are different.
Structure:1CA9_A; Human TRAF2 binds TNFR-2 peptide; contacts calculated at 3.5A
Structure:1FLL; Human TRAF3 binds CD40 peptide; contacts calculated at 3.5A
Structure:2FOP; Human HAUSP N-terminal MATH domain binds MDM2 peptide; contacts calculated at 3.5A
Structure:2FOJ; Human HAUSP N-terminal MATh domain binds p53 peptide; contacts calculated at 3.5A
Jiyao W et al.(2023). "The conserved domain database in 2023.",