Meprin family, Beta subunit, MATH domain; Meprins are multidomain extracellular metalloproteases capable of cleaving growth factors, cytokines, extracellular matrix proteins, and biologically active peptides. They are composed of two related subunits, alpha and beta, which form homo- or hetro-complexes where the basic unit is a disulfide-linked dimer. The beta subunit is a type I membrane protein, which forms homodimers or heterotetramers (alpha2beta2 or alpha3beta). Meprin beta shows preference for acidic residues at the P1 and P1' sites of its substrate. Among its best substrates are growth factors and chemokines such as gastrin and osteopontin. Both alpha and beta subunits contain a catalytic astacin (M12 family) protease domain followed by the adhesion or interaction domains MAM, MATH and AM. The MATH and MAM domains provide symmetrical intersubunit disulfide bonds necessary for the dimerization of meprin subunits. The MATH domain may also be required for folding of an activable zymogen.
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.
Jiyao W et al.(2023). "The conserved domain database in 2023.",