Speckle-type POZ protein (SPOP) family, MATH domain; composed of proteins with similarity to human SPOP. SPOP was isolated as a novel antigen recognized by serum from a scleroderma patient, whose overexpression in COS cells results in a discrete speckled pattern in the nuclei. It contains an N-terminal MATH domain and a C-terminal BTB (also called POZ) domain. Together with Cul3, SPOP constitutes an ubiquitin E3 ligase which is able to ubiquitinate the PcG protein BMI1, the variant histone macroH2A1 and the death domain-associated protein Daxx. Therefore, SPOP may be involved in the regulation of these proteins and may play a role in transcriptional regulation, apoptosis and X-chromosome inactivation. Cul3 binds to the BTB domain of SPOP whereas Daxx and the macroH2A1 nonhistone region have been shown to bind to the MATH domain. Both MATH and BTB domains are necessary for the nuclear speckled accumulation of SPOP. There are many proteins, mostly uncharacterized, containing both MATH and BTB domains from C. elegans and plants which are excluded from this family.
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.",