Alpha-macroglobulin-like, thiol-ester bond-forming region

Definition

This short highly conserved region, containing the GCGEQ motif, is found in protease inhibitors and complement factors, members of A2MF family. These proteins utilise a unique trapping mechanism that pseudo-inhibits proteases regardless of their catalytic class [[cite:PMID:4201304], [cite:PMID:26100869]]. With a few exceptions (e.g., complement C5), A2MF proteins contain an internal thioester formed between the cysteine and a glutamine side chain in the conserved GCGEQ motif. After bait region cleavage, this thioester is exposed and can react with nucleophilic amine and hydroxyl groups on proteins and carbohydrates. As a result, the nascent activated A2MF protein may become covalently linked to the bait region-cleaving protease. The trapped protease remains catalytically active but is prevented from cleaving protein substrates through steric hindrance imposed by the inhibitor following a proteolytically triggered conformational change.

9 human proteins with this domain

Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.

Download CSV (9 proteins: gene, accession, name)

• A2M
• A2ML1
• C3
• C4A
• C4B
• CD109
• CPAMD8
• OVOS1
• PZP