Rce1

Rce1, short for Ras-converting enzyme 1, is an intramembrane protease that participates in the maturation of prenylated CAAX motif proteins. It is conserved across eukaryotes and functions in the endoplasmic reticulum membranes to process a subset of CAAX-containing substrates, including many Ras family small GTPases, by removing the C-terminal three residues (the AAX tripeptide) after prenylation.

The proteolytic action of Rce1 occurs after prenylation but before C-terminal methylation. Once the AAX segment is cleaved, the newly exposed C-terminal cysteine is typically methylated by isoprenylcysteine carboxyl methyltransferase (ICMT). This sequence of events—prenylation, Rce1-mediated proteolysis, and ICMT methylation—facilitates proper membrane association and signaling of many CAAX proteins. Rce1 shows broad but motif-influenced substrate specificity, and while Ras proteins are common targets, other prenylated CAAX proteins can also be processed by this protease.

Structure and localization are characteristic of multi-pass transmembrane metalloproteases, with Rce1 anchored in the endoplasmic reticulum membrane. In yeast, Rce1 works alongside other CAAX-processing enzymes (such as Ste24p) to ensure maturation of prenylated proteins; in metazoans, RCE1 is the primary known CAAX protease with essential roles in membrane targeting and signaling.

Biological relevance is linked to the proper localization and function of Ras and related GTPases. Disruption of RCE1 activity can mislocalize CAAX proteins and perturb signaling pathways, making RCE1 a focus of research into prenylation-dependent regulation and potential therapeutic targeting in contexts where Ras signaling is implicated. See also CAAX motif, protein prenylation, and ICMT.