Cysteine array matrix metalloproteinase (CA-MMP)/MMP-23 is a type II transmembrane matrix metalloproteinase regulated by a single cleavage for both secretion and activation.

Matrix metalloproteinases characterized so far are either secreted or membrane anchored via a type I transmembrane domain or a glycosylphosphatidylinositol linkage. Lacking either membrane-anchoring mechanism, the newly discovered CA-MMP/MMP-23 was reported to be expressed as a cell-associated protein. In this report, we present evidence that CA-MMP is expressed as an integral membrane zymogen with an N-terminal signal anchor, and secreted as a fully processed mature enzyme. We further demonstrate that L(20)GAALSGLCLLSALALL(36) is required for this unique membrane localization as a signal anchor and its secretion is regulated by a proprotein convertase motif RRRR(79) sandwiched between its pro- and catalytic domains. Thus, CA-MMP is a type II transmembrane MMP that can be regulated by a single proteolytic cleavage for both activation and secretion, establishing a novel paradigm for protein trafficking and processing within the secretory pathway.