Josephin domain-containing protein 1 (JOSD1)

Josephin domain-containing protein 1 (JOSD1) is a cysteine protease that functions as a deubiquitinating enzyme, regulated by its own monoubiquitination. JOSD1 is predominantly localized at the plasma membrane, especially when ubiquitinated, where it regulates cellular processes such as membrane dynamics, cell motility, and endocytosis. It acts upstream of membrane biogenesis, affects endocytosis by increasing macropinocytosis, and suppresses clathrin- and caveolae-mediated endocytosis. JOSD1 is closely related to ataxin-3, a protein involved in Machado-Joseph disease (spinocerebellar ataxia type 3), and is part of the Josephin family of deubiquitinating enzymes, which remove ubiquitin from proteins to regulate their stability and function. JOSD1's unique plasma membrane association distinguishes it from its paralog JOSD2 (which is cytoplasmic). Although it has potential as a therapeutic target, specific drugs or biomarkers are not yet reported.

Other names

Josephin-1JOSD1JSPH1KIAA0063dJ508I15.2josephin domain-containing 1

Deubiquitination (removal of ubiquitin from specific protein substrates, regulated by ubiquitination of JOSD1 itself)