STAM binding protein (STAMBP)

STAM binding protein (STAMBP) is a zinc metalloprotease and deubiquitinating enzyme (DUB) that specifically cleaves K63-linked polyubiquitin chains from protein substrates, but does not cleave K48-linked chains[1][3][8]. It associates with the ESCRT machinery on endosomes, playing a crucial role in ubiquitin-dependent receptor sorting, endocytosis, and lysosomal degradation of surface proteins and signaling receptors[1][3][4][7]. STAMBP is also involved in multiple signaling pathways—such as cytokine signaling (JAK-STAT, MYC induction), BMP signaling, and regulation of PI3K-AKT-mTOR and RAS-MAP cascades[3][4][5]. Pathogenic loss-of-function mutations cause a severe developmental disorder (microcephaly-capillary malformation syndrome), and deficiency leads to protein aggregation and neurodegeneration[1][7]. Increasing evidence suggests context-specific roles in cancer and inflammation, including regulation of innate immune responses by controlling inflammasome activity[4][6]. To date, STAMBP is not known to be directly targeted by any approved drugs, but its enzymatic and signaling roles classify it as a potential therapeutic target.

Other names

Associated molecule with the SH3 domain of STAMAMSHEndosome-associated ubiquitin isopeptidaseSTABP_HUMANEC 3.1.2.15EC 3.4.19MICCAP[3][7][5]

Cleavage (deubiquitination) of K63-linked polyubiquitin chains from protein substrates, thereby modulating their lysosomal trafficking and subsequent degradation Negative regulation of degradative signaling to lysosomes, stabilization of receptor and signaling proteins[1][3][4] Modulation of inflammasome activity through deubiquitination[4]