Phosphofurin acidic cluster-disseminator protein 1 (PACS-1)

Phosphofurin acidic cluster-disseminator protein 1 (PACS-1) is a cytosolic sorting protein that plays a critical role in the intracellular trafficking of various cargo proteins between the trans-Golgi network (TGN) and endosomes (UniProt P53351). It functions by recognizing and binding to acidic cluster motifs on the cytoplasmic tails of its targets, such as the proprotein convertase furin and the cation-independent mannose 6-phosphate receptor (Molecular Biology of the Cell, 2005). Beyond its physiological role in protein sorting, PACS-1 is a significant factor in viral pathogenesis; for instance, the HIV-1 Nef protein hijacks PACS-1 to downregulate MHC-I molecules, thereby allowing the virus to evade the host immune system (Journal of Biological Chemistry, 2008). Mutations in the PACS1 gene, most notably the recurrent p.Arg203Trp variant, are the primary cause of PACS1 syndrome (Schuurs-Hoeijmakers syndrome), a rare neurodevelopmental disorder characterized by intellectual disability and distinct facial features (Nature Genetics, 2012). While there are currently no FDA-approved drugs targeting PACS-1, it remains a subject of research as a potential therapeutic target for preventing viral immune evasion and managing associated genetic disorders (Frontiers in Cell and Developmental Biology, 2017).

Other names

PACS1KIAA0187Schuurs-Hoeijmakers syndrome protein

Inhibition of PACS-1/cargo protein interactions to prevent viral immune evasion or restore cellular protein trafficking homeostasis.