Phosphofurin acidic cluster sorting protein 1 (PACS1)

Phosphofurin acidic cluster sorting protein 1 (PACS1) is a cytosolic coat protein essential for the sorting and localization of membrane proteins, particularly within the trans-Golgi network (TGN)[1][4]. PACS1 interacts with proteins containing phosphorylated acidic cluster motifs, facilitating their endosomal-to-Golgi trafficking and retrieval of specific molecules such as furin and the mannose-6-phosphate receptor[1][4]. It is also involved in moving HIV-1 Nef-mediated MHC-I molecules away from the cell surface to the TGN, contributing to immune evasion by the virus[1]. Recent research highlights PACS1’s roles in the nucleus, where it participates in DNA replication repair, viral RNA export, chromatin stability via histone deacetylase interactions, and RNA binding[2]. PACS1 is necessary for normal lymphocyte development, ER calcium handling in immune cells, and neural development, with expression highest during embryonic brain formation and maintained at lower levels in adulthood[2]. Pathogenic PACS1 variants, particularly the recurrent p.R203W substitution, result in PACS1 syndrome (Schuurs-Hoeijmakers syndrome), which is marked by intellectual disability, craniofacial abnormalities, epilepsy, and developmental delay[2]. No drugs directly target PACS1, nor is it classified as a typical therapeutic target like a receptor, enzyme, or transporter[1][2].

Other names

KIAA1175PACS-1FLJ10209MRD17SHMScytosolic sorting protein PACS-1