ACBD3

ACBD3 Full Name

acyl-CoA binding domain containing 3

ACBD3 Introduction

Acyl-CoA binding domain containing 3 (ACBD3), also formerly known as Golgi-complex-associated protein of 60 kDa (GCP60) or PAP7, is a highly conserved, multi-functional scaffolding protein that primarily resides at the Golgi apparatus. Structurally, ACBD3 contains an N-terminal acyl-CoA binding (ACB) domain and a C-terminal Golgi dynamics (GOLD) domain, which facilitate its extensive interactome with various cellular factors. In normal cellular physiology, ACBD3 is indispensable for maintaining the structural integrity of the Golgi apparatus, modulating steroidogenesis, and regulating intracellular lipid signaling pathways. One of its most well-characterized and fundamental roles is acting as a critical membrane tether that recruits phosphatidylinositol 4-kinase beta (PI4KB) to the Golgi. This recruitment is vital for synthesizing phosphatidylinositol 4-phosphate (PI4P), a highly specialized lipid molecule that strictly regulates vesicular trafficking, protein secretion, and overall membrane dynamics.

Figure 1. ACBD3 recruitment to the cis-Golgi is achieved through two independent, sequential mechanisms. (Source: Stalder D, et al. 2024)

Clinically and pathologically, the critical role of ACBD3 in lipid regulation makes it a highly vulnerable target during viral infections, particularly by enteroviruses and other picornaviruses (such as poliovirus, coxsackievirus, and enterovirus 71). To successfully multiply, these positive-strand RNA viruses must completely restructure host intracellular membranes to form specialized replication organelles (ROs). During infection, the enteroviral non-structural 3A protein directly binds to and hijacks ACBD3. By doing so, the virus redirects the entire ACBD3-PI4KB enzyme complex away from the Golgi and towards viral replication sites. This forced recruitment creates a heavily PI4P-enriched microenvironment that physically anchors the viral RNA polymerase and drives explosive viral RNA replication. Because knocking out ACBD3 strongly impairs the replication of multiple enterovirus species, this protein is now recognized as an essential pan-enterovirus host factor.

Furthermore, beyond its role in virology, recent bioinformatics and molecular studies have increasingly implicated the dysregulation of ACBD3 in other disease states. Aberrant ACBD3 expression has been identified as a biomarker in pan-cancer progression, influencing cell cycle transitions in gastric and breast cancers. Additionally, it plays a role in neurodegenerative diseases by mediating mutant Huntingtin cytotoxicity via the Golgi network. Consequently, disrupting the specific pathological interactions of ACBD3 presents a promising new frontier for developing broad-spectrum antiviral therapeutics and targeted oncological treatments.

Alternate Names for ACBD3

ACBD3; acyl-CoA binding domain containing 3; PAP7; GCP60; GOCAP1; GOLPH1; Golgi resident protein GCP60; golgi phosphoprotein 1; PKA (RIalpha)-associated protein; PBR- and PKA-associated protein 7

• 1. Stalder D, et al. Recruitment of PI4KIIIβ to the Golgi by ACBD3 is dependent on an upstream pathway of a SNARE complex and golgins. Mol Biol Cell. 2024 Feb 1;35(2):ar20.
  2. Lyoo H, et al. ACBD3 Is an Essential Pan-enterovirus Host Factor That Mediates the Interaction between Viral 3A Protein and Cellular Protein PI4KB. mBio. 2019 Feb 12;10(1):e02742-18.