ARPP19 Gene: Function, Mutations, and Disease Associations

ARPP19 (cAMP-regulated phosphoprotein 19) is a protein-coding gene that encodes a small phosphoprotein involved in the regulation of protein phosphatase 2A (PP2A) activity. It is a key substrate for protein kinase A (PKA) and plays a critical role in cell cycle progression, particularly during mitosis, by inhibiting PP2A to maintain CDK1 activity. ARPP19 is highly expressed in the brain and is implicated in neuronal signaling, learning, and memory. Dysregulation of ARPP19 has been linked to cancer, including breast and lung cancers, where it may contribute to uncontrolled cell proliferation.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Cell Cycle

• Mitotic (Reactome: R-HSA-69278)

• Regulation of PP2A activity (Reactome: R-HSA-165159)

• cAMP/PKA signaling (KEGG: hsa04024)

The ARPP19 protein is a 19 kDa phosphoprotein that acts as a potent inhibitor of protein phosphatase 2A (PP2A). It is phosphorylated by PKA at Ser104 and by CDK1 at multiple sites, enabling it to bind and inhibit PP2A during mitosis. This inhibition is essential for maintaining CDK1 activity and proper cell cycle progression. In neurons, ARPP19 modulates synaptic plasticity and long-term potentiation. Structurally, it contains a conserved PP2A-binding domain and is predominantly cytoplasmic but can translocate to the nucleus upon phosphorylation.