Arrestin domain-containing protein 3 (ARRDC3)

Arrestin domain-containing protein 3 (ARRDC3) is a member of the mammalian α-arrestin family of adaptor proteins and acts as a tumor suppressor in metastatic breast cancer and other contexts. Structurally, ARRDC3 contains arrestin N- and C-domains, a finger loop region, and two conserved PPXY motifs in its C-tail, crucial for binding WW-domain containing E3 ubiquitin ligases such as NEDD4 and WWP2. ARRDC3 is ubiquitinated at these motifs, which determines its protein stability, subcellular trafficking, localization, and ability to regulate receptor (especially GPCR) trafficking and signaling. It functions as an adaptor molecule at the endosome, directing the fate of internalized receptors, and interacts with a large network of signaling partners, displaying context-dependent functions in cancer progression, cell metabolism, and possibly other diseases. Recent research positions ARRDC3 as a key regulatory node in cellular signaling pathways, notably GPCR and Hippo signaling, as well as an emerging target for understanding and potentially treating cancer. Its broad adaptability and interface with multiple protein classes reflect its versatile roles as a signaling scaffold and regulator of cellular homeostasis. No direct pharmacological agents currently target ARRDC3, but its regulatory effects on GPCRs and other surface receptors connect it to major drug targets and disease pathways.

Other names

ARRDC3KIAA1376TLIMP (TBP-2-like inducible membrane protein)Alpha-arrestin 3Arrestin domain-containing protein 3TBP-2-like inducible membrane protein

Drugs targeting GPCRs or receptors regulated by ARRDC3 may affect its adaptor functions, impacting receptor degradation, internalization, or recycling. ARRDC3 itself is an adaptor for ubiquitin ligases, not a direct pharmacological target under current clinical applications.