RALA

RalA, also known as Ras-like protein family member A, is a small GTPase of the Ras superfamily. It is one of two human paralogs in this subfamily, alongside RalB, and is encoded by the RALA gene. The protein is approximately 198 amino acids long and undergoes C-terminal prenylation, a lipid modification that promotes membrane association and function.

RalA acts as a molecular switch that cycles between an active GTP-bound state and an inactive GDP-bound state. Guanine nucleotide exchange factors (GEFs) such as RalGDS and RalGPS promote nucleotide exchange to activate RalA, while GTPase-activating proteins (GAPs) accelerate GTP hydrolysis to inactivate it. Activation of RalA is typically downstream of Ras signaling pathways.

Active RalA interacts with several effector proteins, most notably components of the exocyst complex such as Sec5 and Exo84, as well as the Ral-binding protein 1 (RalBP1). Through these interactions, RalA regulates vesicle trafficking and exocytosis, as well as aspects of cytoskeletal organization, cell polarity, and, in some cell types, migration.

Physiological and pathological relevance: In normal cells, RalA contributes to secretory pathways and membrane dynamics. In cancer, dysregulation of RalA signaling—via overexpression or activating mutations—has been linked to tumorigenesis and metastatic behavior in several cancer types. Because RalA lies downstream of Ras, it has been studied as a potential therapeutic target, though selective inhibitors are still under investigation.

Notes: post-translational prenylation at the C-terminus is essential for RalA membrane localization and activity. RalA and RalB share many effectors but can have distinct cellular roles in different contexts.