RASA2

RASA2, also referred to as RAS p21 protein activator 2, is a human gene that encodes the protein RAS p21 protein activator 2 (also known as p120GAP). The RASA2 gene resides on chromosome 2p13.1 and spans approximately 5.4 kilobases of genomic DNA. The encoded protein functions as a RAS GTPase-activating protein (GAP), which accelerates the hydrolysis of GTP bound to the RAS family of small GTPases, thereby turning off RAS signaling pathways that regulate cell proliferation, differentiation, and survival.

The RASA2 protein contains several functional domains: an N‑terminal pleckstrin homology (PH) domain, a C2 domain, a RasGAP domain that confers catalytic activity, and a C‑terminal proline‑rich region that mediates interactions with SH3 domain‑containing proteins. Through these domains, RASA2 localizes to the plasma membrane and is recruited to activated receptor tyrosine kinases, where it dampens downstream MAPK/ERK, PI3K/AKT, and JNK signaling.

Aberrant expression or mutation of RASA2 has been linked to various pathological conditions. Overexpression has been reported in certain cancers such as melanoma, colorectal, and pancreatic tumors, where it may contribute to tumorigenesis by disrupting normal RAS regulation. Loss‑of‑function mutations have also been identified in a subset of neurodevelopmental disorders, suggesting a role in neuronal development and signaling. Functional studies in cell lines and mouse models demonstrate that changes in RASA2 activity affect cell migration, adhesion, and apoptosis.

Current research continues to explore the therapeutic potential of targeting RASA2‑mediated pathways, with ongoing investigations into small molecules that modulate RASA2’s GAP activity or its protein‑protein interactions. As a key regulator of RAS signaling, RASA2 remains an important candidate for understanding both normal cellular physiology and disease mechanisms.