p120GAPRASA1

p120GAPRASA1, commonly referred to as p120RasGAP, is a protein encoded by the RASA1 gene in humans. It belongs to the Ras GTPase-activating protein (GAP) family and functions as a negative regulator of Ras signaling by accelerating GTP hydrolysis on Ras, converting active Ras-GTP to inactive Ras-GDP. Through this activity, p120GAPRASA1 modulates cellular responses to growth factors, including proliferation, differentiation, and survival.

The protein features domains that support its regulatory role, including SH2 and SH3 regions and a C-terminal RasGAP catalytic domain. The SH2 domains enable binding to phosphotyrosine-containing motifs on activated receptors and adaptor proteins, facilitating recruitment to signaling complexes. The RasGAP domain directly stimulates Ras GTP hydrolysis, attenuating downstream pathways such as the MAPK cascade and influencing signaling outcomes after receptor activation. p120GAPRASA1 is primarily cytoplasmic but can associate with membranes or endomembranes in response to signaling events.

Regulation of p120GAPRASA1 involves phosphorylation events and interactions with other signaling proteins, which modulate its localization and activity within Ras-regulated networks. Its function integrates multiple receptor tyrosine kinase–driven signals to fine-tune Ras activity and cellular responses.

Clinical significance is highlighted by associations between RASA1 mutations and capillary malformation-arteriovenous malformation (CM-AVM) and related vascular anomalies. Abnormal p120GAP activity can contribute to dysregulated Ras signaling, with implications for vascular development and disease.