GAP1 (GTPase-activating protein 1) family members include RASA2 (GAP1m), RASAL (RASAL1), GAP1(IP4BP or RASA3), and CAPRI (RASA4). They all display Ras GAP activity. With the exception of RASA2, they all possess an arginine finger-dependent GAP activity on Rap1 [, ]. They contain N-terminal tandem C2 domain repeats, a centrally located Ras-GAP domain, and a PH (pleckstrin homology) domain containing a Btk motif [].This entry represents the PH domain of Ras GTPase-activating protein 2 (RASA2, also known as GAP1m). The tandem C2 domains of RASA2, like those of GAP1IP4BP, do not contain the conserved C2 motif that is known to be required for calcium-dependent phospholipid binding. RASA2 is regulated by the binding of its PH domains to phophoinositides, PIP3 (phosphatidylinositol 3,4,5-trisphosphate) []. It suppresses RAS, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation []. RASA2 also binds to inositol 1,3,4,5-tetrakisphosphate (IP4) [].
GAP1 (GTPase-activating protein 1) family members include RASA2 (GAP1m), RASAL (RASAL1), GAP1(IP4BP or RASA3), and CAPRI (RASA4). They all display Ras GAP activity. With the exception of RASA2, they all possess an arginine finger-dependent GAP activity on Rap1 [, ]. They contain N-terminal tandem C2 domain repeats, a centrally located Ras-GAP domain, and a PH (pleckstrin homology) domain containing a Btk motif [].This entry represents the PH domain of Ras GTPase-activating protein 3 (RASA3, also known as GAP1 or IP4BP). The RASA3 PH domain binds to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and I(1,3,4,5)P4 []. Its C2 domains, like those of RASA2 (GAP1M), do not contain the C2 motif that is known to be required for calcium-dependent phospholipid binding [].
GAP1 (GTPase-activating protein 1) family members include RASA2 (GAP1m), RASAL (RASAL1), GAP1(IP4BP or RASA3), and CAPRI (RASA4). They all display Ras GAP activity. With the exception of RASA2, they all possess an arginine finger-dependent GAP activity on Rap1 [, ]. They contain N-terminal tandem C2 domain repeats, a centrally located Ras-GAP domain, and a PH (pleckstrin homology) domain containing a Btk motif [].RASAL, like Ca2+ -promoted Ras inactivator (CAPRI, or RASAL4), is a cytosolic protein that undergoes a rapid translocation to the plasma membrane in response to receptor-mediated elevation in the concentration of intracellular free Ca2+, a translocation that activates its ability to function as a RasGAP. However, unlike RASAL4, RASAL undergoes an oscillatory translocation to the plasma membrane that occurs in synchrony with repetitive Ca2+ spikes. Its tandem C2 domains bind phospholipids upon an elevation in the intracellular free Ca2+ concentration ([Ca2+]i) [].
GAP1 (GTPase-activating protein 1) family members include RASA2 (GAP1m), RASAL (RASAL1), GAP1(IP4BP or RASA3), and CAPRI (RASA4). They all display Ras GAP activity. With the exception of RASA2, they all possess an arginine finger-dependent GAP activity on Rap1 [, ]. They contain N-terminal tandem C2 domain repeats, a centrally located Ras-GAP domain, and a PH (pleckstrin homology) domain containing a Btk motif [].This entry represents the PH domain of Ras GTPase-activating protein 4 (RASA4, also known as CAPRI). Both CAPRI and RASAL are calcium-activated RasGAPs that inactivate Ras at the plasma membrane. Its tandem C2 domains bind phospholipids upon an elevation in the intracellular free Ca2+ concentration ([Ca2+]i). CAPRI and RASAL differ in that CAPRI is an amplitude sensor while RASAL senses calcium oscillations [, ]. This difference between them resides not in their C2 domains, but in their PH domains leading to speculation that this might reflect an association with either phosphoinositides and/or proteins [].
GAP1 (GTPase-activating protein 1) family members include RASA2 (GAP1m), RASAL (RASAL1), GAP1(IP4BP or RASA3), and CAPRI (RASA4). They all display Ras GAP activity. With the exception of RASA2, they all possess an arginine finger-dependent GAP activity on Rap1 [, ]. They contain N-terminal tandem C2 domain repeats, a centrally located Ras-GAP domain, and a PH (pleckstrin homology) domain containing a Btk motif [].This entry represents the RasGAP domain of RASAL. RASAL, like Ca2+ -promoted Ras inactivator (CAPRI, or RASA4), is a cytosolic protein that undergoes a rapid translocation to the plasma membrane in response to receptor-mediated elevation in the concentration of intracellular free Ca2+, a translocation that activates its ability to function as a RasGAP. Its tandem C2 domains bind phospholipids upon an elevation in the intracellular free Ca2+ concentration ([Ca2+]i). CAPRI and RASAL differ in that CAPRI is an amplitude sensor while RASAL senses calcium oscillations [, ]. This difference between them resides not in their C2 domains, but in their PH domains leading to speculation that this might reflect an association with either phosphoinositides and/or proteins [].
