Rho/Cdc42/Rac GTPase-activating protein RICS; p200RhoGAP; p250GAP; RhoGAP involved in the beta-catenin-N-cadherin & NMDA receptor signaling; brain-specific Rho GTPase-activating protein; GAB-associated Cdc42/Rac GTPase-activating protein; GC-GAP; GTPase regulator interacting with TrkA (RICS, GRIT, KIAA0712, ARHGAP32)

Function: - GTPase-activating protein (GAP) promoting GTP hydrolysis on RHOA, CDC42 & RAC1 small GTPases - may be involved in differentiation of neuronal cells during the formation of neurite extensions - role in NMDA receptor activity-dependent actin reorganization in dendritic spines - may mediate cross-talks between Ras- & Rho-regulated signaling pathways in cell growth regulation - isoform 2 has higher GAP activity (putative) - interacts with NTRK1 (via cytoplasmic domain); the interaction is independent of the phosphorylation state of NTRK1 - interacts with SHC3 (via SH2 domain) - interacts with RASA1 (via SH3 domain); the interaction is necessary for the Ras activation & cell transforming activities of RICS (putative) - interacts with GAB1 & GAB2 - interacts with CRK & CRKL - found in a complex with CRKL & BCAR1; upon EGF stimulation, BCAR1 may be replaced by EGFR - interacts with NCK1 (via SH3 domain); NCK1 recruits phosphorylated BCAR1 to the complex - isoform 2 interacts with FYN; the interaction appears to be dependent on Tyr phosphorylation of RICS - interacts with EGFR; the interaction requires EGF stimulation & is increased by SHC3 - interacts with CDC42; the interaction requires constitutively active CDC42 - interacts with CTNNB1, DLG4, CDH2 & GRIN2B (putative) - isoform 2 is phosphorylated on multiple Tyr by FYN - phosphorylated Tyr undergo dephosphorylation after stimulation of NMDA receptors (putative) - phosphorylated in vitro by CaMK2 in the presence of calmodulin & Ca⁺²; which inhibits GAP activity (putative) Structure: - N-terminal PX domain interacts specifically with phosphatidylinositides (putative) - belongs to the PX domain-containing GAP family - contains 1 PX (phox homology) domain - contains 1 Rho-GAP domain - contains 1 SH3 domain Compartment: - cell junction, synapse - postsynaptic cell membrane, postsynaptic density - cell projection, dendritic spine (putative) - cytoplasm, cell cortex - endosome membrane - Golgi membrane - endoplasmic reticulum membrane (putative) - association to membrane via PX domain - associated with cortical actin in undifferentiated neuroblastoma cells, but localized to dendritic spine & postsynaptic density after differentiation - colocalizes with EGFR at the cell membrane upon EGF treatment - colocalizes with GAB2 at the cell membrane Alternative splicing: named isoforms=3 Expression: - isoform 1 & isoform 2 are highly expressed in brain & testis - isoform 1 is also expressed in other tissues including lung, liver & spleen

General

phosphoprotein receptor rho GTPase-activating protein (rho-GAP)

Properties

SIZE: entity length = 2087 aa MW = 231 kD COMPARTMENT: cytoplasm golgi MOTIF: PX; atypical {131-245} src homology 3 [SH3] domain SITE: 259-321 rho-GAP domain NAME: rho-GAP domain SITE: 372-567 Ser phosphorylation site {S856} Ser phosphorylation site {S892} Ser phosphorylation site {S952} proline-rich region SITE: 1031-1036 MOTIF: proline residue (SEVERAL) proline-rich region SITE: 1305-1310 MOTIF: proline residue (SEVERAL) GAB2 interaction {1391-1711} FYN interaction {1685-2087}

Database Correlations

UniProt A7KAX9 PFAM correlations

References

UniProt :accession A7KAX9