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)
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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