Ras GTPase-activating protein synGAP; neuronal RasGAP; synaptic Ras GTPase-activating protein 1; synaptic Ras-GAP 1 (SYNGAP1, KIAA1938)

Function

• major constituent of the postsynpatic density
  • complexes with SAP-90
  • interacts with all 3 SAP-90 PDZ domains
• inhibitory regulator of the Ras-cAMP pathway
• member of the NMDAR signaling complex in excitatory synapses
• may play a role in NMDAR-dependent control of AMPAR potentiation, AMPAR membrane trafficking & synaptic plasticity
• regulates AMPAR-mediated miniature excitatory postsynaptic currents
• may be involved in certain forms of brain injury, leading to long-term learning & memory deficits (putative)
• phosphorylated by CaM-kinase 2
  • Ras GTPase activity inhibited by phosphorylation by CaM kinase 2
• dephosphorylated upon NMDA receptor activation or SYNGAP1/MPDZ complex disruption
• phosphorylation by PLK2 promotes its activity (putative)
• interacts KLHL17, CAMK2A & CAMK2B (putative)
• interacts with MPDZ

Structure

• contains 1 C2 domain
• contains 1 PH domain
• contains 1 Ras-GAP domain Comparment:
• localizes to the post synaptic density

Alternative splicing

named isoforms=4

Expression

highly expressed in brain

Pathology

• defects in SYNGAP1 are the cause of mental retardation autosomal dominant type 5

Notes

• uncertain whether Met-1 or Met-16 is the initiator Met

More general terms

• ras GTPase activator protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=8831
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:8831
• OMIM: https://mirror.omim.org/entry/603384
• OMIM: https://mirror.omim.org/entry/612621
• UniProt: http://www.uniprot.org/uniprot/Q96PV0.html