SYNGAP1

Synaptic Ras GTPase activating protein 1
Identifiers
Symbols SYNGAP1; DKFZp761G1421; KIAA1938; MRD5; RASA1; RASA5; SYNGAP
External IDs OMIM: 603384 MGI: 3039785 HomoloGene: 84739 GeneCards: SYNGAP1 Gene
Orthologs
Species Human Mouse
Entrez 8831 240057
Ensembl n/a n/a
UniProt Q96PV0 n/a
RefSeq (mRNA) NM_006772 XM_915205
RefSeq (protein) NP_006763 XP_920298
Location (UCSC) n/a n/a
PubMed search [1] [2]

Synaptic Ras GTPase activating protein 1 homolog (rat), also known as SYNGAP1, is a protein which in humans is encoded by the SYNGAP1 gene.[1][2][3] SYNGAP1 is a ras GTPase-activating protein that is critical for cognition and synapse function. Mutations in humans cause mental retardation.

Contents

Function

Unc51.1 and SynGAP function cooperatively in axon formation.[4] SynGAP1 regulated AMPA receptor trafficking and excitatory transmission. SynGAP1 affects these characteristics by regulating the MAP kinase signaling pathway.[5]

Clinical significance

Several mutations in the SYNGAP1 gene were identified as the cause of mental retardation. Mental retardation is sometimes associated with syndromes of other defects caused by the same gene, but SYNGAP1-associated mental retardation is not; it is therefore called non-syndromic mental retardation. Since neither of the parents of children with this condition have the mutation, this means it was a sporadic mutation that occurred during division of the parents' gametes (meiosis) or fertilization of the egg. It is a dominant mutation, which means that the individual will be retarded if only one allele is mutated.[6]

Interactions

SYNGAP1 has been shown to interact with DLG3[2] and ULK1.[4]

References

  1. ^ "Entrez Gene: SYNGAP1 synaptic Ras GTPase activating protein 1 homolog (rat)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8831. 
  2. ^ a b Kim JH, Liao D, Lau LF, Huganir RL (April 1998). "SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family". Neuron 20 (4): 683–91. doi:10.1016/S0896-6273(00)81008-9. PMID 9581761. 
  3. ^ Chen HJ, Rojas-Soto M, Oguni A, Kennedy MB (May 1998). "A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II". Neuron 20 (5): 895–904. doi:10.1016/S0896-6273(00)80471-7. PMID 9620694. 
  4. ^ a b Tomoda T, Kim JH, Zhan C, Hatten ME (March 2004). "Role of Unc51.1 and its binding partners in CNS axon outgrowth". Genes Dev. 18 (5): 541–58. doi:10.1101/gad.1151204. PMC 374236. PMID 15014045. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=374236. 
  5. ^ Rumbaugh G, Adams JP, Kim JH, Huganir RL (March 2006). "SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons". Proc. Natl. Acad. Sci. U.S.A. 103 (12): 4344–51. doi:10.1073/pnas.0600084103. PMC 1450173. PMID 16537406. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1450173. 
  6. ^ Hamdan FF, Gauthier J, Spiegelman D, Noreau A, Yang Y, Pellerin S, Dobrzeniecka S, Côté M, Perreault-Linck E, Carmant L, D'Anjou G, Fombonne E, Addington AM, Rapoport JL, Delisi LE, Krebs MO, Mouaffak F, Joober R, Mottron L, Drapeau P, Marineau C, Lafrenière RG, Lacaille JC, Rouleau GA, Michaud JL (February 2009). "Mutations in SYNGAP1 in Autosomal Nonsyndromic Mental Retardation". N. Engl. J. Med. 360 (6): 599–605. doi:10.1056/NEJMoa0805392. PMC 2925262. PMID 19196676. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2925262. 

Further reading

  • Fantl WJ, Escobedo JA, Martin GA et al. (1992). "Distinct phosphotyrosines on a growth factor receptor bind to specific molecules that mediate different signaling pathways". Cell 69 (3): 413–23. doi:10.1016/0092-8674(92)90444-H. PMID 1374684. 
  • Kroll J, Waltenberger J (1998). "The vascular endothelial growth factor receptor KDR activates multiple signal transduction pathways in porcine aortic endothelial cells". J. Biol. Chem. 272 (51): 32521–7. doi:10.1074/jbc.272.51.32521. PMID 9405464. 
  • Kim JH, Liao D, Lau LF, Huganir RL (1998). "SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family". Neuron 20 (4): 683–91. doi:10.1016/S0896-6273(00)81008-9. PMID 9581761. 
  • Chen HJ, Rojas-Soto M, Oguni A, Kennedy MB (1998). "A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II". Neuron 20 (5): 895–904. doi:10.1016/S0896-6273(00)80471-7. PMID 9620694. 
  • Husi H, Ward MA, Choudhary JS et al. (2000). "Proteomic analysis of NMDA receptor-adhesion protein signaling complexes". Nat. Neurosci. 3 (7): 661–9. doi:10.1038/76615. PMID 10862698. 
  • Li W, Okano A, Tian QB et al. (2001). "Characterization of a novel synGAP isoform, synGAP-beta". J. Biol. Chem. 276 (24): 21417–24. doi:10.1074/jbc.M010744200. PMID 11278737. 
  • Pei L, Teves RL, Wallace MC, Gurd JW (2001). "Transient cerebral ischemia increases tyrosine phosphorylation of the synaptic RAS-GTPase activating protein, SynGAP". J. Cereb. Blood Flow Metab. 21 (8): 955–63. doi:10.1097/00004647-200108000-00008. PMID 11487731. 
  • Nagase T, Kikuno R, Ohara O (2002). "Prediction of the coding sequences of unidentified human genes. XXI. The complete sequences of 60 new cDNA clones from brain which code for large proteins". DNA Res. 8 (4): 179–87. doi:10.1093/dnares/8.4.179. PMID 11572484. 
  • Yi J, Kloeker S, Jensen CC et al. (2002). "Members of the Zyxin family of LIM proteins interact with members of the p130Cas family of signal transducers". J. Biol. Chem. 277 (11): 9580–9. doi:10.1074/jbc.M106922200. PMID 11782456. 
  • Kim JH, Lee HK, Takamiya K, Huganir RL (2003). "The role of synaptic GTPase-activating protein in neuronal development and synaptic plasticity". J. Neurosci. 23 (4): 1119–24. PMID 12598599. 
  • Song B, Meng F, Yan X et al. (2003). "Cerebral ischemia immediately increases serine phosphorylation of the synaptic RAS-GTPase activating protein SynGAP by calcium/calmodulin-dependent protein kinase II alpha in hippocampus of rats". Neurosci. Lett. 349 (3): 183–6. doi:10.1016/S0304-3940(03)00830-9. PMID 12951199. 
  • Mungall AJ, Palmer SA, Sims SK et al. (2003). "The DNA sequence and analysis of human chromosome 6". Nature 425 (6960): 805–11. doi:10.1038/nature02055. PMID 14574404. 
  • Ota T, Suzuki Y, Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. 
  • Oh JS, Manzerra P, Kennedy MB (2004). "Regulation of the neuron-specific Ras GTPase-activating protein, synGAP, by Ca2+/calmodulin-dependent protein kinase II". J. Biol. Chem. 279 (17): 17980–8. doi:10.1074/jbc.M314109200. PMID 14970204. 
  • Tomoda T, Kim JH, Zhan C, Hatten ME (2004). "Role of Unc51.1 and its binding partners in CNS axon outgrowth". Genes Dev. 18 (5): 541–58. doi:10.1101/gad.1151204. PMC 374236. PMID 15014045. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=374236. 
  • Song B, Yan XB, Zhang GY (2004). "PSD-95 promotes CaMKII-catalyzed serine phosphorylation of the synaptic RAS-GTPase activating protein SynGAP after transient brain ischemia in rat hippocampus". Brain Res. 1005 (1–2): 44–50. doi:10.1016/j.brainres.2004.01.032. PMID 15044063. 
  • Brandenberger R, Wei H, Zhang S et al. (2005). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nat. Biotechnol. 22 (6): 707–16. doi:10.1038/nbt971. PMID 15146197. 
  • Krapivinsky G, Medina I, Krapivinsky L et al. (2004). "SynGAP-MUPP1-CaMKII synaptic complexes regulate p38 MAP kinase activity and NMDA receptor-dependent synaptic AMPA receptor potentiation". Neuron 43 (4): 563–74. doi:10.1016/j.neuron.2004.08.003. PMID 15312654. 
  • Jaffe H, Vinade L, Dosemeci A (2004). "Identification of novel phosphorylation sites on postsynaptic density proteins". Biochem. Biophys. Res. Commun. 321 (1): 210–8. doi:10.1016/j.bbrc.2004.06.122. PMID 15358237.