Annotated protein:IQ motif and SEC7 domain-containing protein 3 (Potential synaptic guanine nucleotide exchange factor for Arf) (SynArfGEF-Po). Gene symbol: IQSEC3. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: Q76M68
antibody wiki:
SynGO gene info:SynGO data @ IQSEC3
Ontology domain:Biological Process
SynGO term:postsynapse organization (GO:0099173)
Synapse type(s):hippocampus, GABAergic
Annotated paper:Um JW, et al. "IQ Motif and SEC7 Domain-containing Protein 3 (IQSEC3) Interacts with Gephyrin to Promote Inhibitory Synapse Formation" J Biol Chem. 2016 May 6;291(19):10119-30 PMID:27002143
Figure(s):Fig. 1, 2, 4, 5, 7, 8, 10
Annotation description:SynArfGEF/BRAG3/IQSEC3 is a synaptic guanine nucleotide exchange factor present in inhibitory postsynapses with the capability to activate Arf6. IQSEC3 interacts with gephrin at inhibitory synapses (Fig. 1, 2, 4) and overexpression and knock-down experiments in cultured neurons indicate that IQSEC3 is involved in the regulation of synapse development and this activity is dependent on the Arf-GEF activity of IQSEC3 (Fig. 5, 8,).

The referenced paper demonstrates that IQSEC3 activates Arf6 and localizes to inhibitory synapses.

5/7/2017 Pim
- SynArfGEF/BRAG3/IQSEC3 over-expression is shown to affect the number of DIV10 neuron synapses (Fig.5). Interaction of SynArfGEF/BRAG3/IQSEC3 with the postsynaptic marker protein Gephyrin is needed for this effect (Fig.7). This effect does rely on the ArfGEF activity of SynArfGEF/BRAG3/IQSEC3 (Fig.8). Fig.10 shows effect shRNA SynArfGEF/BRAG3/IQSEC3 KD on postsynaptic specialization size. Together this can be used to justify the term:

"positive regulation of ARF protein signal transduction (GO:0032014)"
occurs_in "postsynapse (GO:0098794)"
part_of "postsynapse organization (GO:0050808)"

29/5/2018 Pim
- Because SynArfGEF/BRAG3/IQSEC3 interacts with gephyrin and is essential in the postsynaptic recruitment of this protein I have annotated to the more specific term 'postsynapse organization (GO:0099173)' instead of 'synapse organization (GO:0050808)'.
Evidence tracking, Biological System:Cultured neurons
Non-neuronal tissue
Evidence tracking, Protein Targeting:RNAi / shRNA
Over-expression
Antibody (detection)
Evidence tracking, Experiment Assay:Confocal
IP + WB/MSMS
Y2H
Annotator(s):Noa Lipstein (ORCID:0000-0002-0755-5899)
Cordelia Imig (ORCID:0000-0001-7351-8706)
Vincent O'connor (ORCID:0000-0003-3185-5709)
Nils Brose (ORCID:0000-0003-0938-8534)
Lab:Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany
Additional literature:An Arf pull down assay was performed using a GST-GGA1 (GAT domain of Golgi-localizing gamma-adaptin ear homology domain, Arf-bindin protein 1) fusion protein. GGA1 is capable of binding GTP-bound Arfs. Co-expression of FLAG-tagged IQSEC3 and HA-tagged Arf6 in COS-7 cells caused a strong increase in the amount of GEF-bound Arf6 in comparison to cells that were transfected with Arf6-HA alone (Fig. 1a, b). Pre-embedding immuno-EM confirmed the presence of IQSEC3-immunoreactivity at postsynaptic specializations of symmetrical synapses (Fig.5).

Antibodies (rabbit and guinea pig) were generated in this study using a GST-IQSEC3 fusion protein and specificity was tested by Western Blot (Fig.2) and for IHC by pre-absorption of the antigen (Fig.3b). @ PMID:21198641
SynGO annotation ID:1052
Dataset release (version):20231201
View annotation as GO-CAM model:Gene Ontology