Descriptions
IQ motif and SEC7 domain-containing protein 2 (IQSEC2, also known as BRAG1) is a guanine nucleotide exchange factor (GEF) that is highly enriched in synapses. The autoinhibition of IQSEC2 is mediated by its IQ motif, which binds to apo-CaM and folds together with its Sec7-PH tandem, leading IQSEC2 to adopt a closed conformation in the absence of Ca2+. This autoinhibition is released by calcium binding, which triggers a conformational change that exposes the DH domain for activation.
Autoinhibitory domains (AIDs)
Target domain |
736-1073 (Sec7-PH domains) |
Relief mechanism |
Ligand binding |
Assay |
|
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
1 structures for Q5DU25
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q5DU25-F1 | Predicted | AlphaFoldDB |
No variants for Q5DU25
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for Q5DU25 | |||||
No associated diseases with Q5DU25
5 regional properties for Q5DU25
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain | 526 - 850 | IPR002073 |
| domain | GAF domain | 154 - 314 | IPR003018-1 |
| domain | GAF domain | 336 - 503 | IPR003018-2 |
| domain | HD/PDEase domain | 600 - 777 | IPR003607 |
| conserved_site | 3'5'-cyclic nucleotide phosphodiesterase, conserved site | 643 - 654 | IPR023174 |
5 GO annotations of cellular component
| Name | Definition |
|---|---|
| glutamatergic synapse | A synapse that uses glutamate as a neurotransmitter. |
| photoreceptor ribbon synapse | A ribbon synapse between a retinal photoreceptor cell (rod or cone) and a retinal bipolar cell. These contain a plate-like synaptic ribbon. |
| postsynaptic density membrane | The membrane component of the postsynaptic density. This is the region of the postsynaptic membrane in which the population of neurotransmitter receptors involved in synaptic transmission are concentrated. |
| postsynaptic density, intracellular component | A network of proteins adjacent to the postsynaptic membrane forming an electron dense disc. Its major components include neurotransmitter receptors and the proteins that spatially and functionally organize neurotransmitter receptors in the adjacent membrane, such as anchoring and scaffolding molecules, signaling enzymes and cytoskeletal components. |
| presynaptic active zone cytoplasmic component | A specialized region below the presynaptic membrane, characterized by electron-dense material, a specialized cytoskeletal matrix and accumulated (associated) synaptic vesicles. |
1 GO annotations of molecular function
| Name | Definition |
|---|---|
| guanyl-nucleotide exchange factor activity | Stimulates the exchange of GDP to GTP on a signaling GTPase, changing its conformation to its active form. Guanine nucleotide exchange factors (GEFs) act by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP), which is more abundant in the cell under normal cellular physiological conditions. |
5 GO annotations of biological process
| Name | Definition |
|---|---|
| actin cytoskeleton organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins. |
| positive regulation of long-term synaptic depression | Any process that activates or increases the frequency, rate or extent of long term synaptic depression. |
| positive regulation of synapse assembly | Any process that activates, maintains or increases the frequency, rate or extent of synapse assembly, the aggregation, arrangement and bonding together of a set of components to form a synapse. |
| positive regulation of synaptic transmission, glutamatergic | Any process that activates, maintains or increases the frequency, rate or extent of glutamatergic synaptic transmission, the process of communication from a neuron to another neuron across a synapse using the neurotransmitter glutamate. |
| regulation of ARF protein signal transduction | Any process that modulates the frequency, rate or extent of ARF protein signal transduction. |
13 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q9UPP2 | IQSEC3 | IQ motif and SEC7 domain-containing protein 3 | Homo sapiens (Human) | SS |
| Q6DN90 | IQSEC1 | IQ motif and SEC7 domain-containing protein 1 | Homo sapiens (Human) | EV |
| Q5JU85 | IQSEC2 | IQ motif and SEC7 domain-containing protein 2 | Homo sapiens (Human) | EV |
| Q3TES0 | Iqsec3 | IQ motif and SEC7 domain-containing protein 3 | Mus musculus (Mouse) | SS |
| Q8R0S2 | Iqsec1 | IQ motif and SEC7 domain-containing protein 1 | Mus musculus (Mouse) | SS |
| Q9QX11 | Cyth1 | Cytohesin-1 | Mus musculus (Mouse) | SS |
| Q80YW0 | Cyth4 | Cytohesin-4 | Mus musculus (Mouse) | SS |
| G3X9K3 | Arfgef1 | Brefeldin A-inhibited guanine nucleotide-exchange protein 1 | Mus musculus (Mouse) | PR |
| A2A5R2 | Arfgef2 | Brefeldin A-inhibited guanine nucleotide-exchange protein 2 | Mus musculus (Mouse) | PR |
| P63034 | Cyth2 | Cytohesin-2 | Mus musculus (Mouse) | SS |
| O08967 | Cyth3 | Cytohesin-3 | Mus musculus (Mouse) | EV |
| Q76M68 | Iqsec3 | IQ motif and SEC7 domain-containing protein 3 | Rattus norvegicus (Rat) | SS |
| A0A0G2JUG7 | Iqsec1 | IQ motif and SEC7 domain-containing protein 1 | Rattus norvegicus (Rat) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MEAGSGPPGG | PGSESPNRAV | EYLLELNNII | ESQQQLLETQ | RRRIEELEGQ | LDQLTQENRD |
| 70 | 80 | 90 | 100 | 110 | 120 |
| LREESQLHRG | ELHRDPLGAR | DSPGRESQYQ | NLRETQFHHR | ELRESQFHQA | SRDVGYPNRD |
| 130 | 140 | 150 | 160 | 170 | 180 |
| GAYQNREAIY | RDKEREASYQ | LQDTTGYTAR | ERDVAQCHLH | HENPALGRER | GGREAGPAHP |
| 190 | 200 | 210 | 220 | 230 | 240 |
| GREKEAGYSA | AVGVGQRPPR | ERGQLSRGAS | RSSSPGAGGG | HSTSTSTSPA | TTLQRNVEGD |
| 250 | 260 | 270 | 280 | 290 | 300 |
| APGSDLSTAV | DSPGSQPPYR | LSQLPPTSSH | MGGPPAGVGL | PWAQRARLQP | ASVALRKQEE |
| 310 | 320 | 330 | 340 | 350 | 360 |
| EEIKRSKALS | DSYELSTDLQ | DKKVEMLERK | YGGSFLSRRA | ARTIQTAFRQ | YRMNKNFERL |
| 370 | 380 | 390 | 400 | 410 | 420 |
| RSSASESRMS | RRIILSNMRM | QFSFEEYEKA | QNPAYFEGKP | ASLDEGAMAG | ARSHRLERGL |
| 430 | 440 | 450 | 460 | 470 | 480 |
| PYGGSCGGGI | DGGGSSVTTS | GEFSNDITEL | EDSFSKQVKS | LAESIDEALN | CHPSGPMSEE |
| 490 | 500 | 510 | 520 | 530 | 540 |
| PGSAQLEKRE | SKEQQEDSSA | TSFSDLPLYL | DDPVPPPSPE | RLPSTEPPPQ | GRPEFWAPAP |
| 550 | 560 | 570 | 580 | 590 | 600 |
| LPPVPPPMPP | GTREDGSREE | GTRRGPGCLE | CRDFRLRAAH | LPLLTIEPPS | DSSVDLSDRS |
| 610 | 620 | 630 | 640 | 650 | 660 |
| DRGSVHRQLV | YEADGCSPHG | TLKHKGPPGR | APIPHRHYPA | PEGPAPAPPG | PLPPAPNSGT |
| 670 | 680 | 690 | 700 | 710 | 720 |
| GPSGVAGGRR | LGKCEAAGEN | SDGGDNESLE | SSSNSNETIN | CSSGSSSRDS | LREPPATGLC |
| 730 | 740 | 750 | 760 | 770 | 780 |
| KQTYQRETRH | SWDSPAFNND | VVQRRHYRIG | LNLFNKKPEK | GIQYLIERGF | LSDTPVGVAH |
| 790 | 800 | 810 | 820 | 830 | 840 |
| FILERKGLSR | QMIGEFLGNR | QKQFNRDVLD | CVVDEMDFSS | MDLDDALRKF | QSHIRVQGEA |
| 850 | 860 | 870 | 880 | 890 | 900 |
| QKVERLIEAF | SQRYCVCNPA | LVRQFRNPDT | IFILAFAIIL | LNTDMYSPSV | KAERKMKLDD |
| 910 | 920 | 930 | 940 | 950 | 960 |
| FIKNLRGVDN | GEDIPRDLLV | GIYQRIQGRE | LRTNDDHVSQ | VQAVERMIVG | KKPVLSLPHR |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| RLVCCCQLYE | VPDPNRPQRL | GLHQREVFLF | NDLLVVTKIF | QKKKILVTYS | FRQSFPLVEM |
| 1030 | 1040 | 1050 | 1060 | 1070 | 1080 |
| HMQLFQNSYY | QFGIKLLSAV | PGGERKVLII | FNAPSLQDRL | RFTSDLRESI | AEVQEMEKYR |
| 1090 | 1100 | 1110 | 1120 | 1130 | 1140 |
| VESELEKQKG | MMRPNASQPG | GAKDSVNGTL | ARSSLEDTYG | AGDGLKRGAL | SSSLRDLSDA |
| 1150 | 1160 | 1170 | 1180 | 1190 | 1200 |
| GKRGRRNSVG | SLDSTIEGSV | ISSPRPHQRM | PPPPPPPPPE | EYKSQRPVSN | SSSFLGSLFG |
| 1210 | 1220 | 1230 | 1240 | 1250 | 1260 |
| SKRGKGPFQM | PPPPTGQASA | SSSSASSTHH | HHHHHHHGHS | HGGLGVLPDG | QSKLQALHAQ |
| 1270 | 1280 | 1290 | 1300 | 1310 | 1320 |
| YCQGPGPAPP | PYLPPQQPPL | PPPPQQPPPL | PQLGSIPPPP | ASAPPVGPHR | HFHAHGPVPG |
| 1330 | 1340 | 1350 | 1360 | 1370 | 1380 |
| PQHYTLGRPG | RAPRRGAGGH | PQFAPHGRHP | LHQPTSPLPL | YSPAPQHPPA | HKQGPKHFIF |
| 1390 | 1400 | 1410 | 1420 | 1430 | 1440 |
| SHHPQMMPAA | GAAGGPGSRP | PGGSYSHPHH | PQSPLSPHSP | IPPHPSYPPL | PPPSPHTPHS |
| 1450 | 1460 | 1470 | |||
| PLPPTSPHGP | LHASGPPGTA | NPPSANPKAK | PSRISTVV |