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

648-985 (Sec7-PH domains)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q3TES0

Entry ID Method Resolution Chain Position Source
AF-Q3TES0-F1 Predicted AlphaFoldDB

66 variants for Q3TES0

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3544759385 78 P>S No EVA
rs3396893969 135 Q>R No EVA
rs3388854060 234 A>P No EVA
rs3544780982 269 R>Q No EVA
rs3388858851 293 D>A No EVA
rs3396888259 299 I>S No EVA
rs3397056113 301 M>R No EVA
rs3397313266 301 M>V No EVA
rs3388851496 305 K>N No EVA
rs3397261708 306 Y>* No EVA
rs3397227786 306 Y>C No EVA
rs3396893996 355 A>E No EVA
rs3388858102 380 R>H No EVA
rs3388847374 419 L>F No EVA
rs3388857581 456 E>V No EVA
rs3388864074 458 G>D No EVA
rs3388834979 463 D>G No EVA
rs3388857626 482 D>E No EVA
rs3388855258 500 L>M No EVA
rs250826552 515 A>T No EVA
rs223718778 522 A>V No EVA
rs263894200 540 Q>K No EVA
rs3388859261 555 A>V No EVA
rs3544814545 557 S>G No EVA
rs216863181 572 V>L No EVA
rs3388858906 578 E>* No EVA
rs3388857565 581 E>D No EVA
rs3388821613 582 G>W No EVA
rs3388859281 584 K>I No EVA
rs3544776693 589 G>R No EVA
rs3388821569 627 Q>R No EVA
rs3388858080 643 S>R No EVA
rs3388852805 656 K>Q No EVA
rs3388854007 713 K>E No EVA
rs3388834997 723 C>Y No EVA
rs3388854053 728 M>L No EVA
rs3388855321 741 K>E No EVA
rs3388857622 747 R>H No EVA
rs3388821604 748 V>E No EVA
rs3388821634 749 Q>L No EVA
rs3388864097 749 Q>S No EVA
rs3388851489 754 K>N No EVA
rs3388851553 778 H>N No EVA
rs3388864087 790 I>M No EVA
rs3388845462 817 L>P No EVA
rs231278348 844 K>R No EVA
rs3388854062 846 N>H No EVA
rs3388839260 881 F>L No EVA
rs3388858104 890 Q>L No EVA
rs3388859222 891 K>I No EVA
rs3388850868 895 H>Q No EVA
rs3388841646 902 F>I No EVA
rs45636588 906 L>F No EVA
rs3388859214 922 T>I No EVA
rs3388850828 930 L>F No EVA
rs3397148117 944 H>R No EVA
rs3388855261 964 C>Y No EVA
rs3388854043 966 L>V No EVA
rs3388855314 1050 Q>H No EVA
rs3388849935 1067 P>S No EVA
rs3412781027 1097 P>L No EVA
rs3388852761 1104 V>I No EVA
rs3397313265 1115 L>Q No EVA
rs3388821592 1121 A>T No EVA
rs3388858073 1139 S>P No EVA
rs3388858822 1146 P>S No EVA

No associated diseases with Q3TES0

2 regional properties for Q3TES0

Type Name Position InterPro Accession
domain Sec7 domain 648 - 843 IPR000904
domain IQ motif and SEC7 domain-containing protein, PH domain 863 - 1000 IPR033742

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm
  • Postsynaptic density
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

8 GO annotations of cellular component

Name Definition
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
GABA-ergic synapse A synapse that uses GABA as a neurotransmitter. These synapses are typically inhibitory.
glycinergic synapse A synapse that uses glycine as a neurotransmitter.
inhibitory synapse A synapse in which an action potential in the presynaptic cell reduces the probability of an action potential occurring in the postsynaptic cell.
nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus.
postsynaptic density An electron dense network of proteins within and adjacent to the postsynaptic membrane of an asymmetric, neuron-neuron synapse. Its major components include neurotransmitter receptors and the proteins that spatially and functionally organize them such as anchoring and scaffolding molecules, signaling enzymes and cytoskeletal components.
postsynaptic membrane A specialized area of membrane facing the presynaptic membrane on the tip of the nerve ending and separated from it by a minute cleft (the synaptic cleft). Neurotransmitters cross the synaptic cleft and transmit the signal to the postsynaptic membrane.
postsynaptic specialization of symmetric synapse A network of proteins within and adjacent to the postsynaptic membrane of a symmetric synapse, consisting of anchoring and scaffolding molecules, signaling enzymes and cytoskeletal components that spatially and functionally organize the neurotransmitter receptors at the synapse. This structure is not as thick or electron dense as the postsynaptic densities found in asymmetric synapses.

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.

4 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.
postsynapse organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a postsynapse.
regulation of ARF protein signal transduction Any process that modulates the frequency, rate or extent of ARF protein signal transduction.
regulation of small GTPase mediated signal transduction Any process that modulates the frequency, rate or extent of small GTPase mediated signal transduction.

13 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q5JU85 IQSEC2 IQ motif and SEC7 domain-containing protein 2 Homo sapiens (Human) EV
Q6DN90 IQSEC1 IQ motif and SEC7 domain-containing protein 1 Homo sapiens (Human) EV
Q9UPP2 IQSEC3 IQ motif and SEC7 domain-containing protein 3 Homo sapiens (Human) 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
O08967 Cyth3 Cytohesin-3 Mus musculus (Mouse) EV
Q8R0S2 Iqsec1 IQ motif and SEC7 domain-containing protein 1 Mus musculus (Mouse) SS
P63034 Cyth2 Cytohesin-2 Mus musculus (Mouse) SS
Q9QX11 Cyth1 Cytohesin-1 Mus musculus (Mouse) SS
Q5DU25 Iqsec2 IQ motif and SEC7 domain-containing protein 2 Mus musculus (Mouse) SS
A0A0G2JUG7 Iqsec1 IQ motif and SEC7 domain-containing protein 1 Rattus norvegicus (Rat) SS
Q76M68 Iqsec3 IQ motif and SEC7 domain-containing protein 3 Rattus norvegicus (Rat) SS
10 20 30 40 50 60
MESLLENPVR AVLYLKELTA IVQNQQSLIH TQRQRIDELE RRLDELSAEN RSLWEHQQLL
70 80 90 100 110 120
QAQPPPGLVP PPPSAPLPAP AVTAPAAAAA QEPLQDHGQL IPASPEPPLQ HHGQLLAQPQ
130 140 150 160 170 180
PAPSSRVQTP QSPHQHPVAP GAIADKEKER PSSCCAAAGA LLQHASPAAL GKGVLSRRPE
190 200 210 220 230 240
NETVLHQFCC PAADTEQKPA CSDLASQSDG SCAQAGGGME DSVVAAVAAG RPSAHAPKAQ
250 260 270 280 290 300
APELQQEEER PGAVGSPRAG PLRAASPGRQ QPALATALCS HTPAASEYEL SLDLKNKQIE
310 320 330 340 350 360
MLEHKYGGHL VSRRAACTIQ TAFRQYQLSK NFEKIRNSLL ESRLPRRISL RKVRAPTAES
370 380 390 400 410 420
LVAEKALLEG CGLLGLPLGR SPSLPPTFAG SLTELEDSFT EQVQSLAKSI DDALSTWSLK
430 440 450 460 470 480
TMCSLQESGA YQLHQALHPS AGQPGLETEA AAREPESGPG SGDEAGGLPQ GHSGTLMMAF
490 500 510 520 530 540
RDVTVQIANQ NISVSSSTAL SVANCLGAQT AQATAEPAAA QAEQEDTADQ EVSEVPASEQ
550 560 570 580 590 600
MDPPSEDSEA AESRAQSAQE PAVAQAVVEE AVATEAEEEE EGAKQAGKGA EAEGGDNSEQ
610 620 630 640 650 660
LSSSSASTKS AKSSSEASAA ASKEALQAVI LSLPRYHCEN PASCRSPTLS TDTLRKRLYR
670 680 690 700 710 720
IGLNLFNINP DKGIQFLISR GFIPDTPIGV AHFLLQRKGL SRQMIGEFLG NSKKQFNRDV
730 740 750 760 770 780
LDCVVDEMDF SNMELDEALR KFQAHIRVQG EAQKVERLIE AFSQRYCMCN PEVVQQFHNP
790 800 810 820 830 840
DTIFILAFAI ILLNTDMYSP NIKPDRKMML EDFIRNLRGV DDGADIPREL VVGIYERIQQ
850 860 870 880 890 900
KELKSNEDHV TYVTKVEKSI VGMKTVLSMP HRRLVCCSRL FEVTDVNKLQ KQAAHQREVF
910 920 930 940 950 960
LFNDLLVILK LCPKKKSSFT YTFCKAVGLL GMRFHLFENE YYSHGITLAT PLSGSEKKQV
970 980 990 1000 1010 1020
LHFCALGSDE MQKFVEDLKE SIAEVTELEQ IRIEWELEKQ QGTKTLSVRS AGAQGDPQSK
1030 1040 1050 1060 1070 1080
QGSPTAKREA MAGEKAAESS GEVSIHNRLQ TSQHSPKLGV ERGAPAPSPP TSPPPLPPDP
1090 1100 1110 1120 1130 1140
QPSPLREQPP PLPLPPPTPP GTLVQCQQIV KVIVLDKPCL ARMEPLLSQA LSCYASSSSD
1150 1160 1170 1180 1190
SCGSTPLRGP GSPVKVIHQP PLPPPPPPYN HPHQFCPPGS MLLRRRYSSG SRSLV