IQEC1_HUMAN
ID IQEC1_HUMAN Reviewed; 963 AA.
AC Q6DN90; A0A087WWK8; O94863; Q96D85;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=IQ motif and SEC7 domain-containing protein 1 {ECO:0000305};
DE AltName: Full=ADP-ribosylation factors guanine nucleotide-exchange protein 100;
DE AltName: Full=ADP-ribosylation factors guanine nucleotide-exchange protein 2;
DE AltName: Full=Brefeldin-resistant Arf-GEF 2 protein {ECO:0000303|PubMed:16461286};
DE Short=BRAG2 {ECO:0000303|PubMed:24058294, ECO:0000303|PubMed:31607425};
GN Name=IQSEC1 {ECO:0000312|HGNC:HGNC:29112};
GN Synonyms=ARFGEP100, BRAG2 {ECO:0000303|PubMed:31607425}, KIAA0763;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RX PubMed=16461286; DOI=10.1016/j.cub.2005.12.032;
RA Dunphy J.L., Moravec R., Ly K., Lasell T.K., Melancon P., Casanova J.E.;
RT "The Arf6 GEF GEP100/BRAG2 regulates cell adhesion by controlling
RT endocytosis of beta1 integrins.";
RL Curr. Biol. 16:315-320(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9872452; DOI=10.1093/dnares/5.5.277;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XI. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:277-286(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-936 (ISOFORM 2).
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, FUNCTION, AND INTERACTION WITH
RP ARF6.
RX PubMed=11226253; DOI=10.1073/pnas.051634798;
RA Someya A., Sata M., Takeda K., Pacheco-Rodriguez G., Ferrans V.J., Moss J.,
RA Vaughan M.;
RT "ARF-GEP(100), a guanine nucleotide-exchange protein for ADP-ribosylation
RT factor 6.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:2413-2418(2001).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-512, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-180 AND SER-512, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-89; SER-105; SER-107;
RP SER-180; SER-512; SER-515; SER-892 AND SER-925, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-180; SER-253; SER-512;
RP TYR-911; SER-924 AND SER-925, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12] {ECO:0007744|PDB:3QWM}
RP X-RAY CRYSTALLOGRAPHY (2.39 ANGSTROMS) OF 743-880.
RG Structural genomics consortium (SGC);
RT "Crystal Structure of GEP100, the plextrin homology domain of IQ motif and
RT SEC7 domain-containing protein 1 isoform a.";
RL Submitted (FEB-2011) to the PDB data bank.
RN [13] {ECO:0007744|PDB:4C0A}
RP X-RAY CRYSTALLOGRAPHY (3.30 ANGSTROMS) OF 512-885 OF MUTANT LYS-620 IN
RP COMPLEX WITH ARF1, INTERACTION WITH ARF1, FUNCTION, MUTAGENESIS OF GLU-620,
RP AND DOMAIN.
RX PubMed=24058294; DOI=10.1371/journal.pbio.1001652;
RA Aizel K., Biou V., Navaza J., Duarte L.V., Campanacci V., Cherfils J.,
RA Zeghouf M.;
RT "Integrated conformational and lipid-sensing regulation of endosomal ArfGEF
RT BRAG2.";
RL PLoS Biol. 11:E1001652-E1001652(2013).
RN [14]
RP INVOLVEMENT IN IDDSSBA, VARIANTS IDDSSBA GLN-335 AND MET-357,
RP CHARACTERIZATION OF VARIANTS IDDSSBA GLN-335 AND MET-357, AND FUNCTION.
RX PubMed=31607425; DOI=10.1016/j.ajhg.2019.09.013;
RA Ansar M., Chung H.L., Al-Otaibi A., Elagabani M.N., Ravenscroft T.A.,
RA Paracha S.A., Scholz R., Abdel Magid T., Sarwar M.T., Shah S.F.,
RA Qaisar A.A., Makrythanasis P., Marcogliese P.C., Kamsteeg E.J.,
RA Falconnet E., Ranza E., Santoni F.A., Aldhalaan H., Al-Asmari A.,
RA Faqeih E.A., Ahmed J., Kornau H.C., Bellen H.J., Antonarakis S.E.;
RT "Bi-allelic Variants in IQSEC1 Cause Intellectual Disability, Developmental
RT Delay, and Short Stature.";
RL Am. J. Hum. Genet. 105:907-920(2019).
CC -!- FUNCTION: Guanine nucleotide exchange factor for ARF1 and ARF6
CC (PubMed:24058294, PubMed:11226253). Guanine nucleotide exchange factor
CC activity is enhanced by lipid binding (PubMed:24058294). Accelerates
CC GTP binding by ARFs of all three classes. Guanine nucleotide exchange
CC protein for ARF6, mediating internalization of beta-1 integrin
CC (PubMed:16461286). Involved in neuronal development (Probable). In
CC neurons, plays a role in the control of vesicle formation by endocytoc
CC cargo. Upon long term depression, interacts with GRIA2 and mediates the
CC activation of ARF6 to internalize synaptic AMPAR receptors (By
CC similarity). {ECO:0000250|UniProtKB:A0A0G2JUG7,
CC ECO:0000269|PubMed:11226253, ECO:0000269|PubMed:16461286,
CC ECO:0000269|PubMed:24058294, ECO:0000305|PubMed:31607425}.
CC -!- SUBUNIT: Interacts with ARF1 and ARF6. Interacts with GRIA2; the
CC interaction is required for ARF6 activation (By similarity).
CC {ECO:0000250|UniProtKB:A0A0G2JUG7, ECO:0000269|PubMed:11226253,
CC ECO:0000269|PubMed:24058294}.
CC -!- INTERACTION:
CC Q6DN90; P50148: GNAQ; NbExp=2; IntAct=EBI-3044091, EBI-3909604;
CC Q6DN90-2; P01023: A2M; NbExp=3; IntAct=EBI-21911304, EBI-640741;
CC Q6DN90-2; A0A0S2Z5Q7: ALS2; NbExp=3; IntAct=EBI-21911304, EBI-25928834;
CC Q6DN90-2; Q92870-2: APBB2; NbExp=3; IntAct=EBI-21911304, EBI-21535880;
CC Q6DN90-2; P05067: APP; NbExp=3; IntAct=EBI-21911304, EBI-77613;
CC Q6DN90-2; P05067-2: APP; NbExp=3; IntAct=EBI-21911304, EBI-17264467;
CC Q6DN90-2; P54253: ATXN1; NbExp=6; IntAct=EBI-21911304, EBI-930964;
CC Q6DN90-2; Q14203-5: DCTN1; NbExp=3; IntAct=EBI-21911304, EBI-25840379;
CC Q6DN90-2; P50570-2: DNM2; NbExp=3; IntAct=EBI-21911304, EBI-10968534;
CC Q6DN90-2; Q8TB36: GDAP1; NbExp=3; IntAct=EBI-21911304, EBI-11110431;
CC Q6DN90-2; P42858: HTT; NbExp=18; IntAct=EBI-21911304, EBI-466029;
CC Q6DN90-2; P51608: MECP2; NbExp=3; IntAct=EBI-21911304, EBI-1189067;
CC Q6DN90-2; Q99497: PARK7; NbExp=3; IntAct=EBI-21911304, EBI-1164361;
CC Q6DN90-2; Q7Z412: PEX26; NbExp=3; IntAct=EBI-21911304, EBI-752057;
CC Q6DN90-2; Q9BXM7: PINK1; NbExp=3; IntAct=EBI-21911304, EBI-2846068;
CC Q6DN90-2; D3DTS7: PMP22; NbExp=3; IntAct=EBI-21911304, EBI-25882629;
CC Q6DN90-2; O60260-5: PRKN; NbExp=6; IntAct=EBI-21911304, EBI-21251460;
CC Q6DN90-2; P49768-2: PSEN1; NbExp=6; IntAct=EBI-21911304, EBI-11047108;
CC Q6DN90-2; Q16637: SMN2; NbExp=3; IntAct=EBI-21911304, EBI-395421;
CC Q6DN90-2; P37840: SNCA; NbExp=3; IntAct=EBI-21911304, EBI-985879;
CC Q6DN90-2; P00441: SOD1; NbExp=3; IntAct=EBI-21911304, EBI-990792;
CC Q6DN90-2; Q13148: TARDBP; NbExp=6; IntAct=EBI-21911304, EBI-372899;
CC Q6DN90-2; O14656-2: TOR1A; NbExp=3; IntAct=EBI-21911304, EBI-25847109;
CC Q6DN90-2; P09936: UCHL1; NbExp=3; IntAct=EBI-21911304, EBI-714860;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11226253}. Nucleus
CC {ECO:0000269|PubMed:11226253}. Postsynaptic density
CC {ECO:0000250|UniProtKB:Q8R0S2}. Cytoplasmic vesicle, secretory vesicle,
CC synaptic vesicle {ECO:0000250|UniProtKB:Q8R0S2}. Note=At steady state,
CC may be preferentially cytosolic.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=BRAG2b;
CC IsoId=Q6DN90-1; Sequence=Displayed;
CC Name=2; Synonyms=BRAG2a;
CC IsoId=Q6DN90-2; Sequence=VSP_019758;
CC Name=3;
CC IsoId=Q6DN90-3; Sequence=VSP_060581, VSP_060582;
CC -!- TISSUE SPECIFICITY: Expressed in brain, ovary, heart, lung, liver,
CC kidney and leukocytes. Moderate expression was also detected in lung,
CC skeletal muscle, placenta, small intestine, pancreas, spleen and
CC testis. {ECO:0000269|PubMed:11226253, ECO:0000269|PubMed:9872452}.
CC -!- DOMAIN: The PH domain mediates interaction with lipid membranes that
CC contain phosphatidylinositol-4,5-bisphosphate, but does not bind
CC membranes that lack phosphatidylinositol-4,5-bisphosphate.
CC {ECO:0000269|PubMed:24058294}.
CC -!- DISEASE: Intellectual developmental disorder with short stature and
CC behavioral abnormalities (IDDSSBA) [MIM:618687]: An autosomal recessive
CC disorder with onset in infancy and characterized by intellectual
CC disability, developmental delay, short stature, aphasia, and hypotonia.
CC Additional features include seizures and behavioral abnormalities, such
CC as inattention, hyperactivity and aggression.
CC {ECO:0000269|PubMed:31607425}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the BRAG family. {ECO:0000305}.
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DR EMBL; AY653734; AAT72063.1; -; mRNA.
DR EMBL; AC018836; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF495709; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC069246; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC069271; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF457597; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB018306; BAA34483.2; -; mRNA.
DR EMBL; BC010267; AAH10267.1; -; mRNA.
DR CCDS; CCDS33703.1; -. [Q6DN90-1]
DR CCDS; CCDS74902.1; -. [Q6DN90-3]
DR RefSeq; NP_001127854.1; NM_001134382.2. [Q6DN90-3]
DR RefSeq; NP_001317548.1; NM_001330619.1.
DR RefSeq; NP_055684.3; NM_014869.6. [Q6DN90-1]
DR RefSeq; XP_011532617.1; XM_011534315.2.
DR PDB; 3QWM; X-ray; 2.39 A; A=743-880.
DR PDB; 4C0A; X-ray; 3.30 A; A/B/E/F=512-885.
DR PDB; 5NLV; X-ray; 2.40 A; A=512-885.
DR PDB; 5NLY; X-ray; 2.00 A; A/B=512-885.
DR PDB; 6FNE; X-ray; 2.50 A; A/B=512-885.
DR PDBsum; 3QWM; -.
DR PDBsum; 4C0A; -.
DR PDBsum; 5NLV; -.
DR PDBsum; 5NLY; -.
DR PDBsum; 6FNE; -.
DR AlphaFoldDB; Q6DN90; -.
DR SMR; Q6DN90; -.
DR BioGRID; 115250; 103.
DR IntAct; Q6DN90; 53.
DR MINT; Q6DN90; -.
DR STRING; 9606.ENSP00000480301; -.
DR iPTMnet; Q6DN90; -.
DR PhosphoSitePlus; Q6DN90; -.
DR BioMuta; IQSEC1; -.
DR DMDM; 74748429; -.
DR EPD; Q6DN90; -.
DR jPOST; Q6DN90; -.
DR MassIVE; Q6DN90; -.
DR MaxQB; Q6DN90; -.
DR PaxDb; Q6DN90; -.
DR PeptideAtlas; Q6DN90; -.
DR PRIDE; Q6DN90; -.
DR ProteomicsDB; 66252; -. [Q6DN90-1]
DR ProteomicsDB; 66253; -. [Q6DN90-2]
DR Antibodypedia; 26313; 50 antibodies from 22 providers.
DR DNASU; 9922; -.
DR Ensembl; ENST00000273221.8; ENSP00000273221.4; ENSG00000144711.16. [Q6DN90-1]
DR Ensembl; ENST00000613206.2; ENSP00000480301.1; ENSG00000144711.16. [Q6DN90-3]
DR GeneID; 9922; -.
DR KEGG; hsa:9922; -.
DR MANE-Select; ENST00000613206.2; ENSP00000480301.1; NM_001134382.3; NP_001127854.1. [Q6DN90-3]
DR UCSC; uc003bxt.4; human. [Q6DN90-1]
DR CTD; 9922; -.
DR DisGeNET; 9922; -.
DR GeneCards; IQSEC1; -.
DR HGNC; HGNC:29112; IQSEC1.
DR HPA; ENSG00000144711; Low tissue specificity.
DR MalaCards; IQSEC1; -.
DR MIM; 610166; gene.
DR MIM; 618687; phenotype.
DR neXtProt; NX_Q6DN90; -.
DR OpenTargets; ENSG00000144711; -.
DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability.
DR PharmGKB; PA128394566; -.
DR VEuPathDB; HostDB:ENSG00000144711; -.
DR eggNOG; KOG0931; Eukaryota.
DR GeneTree; ENSGT00940000156915; -.
DR InParanoid; Q6DN90; -.
DR OMA; SMDHHKL; -.
DR OrthoDB; 837077at2759; -.
DR PhylomeDB; Q6DN90; -.
DR TreeFam; TF323811; -.
DR PathwayCommons; Q6DN90; -.
DR SignaLink; Q6DN90; -.
DR BioGRID-ORCS; 9922; 13 hits in 1082 CRISPR screens.
DR ChiTaRS; IQSEC1; human.
DR GeneWiki; IQSEC1; -.
DR GenomeRNAi; 9922; -.
DR Pharos; Q6DN90; Tbio.
DR PRO; PR:Q6DN90; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q6DN90; protein.
DR Bgee; ENSG00000144711; Expressed in Brodmann (1909) area 46 and 192 other tissues.
DR ExpressionAtlas; Q6DN90; baseline and differential.
DR Genevisible; Q6DN90; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell.
DR GO; GO:0008021; C:synaptic vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IEA:UniProtKB-KW.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0060996; P:dendritic spine development; ISS:UniProtKB.
DR GO; GO:0120183; P:positive regulation of focal adhesion disassembly; ISS:ARUK-UCL.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IEA:InterPro.
DR GO; GO:0051549; P:positive regulation of keratinocyte migration; ISS:ARUK-UCL.
DR GO; GO:0032012; P:regulation of ARF protein signal transduction; IEA:InterPro.
DR CDD; cd13318; PH_IQSEC; 1.
DR CDD; cd00171; Sec7; 1.
DR Gene3D; 1.10.1000.11; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR InterPro; IPR030737; IQSEC1.
DR InterPro; IPR033742; IQSEC_PH.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR023394; Sec7_C_sf.
DR InterPro; IPR000904; Sec7_dom.
DR InterPro; IPR035999; Sec7_dom_sf.
DR PANTHER; PTHR10663:SF327; PTHR10663:SF327; 1.
DR Pfam; PF16453; IQ_SEC7_PH; 1.
DR Pfam; PF01369; Sec7; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00222; Sec7; 1.
DR SUPFAM; SSF48425; SSF48425; 1.
DR PROSITE; PS50096; IQ; 1.
DR PROSITE; PS50190; SEC7; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Cytoplasm;
KW Cytoplasmic vesicle; Dwarfism; Guanine-nucleotide releasing factor;
KW Intellectual disability; Lipid-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Synapse.
FT CHAIN 1..963
FT /note="IQ motif and SEC7 domain-containing protein 1"
FT /id="PRO_0000245606"
FT DOMAIN 134..163
FT /note="IQ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT DOMAIN 517..710
FT /note="SEC7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00189"
FT DOMAIN 774..866
FT /note="PH"
FT REGION 21..88
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 312..332
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 349..513
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 922..947
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 848..879
FT /evidence="ECO:0000255"
FT COMPBIAS 27..47
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 390..404
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 426..443
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 468..498
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 89
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 105
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 107
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 180
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 249
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8R0S2"
FT MOD_RES 253
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 512
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 515
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 892
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 911
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 924
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 925
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..122
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9872452"
FT /id="VSP_019758"
FT VAR_SEQ 1..22
FT /note="MWCLHCNSERTQSLLELELDSG -> MACRRRYF (in isoform 3)"
FT /id="VSP_060581"
FT VAR_SEQ 950..963
FT /note="FQPFEPLQPSVLCS -> GSIISSPHMRRRATSTRECPSRPHQTMPNSSSLL
FT GSLFGSKRGKPPPQAHLPSAPALPPPHPPVVLPHLQHSVAGHHLGPPEGLPQAAMHGHH
FT TQYCHMQNPPPYHHHHHHHPPQHIQHAHQYHHGPHGGHPAYGAHAHGHPPLPSAHVGHT
FT VHHHGQPPAPPPPTSSKAKPSGISTIV (in isoform 3)"
FT /id="VSP_060582"
FT VARIANT 335
FT /note="R -> Q (in IDDSSBA; loss of function;
FT dbSNP:rs758170522)"
FT /evidence="ECO:0000269|PubMed:31607425"
FT /id="VAR_083480"
FT VARIANT 357
FT /note="T -> M (in IDDSSBA; loss of function;
FT dbSNP:rs765723607)"
FT /evidence="ECO:0000269|PubMed:31607425"
FT /id="VAR_083481"
FT VARIANT 640
FT /note="P -> S (in dbSNP:rs35319679)"
FT /id="VAR_051927"
FT VARIANT 882
FT /note="V -> I (in dbSNP:rs17541405)"
FT /id="VAR_027004"
FT MUTAGEN 620
FT /note="E->K: Abolishes guanosine nucleotide exchange factor
FT activity."
FT /evidence="ECO:0000269|PubMed:24058294"
FT CONFLICT 934..936
FT /note="KRG -> VHH (in Ref. 4)"
FT /evidence="ECO:0000305"
FT HELIX 516..518
FT /evidence="ECO:0007829|PDB:5NLV"
FT HELIX 522..537
FT /evidence="ECO:0007829|PDB:5NLY"
FT HELIX 539..548
FT /evidence="ECO:0007829|PDB:5NLY"
FT HELIX 556..565
FT /evidence="ECO:0007829|PDB:5NLY"
FT HELIX 571..578
FT /evidence="ECO:0007829|PDB:5NLY"
FT HELIX 584..594
FT /evidence="ECO:0007829|PDB:5NLY"
FT HELIX 604..614
FT /evidence="ECO:0007829|PDB:5NLY"
FT HELIX 621..638
FT /evidence="ECO:0007829|PDB:5NLY"
FT HELIX 640..643
FT /evidence="ECO:0007829|PDB:5NLY"
FT STRAND 646..648
FT /evidence="ECO:0007829|PDB:5NLY"
FT HELIX 651..666
FT /evidence="ECO:0007829|PDB:5NLY"
FT TURN 669..671
FT /evidence="ECO:0007829|PDB:4C0A"
FT HELIX 673..675
FT /evidence="ECO:0007829|PDB:5NLY"
FT HELIX 679..685
FT /evidence="ECO:0007829|PDB:5NLY"
FT TURN 686..689
FT /evidence="ECO:0007829|PDB:5NLY"
FT HELIX 697..709
FT /evidence="ECO:0007829|PDB:5NLY"
FT HELIX 718..728
FT /evidence="ECO:0007829|PDB:5NLY"
FT STRAND 729..731
FT /evidence="ECO:0007829|PDB:5NLY"
FT STRAND 753..761
FT /evidence="ECO:0007829|PDB:5NLY"
FT STRAND 774..781
FT /evidence="ECO:0007829|PDB:5NLY"
FT STRAND 784..793
FT /evidence="ECO:0007829|PDB:5NLY"
FT STRAND 798..807
FT /evidence="ECO:0007829|PDB:5NLY"
FT STRAND 811..816
FT /evidence="ECO:0007829|PDB:5NLY"
FT STRAND 824..829
FT /evidence="ECO:0007829|PDB:5NLY"
FT STRAND 832..834
FT /evidence="ECO:0007829|PDB:5NLY"
FT STRAND 837..843
FT /evidence="ECO:0007829|PDB:5NLY"
FT HELIX 847..871
FT /evidence="ECO:0007829|PDB:5NLY"
FT HELIX 874..877
FT /evidence="ECO:0007829|PDB:5NLY"
SQ SEQUENCE 963 AA; 108314 MW; 5B31F9918F9CFF11 CRC64;
MWCLHCNSER TQSLLELELD SGVEGEAPSS ETGTSLDSPS AYPQGPLVPG SSLSPDHYEH
TSVGAYGLYS GPPGQQQRTR RPKLQHSTSI LRKQAEEEAI KRSRSLSESY ELSSDLQDKQ
VEMLERKYGG RLVTRHAART IQTAFRQYQM NKNFERLRSS MSENRMSRRI VLSNMRMQFS
FEGPEKVHSS YFEGKQVSVT NDGSQLGALV SPECGDLSEP TTLKSPAPSS DFADAITELE
DAFSRQVKSL AESIDDALNC RSLHTEEAPA LDAARARDTE PQTALHGMDH RKLDEMTASY
SDVTLYIDEE ELSPPLPLSQ AGDRPSSTES DLRLRAGGAA PDYWALAHKE DKADTDTSCR
STPSLERQEQ RLRVEHLPLL TIEPPSDSSV DLSDRSERGS LKRQSAYERS LGGQQGSPKH
GPHSGAPKSL PREEPELRPR PPRPLDSHLA INGSANRQSK SESDYSDGDN DSINSTSNSN
DTINCSSESS SRDSLREQTL SKQTYHKEAR NSWDSPAFSN DVIRKRHYRI GLNLFNKKPE
KGVQYLIERG FVPDTPVGVA HFLLQRKGLS RQMIGEFLGN RQKQFNRDVL DCVVDEMDFS
TMELDEALRK FQAHIRVQGE AQKVERLIEA FSQRYCICNP GVVRQFRNPD TIFILAFAII
LLNTDMYSPN VKPERKMKLE DFIKNLRGVD DGEDIPREML MGIYERIRKR ELKTNEDHVS
QVQKVEKLIV GKKPIGSLHP GLGCVLSLPH RRLVCYCRLF EVPDPNKPQK LGLHQREIFL
FNDLLVVTKI FQKKKNSVTY SFRQSFSLYG MQVLLFENQY YPNGIRLTSS VPGADIKVLI
NFNAPNPQDR KKFTDDLRES IAEVQEMEKH RIESELEKQK GVVRPSMSQC SSLKKESGNG
TLSRACLDDS YASGEGLKRS ALSSSLRDLS EAGKRGRRSS AGSLESNVEF QPFEPLQPSV
LCS
