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 27-MAR-2024, entry version 175. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7VMB; X-ray; 2.00 A; A=517-882, B=106-173. DR PDBsum; 3QWM; -. DR PDBsum; 4C0A; -. DR PDBsum; 5NLV; -. DR PDBsum; 5NLY; -. DR PDBsum; 6FNE; -. DR PDBsum; 7VMB; -. DR AlphaFoldDB; Q6DN90; -. DR SMR; Q6DN90; -. DR BioGRID; 115250; 118. DR IntAct; Q6DN90; 55. 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; 9606-ENSP00000480301; -. DR PeptideAtlas; Q6DN90; -. DR ProteomicsDB; 66252; -. [Q6DN90-1] DR ProteomicsDB; 66253; -. [Q6DN90-2] DR Pumba; Q6DN90; -. DR Antibodypedia; 26313; 69 antibodies from 23 providers. DR DNASU; 9922; -. DR Ensembl; ENST00000273221.8; ENSP00000273221.4; ENSG00000144711.17. [Q6DN90-1] DR Ensembl; ENST00000613206.2; ENSP00000480301.1; ENSG00000144711.17. [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 AGR; HGNC:29112; -. 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; AGHSAHH; -. DR OrthoDB; 204547at2759; -. DR PhylomeDB; Q6DN90; -. DR TreeFam; TF323811; -. DR PathwayCommons; Q6DN90; -. DR SignaLink; Q6DN90; -. DR BioGRID-ORCS; 9922; 13 hits in 1161 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 194 other cell types or tissues. DR ExpressionAtlas; Q6DN90; baseline and differential. 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: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; 1.10.220.20; -; 1. DR Gene3D; 1.10.1000.11; Arf Nucleotide-binding Site Opener,domain 2; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR InterPro; IPR000048; IQ_motif_EF-hand-BS. 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; GUANYL-NUCLEOTIDE EXCHANGE FACTOR; 1. DR PANTHER; PTHR10663:SF327; IQ MOTIF AND SEC7 DOMAIN-CONTAINING PROTEIN 1; 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; SSF50729; PH domain-like; 1. DR SUPFAM; SSF48425; Sec7 domain; 1. DR PROSITE; PS50096; IQ; 1. DR PROSITE; PS50190; SEC7; 1. DR Genevisible; Q6DN90; HS. 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 114..127 FT /evidence="ECO:0007829|PDB:7VMB" FT HELIX 131..158 FT /evidence="ECO:0007829|PDB:7VMB" FT HELIX 516..518 FT /evidence="ECO:0007829|PDB:5NLV" FT HELIX 522..537 FT /evidence="ECO:0007829|PDB:7VMB" FT HELIX 539..548 FT /evidence="ECO:0007829|PDB:7VMB" FT HELIX 556..565 FT /evidence="ECO:0007829|PDB:7VMB" FT HELIX 571..578 FT /evidence="ECO:0007829|PDB:7VMB" FT HELIX 584..595 FT /evidence="ECO:0007829|PDB:7VMB" FT HELIX 604..614 FT /evidence="ECO:0007829|PDB:7VMB" FT HELIX 621..638 FT /evidence="ECO:0007829|PDB:7VMB" FT HELIX 640..644 FT /evidence="ECO:0007829|PDB:7VMB" FT STRAND 646..648 FT /evidence="ECO:0007829|PDB:5NLY" FT HELIX 650..667 FT /evidence="ECO:0007829|PDB:7VMB" FT TURN 669..671 FT /evidence="ECO:0007829|PDB:4C0A" FT HELIX 673..675 FT /evidence="ECO:0007829|PDB:7VMB" FT HELIX 679..685 FT /evidence="ECO:0007829|PDB:7VMB" FT TURN 686..689 FT /evidence="ECO:0007829|PDB:7VMB" FT HELIX 697..709 FT /evidence="ECO:0007829|PDB:7VMB" FT HELIX 718..730 FT /evidence="ECO:0007829|PDB:7VMB" FT STRAND 753..761 FT /evidence="ECO:0007829|PDB:7VMB" FT TURN 771..774 FT /evidence="ECO:0007829|PDB:7VMB" FT STRAND 775..781 FT /evidence="ECO:0007829|PDB:7VMB" FT STRAND 784..793 FT /evidence="ECO:0007829|PDB:7VMB" FT STRAND 798..807 FT /evidence="ECO:0007829|PDB:7VMB" FT STRAND 811..816 FT /evidence="ECO:0007829|PDB:7VMB" FT STRAND 824..830 FT /evidence="ECO:0007829|PDB:7VMB" FT STRAND 832..834 FT /evidence="ECO:0007829|PDB:5NLY" FT STRAND 836..843 FT /evidence="ECO:0007829|PDB:7VMB" FT HELIX 847..875 FT /evidence="ECO:0007829|PDB:7VMB" 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 //