Entry sw:IQEC1_HUMAN

ID   IQEC1_HUMAN             Reviewed;         963 AA.
AC   Q6DN90; O94863; Q96D85;
DT   11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT   16-AUG-2004, sequence version 1.
DT   30-NOV-2016, entry version 125.
DE   RecName: Full=IQ motif and SEC7 domain-containing protein 1;
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};
GN   Name=IQSEC1; Synonyms=ARFGEP100, BRAG2, KIAA0763;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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.,
RA   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 MRNA] (ISOFORM 2), AND TISSUE
RP   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.
RT   The complete sequences of 100 new cDNA clones from brain which code
RT   for large proteins in vitro.";
RL   DNA Res. 5:277-286(1998).
RN   [3]
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   TISSUE SPECIFICITY, SUBCELLULAR LOCATION, FUNCTION, AND INTERACTION
RP   WITH ARF6.
RX   PubMed=11226253; DOI=10.1073/pnas.051634798;
RA   Someya A., Sata M., Takeda K., Pacheco-Rodriguez G., Ferrans V.J.,
RA   Moss J., Vaughan M.;
RT   "ARF-GEP(100), a guanine nucleotide-exchange protein for ADP-
RT   ribosylation factor 6.";
RL   Proc. Natl. Acad. Sci. U.S.A. 98:2413-2418(2001).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-512, AND IDENTIFICATION
RP   BY 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   [6]
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   [7]
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.,
RA   Buerckstuemmer T., 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   [8]
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.,
RA   Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA   Blagoev B.;
RT   "System-wide temporal characterization of the proteome and
RT   phosphoproteome of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [9]
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
RP   MASS 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   [10]
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.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [11] {ECO:0000244|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
RT   and SEC7 domain-containing protein 1 isoform a.";
RL   Submitted (FEB-2011) to the PDB data bank.
RN   [12] {ECO:0000244|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
RP   GLU-620, 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
RT   ArfGEF BRAG2.";
RL   PLoS Biol. 11:E1001652-E1001652(2013).
CC   -!- FUNCTION: Guanine nucleotide exchange factor for ARF1 and ARF6
CC       (PubMed:24058294). Guanine nucleotide exchange factor activity is
CC       enhanced by lipid binding (PubMed:24058294). Accelerates GTP
CC       binding by ARFs of all three classes. Guanine nucleotide exchange
CC       protein for ARF6, mediating internalisation of beta-1 integrin.
CC       {ECO:0000269|PubMed:11226253, ECO:0000269|PubMed:16461286,
CC       ECO:0000269|PubMed:24058294}.
CC   -!- SUBUNIT: Interacts with ARF1 and ARF6.
CC       {ECO:0000269|PubMed:11226253, ECO:0000269|PubMed:24058294}.
CC   -!- INTERACTION:
CC       P50148:GNAQ; NbExp=2; IntAct=EBI-3044091, EBI-3909604;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11226253}.
CC       Nucleus {ECO:0000269|PubMed:11226253}. Note=At steady state, may
CC       be preferentially cytosolic.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=BRAG2b;
CC         IsoId=Q6DN90-1; Sequence=Displayed;
CC       Name=2; Synonyms=BRAG2a;
CC         IsoId=Q6DN90-2; Sequence=VSP_019758;
CC         Note=No experimental confirmation available.;
CC   -!- TISSUE SPECIFICITY: Expressed in brain, ovary, heart, lung, liver,
CC       kidney and leukocytes. Moderate expression was also detected in
CC       lung, skeletal muscle, placenta, small intestine, pancreas, spleen
CC       and testis. {ECO:0000269|PubMed:11226253,
CC       ECO:0000269|PubMed:9872452}.
CC   -!- DOMAIN: The PH domain mediates interaction with lipid membranes
CC       that contain phosphatidylinositol-4,5-bisphosphate, but does not
CC       bind membranes that lack phosphatidylinositol-4,5-bisphosphate.
CC       {ECO:0000269|PubMed:24058294}.
CC   -!- SIMILARITY: Belongs to the BRAG family. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 1 IQ domain. {ECO:0000255|PROSITE-
CC       ProRule:PRU00116}.
CC   -!- SIMILARITY: Contains 1 PH domain. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 1 SEC7 domain. {ECO:0000255|PROSITE-
CC       ProRule:PRU00189}.
DR   EMBL; AY653734; AAT72063.1; -; mRNA.
DR   EMBL; AB018306; BAA34483.2; -; mRNA.
DR   EMBL; BC010267; AAH10267.1; -; mRNA.
DR   CCDS; CCDS33703.1; -. [Q6DN90-1]
DR   RefSeq; NP_001127854.1; NM_001134382.2.
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   UniGene; Hs.475506; -.
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   PDBsum; 3QWM; -.
DR   PDBsum; 4C0A; -.
DR   ProteinModelPortal; Q6DN90; -.
DR   SMR; Q6DN90; -.
DR   BioGrid; 115250; 18.
DR   IntAct; Q6DN90; 12.
DR   STRING; 9606.ENSP00000273221; -.
DR   iPTMnet; Q6DN90; -.
DR   PhosphoSitePlus; Q6DN90; -.
DR   BioMuta; IQSEC1; -.
DR   DMDM; 74748429; -.
DR   EPD; Q6DN90; -.
DR   MaxQB; Q6DN90; -.
DR   PaxDb; Q6DN90; -.
DR   PeptideAtlas; Q6DN90; -.
DR   PRIDE; Q6DN90; -.
DR   DNASU; 9922; -.
DR   Ensembl; ENST00000273221; ENSP00000273221; ENSG00000144711. [Q6DN90-1]
DR   GeneID; 9922; -.
DR   KEGG; hsa:9922; -.
DR   UCSC; uc003bxt.4; human. [Q6DN90-1]
DR   CTD; 9922; -.
DR   DisGeNET; 9922; -.
DR   GeneCards; IQSEC1; -.
DR   HGNC; HGNC:29112; IQSEC1.
DR   HPA; HPA038143; -.
DR   HPA; HPA038144; -.
DR   MIM; 610166; gene.
DR   neXtProt; NX_Q6DN90; -.
DR   OpenTargets; ENSG00000144711; -.
DR   PharmGKB; PA128394566; -.
DR   eggNOG; KOG0931; Eukaryota.
DR   eggNOG; COG5307; LUCA.
DR   GeneTree; ENSGT00760000119036; -.
DR   HOGENOM; HOG000113099; -.
DR   HOVERGEN; HBG056324; -.
DR   InParanoid; Q6DN90; -.
DR   KO; K12495; -.
DR   PhylomeDB; Q6DN90; -.
DR   TreeFam; TF323811; -.
DR   ChiTaRS; IQSEC1; human.
DR   GeneWiki; IQSEC1; -.
DR   GenomeRNAi; 9922; -.
DR   PRO; PR:Q6DN90; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   Bgee; ENSG00000144711; -.
DR   CleanEx; HS_IQSEC1; -.
DR   ExpressionAtlas; Q6DN90; baseline and differential.
DR   Genevisible; Q6DN90; HS.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005086; F:ARF guanyl-nucleotide exchange factor activity; IEA:InterPro.
DR   GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR   GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR   GO; GO:0032012; P:regulation of ARF protein signal transduction; IEA:InterPro.
DR   CDD; cd13318; PH_IQSEC; 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_dom-like.
DR   InterPro; IPR001849; PH_domain.
DR   InterPro; IPR023394; Sec7_alpha_orthog.
DR   InterPro; IPR000904; Sec7_dom.
DR   PANTHER; PTHR10663:SF63; PTHR10663:SF63; 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   SUPFAM; SSF50729; SSF50729; 1.
DR   PROSITE; PS50096; IQ; 1.
DR   PROSITE; PS50190; SEC7; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Coiled coil; Complete proteome;
KW   Cytoplasm; Guanine-nucleotide releasing factor; Lipid-binding;
KW   Nucleus; Phosphoprotein; Polymorphism; Reference proteome.
FT   CHAIN         1    963       IQ motif and SEC7 domain-containing
FT                                protein 1.
FT                                /FTId=PRO_0000245606.
FT   DOMAIN      134    163       IQ. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00116}.
FT   DOMAIN      517    710       SEC7. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00189}.
FT   DOMAIN      774    866       PH.
FT   COILED      848    879       {ECO:0000255}.
FT   MOD_RES      89     89       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES     105    105       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES     107    107       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES     180    180       Phosphoserine.
FT                                {ECO:0000244|PubMed:21406692,
FT                                ECO:0000244|PubMed:23186163,
FT                                ECO:0000244|PubMed:24275569}.
FT   MOD_RES     249    249       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q8R0S2}.
FT   MOD_RES     253    253       Phosphoserine.
FT                                {ECO:0000244|PubMed:24275569}.
FT   MOD_RES     512    512       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648,
FT                                ECO:0000244|PubMed:21406692,
FT                                ECO:0000244|PubMed:23186163,
FT                                ECO:0000244|PubMed:24275569}.
FT   MOD_RES     515    515       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES     892    892       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES     911    911       Phosphotyrosine.
FT                                {ECO:0000244|PubMed:24275569}.
FT   MOD_RES     924    924       Phosphoserine.
FT                                {ECO:0000244|PubMed:24275569}.
FT   MOD_RES     925    925       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163,
FT                                ECO:0000244|PubMed:24275569}.
FT   VAR_SEQ       1    122       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:15489334,
FT                                ECO:0000303|PubMed:9872452}.
FT                                /FTId=VSP_019758.
FT   VARIANT     640    640       P -> S (in dbSNP:rs35319679).
FT                                /FTId=VAR_051927.
FT   VARIANT     882    882       V -> I (in dbSNP:rs17541405).
FT                                /FTId=VAR_027004.
FT   MUTAGEN     620    620       E->K: Abolishes guanosine nucleotide
FT                                exchange factor activity.
FT                                {ECO:0000269|PubMed:24058294}.
FT   CONFLICT    934    936       KRG -> VHH (in Ref. 3). {ECO:0000305}.
FT   HELIX       522    537       {ECO:0000244|PDB:4C0A}.
FT   HELIX       539    548       {ECO:0000244|PDB:4C0A}.
FT   HELIX       556    565       {ECO:0000244|PDB:4C0A}.
FT   HELIX       571    578       {ECO:0000244|PDB:4C0A}.
FT   HELIX       584    595       {ECO:0000244|PDB:4C0A}.
FT   HELIX       604    614       {ECO:0000244|PDB:4C0A}.
FT   HELIX       621    638       {ECO:0000244|PDB:4C0A}.
FT   HELIX       640    646       {ECO:0000244|PDB:4C0A}.
FT   HELIX       650    667       {ECO:0000244|PDB:4C0A}.
FT   TURN        669    671       {ECO:0000244|PDB:4C0A}.
FT   STRAND      673    676       {ECO:0000244|PDB:4C0A}.
FT   HELIX       679    685       {ECO:0000244|PDB:4C0A}.
FT   TURN        686    689       {ECO:0000244|PDB:4C0A}.
FT   HELIX       697    709       {ECO:0000244|PDB:4C0A}.
FT   HELIX       718    728       {ECO:0000244|PDB:4C0A}.
FT   STRAND      753    761       {ECO:0000244|PDB:3QWM}.
FT   TURN        771    774       {ECO:0000244|PDB:3QWM}.
FT   STRAND      775    783       {ECO:0000244|PDB:3QWM}.
FT   STRAND      785    789       {ECO:0000244|PDB:3QWM}.
FT   STRAND      803    806       {ECO:0000244|PDB:3QWM}.
FT   STRAND      811    816       {ECO:0000244|PDB:3QWM}.
FT   STRAND      824    829       {ECO:0000244|PDB:3QWM}.
FT   STRAND      832    834       {ECO:0000244|PDB:4C0A}.
FT   STRAND      837    843       {ECO:0000244|PDB:3QWM}.
FT   HELIX       847    878       {ECO:0000244|PDB:3QWM}.
CC   --------------------------------------------------------------------------
CC   The following FT lines are automated annotations from the MyHits database.
CC   --------------------------------------------------------------------------
FT   MYHIT       744    879       ipfam:IQ_SEC7_PH [T]
FT   MYHIT       524    712       ipfam:Sec7 [T]
FT   MYHIT       517    710       iprf:SEC7 [T]
FT   MYHIT       753    864       ismart:PH [T]
FT   MYHIT       134    163       iprf:IQ [T]
FT   MYHIT       521    712       ismart:Sec7 [T]
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
//