RBCC

Full text data of IQGAP1

IQGAP1 (KIAA0051) [Confidence: low (only semi-automatic identification from reviews)]
Ras GTPase-activating-like protein IQGAP1 (p195)

UniProt P46940
ID IQGA1_HUMAN Reviewed; 1657 AA.
AC P46940; A7MBM3;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1995, sequence version 1.
DT 22-JAN-2014, entry version 147.
DE RecName: Full=Ras GTPase-activating-like protein IQGAP1;
DE AltName: Full=p195;
GN Name=IQGAP1; Synonyms=KIAA0051;
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].
RC TISSUE=Liver, and Placenta;
RX PubMed=8051149;
RA Weissbach L., Settleman J., Kalady M.F., Snijders A.J., Murthy A.E.,
RA Yan Y.-X., Bernards A.;
RT "Identification of a human rasGAP-related protein containing
RT calmodulin-binding motifs.";
RL J. Biol. Chem. 269:20517-20521(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow;
RX PubMed=7584044; DOI=10.1093/dnares/1.5.223;
RA Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S.,
RA Seki N., Kawarabayasi Y., Ishikawa K., Tabata S.;
RT "Prediction of the coding sequences of unidentified human genes. II.
RT The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by
RT analysis of cDNA clones from human cell line KG-1.";
RL DNA Res. 1:223-229(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP PROTEIN SEQUENCE OF 2-25; 81-88; 112-143; 192-230; 466-477; 557-585;
RP 923-935; 989-997; 1391-1397; 1466-1475 AND 1506-1516, CLEAVAGE OF
RP INITIATOR METHIONINE, ACETYLATION AT SER-2, AND MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Lilla S., Zebisch A., Kolch W.;
RL Submitted (MAR-2009) to UniProtKB.
RN [6]
RP PROTEIN SEQUENCE OF 1441-1455, PHOSPHORYLATION AT SER-1443,
RP INTERACTION WITH CDC42 AND RAC1, DOMAIN, SUBCELLULAR LOCATION, AND
RP MASS SPECTROMETRY.
RX PubMed=15355962; DOI=10.1074/jbc.M408113200;
RA Grohmanova K., Schlaepfer D., Hess D., Gutierrez P., Beck M.,
RA Kroschewski R.;
RT "Phosphorylation of IQGAP1 modulates its binding to Cdc42, revealing a
RT new type of rho-GTPase regulator.";
RL J. Biol. Chem. 279:48495-48504(2004).
RN [7]
RP PROTEIN SEQUENCE OF 1441-1455, PHOSPHORYLATION AT SER-1441 AND
RP SER-1443, MUTAGENESIS OF SER-1441 AND SER-1443, FUNCTION, AND MASS
RP SPECTROMETRY.
RX PubMed=15695813; DOI=10.1074/jbc.M413482200;
RA Li Z., McNulty D.E., Marler K.J.M., Lim L., Hall C., Annan R.S.,
RA Sacks D.B.;
RT "IQGAP1 promotes neurite outgrowth in a phosphorylation-dependent
RT manner.";
RL J. Biol. Chem. 280:13871-13878(2005).
RN [8]
RP CHARACTERIZATION.
RX PubMed=8670801;
RA Hart M.J., Callow M.G., Souza B., Polakis P.;
RT "IQGAP1, a calmodulin-binding protein with a rasGAP-related domain, is
RT a potential effector for cdc42Hs.";
RL EMBO J. 15:2997-3005(1996).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [10]
RP INTERACTION WITH TSG101.
RX PubMed=17853893; DOI=10.1038/sj.emboj.7601850;
RA Morita E., Sandrin V., Chung H.Y., Morham S.G., Gygi S.P.,
RA Rodesch C.K., Sundquist W.I.;
RT "Human ESCRT and ALIX proteins interact with proteins of the midbody
RT and function in cytokinesis.";
RL EMBO J. 26:4215-4227(2007).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1443, AND MASS
RP SPECTROMETRY.
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 [12]
RP INTERACTION WITH PAK6.
RX PubMed=18642328; DOI=10.1002/pros.20787;
RA Kaur R., Yuan X., Lu M.L., Balk S.P.;
RT "Increased PAK6 expression in prostate cancer and identification of
RT PAK6 associated proteins.";
RL Prostate 68:1510-1516(2008).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-2; SER-330 AND SER-1443, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
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 [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [16]
RP STRUCTURE BY NMR OF 1559-1657.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the carboxyl-terminal RGC domain in human
RT IQGAP1.";
RL Submitted (SEP-2005) to the PDB data bank.
CC -!- FUNCTION: Binds to activated CDC42 but does not stimulate its
CC GTPase activity. It associates with calmodulin. Could serve as an
CC assembly scaffold for the organization of a multimolecular complex
CC that would interface incoming signals to the reorganization of the
CC actin cytoskeleton at the plasma membrane. May promote neurite
CC outgrowth.
CC -!- SUBUNIT: Interacts with CDC42; the interaction is demonstrated
CC with IQGAP1 in GTP-bound and in nucleotide-free state. Interacts
CC with RAC1. Does not interact with RHOA. Interacts with TSG101.
CC Interacts with PAK6.
CC -!- INTERACTION:
CC O43707:ACTN4; NbExp=3; IntAct=EBI-297509, EBI-351526;
CC Q9Y5K6:CD2AP; NbExp=4; IntAct=EBI-297509, EBI-298152;
CC P60953:CDC42; NbExp=2; IntAct=EBI-297509, EBI-81752;
CC P35222:CTNNB1; NbExp=3; IntAct=EBI-297509, EBI-491549;
CC O08808:Diaph1 (xeno); NbExp=8; IntAct=EBI-297509, EBI-1026445;
CC P00533:EGFR; NbExp=4; IntAct=EBI-297509, EBI-297353;
CC P04626:ERBB2; NbExp=5; IntAct=EBI-297509, EBI-641062;
CC Q96QZ7:MAGI1; NbExp=4; IntAct=EBI-297509, EBI-924464;
CC O60500:NPHS1; NbExp=5; IntAct=EBI-297509, EBI-996920;
CC Q9NP85:NPHS2; NbExp=4; IntAct=EBI-297509, EBI-6897706;
CC O00592:PODXL; NbExp=4; IntAct=EBI-297509, EBI-6897823;
CC Q05823:RNASEL; NbExp=2; IntAct=EBI-297509, EBI-8390477;
CC Q99816:TSG101; NbExp=5; IntAct=EBI-297509, EBI-346882;
CC -!- SUBCELLULAR LOCATION: Cell membrane.
CC -!- TISSUE SPECIFICITY: Expressed in the placenta, lung, and kidney. A
CC lower level expression is seen in the heart, liver, skeletal
CC muscle and pancreas.
CC -!- DOMAIN: Regions C1 and C2 can either interact with nucleotide-free
CC CDC42, or interact together, depending on the phosphorylation
CC state of Ser-1443. When Ser-1443 is not phosphorylated, C1 and C2
CC interact, which prevents binding of nucleotide-free CDC42 and
CC promotes binding of GTP-bound CDC42. Phosphorylation of Ser-1443
CC prevents interaction between C1 and C2, which opens the structure
CC of the C-terminus and allows binding and sequestration of
CC nucleotide-free CDC42 on both C1 and C2.
CC -!- PTM: Phosphorylation of Ser-1443 by PKC/PRKCE prevents interaction
CC between C1 and C2, allowing binding of nucleotide-free CDC42. Ser-
CC 1443 phosphorylation enhances the ability to promote neurite
CC outgrowth.
CC -!- SIMILARITY: Contains 1 CH (calponin-homology) domain.
CC -!- SIMILARITY: Contains 4 IQ domains.
CC -!- SIMILARITY: Contains 1 Ras-GAP domain.
CC -!- SIMILARITY: Contains 1 WW domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA06123.2; Type=Erroneous initiation;
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DR EMBL; L33075; AAA59187.1; -; mRNA.
DR EMBL; D29640; BAA06123.2; ALT_INIT; mRNA.
DR EMBL; CH471101; EAX02102.1; -; Genomic_DNA.
DR EMBL; BC151834; AAI51835.1; -; mRNA.
DR PIR; A54854; A54854.
DR RefSeq; NP_003861.1; NM_003870.3.
DR UniGene; Hs.430551; -.
DR PDB; 1X0H; NMR; -; A=1559-1657.
DR PDB; 2RR8; NMR; -; A=26-210.
DR PDB; 3FAY; X-ray; 2.20 A; A=962-1345.
DR PDB; 3I6X; X-ray; 2.50 A; A/B/C/D=1-191.
DR PDBsum; 1X0H; -.
DR PDBsum; 2RR8; -.
DR PDBsum; 3FAY; -.
DR PDBsum; 3I6X; -.
DR ProteinModelPortal; P46940; -.
DR SMR; P46940; 26-210, 962-1339, 1561-1657.
DR IntAct; P46940; 43.
DR MINT; MINT-4999354; -.
DR STRING; 9606.ENSP00000268182; -.
DR PhosphoSite; P46940; -.
DR DMDM; 1170586; -.
DR PaxDb; P46940; -.
DR PeptideAtlas; P46940; -.
DR PRIDE; P46940; -.
DR DNASU; 8826; -.
DR Ensembl; ENST00000268182; ENSP00000268182; ENSG00000140575.
DR GeneID; 8826; -.
DR KEGG; hsa:8826; -.
DR UCSC; uc002bpl.1; human.
DR CTD; 8826; -.
DR GeneCards; GC15P090931; -.
DR H-InvDB; HIX0172824; -.
DR HGNC; HGNC:6110; IQGAP1.
DR HPA; CAB013302; -.
DR HPA; HPA014055; -.
DR MIM; 603379; gene.
DR neXtProt; NX_P46940; -.
DR PharmGKB; PA29910; -.
DR eggNOG; COG5261; -.
DR HOGENOM; HOG000004842; -.
DR HOVERGEN; HBG052143; -.
DR InParanoid; P46940; -.
DR KO; K16848; -.
DR OMA; QDILYQA; -.
DR OrthoDB; EOG7FNC6M; -.
DR PhylomeDB; P46940; -.
DR Reactome; REACT_111155; Cell-Cell communication.
DR Reactome; REACT_111217; Metabolism.
DR ChiTaRS; IQGAP1; human.
DR EvolutionaryTrace; P46940; -.
DR GeneWiki; IQGAP1; -.
DR GenomeRNAi; 8826; -.
DR NextBio; 33114; -.
DR PMAP-CutDB; P46940; -.
DR PRO; PR:P46940; -.
DR ArrayExpress; P46940; -.
DR Bgee; P46940; -.
DR CleanEx; HS_IQGAP1; -.
DR Genevestigator; P46940; -.
DR GO; GO:0005884; C:actin filament; TAS:ProtInc.
DR GO; GO:0031252; C:cell leading edge; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0031234; C:extrinsic to cytoplasmic side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016328; C:lateral plasma membrane; IEA:Ensembl.
DR GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0030529; C:ribonucleoprotein complex; IEA:Ensembl.
DR GO; GO:0036057; C:slit diaphragm; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; TAS:BHF-UCL.
DR GO; GO:0005516; F:calmodulin binding; TAS:ProtInc.
DR GO; GO:0005096; F:GTPase activator activity; TAS:ProtInc.
DR GO; GO:0005095; F:GTPase inhibitor activity; TAS:ProtInc.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:UniProtKB.
DR GO; GO:0005099; F:Ras GTPase activator activity; IEA:InterPro.
DR GO; GO:0071277; P:cellular response to calcium ion; IDA:BHF-UCL.
DR GO; GO:0006112; P:energy reserve metabolic process; TAS:Reactome.
DR GO; GO:0072015; P:glomerular visceral epithelial cell development; ISS:UniProtKB.
DR GO; GO:0035305; P:negative regulation of dephosphorylation; IEA:Ensembl.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IMP:BHF-UCL.
DR GO; GO:0032320; P:positive regulation of Ras GTPase activity; IEA:GOC.
DR GO; GO:0001817; P:regulation of cytokine production; IEA:Ensembl.
DR GO; GO:0050796; P:regulation of insulin secretion; TAS:Reactome.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR Gene3D; 1.10.418.10; -; 1.
DR Gene3D; 1.10.506.10; -; 2.
DR Gene3D; 4.10.270.10; -; 1.
DR InterPro; IPR001715; CH-domain.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR InterPro; IPR027401; Myosin-like_IQ_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR001936; RasGAP.
DR InterPro; IPR000593; RasGAP_C.
DR InterPro; IPR023152; RasGAP_CS.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR001202; WW_dom.
DR Pfam; PF00307; CH; 1.
DR Pfam; PF00612; IQ; 4.
DR Pfam; PF00616; RasGAP; 1.
DR Pfam; PF03836; RasGAP_C; 1.
DR SMART; SM00033; CH; 1.
DR SMART; SM00015; IQ; 4.
DR SMART; SM00323; RasGAP; 1.
DR SMART; SM00456; WW; 1.
DR SUPFAM; SSF47576; SSF47576; 1.
DR SUPFAM; SSF48350; SSF48350; 2.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50021; CH; 1.
DR PROSITE; PS50096; IQ; 4.
DR PROSITE; PS00509; RAS_GTPASE_ACTIV_1; 1.
DR PROSITE; PS50018; RAS_GTPASE_ACTIV_2; 1.
DR PROSITE; PS01159; WW_DOMAIN_1; 1.
DR PROSITE; PS50020; WW_DOMAIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Calmodulin-binding; Cell membrane;
KW Complete proteome; Direct protein sequencing; Membrane;
KW Phosphoprotein; Polymorphism; Reference proteome; Repeat.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 1657 Ras GTPase-activating-like protein
FT IQGAP1.
FT /FTId=PRO_0000056648.
FT DOMAIN 44 159 CH.
FT DOMAIN 679 712 WW.
FT DOMAIN 745 774 IQ 1.
FT DOMAIN 775 804 IQ 2.
FT DOMAIN 805 834 IQ 3.
FT DOMAIN 835 864 IQ 4.
FT DOMAIN 1004 1237 Ras-GAP.
FT REGION 956 1274 C1.
FT REGION 1276 1657 C2.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 2 2 Phosphoserine.
FT MOD_RES 172 172 Phosphotyrosine (By similarity).
FT MOD_RES 330 330 Phosphoserine.
FT MOD_RES 1441 1441 Phosphoserine; by PKC (Probable).
FT MOD_RES 1443 1443 Phosphoserine; by PKC/PRKCE.
FT VARIANT 256 256 S -> A (in dbSNP:rs12324924).
FT /FTId=VAR_049134.
FT MUTAGEN 1441 1441 S->A: Abolishes neurite outgrowth
FT promoting activity; when associated with
FT A-1443.
FT MUTAGEN 1441 1441 S->E: Strongly enhances neurite outgrowth
FT promoting activity; when associated with
FT A-1443.
FT MUTAGEN 1443 1443 S->A: Abolishes neurite outgrowth
FT promoting activity; when associated with
FT A-1441.
FT MUTAGEN 1443 1443 S->D: Strongly enhances neurite outgrowth
FT promoting activity; when associated with
FT A-1441.
FT HELIX 31 58
FT HELIX 65 67
FT HELIX 68 72
FT HELIX 76 85
FT TURN 87 89
FT HELIX 92 94
FT TURN 96 99
FT HELIX 101 105
FT HELIX 110 112
FT HELIX 113 126
FT HELIX 130 132
FT HELIX 136 140
FT HELIX 145 161
FT TURN 172 174
FT HELIX 179 188
FT HELIX 199 201
FT TURN 206 208
FT HELIX 962 981
FT HELIX 984 991
FT HELIX 1000 1009
FT TURN 1010 1013
FT HELIX 1016 1037
FT STRAND 1039 1042
FT HELIX 1043 1046
FT HELIX 1050 1058
FT HELIX 1062 1081
FT HELIX 1091 1106
FT HELIX 1118 1121
FT HELIX 1125 1150
FT HELIX 1151 1155
FT HELIX 1158 1174
FT HELIX 1180 1191
FT HELIX 1192 1196
FT HELIX 1197 1201
FT TURN 1203 1207
FT HELIX 1219 1236
FT HELIX 1246 1248
FT HELIX 1249 1270
FT HELIX 1275 1278
FT STRAND 1282 1284
FT TURN 1285 1287
FT STRAND 1290 1292
FT HELIX 1299 1311
FT HELIX 1313 1316
FT HELIX 1323 1331
FT STRAND 1561 1564
FT HELIX 1565 1571
FT STRAND 1572 1577
FT HELIX 1583 1587
FT STRAND 1589 1593
FT STRAND 1596 1599
FT STRAND 1601 1608
FT STRAND 1615 1617
FT HELIX 1619 1628
FT STRAND 1632 1635
FT TURN 1636 1638
FT STRAND 1639 1642
FT HELIX 1643 1652
SQ SEQUENCE 1657 AA; 189252 MW; A52EC629596EAC33 CRC64;
MSAADEVDGL GVARPHYGSV LDNERLTAEE MDERRRQNVA YEYLCHLEEA KRWMEACLGE
DLPPTTELEE GLRNGVYLAK LGNFFSPKVV SLKKIYDREQ TRYKATGLHF RHTDNVIQWL
NAMDEIGLPK IFYPETTDIY DRKNMPRCIY CIHALSLYLF KLGLAPQIQD LYGKVDFTEE
EINNMKTELE KYGIQMPAFS KIGGILANEL SVDEAALHAA VIAINEAIDR RIPADTFAAL
KNPNAMLVNL EEPLASTYQD ILYQAKQDKM TNAKNRTENS ERERDVYEEL LTQAEIQGNI
NKVNTFSALA NIDLALEQGD ALALFRALQS PALGLRGLQQ QNSDWYLKQL LSDKQQKRQS
GQTDPLQKEE LQSGVDAANS AAQQYQRRLA AVALINAAIQ KGVAEKTVLE LMNPEAQLPQ
VYPFAADLYQ KELATLQRQS PEHNLTHPEL SVAVEMLSSV ALINRALESG DVNTVWKQLS
SSVTGLTNIE EENCQRYLDE LMKLKAQAHA ENNEFITWND IQACVDHVNL VVQEEHERIL
AIGLINEALD EGDAQKTLQA LQIPAAKLEG VLAEVAQHYQ DTLIRAKREK AQEIQDESAV
LWLDEIQGGI WQSNKDTQEA QKFALGIFAI NEAVESGDVG KTLSALRSPD VGLYGVIPEC
GETYHSDLAE AKKKKLAVGD NNSKWVKHWV KGGYYYYHNL ETQEGGWDEP PNFVQNSMQL
SREEIQSSIS GVTAAYNREQ LWLANEGLIT RLQARCRGYL VRQEFRSRMN FLKKQIPAIT
CIQSQWRGYK QKKAYQDRLA YLRSHKDEVV KIQSLARMHQ ARKRYRDRLQ YFRDHINDII
KIQAFIRANK ARDDYKTLIN AEDPPMVVVR KFVHLLDQSD QDFQEELDLM KMREEVITLI
RSNQQLENDL NLMDIKIGLL VKNKITLQDV VSHSKKLTKK NKEQLSDMMM INKQKGGLKA
LSKEKREKLE AYQHLFYLLQ TNPTYLAKLI FQMPQNKSTK FMDSVIFTLY NYASNQREEY
LLLRLFKTAL QEEIKSKVDQ IQEIVTGNPT VIKMVVSFNR GARGQNALRQ ILAPVVKEIM
DDKSLNIKTD PVDIYKSWVN QMESQTGEAS KLPYDVTPEQ ALAHEEVKTR LDSSIRNMRA
VTDKFLSAIV SSVDKIPYGM RFIAKVLKDS LHEKFPDAGE DELLKIIGNL LYYRYMNPAI
VAPDAFDIID LSAGGQLTTD QRRNLGSIAK MLQHAASNKM FLGDNAHLSI INEYLSQSYQ
KFRRFFQTAC DVPELQDKFN VDEYSDLVTL TKPVIYISIG EIINTHTLLL DHQDAIAPEH
NDPIHELLDD LGEVPTIESL IGESSGNLND PNKEALAKTE VSLTLTNKFD VPGDENAEMD
ARTILLNTKR LIVDVIRFQP GETLTEILET PATSEQEAEH QRAMQRRAIR DAKTPDKMKK
SKSVKEDSNL TLQEKKEKIQ TGLKKLTELG TVDPKNKYQE LINDIARDIR NQRRYRQRRK
AELVKLQQTY AALNSKATFY GEQVDYYKSY IKTCLDNLAS KGKVSKKPRE MKGKKSKKIS
LKYTAARLHE KGVLLEIEDL QVNQFKNVIF EISPTEEVGD FEVKAKFMGV QMETFMLHYQ
DLLQLQYEGV AVMKLFDRAK VNVNLLIFLL NKKFYGK
//

MIM 603379
*RECORD*
*FIELD* NO
603379
*FIELD* TI
*603379 IQ MOTIF-CONTAINING GTPase-ACTIVATING PROTEIN 1; IQGAP1
;;RASGAP-LIKE WITH IQ MOTIFS;;
read morep195;;
SAR1, S. POMBE, HOMOLOG OF; SAR1;;
HUMORFA01
*FIELD* TX

DESCRIPTION

IQGAP1 is a multidomain scaffold protein that binds to a wide variety of
targets and modulates several cellular activities, including cell-cell
adhesion, transcription, cytoskeletal architecture, and signaling
pathways (Ren et al., 2007).

CLONING

Weissbach et al. (1994) identified a novel sequence during PCR of RNA
from osteosarcoma tissue. They cloned the full-length cDNA, which they
named IQGAP1, from human placenta, liver, and lymphocyte libraries. The
IQGAP1 cDNA encodes a 1,657-amino acid polypeptide with significant
similarity to the Ras-related GTPase-activating (RasGAP) family of
proteins (see 139150). The N-terminal domain contains 6 copies of a
unique motif and 4 IQ motifs (named for the presence of tandem
isoleucine and glutamine residues), which are known to modulate binding
with calmodulin (see 114180).

Based on its binding to a Ras protein affinity column, Hart et al.
(1996) identified the 195-kD IQGAP protein (p195), and cloned the
corresponding cDNA.

GENE FUNCTION

Hart et al. (1996) found that the C-terminal domain of IQGAP inhibited
the GTPase activity of cdc42 (116952). IQGAP and cdc42 could be
coimmunoprecipitated, suggesting that the 2 proteins interact in vivo.
IQGAP colocalized with actin in lamellipodia and ruffling cell
membranes, suggesting that IQGAP may regulate cell morphology.

Sugimoto et al. (2001) demonstrated that IQGAP1, a negative regulator of
cell-cell adhesion, was upregulated by gene amplification at chromosome
15q26 in 2 gastric cancer cell lines. Amplification at 15q26 had been
found in various malignancies, including breast cancers, and FES
(190030) and/or IGF1R (147370) had been identified as targets for gene
amplification in breast cancer, melanoma, and pancreatic adenocarcinoma.
In contrast, Sugimoto et al. (2001) found that both genes are located
telomeric to the amplicon at 15q26 in the 2 gastric cancer cell lines
they studied.

Fukata et al. (2002) found that IQGAP1, an effector of RAC1 (602048) and
CDC42, interacts with CLIP170 (RSN; 179838). In Vero fibroblasts, IQGAP1
localized at the polarized leading edge. Expression of a C-terminal
fragment of IQGAP1 that included the CLIP170-binding region delocalized
GFP-CLIP170 from the tips of microtubules and altered the microtubule
array. The authors found that activated RAC1/CDC42, IQGAP1, and CLIP170
form a tripartite complex. Furthermore, expression of an IQGAP1 mutant
defective in RAC1/CDC42 binding induced multiple leading edges. These
results indicated that RAC1/CDC42 marks special cortical spots where the
IQGAP1 and CLIP170 complex is targeted, leading to a polarized
microtubule array and cell polarization.

Watanabe et al. (2004) found that monkey Iqgap1 and Apc (611731)
interacted directly via the armadillo repeats of Apc and the C terminus
of Iqgap1. Clip170 also immunoprecipitated with Apc and Iqgap1. Apc and
Iqgap1 localized interdependently to the leading edge in migrating Vero
cells, and transfection of cells with constitutively active human IQGAP1
provided accumulation sites with APC in a manner dependent on actin
filaments. Watanabe et al. (2004) concluded that RAC1 and CDC42 recruit
the IQGAP1/APC complex and that IQGAP1 links APC to actin filaments for
cell polarization and directional migration.

Briggs et al. (2002) investigated the relationship between IQGAP1,
beta-catenin (116806), and calmodulin using COS-7 cells and several
human cell lines. In vitro competition assays revealed a dynamic
association of IQGAP1 with Ca(2+)/calmodulin and beta-catenin.
Overexpression of IQGAP1 in colon carcinoma cells enhanced
beta-catenin-mediated transcriptional coactivation, and this effect
required calmodulin; an IQGAP1 mutant that did not bind calmodulin did
not stimulate beta-catenin transcriptional function. Overexpression of
IQGAP1 increased the amount of beta-catenin located in the nucleus, and
incubation of cells with a calmodulin antagonist blocked nuclear
accumulation.

Swart-Mataraza et al. (2002) overexpressed IQGAP1 in COS-7 and several
human cell lines. Transfection of IQGAP1 significantly increased the
levels of active, GTP-bound CDC42, resulting in the formation of
peripheral actin microspikes. Transfection of a mutant IQGAP1 lacking
part of the GAP-related domain decreased the amount of GTP-bound CDC42
in cell lysates. Expression of the mutant also produced small, round
cells that resembled CDC42 null cells. Swart-Mataraza et al. (2002)
concluded that IQGAP1 has a role in transducing CDC42 signaling to the
cytoskeleton.

Mateer et al. (2002) analyzed proteins purified from bovine adrenal
tissue and rabbit muscle as well as human IQGAP1. They found that
purified adrenal IQGAP1 consisted of 2 distinct protein pools, one of
which bound F-actin and lacked calmodulin, and the other of which did
not bind F-actin but was tightly associated with calmodulin. In vitro,
the affinity of IQGAP1 for F-actin decreased with increasing
concentrations of calmodulin, and this effect was dramatically enhanced
by Ca(2+) and required the IQ domain of IQGAP1. Calmodulin also bound
wildtype IQGAP1 more efficiently in the presence of Ca(2+) than in its
absence, and all 8 IQ motifs in each IQGAP1 dimer could bind calmodulin
simultaneously. Fluorescence-tagged IQGAP1 localized to the cell cortex
of mouse fibroblasts, but elevated intracellular Ca(2+) reversibly
induced a diffuse distribution.

Stinchcombe et al. (2006) showed that cytotoxic T lymphocytes do not
require actin or plus-end microtubule motors for secretion of lytic
granules, but instead the centrosome moves to and contacts the plasma
membrane at the central supramolecular activation cluster of the
immunological synapse. Actin and IQGAP1 are cleared away from the
synapse, and granules delivered directly to the plasma membrane.
Stinchcombe et al. (2006) concluded that their data show that CTLs use a
previously unreported mechanism for delivering secretory granules to the
immunologic synapse, with granule secretion controlled by centrosome
delivery to the plasma membrane.

Ren et al. (2007) had previously identified IQGAP1 as a scaffold in the
MEK (MAP2K1; 176872)/ERK (see MAPK3; 601795) signal transduction
pathway. They found that BRAF (164757), an important MEK activator,
bound directly to IQGAP1 in vitro and coimmunoprecipitated with IQGAP1
from human embryonic kidney cell lysates. EGF (131530) was unable to
stimulate Braf activity in Iqgap1-null mouse embryonic kidney cells and
in cells transfected with an IQGAP1 mutant unable to bind Braf.
Cotransfection of IQGAP1 with BRAF in human embryonic kidney cells
significantly elevated EGF-stimulated BRAF serine/threonine kinase
activity. Ren et al. (2007) concluded that IQGAP1 is a scaffold protein
necessary for EGF activation of BRAF and the MEK/ERK signaling pathway.

MAPPING

By analysis of a human/rodent somatic cell hybrid panel, Weissbach et
al. (1994) localized the IQGAP1 gene to human chromosome 15.

ANIMAL MODEL

Li et al. (2000) developed Iqgap1-null mice. These mice showed no
obvious defects during development or for most of their adult life. Loss
of Iqgap1 did not affect tumor development or tumor progression, but
mutant mice exhibited a significant increase in late-onset gastric
hyperplasia. Li et al. (2000) noted that the lack of a phenotype may be
due to functional redundance with Iqgap2 (605401) and concluded that
Iqgap1 serves no unique function during mouse development and may serve
to maintain the integrity of the gastric mucosa in older animals.

*FIELD* RF
1. Briggs, M. W.; Li, Z.; Sacks, D. B.: IQGAP1-mediated stimulation
of transcriptional co-activation by beta-catenin is modulated by calmodulin. J.
Biol. Chem. 277: 7453-7465, 2002.

2. Fukata, M.; Watanabe, T.; Noritake, J.; Nakagawa, M.; Yamaga, M.;
Kuroda, S.; Matsuura, Y.; Iwamatsu, A.; Perez, F.; Kaibuchi, K.:
Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170. Cell 109:
873-885, 2002.

3. Hart, M. J.; Callow, M. G.; Souza, B.; Polakis, P.: IQGAP1, a
calmodulin-binding protein with a rasGAP-related domain, is a potential
effector for cdc42Hs. EMBO J. 15: 2997-3005, 1996.

4. Li, S.; Wang, Q.; Chakladar, A.; Bronson, R. T.; Bernards, A.:
Gastric hyperplasia in mice lacking the putative Cdc42 effector IQGAP1. Molec.
Cell. Biol. 20: 697-701, 2000.

5. Mateer, S. C.; McDaniel, A. E.; Nicolas, V.; Habermacher, G. M.;
Lin, M.-J. S.; Cromer, D. A.; King, M. E.; Bloom, G. S.: The mechanism
for regulation of the F-actin binding activity of IQGAP1 by calcium/calmodulin. J.
Biol. Chem. 277: 12324-12333, 2002.

6. Ren, J.-G.; Li, Z.; Sacks, D. B.: IQGAP1 modulates activation
of B-Raf. Proc. Nat. Acad. Sci. 104: 10465-10469, 2007.

7. Stinchcombe, J. C.; Majorovits, E.; Bossi, G.; Fuller, S.; Griffiths,
G. M.: Centrosome polarization delivers secretory granules to the
immunological synapse. Nature 443: 462-465, 2006. Note: Erratum:
Nature 444: 236 only, 2006.

8. Sugimoto, N.; Imoto, I.; Fukuda, Y.; Kurihara, N.; Kuroda, S.;
Tanigami, A.; Kaibuchi, K.; Kamiyama, R.; Inazawa, J.: IQGAP1, a
negative regulator of cell-cell adhesion, is upregulated by gene amplification
at 15q26 in gastric cancer cell lines HSC39 and 40A. J. Hum. Genet. 46:
21-25, 2001.

9. Swart-Mataraza, J. M.; Li, Z.; Sacks, D. B.: IQGAP1 is a component
of Cdc42 signaling to the cytoskeleton. J. Biol. Chem. 277: 24753-24763,
2002.

10. Watanabe, T.; Wang, S.; Noritake, J.; Sato, K.; Fukata, M.; Takefuji,
M.; Nakagawa, M.; Izumi, N.; Akiyama, T.; Kaibuchi, K.: Interaction
with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell
polarization and migration. Dev. Cell 7: 871-883, 2004.

11. Weissbach, L.; Settleman, J.; Kalady, M. F.; Snijders, A. J.;
Murthy, A. E.; Yan, Y.-X.; Bernards, A.: Identification of a human
RasGAP-related protein containing calmodulin-binding motifs. J. Biol.
Chem. 269: 20517-20521, 1994.

*FIELD* CN
Patricia A. Hartz - updated: 7/10/2007
Ada Hamosh - updated: 11/28/2006
Ada Hamosh - updated: 10/24/2006
Patricia A. Hartz - updated: 1/6/2005
Patricia A. Hartz - updated: 1/6/2003
Stylianos E. Antonarakis - updated: 7/31/2002
Victor A. McKusick - updated: 1/31/2001

*FIELD* CD
Jennifer P. Macke: 12/23/1998

*FIELD* ED
ckniffin: 02/05/2008
mgross: 8/7/2007
terry: 7/10/2007
alopez: 3/21/2007
terry: 3/12/2007
alopez: 12/7/2006
terry: 11/28/2006
alopez: 11/1/2006
terry: 10/24/2006
mgross: 1/7/2005
terry: 1/6/2005
terry: 7/19/2004
mgross: 1/7/2003
terry: 1/6/2003
mgross: 7/31/2002
mcapotos: 2/6/2001
terry: 1/31/2001
alopez: 8/10/1999
alopez: 12/23/1998

RBCC Red Blood Cell Collection

Full text data of IQGAP1