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Protein

Ras GTPase-activating-like protein IQGAP1

Gene

IQGAP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Plays a crucial role in regulating the dynamics and assembly of the actin cytoskeleton. Binds to activated CDC42 but does not stimulate its GTPase activity. It associates with calmodulin. Could serve as an assembly scaffold for the organization of a multimolecular complex that would interface incoming signals to the reorganization of the actin cytoskeleton at the plasma membrane. May promote neurite outgrowth (PubMed:15695813). May play a possible role in cell cycle regulation by contributing to cell cycle progression after DNA replication arrest (PubMed:20883816).2 Publications

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • calcium ion binding Source: BHF-UCL
  • calmodulin binding Source: BHF-UCL
  • GTPase activator activity Source: ProtInc
  • GTPase inhibitor activity Source: ProtInc
  • mitogen-activated protein kinase binding Source: Ensembl
  • phosphatidylinositol-3,4,5-trisphosphate binding Source: UniProtKB
  • protein-containing complex binding Source: Ensembl
  • protein domain specific binding Source: UniProtKB
  • protein kinase binding Source: BHF-UCL
  • protein phosphatase binding Source: UniProtKB
  • protein serine/threonine kinase activator activity Source: BHF-UCL
  • Rac GTPase binding Source: Ensembl
  • S100 protein binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding

Enzyme and pathway databases

ReactomeiR-HSA-373753 Nephrin family interactions
R-HSA-381676 Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-HSA-5626467 RHO GTPases activate IQGAPs
R-HSA-5674135 MAP2K and MAPK activation
R-HSA-6798695 Neutrophil degranulation
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants
R-HSA-6802949 Signaling by RAS mutants
R-HSA-6802952 Signaling by BRAF and RAF fusions
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF
SIGNORiP46940

Names & Taxonomyi

Protein namesi
Recommended name:
Ras GTPase-activating-like protein IQGAP1
Alternative name(s):
p195
Gene namesi
Name:IQGAP1
Synonyms:KIAA0051
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000140575.12
HGNCiHGNC:6110 IQGAP1
MIMi603379 gene
neXtProtiNX_P46940

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1441S → A: Abolishes neurite outgrowth promoting activity; when associated with A-1443. 1 Publication1
Mutagenesisi1441S → E: Strongly enhances neurite outgrowth promoting activity; when associated with A-1443. 1 Publication1
Mutagenesisi1443S → A: Abolishes neurite outgrowth promoting activity; when associated with A-1441. 1 Publication1
Mutagenesisi1443S → D: Strongly enhances neurite outgrowth promoting activity; when associated with A-1441. 1 Publication1

Organism-specific databases

DisGeNETi8826
OpenTargetsiENSG00000140575
PharmGKBiPA29910

Polymorphism and mutation databases

BioMutaiIQGAP1
DMDMi1170586

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00000566482 – 1657Ras GTPase-activating-like protein IQGAP1Add BLAST1656

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1 Publication1
Modified residuei2PhosphoserineCombined sources1
Modified residuei172PhosphotyrosineBy similarity1
Modified residuei330PhosphoserineCombined sources1
Modified residuei1441Phosphoserine; by PKC1 Publication1
Modified residuei1443Phosphoserine; by PKC/PRKCECombined sources2 Publications1

Post-translational modificationi

Phosphorylation of Ser-1443 by PKC/PRKCE prevents interaction between C1 and C2, allowing binding of nucleotide-free CDC42. Ser-1443 phosphorylation enhances the ability to promote neurite outgrowth.2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP46940
MaxQBiP46940
PaxDbiP46940
PeptideAtlasiP46940
PRIDEiP46940
ProteomicsDBi55776

PTM databases

CarbonylDBiP46940
iPTMnetiP46940
PhosphoSitePlusiP46940
SwissPalmiP46940

Miscellaneous databases

PMAP-CutDBiP46940

Expressioni

Tissue specificityi

Expressed in the placenta, lung, and kidney. A lower level expression is seen in the heart, liver, skeletal muscle and pancreas.

Developmental stagei

Expressed widely in developing cortex.1 Publication

Gene expression databases

BgeeiENSG00000140575
CleanExiHS_IQGAP1
ExpressionAtlasiP46940 baseline and differential
GenevisibleiP46940 HS

Organism-specific databases

HPAiCAB013302
HPA014055

Interactioni

Subunit structurei

Interacts with CDC42; the interaction is demonstrated with IQGAP1 in GTP-bound and in nucleotide-free state (PubMed:15355962). Interacts with RAC1 (PubMed:15355962). Does not interact with RHOA. Interacts with TSG101 (PubMed:17853893). Interacts with PAK6 (PubMed:18642328). Interacts with TMEM14B; this interaction increases IQGAP1 phosphorylation and induces its nuclear translocation (PubMed:29033352).4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • calmodulin binding Source: BHF-UCL
  • mitogen-activated protein kinase binding Source: Ensembl
  • protein domain specific binding Source: UniProtKB
  • protein kinase binding Source: BHF-UCL
  • protein phosphatase binding Source: UniProtKB
  • Rac GTPase binding Source: Ensembl
  • S100 protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114353, 274 interactors
CORUMiP46940
DIPiDIP-32597N
IntActiP46940, 197 interactors
MINTiP46940
STRINGi9606.ENSP00000268182

Structurei

Secondary structure

11657
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi31 – 58Combined sources28
Helixi65 – 67Combined sources3
Helixi70 – 72Combined sources3
Helixi76 – 85Combined sources10
Turni87 – 89Combined sources3
Helixi92 – 94Combined sources3
Turni96 – 99Combined sources4
Helixi101 – 105Combined sources5
Helixi110 – 112Combined sources3
Helixi113 – 125Combined sources13
Helixi130 – 132Combined sources3
Helixi136 – 140Combined sources5
Helixi145 – 161Combined sources17
Turni172 – 174Combined sources3
Helixi179 – 190Combined sources12
Helixi199 – 201Combined sources3
Turni206 – 208Combined sources3
Helixi962 – 981Combined sources20
Helixi984 – 991Combined sources8
Helixi1000 – 1009Combined sources10
Turni1010 – 1013Combined sources4
Helixi1016 – 1037Combined sources22
Beta strandi1039 – 1042Combined sources4
Helixi1043 – 1046Combined sources4
Helixi1050 – 1058Combined sources9
Helixi1062 – 1081Combined sources20
Helixi1091 – 1106Combined sources16
Helixi1118 – 1121Combined sources4
Helixi1125 – 1150Combined sources26
Helixi1151 – 1155Combined sources5
Helixi1158 – 1174Combined sources17
Helixi1180 – 1191Combined sources12
Helixi1192 – 1196Combined sources5
Helixi1197 – 1201Combined sources5
Turni1203 – 1207Combined sources5
Helixi1219 – 1236Combined sources18
Helixi1246 – 1248Combined sources3
Helixi1249 – 1270Combined sources22
Helixi1275 – 1278Combined sources4
Beta strandi1282 – 1284Combined sources3
Turni1285 – 1287Combined sources3
Beta strandi1290 – 1292Combined sources3
Helixi1299 – 1311Combined sources13
Helixi1313 – 1316Combined sources4
Helixi1323 – 1331Combined sources9
Beta strandi1561 – 1564Combined sources4
Helixi1565 – 1571Combined sources7
Beta strandi1572 – 1577Combined sources6
Helixi1583 – 1587Combined sources5
Beta strandi1589 – 1593Combined sources5
Beta strandi1596 – 1599Combined sources4
Beta strandi1601 – 1608Combined sources8
Beta strandi1615 – 1617Combined sources3
Helixi1619 – 1628Combined sources10
Beta strandi1632 – 1635Combined sources4
Turni1636 – 1638Combined sources3
Beta strandi1639 – 1642Combined sources4
Helixi1643 – 1652Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1X0HNMR-A1559-1657[»]
2RR8NMR-A26-210[»]
3FAYX-ray2.20A962-1345[»]
3I6XX-ray2.50A/B/C/D1-191[»]
5L0OX-ray2.36A/B/C/D1-191[»]
ProteinModelPortaliP46940
SMRiP46940
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP46940

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini44 – 159Calponin-homology (CH)PROSITE-ProRule annotationAdd BLAST116
Domaini679 – 712WWPROSITE-ProRule annotationAdd BLAST34
Domaini745 – 774IQ 1PROSITE-ProRule annotationAdd BLAST30
Domaini775 – 804IQ 2PROSITE-ProRule annotationAdd BLAST30
Domaini805 – 834IQ 3PROSITE-ProRule annotationAdd BLAST30
Domaini835 – 864IQ 4PROSITE-ProRule annotationAdd BLAST30
Domaini1004 – 1237Ras-GAPPROSITE-ProRule annotationAdd BLAST234

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni956 – 1274C1Add BLAST319
Regioni1276 – 1657C2Add BLAST382

Domaini

Regions C1 and C2 can either interact with nucleotide-free CDC42, or interact together, depending on the phosphorylation state of Ser-1443. When Ser-1443 is not phosphorylated, C1 and C2 interact, which prevents binding of nucleotide-free CDC42 and promotes binding of GTP-bound CDC42. Phosphorylation of Ser-1443 prevents interaction between C1 and C2, which opens the structure of the C-terminus and allows binding and sequestration of nucleotide-free CDC42 on both C1 and C2.1 Publication

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG2128 Eukaryota
COG5261 LUCA
GeneTreeiENSGT00600000084379
HOGENOMiHOG000004842
HOVERGENiHBG052143
InParanoidiP46940
KOiK16848
OMAiVDFRIGN
OrthoDBiEOG091G00ET
PhylomeDBiP46940
TreeFamiTF313078

Family and domain databases

CDDicd00014 CH, 1 hit
cd00201 WW, 1 hit
Gene3Di1.10.418.10, 1 hit
InterProiView protein in InterPro
IPR001715 CH-domain
IPR036872 CH_dom_sf
IPR000048 IQ_motif_EF-hand-BS
IPR027417 P-loop_NTPase
IPR000593 RasGAP_C
IPR023152 RasGAP_CS
IPR001936 RasGAP_dom
IPR008936 Rho_GTPase_activation_prot
IPR001202 WW_dom
PfamiView protein in Pfam
PF00307 CH, 1 hit
PF00612 IQ, 4 hits
PF00616 RasGAP, 1 hit
PF03836 RasGAP_C, 1 hit
SMARTiView protein in SMART
SM00033 CH, 1 hit
SM00015 IQ, 4 hits
SM00323 RasGAP, 1 hit
SM00456 WW, 1 hit
SUPFAMiSSF47576 SSF47576, 1 hit
SSF48350 SSF48350, 2 hits
SSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS50021 CH, 1 hit
PS50096 IQ, 4 hits
PS00509 RAS_GTPASE_ACTIV_1, 1 hit
PS50018 RAS_GTPASE_ACTIV_2, 1 hit
PS01159 WW_DOMAIN_1, 1 hit
PS50020 WW_DOMAIN_2, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P46940-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSAADEVDGL GVARPHYGSV LDNERLTAEE MDERRRQNVA YEYLCHLEEA
60 70 80 90 100
KRWMEACLGE DLPPTTELEE GLRNGVYLAK LGNFFSPKVV SLKKIYDREQ
110 120 130 140 150
TRYKATGLHF RHTDNVIQWL NAMDEIGLPK IFYPETTDIY DRKNMPRCIY
160 170 180 190 200
CIHALSLYLF KLGLAPQIQD LYGKVDFTEE EINNMKTELE KYGIQMPAFS
210 220 230 240 250
KIGGILANEL SVDEAALHAA VIAINEAIDR RIPADTFAAL KNPNAMLVNL
260 270 280 290 300
EEPLASTYQD ILYQAKQDKM TNAKNRTENS ERERDVYEEL LTQAEIQGNI
310 320 330 340 350
NKVNTFSALA NIDLALEQGD ALALFRALQS PALGLRGLQQ QNSDWYLKQL
360 370 380 390 400
LSDKQQKRQS GQTDPLQKEE LQSGVDAANS AAQQYQRRLA AVALINAAIQ
410 420 430 440 450
KGVAEKTVLE LMNPEAQLPQ VYPFAADLYQ KELATLQRQS PEHNLTHPEL
460 470 480 490 500
SVAVEMLSSV ALINRALESG DVNTVWKQLS SSVTGLTNIE EENCQRYLDE
510 520 530 540 550
LMKLKAQAHA ENNEFITWND IQACVDHVNL VVQEEHERIL AIGLINEALD
560 570 580 590 600
EGDAQKTLQA LQIPAAKLEG VLAEVAQHYQ DTLIRAKREK AQEIQDESAV
610 620 630 640 650
LWLDEIQGGI WQSNKDTQEA QKFALGIFAI NEAVESGDVG KTLSALRSPD
660 670 680 690 700
VGLYGVIPEC GETYHSDLAE AKKKKLAVGD NNSKWVKHWV KGGYYYYHNL
710 720 730 740 750
ETQEGGWDEP PNFVQNSMQL SREEIQSSIS GVTAAYNREQ LWLANEGLIT
760 770 780 790 800
RLQARCRGYL VRQEFRSRMN FLKKQIPAIT CIQSQWRGYK QKKAYQDRLA
810 820 830 840 850
YLRSHKDEVV KIQSLARMHQ ARKRYRDRLQ YFRDHINDII KIQAFIRANK
860 870 880 890 900
ARDDYKTLIN AEDPPMVVVR KFVHLLDQSD QDFQEELDLM KMREEVITLI
910 920 930 940 950
RSNQQLENDL NLMDIKIGLL VKNKITLQDV VSHSKKLTKK NKEQLSDMMM
960 970 980 990 1000
INKQKGGLKA LSKEKREKLE AYQHLFYLLQ TNPTYLAKLI FQMPQNKSTK
1010 1020 1030 1040 1050
FMDSVIFTLY NYASNQREEY LLLRLFKTAL QEEIKSKVDQ IQEIVTGNPT
1060 1070 1080 1090 1100
VIKMVVSFNR GARGQNALRQ ILAPVVKEIM DDKSLNIKTD PVDIYKSWVN
1110 1120 1130 1140 1150
QMESQTGEAS KLPYDVTPEQ ALAHEEVKTR LDSSIRNMRA VTDKFLSAIV
1160 1170 1180 1190 1200
SSVDKIPYGM RFIAKVLKDS LHEKFPDAGE DELLKIIGNL LYYRYMNPAI
1210 1220 1230 1240 1250
VAPDAFDIID LSAGGQLTTD QRRNLGSIAK MLQHAASNKM FLGDNAHLSI
1260 1270 1280 1290 1300
INEYLSQSYQ KFRRFFQTAC DVPELQDKFN VDEYSDLVTL TKPVIYISIG
1310 1320 1330 1340 1350
EIINTHTLLL DHQDAIAPEH NDPIHELLDD LGEVPTIESL IGESSGNLND
1360 1370 1380 1390 1400
PNKEALAKTE VSLTLTNKFD VPGDENAEMD ARTILLNTKR LIVDVIRFQP
1410 1420 1430 1440 1450
GETLTEILET PATSEQEAEH QRAMQRRAIR DAKTPDKMKK SKSVKEDSNL
1460 1470 1480 1490 1500
TLQEKKEKIQ TGLKKLTELG TVDPKNKYQE LINDIARDIR NQRRYRQRRK
1510 1520 1530 1540 1550
AELVKLQQTY AALNSKATFY GEQVDYYKSY IKTCLDNLAS KGKVSKKPRE
1560 1570 1580 1590 1600
MKGKKSKKIS LKYTAARLHE KGVLLEIEDL QVNQFKNVIF EISPTEEVGD
1610 1620 1630 1640 1650
FEVKAKFMGV QMETFMLHYQ DLLQLQYEGV AVMKLFDRAK VNVNLLIFLL

NKKFYGK
Length:1,657
Mass (Da):189,252
Last modified:November 1, 1995 - v1
Checksum:iA52EC629596EAC33
GO

Sequence cautioni

The sequence BAA06123 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049134256S → A. Corresponds to variant dbSNP:rs12324924Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L33075 mRNA Translation: AAA59187.1
D29640 mRNA Translation: BAA06123.2 Different initiation.
CH471101 Genomic DNA Translation: EAX02102.1
BC151834 mRNA Translation: AAI51835.1
CCDSiCCDS10362.1
PIRiA54854
RefSeqiNP_003861.1, NM_003870.3
UniGeneiHs.430551

Genome annotation databases

EnsembliENST00000268182; ENSP00000268182; ENSG00000140575
GeneIDi8826
KEGGihsa:8826
UCSCiuc002bpl.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiIQGA1_HUMAN
AccessioniPrimary (citable) accession number: P46940
Secondary accession number(s): A7MBM3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: June 20, 2018
This is version 195 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

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