Ras GTPase-activating-like protein IQGAP1 (IQGAP1)
The protein contains 1657 amino acids for an estimated molecular weight of 189252 Da.
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). (updated: March 28, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| dbSNP:rs12324924 |
Biological Process
Cell migration
Cellular response to calcium ion
Cellular response to epidermal growth factor stimulus
Cellular response to platelet-derived growth factor stimulus
Energy reserve metabolic process
Epidermal growth factor receptor signaling pathway
Fibroblast growth factor receptor signaling pathway
Fibroblast migration
Glomerular visceral epithelial cell development
Negative regulation of catalytic activity
Negative regulation of dephosphorylation
Neuron projection extension
Neutrophil degranulation
Platelet-derived growth factor receptor signaling pathway
Positive regulation of cellular protein localization
Positive regulation of dendrite development
Positive regulation of focal adhesion assembly
Positive regulation of GTPase activity
Positive regulation of MAP kinase activity
Positive regulation of MAPK cascade
Positive regulation of peptidyl-tyrosine autophosphorylation
Positive regulation of protein kinase activity
Positive regulation of protein serine/threonine kinase activity
Positive regulation of vascular associated smooth muscle cell migration
Regulation of actin cytoskeleton organization
Regulation of cytokine production
Regulation of insulin secretion
Regulation of mitotic cell cycle
Response to angiotensin
Signal transduction
Small GTPase mediated signal transduction
Small molecule metabolic process
Viral process
Cellular Component
Actin filament
Axon
Cell junction
Cell leading edge
Cortical actin cytoskeleton
Cytoplasm
Cytoplasmic ribonucleoprotein granule
Cytosol
Extracellular exosome
Extrinsic component of cytoplasmic side of plasma membrane
Focal adhesion
Growth cone
Lateral plasma membrane
Membrane raft
Microtubule
Midbody
Neuron projection
Nucleoplasm
Nucleus
Plasma membrane
Protein complex
Protein-containing complex
Ribonucleoprotein complex
Ruffle
Secretory granule membrane
Slit diaphragm
Molecular Function
Actin filament binding
Cadherin binding
Calcium ion binding
Calmodulin binding
GTPase activator activity
GTPase inhibitor activity
MAP-kinase scaffold activity
Mitogen-activated protein kinase binding
Molecular adaptor activity
Phosphatidylinositol-3,4,5-trisphosphate binding
Protein complex binding
Protein domain specific binding
Protein kinase binding
Protein phosphatase binding
Protein serine/threonine kinase activator activity
Protein-containing complex binding
Protein-containing complex scaffold activity
Rac GTPase binding
Ras GTPase binding
S100 protein binding
Small GTPase binding
The reference OMIM entry for this protein is 603379
Iq motif-containing gtpase-activating protein 1; iqgap1
Rasgap-like with iq motifs
P195
Sar1, s. pombe, homolog of; sar1
Humorfa01
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 d ... More on the omim web site
April 12, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603379 was added.