Ras-related C3 botulinum toxin substrate 1 (RAC1)
The protein contains 192 amino acids for an estimated molecular weight of 21450 Da.
Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles (PubMed:1643658, PubMed:28886345). Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity in macrophages. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Stimulates PKN2 kinase activity (PubMed:9121475). In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts (PubMed:1643658). In podocytes, promotes nuclear shuttling of NR3C2; this modulation is required for a proper kidney functioning. Required for atypical chemokine receptor ACKR2-induced LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In neurons, is involved in dendritic spine formation and synaptic plasticity (By similarity). In hippocampal neurons, involved in spine morphogenesis and synapse formation, through local activation at synapses by guanine nucleotide exchange factors (GEFs), such as (updated: June 2, 2021)
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.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- 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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- 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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Biological Process
Actin cytoskeleton organization
Actin filament organization
Actin filament polymerization
Anatomical structure arrangement
Anatomical structure morphogenesis
Apoptotic signaling pathway
Auditory receptor cell morphogenesis
Axon guidance
Blood coagulation
Bone resorption
Cell adhesion
Cell migration
Cell motility
Cell population proliferation
Cell projection assembly
Cell-cell junction organization
Cell-matrix adhesion
Cellular response to mechanical stimulus
Cerebral cortex radially oriented cell migration
Cochlea morphogenesis
Cortical cytoskeleton organization
Dendrite morphogenesis
Dopaminergic neuron differentiation
Embryonic olfactory bulb interneuron precursor migration
Engulfment of apoptotic cell
Ephrin receptor signaling pathway
Epithelial cell morphogenesis
Establishment or maintenance of cell polarity
Fc-epsilon receptor signaling pathway
Fc-gamma receptor signaling pathway involved in phagocytosis
G protein-coupled receptor signaling pathway
Hepatocyte growth factor receptor signaling pathway
Hyperosmotic response
Inflammatory response
Innate immune response
Intracellular signal transduction
Lamellipodium assembly
Localization within membrane
Mast cell chemotaxis
Metabolic process
Motor neuron axon guidance
Movement of cell or subcellular component
Negative regulation of fibroblast migration
Negative regulation of interleukin-23 production
Negative regulation of receptor-mediated endocytosis
Neuron migration
Neurotrophin TRK receptor signaling pathway
Neutrophil degranulation
Platelet activation
Positive regulation of actin filament polymerization
Positive regulation of apoptotic process
Positive regulation of cell killing
Positive regulation of cell-substrate adhesion
Positive regulation of DNA replication
Positive regulation of endothelial cell migration
Positive regulation of focal adhesion assembly
Positive regulation of insulin secretion involved in cellular response to glucose stimulus
Positive regulation of lamellipodium assembly
Positive regulation of microtubule polymerization
Positive regulation of neutrophil chemotaxis
Positive regulation of phosphatidylinositol 3-kinase activity
Positive regulation of protein kinase B signaling
Positive regulation of protein phosphorylation
Positive regulation of Rho protein signal transduction
Positive regulation of stress fiber assembly
Positive regulation of substrate adhesion-dependent cell spreading
Protein localization to plasma membrane
Rac protein signal transduction
Regulation of actin cytoskeleton organization
Regulation of cell migration
Regulation of cell shape
Regulation of cell size
Regulation of defense response to virus by virus
Regulation of hydrogen peroxide metabolic process
Regulation of lamellipodium assembly
Regulation of neutrophil migration
Regulation of nitric oxide biosynthetic process
Regulation of respiratory burst
Regulation of small GTPase mediated signal transduction
Regulation of stress fiber assembly
Response to wounding
Rho protein signal transduction
Ruffle assembly
Ruffle organization
Semaphorin-plexin signaling pathway
Small GTPase mediated signal transduction
Sphingosine-1-phosphate receptor signaling pathway
Substrate adhesion-dependent cell spreading
T cell costimulation
Vascular endothelial growth factor receptor signaling pathway
Viral process
Wnt signaling pathway, planar cell polarity pathway
Cellular Component
Cell cortex
Cell projection
Cytoplasm
Cytoplasmic ribonucleoprotein granule
Cytoplasmic vesicle
Cytoskeleton
Cytosol
Dendritic spine
Endoplasmic reticulum membrane
Extracellular exosome
Extracellular matrix
Extrinsic component of cytoplasmic side of plasma membrane
Extrinsic component of plasma membrane
Ficolin-1-rich granule membrane
Filopodium
Focal adhesion
Glutamatergic synapse
Golgi membrane
Intracellular membrane-bounded organelle
Lamellipodium
Melanosome
Membrane
Phagocytic cup
Plasma membrane
Postsynapse
Recycling endosome membrane
Ruffle membrane
Secretory granule membrane
Trans-Golgi network
Vesicle
Molecular Function
ATPase binding
Enzyme binding
G protein activity
GTP binding
GTPase activity
Histone deacetylase binding
Protein kinase binding
Protein serine/threonine kinase activity
Protein-containing complex binding
Rab GTPase binding
Rho GDP-dissociation inhibitor binding
Small GTPase binding
Thioesterase binding
The reference OMIM entry for this protein is 602048
Ras-related c3 botulinum toxin substrate 1; rac1
Rho family, small gtp-binding protein rac1
Ced10, c. elegans, homolog of
GENE FAMILY
Members of the RAS superfamily of small GTP-binding proteins (see 190020) appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases.CLONING
Didsbury et al. (1989) identified 2 human cDNAs, called RAC1 and RAC2 (602049) by them, that are 92% identical and share 58% and 26 to 30% amino acid identity with human RHOS and RAS, respectively. The 2 genes encode the C-terminal consensus sequence (CXXX-COOH), which localizes RAS to the inner plasma membrane, and the residues gly12 and ala59, at which sites mutations elicit transforming potential to RAS. The authors detected RAC1 mRNA in brain and liver tissue and in HL-60 cells differentiating to neutrophil-like morphology. Using transfection experiments, Didsbury et al. (1989) showed that RAC1 and RAC2 are substrates for ADP-ribosylation by the C3 component of botulinum toxin. Drivas et al. (1990) cloned 4 RAS-like sequences, 1 of which, TC25, appears to be identical to RAC1. See also RAC3 (602050). Matos et al. (2000) isolated the RAC1 gene from genomic DNA. Northern blot analysis demonstrated expression of 1.2- and 2.5-kb transcripts in all 12 tissues studied, with the strongest expression in heart, placenta, and kidney. The 2 transcripts were expressed in tissue-specific ratios, and multiple polyadenylation sites were found. By RT-PCR, Matos et al. (2000) found alternative splicing within the coding region of RAC1; a second gene product with an additional 57 nucleotides, which corresponded to RAC1B, a splice variant previously described by Jordan et al. (1999). Matos et al. (2000) showed that RAC1B is a constitutively active mutant which induces the formation of lamellipodia in fibroblasts.GENE STRUCTURE
Matos et al. (2000) demonstrated that the RAC1 gene is 29 kb long and contains 7 exons. The RAC1 promoter lacks both a TATA box and CCAAT box, contains a CpG island surrounding the transcription initiation sites, and is GC rich, all characteristics of a housekeeping gene.MAPPING
By FISH and inclusion within a mapped clone, Matos et al. (2000) mapped the RAC1 gene to 7p22 near PMS2 (600259). They also found a processed RAC1 pseudogene at Xq26.2-q27.2.GENE FUNCTION
By screening rat brain cytosol for proteins that interacted with Ras (HRAS; 190020)-related GTPases, or p21 proteins, of the Rho (RHOA; 165390) subfamily, Manser et al. (1994) identified 3 proteins, designated PAKs (see PAK1; 602590) that interacted with the GTP-bound forms of human CDC42 and RAC1, but not RHOA. To identify the effector pathways that mediate the activities induced by RAC, Joneson et al. (1996) isolated mutant RAC proteins that could discriminate among the RAC targets PAK and POR1 (601638) in the yeast 2-hybrid system. PAK proteins are a family of highly conserved serine/threonine kinases that are activated by interaction with RAC1 (Manser et al., 1994). POR1 interacts with RAC1 and appears to function in RAC-induced membrane ruffling which is apparently induced by actin polymerization (Van Aelst et al., 1996). Joneson et al. (1996) reported that 1 mutant of activated human RAC protein was defective in its binding to PAK3 (300142) and failed to stimulate PAK and JNK (see 601158) activity. This mutant did bind to POR1 and it induced membrane ruffling and transformation. A second RAC mutant, which bound PAK but not POR1, induced JNK activation but w ... More on the omim web site
July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
July 4, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
July 2, 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 25, 2017: Additional information
No protein expression data in P. Mayeux work for RAC1
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602048 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed