RAC1

Rac1 is a GTPase which belongs to the RAS superfamily of small GTP-binding proteins. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases. Two transcript variants encoding different isoforms have been found for RAC1 gene. Rac1 is a 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 and growth-factor induced formation of membrane ruffles. 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 macrophage. Rac1 is essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Rac1's isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins. It is able to bind to the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner, suggesting that the insertion does not completely abolish effector interaction.

RAC1 Related Areas

Stem Cell>>Neural Stem Cell (NSC)>>Neural Crest Stem Cell>>Neural Crest Effector>>RAC1

RAC1 Related Pathways

• TGF-beta Signaling
• EGFR Signaling Pathway
• non-Canonical (beta-Catenin-Independent) Wnt Signaling

RAC1 Alternative Names

RAC1, MIG5, MGC111543, TC-25, p21-Rac1 [Homo sapiens]

Rac1, AL023026, D5Ertd559e [Mus musculus]

Summaries for RAC1

Entrez Gene summary for RAC1:

The rac1 protein encoded by RAC1 gene is a GTPase which belongs to the RAS superfamily of small GTP-binding proteins. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases. Two transcript variants encoding different isoforms have been found for this RAC1 gene. [provided by RefSeq, Mar 2009]

Wikipedia summary for RAC1:

Ras-related C3 botulinum toxin substrate 1 also known as rac1 is a protein that in humans is encoded by the RAC1 gene. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.

Human RAC1 Protein General Information

 

• Protein names: Ras-related C3 botulinum toxin substrate 1, Short Name=RAC1
• Sequence length: 192 AA.
• Domain: The effector region mediates interaction with DEF6.
• Sequence similarities: Rac1 belongs to the small GTPase superfamily. Rho family.
• Post-translational modification: AMPylation at Tyr-32 and Thr-35 are mediated by bacterial enzymes in case of infection by H.somnus and V.parahaemolyticus, respectively. AMPylation occurs in the effector region and leads to inactivation of the GTPase activity by preventing the interaction with downstream effectors, thereby inhibiting actin assembly in infected cells. It is unclear whether some human enzyme mediates AMPylation; FICD has such ability in vitro but additional experiments remain to be done to confirm results in vivo.
• Subunit structure: Probably found in a ternary complex composed of DSCAM, PAK1 and RAC1. Interacts with DSCAM; the interaction requires PAK1. Part of a complex with MAP2K3, MAP3K3, CCM2 and DEF6. Interacts with BAIAP2, BAIAP2L1, CYFIP1/SRA-1 and DEF6. Interacts with Y.pseudotuberculosis YPKA and PLCB2. Interacts with NOXA1. Interacts with ARHGEF2. Interacts with NISCH. Interacts with TBC1D2. Interacts with UNKL. Interacts with USP6. Interacts with SPATA13. Interacts with ARHGEF16; mediates activation of RAC1 by EPHA2. Interacts with ITGB4. Interacts with PIP5K1A
• Subcellular location: Cell membrane; Lipid-anchor; Cytoplasmic side By similarity. Melanosome. Note: Inner surface of plasma membrane possibly with attachment requiring prenylation of the C-terminal cysteine By similarity. Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
• Tissue specificity: Isoform B is predominantly identified in skin and epithelial tissues from the intestinal tract. Its expression is elevated in colorectal tumors at various stages of neoplastic progression, as compared to their respective adjacent tissues.
• Enzyme regulation: RAC1 is regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. GTP hydrolysis is stimulated by ARHGAP30.
• Sequence caution: The sequence AAZ80485.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

General information above from UniProt

Function for RAC1 Protein

UniProtKB:

Rac1 is plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, rac1 binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization and growth-factor induced formation of membrane ruffles. 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. Rac1 is essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly.

Genatlas:

• Rac1 plays a significant role in the bone resorptive activity of cells, probably by regulating the motility of osteoclasts
• RAC1 is potent activator of mineralocorticoid receptor signal transduction (Pubmed 19029984)
• Rac1 is involved in the production of superoxide in neutrophils
• Rac1 is putative regulator of mitogen-induced cytoskeletal changes essential for membrane ruffling and C-jun aminoterminal kinase JNK
• Rac1 is regulator of actin filament at the plasma membrane to produce lamellipodia and membrane ruffles, controlling proliferation, adhesion, migration during embryonic development
• Rac1 is key downstream target in Ras signaling
• Rac1 links growth factor receptor to the activator of actin polymerization
• Rac1 activates JNK signaling pathway
• reduction of oxygen to O-2 at the expense of NADPH, the O2-generated is the precursor of potent oxidants used to kill the invading microorganisms
• exerting its effects in the epidermis by negatively regulating c-Myc through p21-activated kinase 2 (PAK2) phosphorylation
• Rac1 may playing an important role in corneal wound healing
• Rac1 has distinct roles in regulating cell morphology, migration and invasion, but is not essential for macrophage migration or chemotaxis
• Rac1 is critically involved in M-CSF receptor signaling and mediates survival signaling primarily through PI3K/Akt pathways
• Rac1 regulates cell adhesion, migration and differentiation in various cell types
• Rac1 plays a role in hematopoietic development and function (Pubmed 14564009)
• Rac1 has a critical role in B cell development and signaling (Pubmed 14564011)
• Rac1 controles the formation of dendrites in mature dendritic cells, their polarized short-range migration toward T cells, and T cell priming (Pubmed 15326354)
• Rac1 is critical for the hypertrophic response in the heart (Pubmed 16651530)
• Rac1 negatively controls LPS-induced IL-23 p19 expression through an NF-kappaB p65 trans activation-dependent (Pubmed 16982892)
• Rac1 is mediator of colony-stimulating factor 1 (CSF-1)-dependent actin remodeling in osteoclasts (Pubmed 17227220)
• Rac1 plays central role for Rac1 in the control of NDRG1-induced breast cancer cell-cycle progression and proliferation through up-regulating the expression of cyclin D1 and CDKN1A (Pubmed 17941827)
• Rac1 is essential player for mediating the induction of cyclin D1 and CDKN1A by HRG in breast cancer cells (Pubmed 17941827)
• Rac1 is involved in endothelial cell cytoskeletal reorganization and in neovessel formation (Pubmed 18156211)
• overexpression of rac1 contributes to the accelerated migration and high proliferation potential of leukemia cells, which could be implicated in leukemia development and progression (Pubmed 19563775)
• Rac1 with RHOA, and RHOB, are involved in the establishment of the migratory and invasive phenotype of tumour cells that have CDH1 mutation (Pubmed 19584084)
• Rac1 plays essential roles in coordinating directional migration and superoxide production during neutrophil responses to chemoattractants (Pubmed 19625648)
• Rac1 and rac2 GTPases are essential for normal bone marrow erythropoiesis but that they are dispensable for erythropoiesis in the spleen, implying different signaling pathways for homeostatic and stress erythropoiesis (Pubmed 20065081)
• Rac1 is critical regulator of both MTOR and CRTC2 in response to growth-factor stimulation (Pubmed 21474067)

Homology for human RAC1

• ortholog to rac1, danio rerio
• ortholog to Rac1, Mus musculus
• ortholog to Rac1, Rattus norvegicus