Scientific Background: RAC1 is a member of the Rho family and is a GTPase that is part of the small GTP-binding protein superfamily. RAC1 is involved in a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases (1). Role of RAC1 in colorectal cancer has been reported after analysis of the protein expression level and activities of this protein in matched sets of tumor and non-tumor tissues. Overexpression of RAC1 leads to increased tumour growth in xenografts of human colorectal tumour cells (2). RAC1 is also involved in the regulation of critical cellular functions including organization of actin cytoskeleton, transcription control and cell cycle.
2. del Pulgar, T.G. et al: Differential expression of Rac1 identifies its target genes and its contribution to progression of colorectal cancer. Int. J. Biochem. Cell Biol. 2007;39(12):2289-302.
NCBI and Uniprot Product Information
NCBI Description
The protein encoded by this 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 gene. [provided by RefSeq, Mar 2009]
Uniprot Description
Function: 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 macrophages. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Stimulates PKN2 kinase activity. In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. In glioma cells, promotes cell migration and invasion. In podocytes, promotes nuclear shuttling of NR3C2; this modulation is required for a proper kidney functioning. Ref.13 Ref.15 Ref.35 Ref.37 Ref.39 Ref.43 Ref.44 Ref.49Isoform 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. Ref.13 Ref.15 Ref.35 Ref.37 Ref.39 Ref.43 Ref.44 Ref.49
Enzyme regulation: 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. Ref.47
Subunit structure: Interacts with NISCH. Interacts with PIP5K1A. Interacts with the GTP-bound form of RAB7A. Interacts with SRGAP2. Interacts with CYFIP1/SRA-1. Interacts with PLXNB3. Interacts with ARHGDIA; the interaction is induced by SEMA5A, mediated through PLXNB3 and inactivates and stabilizes RAC1. Interacts (GTP-bound form preferentially) with PKN2 (via the REM repeats); the interaction stimulates autophosphorylation and phosphorylation of PKN2. Interacts with the GEF proteins PREX1, RASGRF2, FARP1, FARP2, DOCK1, DOCK2 and DOCK7, which promote the exchange between GDP and GTP, and therefore activate it. Interacts with PARD6A, PARD6B and PARD6G in a GTP-dependent manner. Part of a quaternary complex containing PARD3, some PARD6 protein (PARD6A, PARD6B or PARD6G) and some atypical PKC protein (PRKCI or PRKCZ), which plays a central role in epithelial cell polarization. Found in a trimeric complex composed of DOCK1 and ELMO1, which plays a central role in phagocytosis of apoptotic cells. Interacts with RALBP1 via its effector domain. Interacts with PLXNB1. 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 and DEF6. Interacts with Y.pseudotuberculosis YPKA and PLCB2. Interacts with NOXA1. Interacts with ARHGEF2. 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 S100A8 and calprotectin (S100A8/9). Interacts with PACSIN2. Interacts with ITGB1BP1. Interacts (when active) with PPP5C (via TPR repeats); activates PPP5C phosphatase activity and translocates PPP5C to the cell membrane. Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.30 Ref.31 Ref.32 Ref.33 Ref.38 Ref.39 Ref.42 Ref.44 Ref.45 Ref.49 Ref.50 Ref.51 Ref.52 Ref.53
Subcellular location: Cell membrane; Lipid-anchor; Cytoplasmic side
By similarity. Melanosome. Cytoplasm
By similarity. 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. Found in the ruffled border (a late endosomal-like compartment in the plasma membrane) of bone-resorbing osteoclasts
By similarity. Ref.29 Ref.44 Ref.49
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.
Domain: The effector region mediates interaction with DEF6. Ref.31
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.GTP-bound active form is ubiquitinated by HACE1, leading to its degradation by the proteasome.
Sequence similarities: Belongs to the small GTPase superfamily. Rho family.
Sequence caution: The sequence AAZ80485.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
Research Articles on RAC1
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Product Notes
The RAC1 rac1 (Catalog #AAA515253) is a Recombinant Protein produced from E Coli and is intended for research purposes only. The product is available for immediate purchase. The tag for this protein is GST tag!!Expression System||E.coli!!Source Note||Recombinant full-length human RAC1 was expressed in E. coli cells. AAA Biotech's RAC1 can be used in a range of immunoassay formats including, but not limited to, Kinase Assay, Western Blot (WB). Researchers should empirically determine the suitability of the RAC1 rac1 for an application not listed in the data sheet. Researchers commonly develop new applications and it is an integral, important part of the investigative research process. It is sometimes possible for the material contained within the vial of "RAC1, Recombinant Protein" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
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