RAC1

Ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)
PDB rendering based on 1ds6.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1E96, 1FOE, 1G4U, 1HE1, 1HH4, 1I4D, 1I4L, 1I4T, 1MH1, 1RYF, 1RYH, 2FJU, 2H7V, 2NZ8, 2P2L, 2RMK, 2VRW, 2WKP, 2WKQ, 2WKR, 2YIN, 3B13, 3BJI, 3RYT, 3SBD, 3SBE, 3SU8, 3SUA, 3TH5, 4GZL, 4GZM
Identifiers
Symbols	RAC1 ; Rac-1; TC-25; p21-Rac1
External IDs	OMIM: 602048 MGI: 97845 HomoloGene: 69035 ChEMBL: 6094 GeneCards: RAC1 Gene
Gene ontology Molecular function • GTPase activity • protein binding • GTP binding • Rab GTPase binding • enzyme binding • protein kinase binding • GTP-dependent protein binding • thioesterase binding • Rho GDP-dissociation inhibitor binding Cellular component • Golgi membrane • phagocytic cup • trans-Golgi network • cytosol • plasma membrane • membrane • extrinsic component of plasma membrane • lamellipodium • ruffle membrane • cytoplasmic ribonucleoprotein granule • melanosome • extracellular vesicular exosome Biological process • positive regulation of protein phosphorylation • auditory receptor cell morphogenesis • mast cell chemotaxis • epithelial cell morphogenesis • GTP catabolic process • cellular component movement • inflammatory response • hyperosmotic response • cell adhesion • cell-matrix adhesion • small GTPase mediated signal transduction • axon guidance • blood coagulation • cell proliferation • response to wounding • anatomical structure morphogenesis • regulation of hydrogen peroxide metabolic process • positive regulation of lamellipodium assembly • viral process • cerebral cortex radially oriented cell migration • embryonic olfactory bulb interneuron precursor migration • lamellipodium assembly • actin cytoskeleton organization • actin filament polymerization • platelet activation • regulation of cell migration • positive regulation of actin filament polymerization • T cell costimulation • ruffle organization • negative regulation of interleukin-23 production • substrate adhesion-dependent cell spreading • positive regulation of Rho protein signal transduction • intracellular signal transduction • Fc-epsilon receptor signaling pathway • Fc-gamma receptor signaling pathway involved in phagocytosis • positive regulation of apoptotic process • positive regulation of phosphatidylinositol 3-kinase activity • engulfment of apoptotic cell • innate immune response • cell-cell junction organization • bone resorption • positive regulation of DNA replication • neurotrophin TRK receptor signaling pathway • negative regulation of receptor-mediated endocytosis • anatomical structure arrangement • dendrite morphogenesis • cell motility • regulation of defense response to virus by virus • localization within membrane • Wnt signaling pathway, planar cell polarity pathway • regulation of respiratory burst • semaphorin-plexin signaling pathway • dopaminergic neuron differentiation • cochlea morphogenesis • ruffle assembly • apoptotic signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5879	19353
Ensembl	ENSG00000136238	ENSMUSG00000001847
UniProt	P63000	P63001
RefSeq (mRNA)	NM_006908	NM_009007
RefSeq (protein)	NP_008839	NP_033033
Location (UCSC)	Chr 7: 6.41 – 6.44 Mb	Chr 5: 143.51 – 143.53 Mb
PubMed search

Rac1, also known as Ras-related C3 botulinum toxin substrate 1, is a protein found in human cells. It is encoded by the RAC1 gene.^[1][2] This gene can produce a variety of alternatively spliced versions of the Rac1 protein, which appear to carry out different functions.^[3]

Function

Rac1 is a small (~21 kDa) signaling G protein (more specifically a GTPase), and is a member of the Rac subfamily of the family Rho family of GTPases. 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.^[4]

Rac1 is a pleiotropic regulator of many cellular processes, including the cell cycle, cell-cell adhesion, motility (through the actin network), and of epithelial differentiation (proposed to be necessary for maintaining epidermal stem cells).

Role in cancer

Along with other subfamily of Rac and Rho proteins, they exert an important regulatory role specifically in cell motility and cell growth. Rac1 has ubiquitous tissue expression, and drives cell motility by formation of lamellipodia.^[5] In order for cancer cells to grow and invade local and distant tissues, deregulation of cell motility is one of the hallmark events in cancer cell invasion and metastasis.^[6] Activating or gain-of-function mutations of Rac1 are shown to play active roles in promoting mesenchymal-type of cell movement assisted by NEDD9 and DOCK3 protein complex.^[7] Such abnormal cell motility may result in epithelial mesenchymal transition (EMT) – a driving mechanism for tumor metastasis as well as drug-resistant tumor relapse.^[8][9]

Clinical significance

Activating mutations in Rac1 have been recently discovered in large-scale genomic studies involving melanoma ^[10][11][12] and non-small cell lung cancer.^[13] As a result, Rac1 is considered a therapeutic target for many of these diseases.^[14]

A few recent studies have also exploited targeted therapy to suppress tumor growth by pharmacological inhibition of Rac1 activity in metastatic melanoma and liver cancer as well as in human breast cancer.^[15][16][17] For example, Rac1-dependent pathway inhibition resulted in the reversal of tumor cell phenotypes, suggesting Rac1 as a predictive marker and therapeutic target for trastuzumab-resistant breast cancer.^[16]

Interactions

RAC1 has been shown to interact with:

• ARFIP2,^[18][19][20]
• ARHGDIA,^{[21][22][23][24][25][26]}
• BAIAP2,^[27]
• FHOD1,^[28]
• FMNL1,^[29]
• IQGAP1,^{[30][31][32][33]}
• IQGAP2,^[34]
• Myd88,^[35]
• DMPK,^[36]
• NCKAP1,^[37]
• PAK1,^[30][38][39]
• PAK3,^[18]
• PARD6A,^[40][41]
• PARD6B,^[40]
• RICS^[42][43]
• STAT3,^[44] and
• TIAM1.^[45][46]

References

Further reading

External links

• rac1 GTP-Binding Protein at the US National Library of Medicine Medical Subject Headings (MeSH)
• RAC1 Info with links in the Cell Migration Gateway

PDB gallery 1ds6: CRYSTAL STRUCTURE OF A RAC-RHOGDI COMPLEX  1e96: STRUCTURE OF THE RAC/P67PHOX COMPLEX  1foe: CRYSTAL STRUCTURE OF RAC1 IN COMPLEX WITH THE GUANINE NUCLEOTIDE EXCHANGE REGION OF TIAM1  1g4u: CRYSTAL STRUCTURE OF THE SALMONELLA TYROSINE PHOSPHATASE AND GTPASE ACTIVATING PROTEIN SPTP BOUND TO RAC1  1he1: CRYSTAL STRUCTURE OF THE COMPLEX BETWEEN THE GAP DOMAIN OF THE PSEUDOMONAS AERUGINOSA EXOS TOXIN AND HUMAN RAC  1hh4: RAC1-RHOGDI COMPLEX INVOLVED IN NADPH OXIDASE ACTIVATION  1i4d: CRYSTAL STRUCTURE ANALYSIS OF RAC1-GDP COMPLEXED WITH ARFAPTIN (P21)  1i4l: CRYSTAL STRUCTURE ANALYSIS OF RAC1-GDP IN COMPLEX WITH ARFAPTIN (P41)  1i4t: CRYSTAL STRUCTURE ANALYSIS OF RAC1-GMPPNP IN COMPLEX WITH ARFAPTIN  1mh1: SMALL G-PROTEIN  1ryf: Alternative Splicing of Rac1 Generates Rac1b, a Self-activating GTPase  1ryh: Alternative Splicing of Rac1 Generates Rac1b, a Self-activating GTPase  2c2h: CRYSTAL STRUCTURE OF THE HUMAN RAC3 IN COMPLEX WITH GDP  2fju: Activated Rac1 bound to its effector phospholipase C beta 2  2g0n: The Crystal Structure of the Human RAC3 in complex with GDP and Chloride  2h7v: Co-crystal structure of YpkA-Rac1  2ic5: Crystal structure of human RAC3 grown in the presence of Gpp(NH)p.  2nz8: N-terminal DHPH cassette of Trio in complex with nucleotide-free Rac1  2ov2: The crystal structure of the human RAC3 in complex with the CRIB domain of human p21-activated kinase 4 (PAK4)  2p2l: Rac1-GDP-Zinc Complex