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Protein

Ras-related C3 botulinum toxin substrate 1

Gene

Rac1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. 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 podocytes, promotes nuclear shuttling of NR3C2; this modulation is required for a proper kidney functioning. In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3.1 Publication

Enzyme regulationi

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 (By similarity).By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi10 – 17GTPBy similarity8
Nucleotide bindingi57 – 61GTPBy similarity5
Nucleotide bindingi115 – 118GTPBy similarity4

GO - Molecular functioni

  • enzyme binding Source: MGI
  • GTPase activity Source: MGI
  • GTP binding Source: MGI
  • GTP-dependent protein binding Source: UniProtKB
  • protein kinase binding Source: MGI
  • Rho GDP-dissociation inhibitor binding Source: UniProtKB
  • thioesterase binding Source: MGI

GO - Biological processi

  • actin cytoskeleton organization Source: MGI
  • actin filament polymerization Source: MGI
  • anatomical structure arrangement Source: MGI
  • auditory receptor cell morphogenesis Source: MGI
  • axon guidance Source: MGI
  • cell adhesion Source: MGI
  • cell-cell junction organization Source: MGI
  • cell migration Source: MGI
  • cell motility Source: UniProtKB
  • cerebral cortex GABAergic interneuron development Source: MGI
  • cerebral cortex radially oriented cell migration Source: MGI
  • cochlea morphogenesis Source: MGI
  • cytoskeleton organization Source: MGI
  • dendrite development Source: MGI
  • dendrite morphogenesis Source: MGI
  • dopaminergic neuron differentiation Source: MGI
  • embryonic olfactory bulb interneuron precursor migration Source: MGI
  • endocytosis Source: MGI
  • engulfment of apoptotic cell Source: BHF-UCL
  • epithelial cell morphogenesis Source: MGI
  • G-protein coupled receptor signaling pathway Source: MGI
  • hepatocyte growth factor receptor signaling pathway Source: MGI
  • homeostasis of number of cells within a tissue Source: MGI
  • hyperosmotic response Source: MGI
  • lamellipodium assembly Source: MGI
  • localization within membrane Source: MGI
  • midbrain dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
  • negative regulation of interleukin-23 production Source: MGI
  • neuron projection morphogenesis Source: ParkinsonsUK-UCL
  • non-canonical Wnt signaling pathway Source: ParkinsonsUK-UCL
  • phagocytosis, engulfment Source: UniProtKB
  • positive regulation of actin filament polymerization Source: MGI
  • positive regulation of cell-substrate adhesion Source: MGI
  • positive regulation of dendritic spine development Source: MGI
  • positive regulation of focal adhesion assembly Source: MGI
  • positive regulation of lamellipodium assembly Source: MGI
  • positive regulation of microtubule polymerization Source: MGI
  • positive regulation of neutrophil chemotaxis Source: UniProtKB
  • positive regulation of phosphatidylinositol 3-kinase activity Source: MGI
  • positive regulation of protein phosphorylation Source: UniProtKB
  • positive regulation of stress fiber assembly Source: MGI
  • positive regulation of substrate adhesion-dependent cell spreading Source: MGI
  • protein localization to plasma membrane Source: MGI
  • regulation of cell migration Source: MGI
  • regulation of cell morphogenesis Source: MGI
  • regulation of cell size Source: MGI
  • regulation of fibroblast migration Source: UniProtKB
  • regulation of lamellipodium assembly Source: MGI
  • regulation of neuronal synaptic plasticity Source: MGI
  • regulation of neuron maturation Source: MGI
  • regulation of respiratory burst Source: MGI
  • regulation of stress fiber assembly Source: MGI
  • ruffle assembly Source: UniProtKB
  • ruffle organization Source: MGI
  • semaphorin-plexin signaling pathway Source: UniProtKB
  • small GTPase mediated signal transduction Source: MGI
  • substrate adhesion-dependent cell spreading Source: MGI
  • synaptic transmission, GABAergic Source: MGI
  • Wnt signaling pathway, planar cell polarity pathway Source: MGI

Keywordsi

LigandGTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-114604 GPVI-mediated activation cascade
R-MMU-1433557 Signaling by SCF-KIT
R-MMU-193648 NRAGE signals death through JNK
R-MMU-194840 Rho GTPase cycle
R-MMU-2029482 Regulation of actin dynamics for phagocytic cup formation
R-MMU-2424491 DAP12 signaling
R-MMU-2871796 FCERI mediated MAPK activation
R-MMU-376172 DSCAM interactions
R-MMU-389359 CD28 dependent Vav1 pathway
R-MMU-3928662 EPHB-mediated forward signaling
R-MMU-3928664 Ephrin signaling
R-MMU-3928665 EPH-ephrin mediated repulsion of cells
R-MMU-399954 Sema3A PAK dependent Axon repulsion
R-MMU-4086400 PCP/CE pathway
R-MMU-416482 G alpha (12/13) signalling events
R-MMU-416550 Sema4D mediated inhibition of cell attachment and migration
R-MMU-418885 DCC mediated attractive signaling
R-MMU-4420097 VEGFA-VEGFR2 Pathway
R-MMU-445144 Signal transduction by L1
R-MMU-5218920 VEGFR2 mediated vascular permeability
R-MMU-5625740 RHO GTPases activate PKNs
R-MMU-5625900 RHO GTPases activate CIT
R-MMU-5625970 RHO GTPases activate KTN1
R-MMU-5626467 RHO GTPases activate IQGAPs
R-MMU-5627123 RHO GTPases activate PAKs
R-MMU-5663213 RHO GTPases Activate WASPs and WAVEs
R-MMU-5668599 RHO GTPases Activate NADPH Oxidases
R-MMU-5687128 MAPK6/MAPK4 signaling
R-MMU-6798695 Neutrophil degranulation
R-MMU-8849471 PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases
R-MMU-8875555 MET activates RAP1 and RAC1
R-MMU-983231 Factors involved in megakaryocyte development and platelet production

Names & Taxonomyi

Protein namesi
Recommended name:
Ras-related C3 botulinum toxin substrate 1
Alternative name(s):
p21-Rac1
Gene namesi
Name:Rac1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:97845 Rac1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi12G → V: Constitutively active. Interacts with PARD6 proteins. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL5628

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000420381 – 189Ras-related C3 botulinum toxin substrate 1Add BLAST189
PropeptideiPRO_0000042039190 – 192Removed in mature formBy similarity3

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki147Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei189Cysteine methyl esterBy similarity1
Lipidationi189S-geranylgeranyl cysteineBy similarity1

Post-translational modificationi

GTP-bound active form is ubiquitinated by HACE1, leading to its degradation by the proteasome.By similarity

Keywords - PTMi

Isopeptide bond, Lipoprotein, Methylation, Prenylation, Ubl conjugation

Proteomic databases

EPDiP63001
MaxQBiP63001
PaxDbiP63001
PRIDEiP63001

PTM databases

iPTMnetiP63001
PhosphoSitePlusiP63001
SwissPalmiP63001

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSMUSG00000001847
CleanExiMM_RAC1
ExpressionAtlasiP63001 baseline and differential
GenevisibleiP63001 MM

Interactioni

Subunit structurei

Interacts with the GEF proteins PREX1, FARP1, FARP2, DOCK1, DOCK2 and DOCK7, which promote the exchange between GDP and GTP, and therefore activate it. 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 BAIAP2, BAIAP2L1, PLXNB1, CYFIP1/SRA-1 and DEF6. Probably found in a ternary complex composed of DSCAM, PAK1 and RAC1. Interacts with DSCAM; the interaction requires PAK1. Interacts with TBC1D2. Interacts with UNKL. Interacts with USP6. Interacts with SPATA13. Interacts with ITGB4. Interacts with the GTP-bound form of RAB7A. Interacts with ARHGEF2. Interacts with ARHGEF16; mediates activation of RAC1 by EPHA2. Interacts with NOXA1. Interacts with S100A8 and calprotectin (S100A8/9). Interacts with ARHGDIA; the interaction is induced by SEMA5A, mediated through PLXNB3 and inactivates and stabilizes RAC1. Interacts with PACSIN2. Interacts with ITGB1BP1 (By similarity). Interacts with the GEF protein RASGRF2, which promotes the exchange between GDP and GTP, and therefore activates it. Interacts with PARD6A, PARD6B and PARD6G in a GTP-dependent manner. Part of a complex with MAP2K3, MAP3K3 and CCM2. Interacts with NISCH. Interacts with PIP5K1A. Interacts (GTP-bound form preferentially) with PKN2 (via the REM repeats); the interaction stimulates autophosphorylation and phosphorylation of PKN2. Interacts with SRGAP2. Interacts with PLXNB3. Interacts (when active) with PPP5C (via TPR repeats); activates PPP5C phosphatase activity and translocates PPP5C to the cell membrane. Interacts with RAPH1 (via Ras associating and PH domains) (By similarity). Interacts with MTSS1L (via IMD domain); this interaction may be important to potentiate PDGF-induced RAC1 activation (By similarity).By similarity10 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi20255632 interactors.
CORUMiP63001
DIPiDIP-31545N
IntActiP63001 36 interactors.
MINTiP63001
STRINGi10090.ENSMUSP00000079380

Chemistry databases

BindingDBiP63001

Structurei

3D structure databases

ProteinModelPortaliP63001
SMRiP63001
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi32 – 40Effector regionSequence analysis9

Domaini

The effector region mediates interaction with DEF6.By similarity

Sequence similaritiesi

Belongs to the small GTPase superfamily. Rho family.Curated

Phylogenomic databases

eggNOGiKOG0393 Eukaryota
COG1100 LUCA
GeneTreeiENSGT00760000118978
HOGENOMiHOG000233974
HOVERGENiHBG009351
InParanoidiP63001
KOiK04392
PhylomeDBiP63001
TreeFamiTF101109

Family and domain databases

InterProiView protein in InterPro
IPR027417 P-loop_NTPase
IPR005225 Small_GTP-bd_dom
IPR001806 Small_GTPase
IPR003578 Small_GTPase_Rho
PfamiView protein in Pfam
PF00071 Ras, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR00231 small_GTP, 1 hit
PROSITEiView protein in PROSITE
PS51420 RHO, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P63001-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQAIKCVVVG DGAVGKTCLL ISYTTNAFPG EYIPTVFDNY SANVMVDGKP
60 70 80 90 100
VNLGLWDTAG QEDYDRLRPL SYPQTDVFLI CFSLVSPASF ENVRAKWYPE
110 120 130 140 150
VRHHCPNTPI ILVGTKLDLR DDKDTIEKLK EKKLTPITYP QGLAMAKEIG
160 170 180 190
AVKYLECSAL TQRGLKTVFD EAIRAVLCPP PVKKRKRKCL LL
Length:192
Mass (Da):21,450
Last modified:August 31, 2004 - v1
Checksum:iACEDF83A45E5EA67
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X57277 mRNA Translation: CAA40545.1
AK009017 mRNA Translation: BAB26027.1
AK011072 mRNA Translation: BAB69451.1
AK034601 mRNA Translation: BAC28767.1
AK047969 mRNA Translation: BAC33203.1
AK088825 mRNA Translation: BAC40596.1
BC003828 mRNA Translation: AAH03828.1
BC051053 mRNA Translation: AAH51053.1
CCDSiCCDS19843.1
PIRiA60347
RefSeqiNP_033033.1, NM_009007.2
UniGeneiMm.292510
Mm.469963
Mm.475073

Genome annotation databases

EnsembliENSMUST00000080537; ENSMUSP00000079380; ENSMUSG00000001847
GeneIDi19353
KEGGimmu:19353
UCSCiuc009akk.1 mouse

Similar proteinsi

Entry informationi

Entry nameiRAC1_MOUSE
AccessioniPrimary (citable) accession number: P63001
Secondary accession number(s): O95501, P15154, Q9BTB4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 31, 2004
Last sequence update: August 31, 2004
Last modified: April 25, 2018
This is version 163 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome