P63001 · RAC1_MOUSE

  • Protein
    Ras-related C3 botulinum toxin substrate 1
  • Gene
    Rac1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states (PubMed:24352656).
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. 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 neurons, is involved in dendritic spine formation and synaptic plasticity (PubMed:24352656, PubMed:26969129).
In hippocampal neurons, involved in spine morphogenesis and synapse formation, through local activation at synapses by guanine nucleotide exchange factors (GEFs), such as ARHGEF6/ARHGEF7/PIX (PubMed:12695502).
In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3. In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in PAK1 activation and eventually F-actin stabilization (By similarity).
Required for DSG3 translocation to cell-cell junctions, DSG3-mediated organization of cortical F-actin bundles and anchoring of actin at cell junctions; via interaction with DSG3 (By similarity).
Subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion (O2-) (By similarity).

Catalytic activity

Activity 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 and ARHGAP44.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site12GTP (UniProtKB | ChEBI)
Binding site13GTP (UniProtKB | ChEBI)
Binding site14GTP (UniProtKB | ChEBI)
Binding site15GTP (UniProtKB | ChEBI)
Binding site16GTP (UniProtKB | ChEBI)
Binding site17GTP (UniProtKB | ChEBI)
Binding site18GTP (UniProtKB | ChEBI)
Binding site31GTP (UniProtKB | ChEBI)
Binding site32GTP (UniProtKB | ChEBI)
Binding site34GTP (UniProtKB | ChEBI)
Binding site35GTP (UniProtKB | ChEBI)
Binding site59GTP (UniProtKB | ChEBI)
Binding site60GTP (UniProtKB | ChEBI)
Binding site116GTP (UniProtKB | ChEBI)
Binding site118GTP (UniProtKB | ChEBI)
Binding site119GTP (UniProtKB | ChEBI)
Binding site159GTP (UniProtKB | ChEBI)
Binding site160GTP (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcell projection
Cellular Componentcytoplasm
Cellular Componentcytoplasmic vesicle
Cellular Componentcytosol
Cellular Componentdendrite
Cellular Componentearly endosome membrane
Cellular Componentglutamatergic synapse
Cellular Componentkinocilium
Cellular Componentlamellipodium
Cellular Componentmelanosome
Cellular Componentmembrane
Cellular Componentnucleus
Cellular Componentpericentriolar material
Cellular Componentphagocytic cup
Cellular Componentplasma membrane
Cellular Componentpostsynaptic membrane
Cellular Componentpresynaptic membrane
Cellular Componentruffle membrane
Cellular Componentsynaptic vesicle membrane
Molecular FunctionG protein activity
Molecular FunctionGTP binding
Molecular FunctionGTP-dependent protein binding
Molecular FunctionGTPase activity
Molecular Functionmembrane scission GTPase motor activity
Molecular FunctionRho GDP-dissociation inhibitor binding
Biological Processactin cytoskeleton organization
Biological Processactin filament polymerization
Biological Processanatomical structure arrangement
Biological Processangiotensin-activated signaling pathway involved in heart process
Biological Processauditory receptor cell morphogenesis
Biological Processaxon guidance
Biological Processcell adhesion
Biological Processcell migration
Biological Processcell motility
Biological Processcell-cell junction organization
Biological Processcerebral cortex GABAergic interneuron development
Biological Processcerebral cortex radially oriented cell migration
Biological Processcochlea morphogenesis
Biological Processcytoskeleton organization
Biological Processdendrite development
Biological Processdendrite morphogenesis
Biological Processdopaminergic neuron differentiation
Biological Processembryonic olfactory bulb interneuron precursor migration
Biological Processendocytosis
Biological Processengulfment of apoptotic cell
Biological Processenzyme-linked receptor protein signaling pathway
Biological Processepithelial cell morphogenesis
Biological Processerythrocyte enucleation
Biological Processforebrain development
Biological ProcessG protein-coupled receptor signaling pathway
Biological Processhomeostasis of number of cells within a tissue
Biological Processhyperosmotic response
Biological Processinterneuron migration
Biological Processlamellipodium assembly
Biological Processmidbrain dopaminergic neuron differentiation
Biological Processneuron migration
Biological Processneuron projection morphogenesis
Biological Processnon-canonical Wnt signaling pathway
Biological Processphagocytosis, engulfment
Biological Processpositive regulation of actin filament polymerization
Biological Processpositive regulation of bicellular tight junction assembly
Biological Processpositive regulation of dendritic spine development
Biological Processpositive regulation of insulin secretion involved in cellular response to glucose stimulus
Biological Processpositive regulation of lamellipodium assembly
Biological Processpositive regulation of neutrophil chemotaxis
Biological Processpositive regulation of ovarian follicle development
Biological Processpositive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Processpositive regulation of protein phosphorylation
Biological Processpositive regulation of skeletal muscle acetylcholine-gated channel clustering
Biological Processprotein localization to plasma membrane
Biological ProcessRac protein signal transduction
Biological Processregulation of cell adhesion involved in heart morphogenesis
Biological Processregulation of cell morphogenesis
Biological Processregulation of ERK5 cascade
Biological Processregulation of fibroblast migration
Biological Processregulation of neuron maturation
Biological Processregulation of neuron migration
Biological Processregulation of neuronal synaptic plasticity
Biological Processregulation of postsynapse assembly
Biological Processregulation of receptor signaling pathway via JAK-STAT
Biological Processregulation of synaptic vesicle endocytosis
Biological Processresponse to lipopolysaccharide
Biological Processruffle assembly
Biological Processruffle organization
Biological Processsemaphorin-plexin signaling pathway
Biological Processsmall GTPase-mediated signal transduction
Biological Processsubstrate adhesion-dependent cell spreading
Biological Processsynaptic transmission, GABAergic
Biological ProcessWnt signaling pathway, planar cell polarity pathway

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Ras-related C3 botulinum toxin substrate 1
  • EC number
  • Alternative names
    • p21-Rac1

Gene names

    • Name
      Rac1

Organism names

  • Taxonomic identifier
  • Strains
    • C57BL/6J
    • NOD
    • Czech II
    • FVB/N
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    P63001
  • Secondary accessions
    • O95501
    • P15154
    • Q9BTB4

Proteomes

Organism-specific databases

Subcellular Location

Cell membrane
; Lipid-anchor
Melanosome
Cytoplasm
Synapse
Nucleus
Note: Inner surface of plasma membrane possibly with attachment requiring prenylation of the C-terminal cysteine (By similarity).
Found in the ruffled border (a late endosomal-like compartment in the plasma membrane) of bone-resorbing osteoclasts (By similarity).
Localizes to the lamellipodium in a SH3RF1-dependent manner. In macrophages, cytoplasmic location increases upon CSF1 stimulation (PubMed:17116687).
Activation by GTP-binding promotes nuclear localization (By similarity).

Keywords

Phenotypes & Variants

Disruption phenotype

Conditional knockout of Rac1 in the telencephalic ventricular zone of embryos leads to primary microcephaly. Self-renewal, survival, and differentiation of telencephalic neural progenitor cells is affected.

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis12Constitutively active. Interacts with PARD6 proteins.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 17 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Chemistry

PTM/Processing

Features

Showing features for chain, modified residue (large scale data), modified residue, cross-link, lipidation, propeptide.

Type
IDPosition(s)Source
Description
ChainPRO_00000420381-189UniProtRas-related C3 botulinum toxin substrate 1
Modified residue (large scale data)64PTMeXchangePhosphotyrosine
Modified residue71UniProtPhosphoserine
Modified residue (large scale data)98PTMeXchangePhosphotyrosine
Modified residue (large scale data)108PTMeXchangePhosphothreonine
Modified residue (large scale data)135PTMeXchangePhosphothreonine
Cross-link147UniProtGlycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-link166UniProtGlycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Modified residue (large scale data)167PTMeXchangePhosphothreonine
Modified residue189UniProtCysteine methyl ester
Lipidation189UniProtS-geranylgeranyl cysteine
PropeptidePRO_0000042039190-192UniProtRemoved in mature form

Post-translational modification

GTP-bound active form is ubiquitinated at Lys-147 by HACE1, leading to its degradation by the proteasome.
Phosphorylated by AKT at Ser-71.
Ubiquitinated at Lys-166 in a FBXL19-mediated manner; leading to proteasomal degradation.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Widely expressed.

Developmental stage

Expressed in the neocortical neurons in the developing brain.

Gene expression databases

Interaction

Subunit

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. 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 MTSS2 (via IMD domain); this interaction may be important to potentiate PDGF-induced RAC1 activation. Interacts (GTP-bound form) with SH3RF3. Interacts with PAK2 (By similarity).
Interacts (GTP-bound form) with SH3RF1 (PubMed:22959435).
Found in a complex with SH3RF1, MAPK8IP1/JIP1, MAP3K11/MLK3, MAP2K7/MKK7 and MAPK8/JNK1 (PubMed:23963642).
Interacts (both active GTP- or inactive GDP-bound forms) with SH3RF2 (By similarity).
Interacts (GTP-bound form preferentially) with CYRIB (By similarity).
Interacts with DOCK4 (via DOCKER domain); functions as a guanine nucleotide exchange factor (GEF) for RAC1 (By similarity).
Interacts with GARRE1 (By similarity).
Interacts with RAP1GDS1 (By similarity).
Interacts with TNFAIP8L2 (By similarity).
May interact with ARHGAP36 (By similarity).
Interacts with CD151 and ITGB1 (By similarity).
Interacts with DSG3; the interaction is required for DSG3 translocation to cell-cell junctions, organization of cortical F-actin bundles and actin anchoring at cell-cell junctions (By similarity).
Component of the phagocyte NADPH oxidase complex composed of an obligatory core heterodimer formed by the membrane proteins CYBA and CYBB and the cytosolic regulatory subunits NCF1/p47-phox, NCF2/p67-phox, NCF4/p40-phox and the small GTPase RAC1 or RAC2. Interacts with NCF2 (By similarity).

Binary interactions

Type
Entry 1Entry 2Number of experimentsIntAct
BINARY P63001Dlg4 Q621083EBI-413646, EBI-300895
XENO P63001PAK1 Q131533EBI-413646, EBI-1307
BINARY P63001Sod1 P082284EBI-413646, EBI-1635090

Protein-protein interaction databases

Chemistry

Miscellaneous

Family & Domains

Features

Showing features for motif.

TypeIDPosition(s)Description
Motif32-40Effector region
Motif179-188Polybasic region; required for nuclear import

Domain

The effector region mediates interaction with DEF6.

Sequence similarities

Belongs to the small GTPase superfamily. Rho family.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    192
  • Mass (Da)
    21,450
  • Last updated
    2004-08-31 v1
  • MD5 Checksum
    77D01C8ED1DBA53DE467E8343EFD019F
MQAIKCVVVGDGAVGKTCLLISYTTNAFPGEYIPTVFDNYSANVMVDGKPVNLGLWDTAGQEDYDRLRPLSYPQTDVFLICFSLVSPASFENVRAKWYPEVRHHCPNTPIILVGTKLDLRDDKDTIEKLKEKKLTPITYPQGLAMAKEIGAVKYLECSALTQRGLKTVFDEAIRAVLCPPPVKKRKRKCLLL

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
Q3TLP8Q3TLP8_MOUSERac1211

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
X57277
EMBL· GenBank· DDBJ
CAA40545.1
EMBL· GenBank· DDBJ
mRNA
AK009017
EMBL· GenBank· DDBJ
BAB26027.1
EMBL· GenBank· DDBJ
mRNA
AK011072
EMBL· GenBank· DDBJ
BAB69451.1
EMBL· GenBank· DDBJ
mRNA
AK034601
EMBL· GenBank· DDBJ
BAC28767.1
EMBL· GenBank· DDBJ
mRNA
AK047969
EMBL· GenBank· DDBJ
BAC33203.1
EMBL· GenBank· DDBJ
mRNA
AK088825
EMBL· GenBank· DDBJ
BAC40596.1
EMBL· GenBank· DDBJ
mRNA
BC003828
EMBL· GenBank· DDBJ
AAH03828.1
EMBL· GenBank· DDBJ
mRNA
BC051053
EMBL· GenBank· DDBJ
AAH51053.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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