RAC1
entrez
5879
canonical
uniprot
P63000
canonical
ensembl
ENSG00000136238
resolver
ensp
ENSP00000258737
resolver
ensp
ENSP00000348461
resolver
genesymbol
RAC1
resolver
genesymbol_syn
TC25
resolver
hgnc
HGNC:9801
resolver
uniprot
A4D2P0
resolver
uniprot
A4D2P1
resolver
uniprot
O95501
resolver
uniprot
P15154
resolver
uniprot
Q3Y4D3
resolver
uniprot
Q5JAA8
resolver
uniprot
Q9BTB4
resolver
uniprot_entry
A4D2P0_HUMAN
resolver
uniprot_entry
A4D2P1_HUMAN
resolver
uniprot_entry
RAC1_HUMAN
resolver
uniprot_sec
O95501
resolver
uniprot_sec
P15154
resolver
uniprot_sec
Q3Y4D3
resolver
uniprot_sec
Q5JAA8
resolver
uniprot_sec
Q9BTB4
resolver
activity_regulation
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. {ECO:0000269|PubMed:21565175}.
uniprot
proteins
amino_acid_sequence
MQAIKCVVVGDGAVGKTCLLISYTTNAFPGEYIPTVFDNYSANVMVDGKPVNLGLWDTAGQEDYDRLRPLSYPQTDVFLICFSLVSPASFENVRAKWYPEVRHHCPNTPIILVGTKLDLRDDKDTIEKLKEKKLTPITYPQGLAMAKEIGAVKYLECSALTQRGLKTVFDEAIRAVLCPPPVKKRKRKCLLL
uniprot
proteins
disease_involvement
DISEASE: Intellectual developmental disorder, autosomal dominant 48 (MRD48) [MIM:617751]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD48 patients manifest global developmental delay and moderate to severe intellectual disability. {ECO:0000269|PubMed:28886345}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.6.5.2
uniprot
proteins
function
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, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles (PubMed:1643658, PubMed:22843693, PubMed:23512198, PubMed:28886345). 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 (PubMed:9121475). In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts (PubMed:1643658). In podocytes, promotes nuclear shuttling of NR3C2; this modulation is required for a proper kidney functioning. 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 neurons, is involved in dendritic spine formation and synaptic plasticity (By similarity). 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 (PubMed:22796473). Subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion (O2(-)) (PubMed:38355798). {ECO:0000250|UniProtKB:P63001, ECO:0000250|UniProtKB:Q6RUV5, ECO:0000269|PubMed:12695502, ECO:0000269|PubMed:1643658, ECO:0000269|PubMed:22796473, ECO:0000269|PubMed:22843693, ECO:0000269|PubMed:23512198, ECO:0000269|PubMed:28886345, ECO:0000269|PubMed:38355798, ECO:0000269|PubMed:9121475}.; FUNCTION: [Isoform B]: Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins (PubMed:14625275). 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 (PubMed:14625275). {ECO:0000269|PubMed:14625275}.
uniprot
proteins
mass_dalton
21450
uniprot
proteins
mutagenesis
MUTAGEN 12; /note="G->V: Constitutively active. Interacts with PARD6 proteins. Increases nuclear localization and up-regulates transcriptional activity of NR3C2. Doesn't interact with CYRIB. Increases interaction with GARRE1."; /evidence="ECO:0000269|PubMed:11260256, ECO:0000269|PubMed:19029984, ECO:0000269|PubMed:30250061, ECO:0000269|PubMed:31871319"; MUTAGEN 17; /note="T->N: Constitutively inactivated. Abolishes interaction with PARD6 proteins. No effect on NR3C2 transcriptional activity. No interaction with PPP5C. Doesn't activate PPP5C phosphatase activity and translocate PPP5C to the plasma membrane. Doesn't interact with CYRIB."; /evidence="ECO:0000269|PubMed:11260256, ECO:0000269|PubMed:19029984, ECO:0000269|PubMed:19948726, ECO:0000269|PubMed:30250061"; MUTAGEN 30; /note="G->V: No interaction with PPP5C; when associated with L-61. Translocates to the plasma membrane; also when associated with L-61."; /evidence="ECO:0000269|PubMed:19948726"; MUTAGEN 32; /note="Y->F: Abolishes AMPylation by Haemophilus IbpA."; /evidence="ECO:0000269|PubMed:19362538"; MUTAGEN 35; /note="T->A: Abolishes AMPylation by Vibrio VopS."; /evidence="ECO:0000269|PubMed:19039103, ECO:0000269|PubMed:19948726"; MUTAGEN 35; /note="T->S: No interaction with PPP5C; when associated with L-61. Translocates to the plasma membrane; also when associated with L-61."; /evidence="ECO:0000269|PubMed:19039103, ECO:0000269|PubMed:19948726"; MUTAGEN 37; /note="F->A: Strongly reduced interaction with PLCB2."; /evidence="ECO:0000269|PubMed:17115053"; MUTAGEN 56; /note="W->A: Strongly reduced interaction with PLCB2."; /evidence="ECO:0000269|PubMed:17115053"; MUTAGEN 61; /note="Q->L: Constitutively active. Interacts with PARD6 proteins. Interacts with PPP5C, activates its phosphatase activity and translocates PPP5C to the plasma membrane. No effect on interaction with RAPH1. Interacts with CYRIB. No interaction with PPP5C; when associated with V-30 or S-35. Translocates to the plasma membrane; also when associated with V-30 or S-35."; /evidence="ECO:0000269|PubMed:10954424, ECO:0000269|PubMed:18499456, ECO:0000269|PubMed:19948726, ECO:0000269|PubMed:29074776, ECO:0000269|PubMed:30250061, ECO:0000269|PubMed:38332367"; MUTAGEN 67; /note="L->A: Strongly reduced interaction with PLCB2."; /evidence="ECO:0000269|PubMed:17115053"; MUTAGEN 70; /note="L->A: Strongly reduced interaction with PLCB2."; /evidence="ECO:0000269|PubMed:17115053"; MUTAGEN 71; /note="S->A: Loss of AKT-mediated phosphorylation and FBXL19-induced polyubiquitination."; /evidence="ECO:0000269|PubMed:10617634, ECO:0000269|PubMed:23512198"; MUTAGEN 166; /note="K->R: Loss of FBXL19-induced polyubiquitination."; /evidence="ECO:0000269|PubMed:23512198"; MUTAGEN 183..188; /note="KKRKRK->AARARA: In 4KA mutant; abolished palmitoylation by the V.cholerae toxin RtxA."; /evidence="ECO:0000269|PubMed:29074776"; MUTAGEN 183; /note="K->A: Slightly decreased palmitoylation by the V.cholerae toxin RtxA."; /evidence="ECO:0000269|PubMed:29074776"; MUTAGEN 184; /note="K->A: Slightly decreased palmitoylation by the V.cholerae toxin RtxA."; /evidence="ECO:0000269|PubMed:29074776"; MUTAGEN 185..187; /note="RKR->AKA: In 2RA mutant; does not affect palmitoylation by the V.cholerae toxin RtxA."; /evidence="ECO:0000269|PubMed:29074776"; MUTAGEN 186; /note="K->A: Decreased palmitoylation by the V.cholerae toxin RtxA."; /evidence="ECO:0000269|PubMed:29074776"; MUTAGEN 188; /note="K->A: Decreased palmitoylation by the V.cholerae toxin RtxA."; /evidence="ECO:0000269|PubMed:29074776
uniprot
proteins
post_translational_modification
PTM: GTP-bound active form is ubiquitinated at Lys-147 by HACE1, leading to its degradation by the proteasome. {ECO:0000269|PubMed:18093184, ECO:0000269|PubMed:22036506, ECO:0000269|PubMed:38332367}.; PTM: Phosphorylated by AKT at Ser-71. {ECO:0000269|PubMed:10617634}.; PTM: Ubiquitinated at Lys-166 in a FBXL19-mediated manner; leading to proteasomal degradation. {ECO:0000269|PubMed:23512198}.; PTM: (Microbial infection) 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. {ECO:0000269|PubMed:19039103, ECO:0000269|PubMed:19362538}.; PTM: (Microbial infection) Glycosylated at Tyr-32 by Photorhabdus asymbiotica toxin PAU_02230. Mono-O-GlcNAcylation by PAU_02230 inhibits downstream signaling by an impaired interaction with diverse regulator and effector proteins of Rac and leads to actin disassembly. {ECO:0000269|PubMed:24141704}.; PTM: (Microbial infection) Glucosylated at Thr-35 by C.difficile toxins TcdA and TcdB in the colonic epithelium, and by P.sordellii toxin TcsL in the vascular endothelium (PubMed:19744486, PubMed:24905543, PubMed:7775453, PubMed:7777059, PubMed:8626575). Monoglucosylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to actin cytoskeleton disruption and cell death, resulting in the loss of colonic epithelial barrier function (PubMed:7775453, PubMed:7777059). {ECO:0000269|PubMed:19744486, ECO:0000269|PubMed:24905543, ECO:0000269|PubMed:7775453, ECO:0000269|PubMed:7777059, ECO:0000269|PubMed:8626575}.; PTM: (Microbial infection) Glycosylated (O-GlcNAcylated) at Thr-35 by C.novyi toxin TcdA (PubMed:8810274). O-GlcNAcylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to actin cytoskeleton disruption (PubMed:8810274). {ECO:0000269|PubMed:8810274}.; PTM: (Microbial infection) Palmitoylated by the N-epsilon-fatty acyltransferase F2 chain of V.cholerae toxin RtxA (PubMed:29074776). Palmitoylation inhibits activation by guanine nucleotide exchange factors (GEFs), preventing Rho GTPase signaling (PubMed:29074776). {ECO:0000269|PubMed:29074776}.
uniprot
proteins
protein_family
Rho family
uniprot
proteins
protein_family
Small GTPase superfamily
uniprot
proteins
pubmed
10559471
uniprot
proteins
pubmed
10597294
uniprot
proteins
pubmed
10617634
uniprot
proteins
pubmed
10954424
uniprot
proteins
pubmed
11035813
uniprot
proteins
pubmed
11062023
uniprot
proteins
pubmed
11084340
uniprot
proteins
pubmed
11090627
uniprot
proteins
pubmed
11130063
uniprot
proteins
pubmed
11130076
uniprot
proteins
pubmed
11135665
uniprot
proteins
pubmed
11163217
uniprot
proteins
pubmed
11260256
uniprot
proteins
pubmed
11346801
uniprot
proteins
pubmed
11513578
uniprot
proteins
pubmed
11807099
uniprot
proteins
pubmed
11955434
uniprot
proteins
pubmed
12134158
uniprot
proteins
pubmed
12551911
uniprot
proteins
pubmed
12612085
uniprot
proteins
pubmed
12695502
uniprot
proteins
pubmed
12716910
uniprot
proteins
pubmed
12853948
uniprot
proteins
pubmed
14625275
uniprot
proteins
pubmed
15169762
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15642721
uniprot
proteins
pubmed
1643658
uniprot
proteins
pubmed
16464467
uniprot
proteins
pubmed
16959567
uniprot
proteins
pubmed
16982419
uniprot
proteins
pubmed
17081065
uniprot
proteins
pubmed
17115053
uniprot
proteins
pubmed
17121847
uniprot
proteins
pubmed
17145773
uniprot
proteins
pubmed
17430976
uniprot
proteins
pubmed
18093184
uniprot
proteins
pubmed
18499456
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19029984
uniprot
proteins
pubmed
1903399
uniprot
proteins
pubmed
19039103
uniprot
proteins
pubmed
19362538
uniprot
proteins
pubmed
19403692
uniprot
proteins
pubmed
19744486
uniprot
proteins
pubmed
19934221
uniprot
proteins
pubmed
19948726
uniprot
proteins
pubmed
20116244
uniprot
proteins
pubmed
20148946
uniprot
proteins
pubmed
20679435
uniprot
proteins
pubmed
20696164
uniprot
proteins
pubmed
20696765
uniprot
proteins
pubmed
20709748
uniprot
proteins
pubmed
20875796
uniprot
proteins
pubmed
20974804
uniprot
proteins
pubmed
2108320
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21565175
uniprot
proteins
pubmed
21613211
uniprot
proteins
pubmed
21693584
uniprot
proteins
pubmed
22036506
uniprot
proteins
pubmed
22796473
uniprot
proteins
pubmed
22843693
uniprot
proteins
pubmed
23209303
uniprot
proteins
pubmed
23375260
uniprot
proteins
pubmed
23434736
uniprot
proteins
pubmed
23512198
uniprot
proteins
pubmed
23633677
uniprot
proteins
pubmed
24141704
uniprot
proteins
pubmed
24905543
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26048998
uniprot
proteins
pubmed
2674130
uniprot
proteins
pubmed
28886345
uniprot
proteins
pubmed
29074776
uniprot
proteins
pubmed
30250061
uniprot
proteins
pubmed
31285585
uniprot
proteins
pubmed
31871319
uniprot
proteins
pubmed
32460619
uniprot
proteins
pubmed
32651375
uniprot
proteins
pubmed
35986704
uniprot
proteins
pubmed
38332367
uniprot
proteins
pubmed
38355798
uniprot
proteins
pubmed
38857861
uniprot
proteins
pubmed
7673236
uniprot
proteins
pubmed
7775453
uniprot
proteins
pubmed
7777059
uniprot
proteins
pubmed
8626575
uniprot
proteins
pubmed
8810274
uniprot
proteins
pubmed
9033596
uniprot
proteins
pubmed
9121475
uniprot
proteins
pubmed
9857026
uniprot
proteins
sequence_length
192
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1643658, ECO:0000269|PubMed:22843693, ECO:0000269|PubMed:29074776}; Lipid-anchor {ECO:0000269|PubMed:1903399}; Cytoplasmic side {ECO:0000269|PubMed:1643658, ECO:0000269|PubMed:19948726}. Melanosome {ECO:0000269|PubMed:17081065, ECO:0000269|PubMed:19948726, ECO:0000269|PubMed:21693584}. Cytoplasm {ECO:0000269|PubMed:19948726, ECO:0000269|PubMed:29074776}. Cell projection, lamellipodium {ECO:0000250|UniProtKB:P63001}. Cell projection, dendrite {ECO:0000250|UniProtKB:P63001}. Synapse {ECO:0000250|UniProtKB:Q6RUV5}. Nucleus {ECO:0000269|PubMed:12551911}. Cell projection, ruffle membrane {ECO:0000269|PubMed:11084340}. Note=Inner surface of plasma membrane possibly with attachment requiring prenylation of the C-terminal cysteine (PubMed:1903399). Identified by mass spectrometry in melanosome fractions from stage I to stage IV (PubMed:17081065). Found in the ruffled border (a late endosomal-like compartment in the plasma membrane) of bone-resorbing osteoclasts. Localizes to the lamellipodium in a SH3RF1-dependent manner (By similarity). In macrophages, cytoplasmic location increases upon CSF1 stimulation (By similarity). Activation by GTP-binding promotes nuclear localization (PubMed:12551911). {ECO:0000250|UniProtKB:P63001, ECO:0000250|UniProtKB:Q6RUV5, ECO:0000269|PubMed:12551911, ECO:0000269|PubMed:17081065, ECO:0000269|PubMed:1903399}.
uniprot
proteins