RAC1_BOVIN
ID RAC1_BOVIN Reviewed; 192 AA.
AC P62998; O95501; P15154; Q3ZBW9; Q9BTB4;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 31-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Ras-related C3 botulinum toxin substrate 1;
DE EC=3.6.5.2 {ECO:0000250|UniProtKB:P63000};
DE AltName: Full=p21-Rac1;
DE Flags: Precursor;
GN Name=RAC1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10802295; DOI=10.1016/s0165-2427(00)00176-8;
RA Davis A.R., Clements M.K., Bunger P.L., Siemsen D.W., Quinn M.T.;
RT "Cloning of bovine low molecular weight GTPases (Rac1 and Rac2) and Rho
RT GDP-dissociation inhibitor 2 (D4-GDI).";
RL Vet. Immunol. Immunopathol. 74:285-301(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Thymus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP INTERACTION WITH CYFIP1.
RX PubMed=9417078; DOI=10.1074/jbc.273.1.291;
RA Kobayashi K., Kuroda S., Fukata M., Nakamura T., Nagase T., Nomura N.,
RA Matsuura Y., Yoshida-Kubomura N., Iwamatsu A., Kaibuchi K.;
RT "p140Sra-1 (specifically Rac1-associated protein) is a novel specific
RT target for Rac1 small GTPase.";
RL J. Biol. Chem. 273:291-295(1998).
CC -!- FUNCTION: Plasma membrane-associated small GTPase which cycles between
CC active GTP-bound and inactive GDP-bound states. In its active state,
CC binds to a variety of effector proteins to regulate cellular responses
CC such as secretory processes, phagocytosis of apoptotic cells,
CC epithelial cell polarization, neurons adhesion, migration and
CC differentiation, and growth-factor induced formation of membrane
CC ruffles. Rac1 p21/rho GDI heterodimer is the active component of the
CC cytosolic factor sigma 1, which is involved in stimulation of the NADPH
CC oxidase activity in macrophages. Essential for the SPATA13-mediated
CC regulation of cell migration and adhesion assembly and disassembly.
CC Stimulates PKN2 kinase activity. In concert with RAB7A, plays a role in
CC regulating the formation of RBs (ruffled borders) in osteoclasts. In
CC podocytes, promotes nuclear shuttling of NR3C2; this modulation is
CC required for a proper kidney functioning. Required for atypical
CC chemokine receptor ACKR2-induced LIMK1-PAK1-dependent phosphorylation
CC of cofilin (CFL1) and for up-regulation of ACKR2 from endosomal
CC compartment to cell membrane, increasing its efficiency in chemokine
CC uptake and degradation (By similarity). In neurons, is involved in
CC dendritic spine formation and synaptic plasticity (By similarity). In
CC hippocampal neurons, involved in spine morphogenesis and synapse
CC formation, through local activation at synapses by guanine nucleotide
CC exchange factors (GEFs), such as ARHGEF6/ARHGEF7/PIX (By similarity).
CC In synapses, seems to mediate the regulation of F-actin cluster
CC formation performed by SHANK3 (By similarity). In neurons, plays a
CC crucial role in regulating GABA(A) receptor synaptic stability and
CC hence GABAergic inhibitory synaptic transmission through its role in
CC PAK1 activation and eventually F-actin stabilization (By similarity).
CC {ECO:0000250|UniProtKB:P63000, ECO:0000250|UniProtKB:P63001,
CC ECO:0000250|UniProtKB:Q6RUV5}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.2;
CC Evidence={ECO:0000250|UniProtKB:P63000};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000250|UniProtKB:P63000};
CC -!- ACTIVITY REGULATION: Regulated by guanine nucleotide exchange factors
CC (GEFs) which promote the exchange of bound GDP for free GTP, GTPase
CC activating proteins (GAPs) which increase the GTP hydrolysis activity,
CC and GDP dissociation inhibitors which inhibit the dissociation of the
CC nucleotide from the GTPase. GTP hydrolysis is stimulated by ARHGAP30.
CC {ECO:0000250|UniProtKB:P63000}.
CC -!- SUBUNIT: Interacts with NISCH. Interacts with PIP5K1A. Interacts with
CC the GTP-bound form of RAB7A. Interacts with SRGAP2. Interacts with
CC CYFIP1/SRA-1. Interacts with PLXNB3. Interacts with ARHGDIA; the
CC interaction is induced by SEMA5A, mediated through PLXNB3 and
CC inactivates and stabilizes RAC1. Interacts (GTP-bound form
CC preferentially) with PKN2 (via the REM repeats); the interaction
CC stimulates autophosphorylation and phosphorylation of PKN2. Interacts
CC with the GEF proteins PREX1, RASGRF2, FARP1, FARP2, DOCK1, DOCK2 and
CC DOCK7, which promote the exchange between GDP and GTP, and therefore
CC activate it. Interacts with PARD6A, PARD6B and PARD6G in a GTP-
CC dependent manner. Part of a quaternary complex containing PARD3, some
CC PARD6 protein (PARD6A, PARD6B or PARD6G) and some atypical PKC protein
CC (PRKCI or PRKCZ), which plays a central role in epithelial cell
CC polarization. Found in a trimeric complex composed of DOCK1 and ELMO1,
CC which plays a central role in phagocytosis of apoptotic cells.
CC Interacts with RALBP1 via its effector domain. Interacts with PLXNB1.
CC Probably found in a ternary complex composed of DSCAM, PAK1 and RAC1.
CC Interacts with DSCAM; the interaction requires PAK1. Part of a complex
CC with MAP2K3, MAP3K3, CCM2 and DEF6. Interacts with BAIAP2, BAIAP2L1 and
CC DEF6. Interacts with Y.pseudotuberculosis YPKA and PLCB2. Interacts
CC with NOXA1. Interacts with ARHGEF2. Interacts with TBC1D2. Interacts
CC with UNKL. Interacts with USP6. Interacts with SPATA13. Interacts with
CC ARHGEF16; mediates activation of RAC1 by EPHA2. Interacts with ITGB4.
CC Interacts with S100A8 and calprotectin (S100A8/9). Interacts with
CC PACSIN2. Interacts with ITGB1BP1. Interacts with ITGB1BP1. Interacts
CC (when active) with PPP5C (via TPR repeats); activates PPP5C phosphatase
CC activity and translocates PPP5C to the cell membrane. Interacts with
CC RAPH1 (via Ras associating and PH domains) (By similarity). Interacts
CC with MTSS2 (via IMD domain); this interaction may be important to
CC potentiate PDGF-induced RAC1 activation. Interacts with PAK2. Interacts
CC (GTP-bound form) with SH3RF1 and SH3RF3. Found in a complex with
CC SH3RF1, MAPK8IP1/JIP1, MAP3K11/MLK3, MAP2K7/MKK7 and MAPK8/JNK1.
CC Interacts (both active GTP- or inactive GDP-bound forms) with SH3RF2.
CC Interacts (GTP-bound form preferentially) with CYRIB (By similarity).
CC Interacts with DOCK4 (via DOCKER domain); functions as a guanine
CC nucleotide exchange factor (GEF) for RAC1 (By similarity). Interacts
CC with GARRE1 (By similarity). Interacts with RAP1GDS1 (By similarity).
CC {ECO:0000250|UniProtKB:P63000, ECO:0000250|UniProtKB:P63001}.
CC -!- INTERACTION:
CC P62998; P00442: SOD1; NbExp=2; IntAct=EBI-6654511, EBI-6654424;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P63000};
CC Lipid-anchor {ECO:0000250|UniProtKB:P63000}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P63000}. Melanosome
CC {ECO:0000250|UniProtKB:P63000}. Cytoplasm
CC {ECO:0000250|UniProtKB:P63000}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:P63001}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:P63001}. Synapse {ECO:0000250|UniProtKB:Q6RUV5}.
CC Nucleus {ECO:0000250|UniProtKB:P63000}. Note=Inner surface of plasma
CC membrane possibly with attachment requiring prenylation of the C-
CC terminal cysteine (By similarity). Found in the ruffled border (a late
CC endosomal-like compartment in the plasma membrane) of bone-resorbing
CC osteoclasts. Localizes to the lamellipodium in a SH3RF1-dependent
CC manner (By similarity). In macrophages, cytoplasmic location increases
CC upon CSF1 stimulation (By similarity). Activation by GTP-binding
CC promotes nuclear localization (By similarity).
CC {ECO:0000250|UniProtKB:P63000, ECO:0000250|UniProtKB:P63001,
CC ECO:0000250|UniProtKB:Q6RUV5}.
CC -!- DOMAIN: The effector region mediates interaction with DEF6.
CC {ECO:0000250|UniProtKB:P63000}.
CC -!- PTM: GTP-bound active form is ubiquitinated by HACE1, leading to its
CC degradation by the proteasome. {ECO:0000250|UniProtKB:P63000}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rho family.
CC {ECO:0000305}.
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DR EMBL; AF175262; AAF00714.1; -; mRNA.
DR EMBL; BC103061; AAI03062.1; -; mRNA.
DR RefSeq; NP_776588.1; NM_174163.2.
DR AlphaFoldDB; P62998; -.
DR BMRB; P62998; -.
DR SMR; P62998; -.
DR IntAct; P62998; 1.
DR STRING; 9913.ENSBTAP00000012170; -.
DR SwissPalm; P62998; -.
DR PaxDb; P62998; -.
DR PeptideAtlas; P62998; -.
DR PRIDE; P62998; -.
DR GeneID; 281440; -.
DR KEGG; bta:281440; -.
DR CTD; 5879; -.
DR eggNOG; KOG0393; Eukaryota.
DR HOGENOM; CLU_041217_21_3_1; -.
DR InParanoid; P62998; -.
DR OrthoDB; 1091615at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005938; C:cell cortex; IBA:GO_Central.
DR GO; GO:0042995; C:cell projection; IBA:GO_Central.
DR GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; IBA:GO_Central.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC.
DR GO; GO:0005525; F:GTP binding; ISS:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR GO; GO:0051022; F:Rho GDP-dissociation inhibitor binding; ISS:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0048870; P:cell motility; ISS:UniProtKB.
DR GO; GO:0030031; P:cell projection assembly; IBA:GO_Central.
DR GO; GO:0030865; P:cortical cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0043652; P:engulfment of apoptotic cell; IBA:GO_Central.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IBA:GO_Central.
DR GO; GO:0008045; P:motor neuron axon guidance; IBA:GO_Central.
DR GO; GO:0001764; P:neuron migration; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0016601; P:Rac protein signal transduction; IBA:GO_Central.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0030334; P:regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IBA:GO_Central.
DR GO; GO:1902622; P:regulation of neutrophil migration; IBA:GO_Central.
DR GO; GO:0071526; P:semaphorin-plexin signaling pathway; ISS:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR InterPro; IPR003578; Small_GTPase_Rho.
DR PANTHER; PTHR24072; PTHR24072; 1.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51420; RHO; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Cytoplasm; GTP-binding; Hydrolase;
KW Isopeptide bond; Lipoprotein; Membrane; Methylation; Nucleotide-binding;
KW Nucleus; Prenylation; Reference proteome; Synapse; Ubl conjugation.
FT CHAIN 1..189
FT /note="Ras-related C3 botulinum toxin substrate 1"
FT /id="PRO_0000042032"
FT PROPEP 190..192
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:P63000"
FT /id="PRO_0000042033"
FT MOTIF 32..40
FT /note="Effector region"
FT /evidence="ECO:0000255"
FT MOTIF 179..188
FT /note="Polybasic region; required for nuclear import"
FT /evidence="ECO:0000250|UniProtKB:P63000"
FT BINDING 13..18
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P63000"
FT BINDING 30..35
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P63000"
FT BINDING 60
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P63000"
FT BINDING 116..118
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P63000"
FT BINDING 159..160
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P63000"
FT MOD_RES 189
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250|UniProtKB:P63000"
FT LIPID 189
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P63000"
FT CROSSLNK 147
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P63000"
SQ SEQUENCE 192 AA; 21450 MW; ACEDF83A45E5EA67 CRC64;
MQAIKCVVVG DGAVGKTCLL ISYTTNAFPG EYIPTVFDNY SANVMVDGKP VNLGLWDTAG
QEDYDRLRPL SYPQTDVFLI CFSLVSPASF ENVRAKWYPE VRHHCPNTPI ILVGTKLDLR
DDKDTIEKLK EKKLTPITYP QGLAMAKEIG AVKYLECSAL TQRGLKTVFD EAIRAVLCPP
PVKKRKRKCL LL
