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Ras-related C3 botulinum toxin substrate 1 (Rac2) (p21-Rac1)

 RAC1_CANLF              Reviewed;         192 AA.
P62999; O95501; P15154; Q9BTB4;
31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
31-AUG-2004, sequence version 1.
05-DEC-2018, entry version 121.
RecName: Full=Ras-related C3 botulinum toxin substrate 1;
AltName: Full=Rac2;
AltName: Full=p21-Rac1;
Flags: Precursor;
Canis lupus familiaris (Dog) (Canis familiaris).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae;
STRAIN=Cocker spaniel; TISSUE=Kidney;
PubMed=2123294; DOI=10.1128/MCB.10.12.6578;
Chavrier P., Vingron M., Sander C., Simons K., Zerial M.;
"Molecular cloning of YPT1/SEC4-related cDNAs from an epithelial cell
Mol. Cell. Biol. 10:6578-6585(1990).
-!- 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 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. 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 plasma membrane, increasing its
efficiency in chemokine uptake and degradation. In synapses, seems
to mediate the regulation of F-actin cluster formation performed
by SHANK3 (By similarity). {ECO:0000250|UniProtKB:P63000}.
-!- 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 (By similarity). {ECO:0000250}.
-!- SUBUNIT: Interacts with NISCH. Interacts with PIP5K1A. Interacts
with the GTP-bound form of RAB7A. Interacts with SRGAP2. Interacts
with CYFIP1/SRA-1. Interacts with PLXNB3. Interacts with ARHGDIA;
the interaction is induced by SEMA5A, mediated through PLXNB3 and
inactivates and stabilizes RAC1. Interacts (GTP-bound form
preferentially) with PKN2 (via the REM repeats); the interaction
stimulates autophosphorylation and phosphorylation of PKN2.
Interacts with the GEF proteins PREX1, RASGRF2, FARP1, FARP2,
DOCK1, DOCK2 and DOCK7, which promote the exchange between GDP and
GTP, and therefore activate it. Interacts with PARD6A, PARD6B and
PARD6G in a GTP-dependent manner. 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 PLXNB1. Probably found in a
ternary complex composed of DSCAM, PAK1 and RAC1. Interacts with
DSCAM; the interaction requires PAK1. Part of a complex with
MAP2K3, MAP3K3, CCM2 and DEF6. Interacts with BAIAP2, BAIAP2L1 and
DEF6. Interacts with Y.pseudotuberculosis YPKA and PLCB2.
Interacts with NOXA1. Interacts with ARHGEF2. Interacts with
TBC1D2. Interacts with UNKL. Interacts with USP6. Interacts with
SPATA13. Interacts with ARHGEF16; mediates activation of RAC1 by
EPHA2. Interacts with ITGB4. Interacts with S100A8 and
calprotectin (S100A8/9). Interacts with PACSIN2. Interacts with
ITGB1BP1. 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). Interacts with MTSS1L (via IMD domain); this interaction
may be important to potentiate PDGF-induced RAC1 activation.
Interacts with PAK2. Interacts (GTP-bound form) with SH3RF1 and
SH3RF3. Found in a complex with SH3RF1, MAPK8IP1/JIP1,
MAP3K11/MLK3, MAP2K7/MKK7 and MAPK8/JNK1. Interacts (both active
GTP- or inactive GDP-bound forms) with SH3RF2.
{ECO:0000250|UniProtKB:P63000, ECO:0000250|UniProtKB:P63001,
{ECO:0000250|UniProtKB:P63000}; Lipid-anchor
{ECO:0000250|UniProtKB:P63000}; Cytoplasmic side
{ECO:0000250|UniProtKB:P63000}. Melanosome
{ECO:0000250|UniProtKB:P63000}. Cytoplasm
{ECO:0000250|UniProtKB:P63000}. Cell projection, lamellipodium
{ECO:0000250|UniProtKB:P63001}. 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. Localizes to the lamellipodium in a SH3RF1-
dependent manner (By similarity). {ECO:0000250|UniProtKB:P63000,
ECO:0000250|UniProtKB:P63001, ECO:0000250|UniProtKB:Q6RUV5}.
-!- DOMAIN: The effector region mediates interaction with DEF6.
-!- PTM: GTP-bound active form is ubiquitinated by HACE1, leading to
its degradation by the proteasome. {ECO:0000250}.
-!- SIMILARITY: Belongs to the small GTPase superfamily. Rho family.
Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
Distributed under the Creative Commons Attribution (CC BY 4.0) License
EMBL; X56390; CAA39801.1; -; mRNA.
PIR; G36364; G36364.
RefSeq; NP_001003274.1; NM_001003274.2.
UniGene; Cfa.40290; -.
ProteinModelPortal; P62999; -.
SMR; P62999; -.
CORUM; P62999; -.
DIP; DIP-40906N; -.
IntAct; P62999; 2.
MINT; P62999; -.
PRIDE; P62999; -.
GeneID; 403955; -.
KEGG; cfa:403955; -.
CTD; 5879; -.
HOGENOM; HOG000233974; -.
HOVERGEN; HBG009351; -.
InParanoid; P62999; -.
KO; K04392; -.
Proteomes; UP000002254; Unplaced.
GO; GO:0005829; C:cytosol; ISS:UniProtKB.
GO; GO:0043197; C:dendritic spine; IBA:GO_Central.
GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
GO; GO:0016020; C:membrane; ISS:UniProtKB.
GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
GO; GO:0005525; F:GTP binding; ISS:UniProtKB.
GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
GO; GO:0051022; F:Rho GDP-dissociation inhibitor binding; ISS:UniProtKB.
GO; GO:0048870; P:cell motility; ISS:UniProtKB.
GO; GO:0030031; P:cell projection assembly; IBA:GO_Central.
GO; GO:0001764; P:neuron migration; ISS:UniProtKB.
GO; GO:0048812; P:neuron projection morphogenesis; IBA:GO_Central.
GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
GO; GO:0016601; P:Rac protein signal transduction; IBA:GO_Central.
GO; GO:0030334; P:regulation of cell migration; ISS:UniProtKB.
GO; GO:0007266; P:Rho protein signal transduction; IBA:GO_Central.
GO; GO:0071526; P:semaphorin-plexin signaling pathway; ISS:UniProtKB.
InterPro; IPR027417; P-loop_NTPase.
InterPro; IPR005225; Small_GTP-bd_dom.
InterPro; IPR001806; Small_GTPase.
InterPro; IPR003578; Small_GTPase_Rho.
Pfam; PF00071; Ras; 1.
SUPFAM; SSF52540; SSF52540; 1.
TIGRFAMs; TIGR00231; small_GTP; 1.
PROSITE; PS51420; RHO; 1.
2: Evidence at transcript level;
Cell membrane; Cell projection; Complete proteome; Cytoplasm;
GTP-binding; Isopeptide bond; Lipoprotein; Membrane; Methylation;
Nucleotide-binding; Prenylation; Reference proteome; Ubl conjugation.
CHAIN 1 189 Ras-related C3 botulinum toxin substrate
PROPEP 190 192 Removed in mature form. {ECO:0000250}.
NP_BIND 13 18 GTP. {ECO:0000250|UniProtKB:P63000}.
NP_BIND 30 35 GTP. {ECO:0000250|UniProtKB:P63000}.
NP_BIND 116 118 GTP. {ECO:0000250|UniProtKB:P63000}.
NP_BIND 159 160 GTP. {ECO:0000250|UniProtKB:P63000}.
MOTIF 32 40 Effector region. {ECO:0000255}.
BINDING 60 60 GTP; via amide nitrogen.
MOD_RES 189 189 Cysteine methyl ester. {ECO:0000250}.
LIPID 189 189 S-geranylgeranyl cysteine.
CROSSLNK 147 147 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in ubiquitin).
SEQUENCE 192 AA; 21450 MW; ACEDF83A45E5EA67 CRC64;

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