UniProt functional annotation for P63000



	UniProt functional annotation for P63000

UniProt code: P63000.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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: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). {ECO:0000250|UniProtKB:P63001, ECO:0000250|UniProtKB:Q6RUV5, ECO:0000269|PubMed:12695502, ECO:0000269|PubMed:1643658, ECO:0000269|PubMed:28886345, ECO:0000269|PubMed:9121475}.

Function: Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase- activating proteins. 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.

Catalytic activity: Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.2; Evidence={ECO:0000269|PubMed:21565175}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; Evidence={ECO:0000305|PubMed:21565175};

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}.

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) (PubMed:18499456). Interacts with MTSS2 (via IMD domain); this interaction may be important to potentiate PDGF- induced RAC1 activation (PubMed:20875796). Interacts with PAK2 (PubMed:20696164). Interacts (GTP-bound form) with SH3RF1 and SH3RF3 (PubMed:20696164). 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 (By similarity). Interacts (GTP-bound form preferentially) with CYRIB (PubMed:31285585, PubMed:30250061). Interacts with DOCK4 (via DOCKER domain); functions as a guanine nucleotide exchange factor (GEF) for RAC1 (PubMed:16464467). Interacts with GARRE1 (PubMed:31871319). {ECO:0000250|UniProtKB:P63001, ECO:0000250|UniProtKB:Q6RUV5, ECO:0000269|PubMed:10559471, ECO:0000269|PubMed:10954424, ECO:0000269|PubMed:11035813, ECO:0000269|PubMed:11090627, ECO:0000269|PubMed:11130063, ECO:0000269|PubMed:11130076, ECO:0000269|PubMed:11135665, ECO:0000269|PubMed:11163217, ECO:0000269|PubMed:11260256, ECO:0000269|PubMed:11346801, ECO:0000269|PubMed:11513578, ECO:0000269|PubMed:11807099, ECO:0000269|PubMed:12134158, ECO:0000269|PubMed:12612085, ECO:0000269|PubMed:12716910, ECO:0000269|PubMed:15169762, ECO:0000269|PubMed:15642721, ECO:0000269|PubMed:16464467, ECO:0000269|PubMed:16959567, ECO:0000269|PubMed:16982419, ECO:0000269|PubMed:17115053, ECO:0000269|PubMed:17121847, ECO:0000269|PubMed:17145773, ECO:0000269|PubMed:17430976, ECO:0000269|PubMed:18499456, ECO:0000269|PubMed:19403692, ECO:0000269|PubMed:19948726, ECO:0000269|PubMed:20116244, ECO:0000269|PubMed:20148946, ECO:0000269|PubMed:20679435, ECO:0000269|PubMed:20696164, ECO:0000269|PubMed:20875796, ECO:0000269|PubMed:20974804, ECO:0000269|PubMed:21613211, ECO:0000269|PubMed:21693584, ECO:0000269|PubMed:23209303, ECO:0000269|PubMed:23375260, ECO:0000269|PubMed:23434736, ECO:0000269|PubMed:30250061, ECO:0000269|PubMed:31285585, ECO:0000269|PubMed:31871319, ECO:0000269|PubMed:7673236, ECO:0000269|PubMed:9033596, ECO:0000269|PubMed:9121475, ECO:0000269|PubMed:9857026}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:1643658}; 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}. Cell projection, lamellipodium {ECO:0000250|UniProtKB:P63001}. Cell projection, dendrite {ECO:0000250|UniProtKB:P63001}. Cell junction, synapse {ECO:0000250|UniProtKB:Q6RUV5}. 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). {ECO:0000250|UniProtKB:P63001, ECO:0000250|UniProtKB:Q6RUV5, ECO:0000269|PubMed:17081065, ECO:0000269|PubMed:1903399}.

Tissue specificity: Isoform B is predominantly identified in skin and epithelial tissues from the intestinal tract. Its expression is elevated in colorectal tumors at various stages of neoplastic progression, as compared to their respective adjacent tissues.

Domain: The effector region mediates interaction with DEF6. {ECO:0000269|PubMed:17121847}.

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: GTP-bound active form is ubiquitinated by HACE1, leading to its degradation by the proteasome. {ECO:0000269|PubMed:18093184, ECO:0000269|PubMed:22036506}.

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:7777059, PubMed:7775453, PubMed:8626575, PubMed:19744486, PubMed:24905543). 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:7777059, PubMed:7775453). {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}.

Disease: Mental retardation, autosomal dominant 48 (MRD48) [MIM:617751]: A form of mental retardation, 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.

Similarity: Belongs to the small GTPase superfamily. Rho family. {ECO:0000305}.

Sequence caution: Sequence=AAZ80485.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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: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). {ECO:0000250\|UniProtKB:P63001, ECO:0000250\|UniProtKB:Q6RUV5, ECO:0000269\|PubMed:12695502, ECO:0000269\|PubMed:1643658, ECO:0000269\|PubMed:28886345, ECO:0000269\|PubMed:9121475}.



Function:		Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase- activating proteins. 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.


Catalytic activity:		Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.2; Evidence={ECO:0000269\|PubMed:21565175}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; Evidence={ECO:0000305\|PubMed:21565175};
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}.
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) (PubMed:18499456). Interacts with MTSS2 (via IMD domain); this interaction may be important to potentiate PDGF- induced RAC1 activation (PubMed:20875796). Interacts with PAK2 (PubMed:20696164). Interacts (GTP-bound form) with SH3RF1 and SH3RF3 (PubMed:20696164). 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 (By similarity). Interacts (GTP-bound form preferentially) with CYRIB (PubMed:31285585, PubMed:30250061). Interacts with DOCK4 (via DOCKER domain); functions as a guanine nucleotide exchange factor (GEF) for RAC1 (PubMed:16464467). Interacts with GARRE1 (PubMed:31871319). {ECO:0000250\|UniProtKB:P63001, ECO:0000250\|UniProtKB:Q6RUV5, ECO:0000269\|PubMed:10559471, ECO:0000269\|PubMed:10954424, ECO:0000269\|PubMed:11035813, ECO:0000269\|PubMed:11090627, ECO:0000269\|PubMed:11130063, ECO:0000269\|PubMed:11130076, ECO:0000269\|PubMed:11135665, ECO:0000269\|PubMed:11163217, ECO:0000269\|PubMed:11260256, ECO:0000269\|PubMed:11346801, ECO:0000269\|PubMed:11513578, ECO:0000269\|PubMed:11807099, ECO:0000269\|PubMed:12134158, ECO:0000269\|PubMed:12612085, ECO:0000269\|PubMed:12716910, ECO:0000269\|PubMed:15169762, ECO:0000269\|PubMed:15642721, ECO:0000269\|PubMed:16464467, ECO:0000269\|PubMed:16959567, ECO:0000269\|PubMed:16982419, ECO:0000269\|PubMed:17115053, ECO:0000269\|PubMed:17121847, ECO:0000269\|PubMed:17145773, ECO:0000269\|PubMed:17430976, ECO:0000269\|PubMed:18499456, ECO:0000269\|PubMed:19403692, ECO:0000269\|PubMed:19948726, ECO:0000269\|PubMed:20116244, ECO:0000269\|PubMed:20148946, ECO:0000269\|PubMed:20679435, ECO:0000269\|PubMed:20696164, ECO:0000269\|PubMed:20875796, ECO:0000269\|PubMed:20974804, ECO:0000269\|PubMed:21613211, ECO:0000269\|PubMed:21693584, ECO:0000269\|PubMed:23209303, ECO:0000269\|PubMed:23375260, ECO:0000269\|PubMed:23434736, ECO:0000269\|PubMed:30250061, ECO:0000269\|PubMed:31285585, ECO:0000269\|PubMed:31871319, ECO:0000269\|PubMed:7673236, ECO:0000269\|PubMed:9033596, ECO:0000269\|PubMed:9121475, ECO:0000269\|PubMed:9857026}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:1643658}; 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}. Cell projection, lamellipodium {ECO:0000250\|UniProtKB:P63001}. Cell projection, dendrite {ECO:0000250\|UniProtKB:P63001}. Cell junction, synapse {ECO:0000250\|UniProtKB:Q6RUV5}. 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). {ECO:0000250\|UniProtKB:P63001, ECO:0000250\|UniProtKB:Q6RUV5, ECO:0000269\|PubMed:17081065, ECO:0000269\|PubMed:1903399}.
Tissue specificity:		Isoform B is predominantly identified in skin and epithelial tissues from the intestinal tract. Its expression is elevated in colorectal tumors at various stages of neoplastic progression, as compared to their respective adjacent tissues.
Domain:		The effector region mediates interaction with DEF6. {ECO:0000269\|PubMed:17121847}.
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:		GTP-bound active form is ubiquitinated by HACE1, leading to its degradation by the proteasome. {ECO:0000269\|PubMed:18093184, ECO:0000269\|PubMed:22036506}.
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:7777059, PubMed:7775453, PubMed:8626575, PubMed:19744486, PubMed:24905543). 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:7777059, PubMed:7775453). {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}.
Disease:		Mental retardation, autosomal dominant 48 (MRD48) [MIM:617751]: A form of mental retardation, 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.
Similarity:		Belongs to the small GTPase superfamily. Rho family. {ECO:0000305}.
Sequence caution:		Sequence=AAZ80485.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};