RHOA_CANLF
ID RHOA_CANLF Reviewed; 193 AA.
AC P24406;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-1992, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Transforming protein RhoA;
DE EC=3.6.5.2 {ECO:0000250|UniProtKB:P61586};
DE AltName: Full=Rho1;
DE Flags: Precursor;
GN Name=RHOA; Synonyms=ARHA, RHO1;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Cocker spaniel; TISSUE=Kidney;
RX PubMed=2123294; DOI=10.1128/mcb.10.12.6578-6585.1990;
RA Chavrier P., Vingron M., Sander C., Simons K., Zerial M.;
RT "Molecular cloning of YPT1/SEC4-related cDNAs from an epithelial cell
RT line.";
RL Mol. Cell. Biol. 10:6578-6585(1990).
CC -!- FUNCTION: Small GTPase which cycles between an active GTP-bound and an
CC inactive GDP-bound state. Mainly associated with cytoskeleton
CC organization, in active state binds to a variety of effector proteins
CC to regulate cellular responses such as cytoskeletal dynamics, cell
CC migration and cell cycle. Regulates a signal transduction pathway
CC linking plasma membrane receptors to the assembly of focal adhesions
CC and actin stress fibers. Involved in a microtubule-dependent signal
CC that is required for the myosin contractile ring formation during cell
CC cycle cytokinesis. Plays an essential role in cleavage furrow
CC formation. Required for the apical junction formation of keratinocyte
CC cell-cell adhesion. Essential for the SPATA13-mediated regulation of
CC cell migration and adhesion assembly and disassembly. The MEMO1-RHOA-
CC DIAPH1 signaling pathway plays an important role in ERBB2-dependent
CC stabilization of microtubules at the cell cortex. It controls the
CC localization of APC and CLASP2 to the cell membrane, via the regulation
CC of GSK3B activity. In turn, membrane-bound APC allows the localization
CC of the MACF1 to the cell membrane, which is required for microtubule
CC capture and stabilization. Regulates KCNA2 potassium channel activity
CC by reducing its location at the cell surface in response to CHRM1
CC activation; promotes KCNA2 endocytosis. Acts as an allosteric activator
CC of guanine nucleotide exchange factor ECT2 by binding in its activated
CC GTP-bound form to the PH domain of ECT2 which stimulates the release of
CC PH inhibition and promotes the binding of substrate RHOA to the ECT2
CC catalytic center. May be an activator of PLCE1. In neurons, involved in
CC the inhibition of the initial spine growth. Upon activation by CaMKII,
CC modulates dendritic spine structural plasticity by relaying CaMKII
CC transient activation to synapse-specific, long-term signaling. Acts as
CC a regulator of platelet alpha-granule release during activation and
CC aggregation of platelets. {ECO:0000250|UniProtKB:P61586,
CC ECO:0000250|UniProtKB:P61589, ECO:0000250|UniProtKB:Q9QUI0}.
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:P61586};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000250|UniProtKB:P61586};
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. Activated by GEFs such as ARHGEF2, ARHGEF3,
CC ARHGEF28 and BCR. Inhibited by GAPs such as ARHGAP30. Inhibited by GDP
CC dissociation inhibitors such as ARHGDIA.
CC {ECO:0000250|UniProtKB:P61586}.
CC -!- SUBUNIT: Interacts with ARHGEF28 (By similarity). Interacts (via GTP-
CC bound form) with RIPOR1 (via N-terminus); this interaction links RHOA
CC to STK24 and STK26 kinases. Interacts with RIPOR2 (via active GTP- or
CC inactive GDP-bound forms) isoform 1 and isoform 2; these interactions
CC are direct, block the loading of GTP to RHOA and decrease upon
CC chemokine CCL19 stimulation in primary T lymphocytes. Binds PRKCL1,
CC ROCK1 and ROCK2. Interacts with ARHGEF2, ARHGEF3, NET1 and RTKN.
CC Interacts with PLCE1 and AKAP13. Interacts with DIAPH1. Interacts (in
CC the constitutively activated, GTP-bound form) with DGKQ. Interacts with
CC RACK1; enhances RHOA activation. Interacts with PKP4; the interaction
CC is detected at the midbody. Interacts (GTP-bound form preferentially)
CC with PKN2; the interaction stimulates autophosphorylation and
CC phosphorylation of PKN2. Interacts with ARHGDIA; this interaction
CC inactivates and stabilizes RHOA. Interacts with ARHGDIB. Interacts
CC (GTP-bound form) with KCNA2 (via cytoplasmic N-terminal domain) (By
CC similarity). Interacts (GTP-bound form) with ECT2; the interaction
CC results in allosteric activation of ECT2. Interacts with RAP1GDS1; the
CC interaction is direct and in a 1:1 stoichiometry (By similarity).
CC {ECO:0000250|UniProtKB:P61586, ECO:0000250|UniProtKB:Q9QUI0}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P61586};
CC Lipid-anchor {ECO:0000250|UniProtKB:P61586}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P61586}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:P61586}. Cleavage furrow
CC {ECO:0000250|UniProtKB:P61586}. Cytoplasm, cell cortex
CC {ECO:0000250|UniProtKB:P61586}. Midbody {ECO:0000250|UniProtKB:P61586}.
CC Cell projection, lamellipodium {ECO:0000250|UniProtKB:Q9QUI0}. Cell
CC projection, dendrite {ECO:0000250|UniProtKB:Q9QUI0}. Nucleus
CC {ECO:0000250|UniProtKB:P61586}. Note=Localized to cell-cell contacts in
CC calcium-treated keratinocytes (By similarity). Translocates to the
CC equatorial region before furrow formation in a ECT2-dependent manner.
CC Localizes to the equatorial cell cortex (at the site of the presumptive
CC furrow) in early anaphase in an activated form and in a myosin- and
CC actin-independent manner. {ECO:0000250|UniProtKB:Q9QUI0}.
CC -!- PTM: Ubiquitinated by the BCR(KCTD13) and BCR(TNFAIP1) E3 ubiquitin
CC ligase complexes, leading to its degradation by the proteasome, thereby
CC regulating the actin cytoskeleton and synaptic transmission in neurons.
CC {ECO:0000250|UniProtKB:Q9QUI0}.
CC -!- PTM: Phosphorylation by PRKG1 at Ser-188 inactivates RHOA signaling (By
CC similarity). Phosphorylation by SLK at Ser-188 in response to AGTR2
CC activation (By similarity). {ECO:0000250|UniProtKB:P61586,
CC ECO:0000250|UniProtKB:P61589}.
CC -!- PTM: Serotonylation of Gln-63 by TGM2 during activation and aggregation
CC of platelets leads to constitutive activation of GTPase activity.
CC {ECO:0000250|UniProtKB:Q9QUI0}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rho family.
CC {ECO:0000305}.
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DR EMBL; X56391; CAA39802.1; -; mRNA.
DR PIR; H36364; H36364.
DR AlphaFoldDB; P24406; -.
DR BMRB; P24406; -.
DR SMR; P24406; -.
DR STRING; 9612.ENSCAFP00000030438; -.
DR PaxDb; P24406; -.
DR eggNOG; KOG0393; Eukaryota.
DR InParanoid; P24406; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0043296; C:apical junction complex; ISS:UniProtKB.
DR GO; GO:0005938; C:cell cortex; ISS:UniProtKB.
DR GO; GO:0042995; C:cell projection; IBA:GO_Central.
DR GO; GO:0032154; C:cleavage furrow; 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:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0030496; C:midbody; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; IBA:GO_Central.
DR GO; GO:0043297; P:apical junction assembly; ISS:UniProtKB.
DR GO; GO:0034329; P:cell junction assembly; ISS:UniProtKB.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:1990869; P:cellular response to chemokine; ISS:UniProtKB.
DR GO; GO:0036089; P:cleavage furrow formation; ISS:UniProtKB.
DR GO; GO:0030865; P:cortical cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0031122; P:cytoplasmic microtubule organization; ISS:UniProtKB.
DR GO; GO:0045198; P:establishment of epithelial cell apical/basal polarity; ISS:UniProtKB.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IBA:GO_Central.
DR GO; GO:1903673; P:mitotic cleavage furrow formation; ISS:UniProtKB.
DR GO; GO:0032467; P:positive regulation of cytokinesis; ISS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:2000406; P:positive regulation of T cell migration; ISS:UniProtKB.
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:0007266; P:Rho protein signal transduction; ISS:UniProtKB.
DR GO; GO:0035385; P:Roundabout signaling pathway; ISS:UniProtKB.
DR GO; GO:1902766; P:skeletal muscle satellite cell migration; ISS:AgBase.
DR GO; GO:0043149; P:stress fiber assembly; ISS:UniProtKB.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; ISS:UniProtKB.
DR GO; GO:0044319; P:wound healing, spreading of cells; ISS:AgBase.
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 2: Evidence at transcript level;
KW Cell cycle; Cell division; Cell membrane; Cell projection; Cytoplasm;
KW Cytoskeleton; GTP-binding; Hydrolase; Lipoprotein; Membrane; Methylation;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Prenylation; Proto-oncogene;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..190
FT /note="Transforming protein RhoA"
FT /id="PRO_0000030409"
FT PROPEP 191..193
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:P61585"
FT /id="PRO_0000030410"
FT REGION 61..78
FT /note="Switch II region; involved in RAP1GDS1 binding"
FT /evidence="ECO:0000250|UniProtKB:P61586"
FT MOTIF 34..42
FT /note="Effector region"
FT /evidence="ECO:0000255"
FT BINDING 12..19
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P61586"
FT BINDING 30..37
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62820"
FT BINDING 59..63
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62820"
FT BINDING 117..120
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P61586"
FT BINDING 160..162
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62820"
FT MOD_RES 63
FT /note="5-glutamyl serotonin"
FT /evidence="ECO:0000250|UniProtKB:Q9QUI0"
FT MOD_RES 188
FT /note="Phosphoserine; by PKG/PRKG1"
FT /evidence="ECO:0000250|UniProtKB:P61589"
FT MOD_RES 190
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250|UniProtKB:P61585"
FT LIPID 190
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P61585"
SQ SEQUENCE 193 AA; 21740 MW; C4DA2DDEB495F3CC CRC64;
MAAIRKKLVI VGDGACGKTC LLIVFSKDQF PEVYVPTVFE NYVADIEVDG KQVELALWDT
AGQEDYDRLR PLSYPDTDVI LMCFSIDSPD SLENIPEKWT PEVKHFCPNV PIILVGNKKD
LRNDEHTRRE LAKMKQEPVK PTEGRDMANR IGAFGYMECS AKTKDGVREV FEMATRAALQ
ARRGKKKSGC LVL
