UniProt functional annotation for P11233



	UniProt functional annotation for P11233

UniProt code: P11233.

Organism: Homo sapiens (Human).

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

Function: Multifunctional GTPase involved in a variety of cellular processes including gene expression, cell migration, cell proliferation, oncogenic transformation and membrane trafficking. Accomplishes its multiple functions by interacting with distinct downstream effectors. Acts as a GTP sensor for GTP-dependent exocytosis of dense core vesicles. The RALA-exocyst complex regulates integrin- dependent membrane raft exocytosis and growth signaling (PubMed:20005108). Key regulator of LPAR1 signaling and competes with GRK2 for binding to LPAR1 thus affecting the signaling properties of the receptor. Required for anchorage-independent proliferation of transformed cells (PubMed:19306925). During mitosis, supports the stabilization and elongation of the intracellular bridge between dividing cells. Cooperates with EXOC2 to recruit other components of the exocyst to the early midbody (PubMed:18756269). During mitosis, also controls mitochondrial fission by recruiting to the mitochondrion RALBP1, which mediates the phosphorylation and activation of DNM1L by the mitotic kinase cyclin B-CDK1. {ECO:0000269|PubMed:18756269, ECO:0000269|PubMed:19306925, ECO:0000269|PubMed:20005108, ECO:0000269|PubMed:21822277}.

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:0000305};

Activity regulation: Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide- exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP).

Subunit: Interacts (via effector domain) with RALBP1; during mitosis, recruits RALBP1 to the mitochondrion where it promotes DNM1L phosphorylation and mitochondrial fission (PubMed:7673236, PubMed:21822277). Interacts with EXOC2/Sec5 and EXOC8/Exo84; binding to EXOC2 and EXOC8 is mutually exclusive (PubMed:14525976, PubMed:18756269, PubMed:15920473). Interacts with Clostridium exoenzyme C3 (PubMed:16177825, PubMed:15809419). Interacts with RALGPS1 (PubMed:10747847). Interacts with LPAR1 and LPAR2. Interacts with GRK2 in response to LPAR1 activation. RALA and GRK2 binding to LPAR1 is mutually exclusive (PubMed:19306925). Interacts with CDC42 (By similarity). {ECO:0000250|UniProtKB:P63322, ECO:0000269|PubMed:10747847, ECO:0000269|PubMed:14525976, ECO:0000269|PubMed:15809419, ECO:0000269|PubMed:15920473, ECO:0000269|PubMed:16177825, ECO:0000269|PubMed:18756269, ECO:0000269|PubMed:19306925, ECO:0000269|PubMed:21822277, ECO:0000269|PubMed:7673236}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:17875936, ECO:0000269|PubMed:18756269, ECO:0000269|PubMed:19306925}; Lipid-anchor {ECO:0000269|PubMed:17875936}; Cytoplasmic side. Cleavage furrow {ECO:0000269|PubMed:18756269}. Midbody, Midbody ring {ECO:0000269|PubMed:16213214}. Mitochondrion {ECO:0000269|PubMed:21822277}. Note=Predominantly at the cell surface in the absence of LPA. In the presence of LPA, colocalizes with LPAR1 and LPAR2 in endocytic vesicles (PubMed:19306925). May colocalize with CNTRL/centriolin at the midbody ring (PubMed:16213214). However, localization at the midbody at late cytokinesis was not confirmed (PubMed:18756269). Relocalizes to the mitochodrion during mitosis where it regulates mitochondrial fission (PubMed:21822277). {ECO:0000269|PubMed:16213214, ECO:0000269|PubMed:18756269, ECO:0000269|PubMed:19306925, ECO:0000269|PubMed:21822277}.

Induction: Activated in an LPA-dependent manner by LPAR1 and in an LPA- independent manner by LPAR2. {ECO:0000269|PubMed:19306925}.

Ptm: Phosphorylated. Phosphorylation at Ser-194 by AURKA/Aurora kinase A, during mitosis, induces RALA localization to the mitochondrion where it regulates mitochondrial fission. {ECO:0000269|PubMed:21822277}.

Ptm: Prenylation is essential for membrane localization. The geranylgeranylated form and the farnesylated mutant do not undergo alternative prenylation in response to geranylgeranyltransferase I inhibitors (GGTIs) and farnesyltransferase I inhibitors (FTIs). {ECO:0000269|PubMed:17875936, ECO:0000269|PubMed:1903399}.

Ptm: (Microbial infection) Glucosylated at Thr-46 by P.sordellii toxin TcsL from strain 6018 (PubMed:8858106). Monoglucosylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form (PubMed:8858106). Not glucosylated by TcsL from strain VPI 9048 (PubMed:8858106). {ECO:0000269|PubMed:8858106}.

Similarity: Belongs to the small GTPase superfamily. Ras family. {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:		Multifunctional GTPase involved in a variety of cellular processes including gene expression, cell migration, cell proliferation, oncogenic transformation and membrane trafficking. Accomplishes its multiple functions by interacting with distinct downstream effectors. Acts as a GTP sensor for GTP-dependent exocytosis of dense core vesicles. The RALA-exocyst complex regulates integrin- dependent membrane raft exocytosis and growth signaling (PubMed:20005108). Key regulator of LPAR1 signaling and competes with GRK2 for binding to LPAR1 thus affecting the signaling properties of the receptor. Required for anchorage-independent proliferation of transformed cells (PubMed:19306925). During mitosis, supports the stabilization and elongation of the intracellular bridge between dividing cells. Cooperates with EXOC2 to recruit other components of the exocyst to the early midbody (PubMed:18756269). During mitosis, also controls mitochondrial fission by recruiting to the mitochondrion RALBP1, which mediates the phosphorylation and activation of DNM1L by the mitotic kinase cyclin B-CDK1. {ECO:0000269\|PubMed:18756269, ECO:0000269\|PubMed:19306925, ECO:0000269\|PubMed:20005108, ECO:0000269\|PubMed:21822277}.


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:0000305};
Activity regulation:		Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide- exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP).
Subunit:		Interacts (via effector domain) with RALBP1; during mitosis, recruits RALBP1 to the mitochondrion where it promotes DNM1L phosphorylation and mitochondrial fission (PubMed:7673236, PubMed:21822277). Interacts with EXOC2/Sec5 and EXOC8/Exo84; binding to EXOC2 and EXOC8 is mutually exclusive (PubMed:14525976, PubMed:18756269, PubMed:15920473). Interacts with Clostridium exoenzyme C3 (PubMed:16177825, PubMed:15809419). Interacts with RALGPS1 (PubMed:10747847). Interacts with LPAR1 and LPAR2. Interacts with GRK2 in response to LPAR1 activation. RALA and GRK2 binding to LPAR1 is mutually exclusive (PubMed:19306925). Interacts with CDC42 (By similarity). {ECO:0000250\|UniProtKB:P63322, ECO:0000269\|PubMed:10747847, ECO:0000269\|PubMed:14525976, ECO:0000269\|PubMed:15809419, ECO:0000269\|PubMed:15920473, ECO:0000269\|PubMed:16177825, ECO:0000269\|PubMed:18756269, ECO:0000269\|PubMed:19306925, ECO:0000269\|PubMed:21822277, ECO:0000269\|PubMed:7673236}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:17875936, ECO:0000269\|PubMed:18756269, ECO:0000269\|PubMed:19306925}; Lipid-anchor {ECO:0000269\|PubMed:17875936}; Cytoplasmic side. Cleavage furrow {ECO:0000269\|PubMed:18756269}. Midbody, Midbody ring {ECO:0000269\|PubMed:16213214}. Mitochondrion {ECO:0000269\|PubMed:21822277}. Note=Predominantly at the cell surface in the absence of LPA. In the presence of LPA, colocalizes with LPAR1 and LPAR2 in endocytic vesicles (PubMed:19306925). May colocalize with CNTRL/centriolin at the midbody ring (PubMed:16213214). However, localization at the midbody at late cytokinesis was not confirmed (PubMed:18756269). Relocalizes to the mitochodrion during mitosis where it regulates mitochondrial fission (PubMed:21822277). {ECO:0000269\|PubMed:16213214, ECO:0000269\|PubMed:18756269, ECO:0000269\|PubMed:19306925, ECO:0000269\|PubMed:21822277}.
Induction:		Activated in an LPA-dependent manner by LPAR1 and in an LPA- independent manner by LPAR2. {ECO:0000269\|PubMed:19306925}.
Ptm:		Phosphorylated. Phosphorylation at Ser-194 by AURKA/Aurora kinase A, during mitosis, induces RALA localization to the mitochondrion where it regulates mitochondrial fission. {ECO:0000269\|PubMed:21822277}.
Ptm:		Prenylation is essential for membrane localization. The geranylgeranylated form and the farnesylated mutant do not undergo alternative prenylation in response to geranylgeranyltransferase I inhibitors (GGTIs) and farnesyltransferase I inhibitors (FTIs). {ECO:0000269\|PubMed:17875936, ECO:0000269\|PubMed:1903399}.
Ptm:		(Microbial infection) Glucosylated at Thr-46 by P.sordellii toxin TcsL from strain 6018 (PubMed:8858106). Monoglucosylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form (PubMed:8858106). Not glucosylated by TcsL from strain VPI 9048 (PubMed:8858106). {ECO:0000269\|PubMed:8858106}.
Similarity:		Belongs to the small GTPase superfamily. Ras family. {ECO:0000305}.