RALA

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 (PubMed:18756269, PubMed:19306925, PubMed:20005108, PubMed:21822277, PubMed:30500825). 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 (PubMed:21822277).

Hiatt-Neu-Cooper neurodevelopmental syndrome

HINCONS

An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, delayed walking or inability to walk, impaired intellectual development, poor or absent speech, axial hypotonia, and facial dysmorphism. Additional variable features may include seizures, autistic or behavioral abnormalities, and brain abnormalities.

None

The disease is caused by variants affecting the gene represented in this entry.

Phosphorylated. Phosphorylation at Ser-194 by AURKA/Aurora kinase A, during mitosis, induces RALA localization to the mitochondrion where it regulates mitochondrial fission.

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).

(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).

Belongs to the small GTPase superfamily. Ras family.

• Cell membrane
• Lipid-anchor
• Cytoplasmic side
• Cleavage furrow
• Midbody
• Midbody ring
• Mitochondrion
• 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 mitochondrion during mitosis where it regulates mitochondrial fission (PubMed:21822277).

RAL, RALA, Ras-related protein Ral-A

• entrezGene:5898
• omim:179550
• swissprot:P11233

Proteins

Metabolism

23567Da