RALA
Description
The RALA (RAS like proto-oncogene A) is a protein-coding gene located on chromosome 7.
Ras-related protein Ral-A (RalA) is a protein that in humans is encoded by the RALA gene on chromosome 7. This protein is one of two paralogs of the Ral protein, the other being RalB, and part of the Ras GTPase family. RalA functions as a molecular switch to activate a number of biological processes, majorly cell division and transport, via signaling pathways. Its biological role thus implicates it in many cancers.
== Structure == The Ral isoforms share an 80% overall match in amino acid sequence and 100% match in their effector-binding region. The two isoforms mainly differ in the C-terminal hypervariable region, which contains multiple sites for post-translational modification, leading to diverging subcellular localization and biological function. For example, phosphorylation of Serine 194 on RalA by the kinase Aurora A results in the relocation of RalA to the inner mitochondrial membrane, where RalA helps carry out mitochondrial fission; whereas phosphorylation of Serine 198 on RalB by the kinase PKC results in the relocation of RalB to other internal membranes and activation of its tumorigenic function.
== Function == RalA is one of two proteins in the Ral family, which is itself a subfamily within the Ras family of small GTPases. As a Ras GTPase, RalA functions as a molecular switch that becomes active when bound to GTP and inactive when bound to GDP. RalA can be activated by RalGEFs and, in turn, activate effectors in signal transduction pathways leading to biological outcomes. For instance, RalA interacts with two components of the exocyst, Exo84 and Sec5, to promote autophagosome assembly, secretory vesicle trafficking, and tethering.
RalA is a multifunctional GTPase involved in a variety of cellular processes, including gene expression, cell migration, cell proliferation, oncogenic transformation, and membrane trafficking. It interacts with distinct downstream effectors to carry out its diverse functions. It acts as a GTP sensor for GTP-dependent exocytosis of dense core vesicles, and the RalA-exocyst complex regulates integrin-dependent membrane raft exocytosis and growth signaling. RalA is a key regulator of LPAR1 signaling and competes with GRK2 for binding to LPAR1, thus affecting the signaling properties of the receptor. RalA is required for anchorage-independent proliferation of transformed cells. During mitosis, RalA supports the stabilization and elongation of the intracellular bridge between dividing cells, and it cooperates with EXOC2 to recruit other components of the exocyst to the early midbody. During mitosis, RalA also controls mitochondrial fission by recruiting RALBP1 to the mitochondrion, where RALBP1 mediates the phosphorylation and activation of DNM1L by the mitotic kinase cyclin B-CDK1.
RALA is also known as HINCONS, RAL.
