RALB

Ras-related protein Ral-B (RalB) is a is_associated_with::protein that in humans is encoded by the RALB is_associated_with::gene on chromosome 2. This protein is one of two is_associated_with::isoforms of the Ral protein, the other being is_associated_with::RalA, and part of the Ras is_associated_with::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 is_associated_with::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, is_associated_with::phosphorylation of Serine 194 on RalA by the is_associated_with::kinase Aurora A results in the relocation of RalA to the is_associated_with::inner mitochondrial membrane, where RalA helps carry out is_associated_with::mitochondrial fission; whereas phosphorylation of Serine 198 on RalB by the kinase is_associated_with::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 is_associated_with::exocyst, Exo84 and is_associated_with::Sec5, to promote is_associated_with::autophagosome assembly, secretory vesicle trafficking, and tethering. Other downstream biological functions include is_associated_with::exocytosis, is_associated_with::receptor-mediated endocytosis, is_associated_with::tight junction biogenesis, is_associated_with::filopodia formation, mitochondrial fission, and is_associated_with::cytokinesis. While the above functions appear to be shared between the two Ral isoforms, their differential subcellular localizations result in their differing involvement in certain biological processes. In particular, RalB is more involved in apoptosis and cell motility. Moreover, RalB specifically interacts with Exo84 to assemble the beclin-1–VPS34 autophagy initiation complex, and with Sec5 to activate the innate immune response via the Tank-binding kinase 1 (is_associated_with::TBK1).

Clinical Significance
Ral proteins have been associated with the progression of several cancers, including bladder cancer and prostate cancer. Though the exact mechanisms remain unclear, studies reveal that RalB promotes tumor invasion and metastasis. As a result, inhibition of RalB inhibits further progression of cancer. In addition, RalB regulates p53 levels in a K-Ras-independent manner during cancer development. RalB also promotes cell survival during infection by double-stranded DNA viruses by activating TBK1 to carry out an immune response.

Interactions
RalB has been shown to interact with:
 * is_associated_with::CDC42,
 * is_associated_with::EXOC8,
 * is_associated_with::RALBP1, and
 * is_associated_with::Sec5.