ARRB2

Description

The ARRB2 (arrestin beta 2) is a protein-coding gene located on chromosome 17.

Beta-arrestin-2, also known as arrestin beta-2, is an intracellular protein that in humans is encoded by the ARRB2 gene. Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals, as well as having signalling roles in their own right. Arrestin beta 2, like arrestin beta 1, was shown to inhibit beta-adrenergic receptor function in vitro. It is expressed at high levels in the central nervous system and may play a role in the regulation of synaptic receptors. Besides the brain, a cDNA for arrestin beta 2 was isolated from thyroid gland, and thus it may also be involved in hormone-specific desensitization of TSH receptors. Multiple alternatively spliced transcript variants have been found for this gene, but the full-length nature of some variants has not been defined. The protein may interact with the agonist DOI in 5-HT2A receptor signaling. Arrestin beta 2 is crucial for the development of tolerance to morphine and other opioids.

== Interactions == Arrestin beta 2 has been shown to interact with

AP2B1, PSCD2, Mdm2, and RALGDS.

== References ==

== Further reading ==

== External links == Human ARRB2 genome location and ARRB2 gene details page in the UCSC Genome Browser. This article incorporates text from the United States National Library of Medicine, which is in the public domain.

ARRB2, also known as beta-arrestin-2 or arrestin beta-2, plays a crucial role in regulating the signaling of G-protein coupled receptors (GPCRs) by mediating both receptor desensitization and resensitization processes. During desensitization, it binds to phosphorylated receptors, preventing their interaction with G-proteins and leading to a decrease in signaling. ARRB2 also acts as an endocytic adapter, facilitating the internalization of many GPCRs into intracellular endosomes, where they remain inactive. The internalization process can be divided into two modes: Class A receptors, like ADRB2, dissociate from ARRB2 near the plasma membrane and undergo rapid recycling, while Class B receptors, like AVPR2, remain bound to ARRB2 as they traffic to endosomes. Resensitization requires the removal of ARRB2 from the receptor, allowing it to be dephosphorylated and return to the plasma membrane. Beyond its role in GPCR desensitization and internalization, ARRB2 also serves as a signaling scaffold, initiating distinct signaling pathways upon receptor internalization. It activates MAPK pathways, including ERK1/2 and JNK3, which are primarily localized to cytoplasmic locations like endocytic vesicles. ARRB2 also acts as a scaffold for the AKT1 pathway. The regulation of GPCR signaling by ARRB2 can be either codependent, where both ARRB1 and ARRB2 are required, or reciprocal, where one beta-arrestin form enhances signaling while the other inhibits it. ARRB2 is involved in various cellular processes, including chemotaxis, inflammation, apoptosis, and the regulation of receptors other than GPCRs. It interacts with numerous proteins, including CHUK, MDM2, TRAF6, and various kinases and phosphatases. ARRB2's diverse functions highlight its importance in regulating cellular signaling and maintaining cellular homeostasis.

ARRB2 is also known as ARB2, ARR2, BARR2.

Associated Diseases

WES Whole Exome Sequencing