ARRB1

Description

The ARRB1 (arrestin beta 1) is a protein-coding gene located on chromosome 11.

Arrestin, beta 1, also known as ARRB1, is a protein which in humans is encoded by the ARRB1 gene.

== Function == 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. Arrestin beta 1 is a cytosolic protein and acts as a cofactor in the beta-adrenergic receptor kinase (BARK) mediated desensitization of beta-adrenergic receptors. Besides the central nervous system, it is expressed at high levels in peripheral blood leukocytes, and thus the BARK/beta-arrestin system is believed to play a major role in regulating receptor-mediated immune functions. Alternatively spliced transcripts encoding different isoforms of arrestin beta 1 have been described, however, their exact functions are not known. Beta-arrestin has been shown to play a role as a scaffold that binds intermediates and may direct G-protein signaling by connecting receptors to clathrin-mediated endocytosis.

== Interactions == Arrestin beta 1 has been shown to interact with

Arf6, PTHLH, DVL2 Mdm2, OPRD1, PSCD2, and RALGDS.

== References ==

== Further reading ==

== External links == Human ARRB1 genome location and ARRB1 gene details page in the UCSC Genome Browser.

ARRB1, also known as beta-arrestin-1, plays a crucial role in regulating the signaling of G-protein coupled receptors (GPCRs) by mediating both receptor desensitization and resensitization processes. During desensitization, ARRB1 binds to the phosphorylated receptor, preventing its interaction with G-proteins. This binding involves specific receptor determinants only exposed in the active state. ARRB1 acts as an endocytic adapter, facilitating the internalization of many receptors by recruiting them to clathrin-coated pits. The extent of ARRB1's involvement varies depending on the receptor, agonist, and cell type. Internalized ARRB1-receptor complexes traffic to endosomes, where they remain detached from G-proteins. Two internalization modes exist: Class A receptors, like ADRB2, dissociate from ARRB1 at the plasma membrane and recycle rapidly. Class B receptors, like AVPR2, remain bound to ARRB1 and traffic to endosomes for prolonged periods. Resensitization requires removal of ARRB1 to allow receptor dephosphorylation and return to the plasma membrane. ARRB1 participates in internalization of P2RY4 and UTP-stimulated internalization of P2RY2. It's involved in phosphorylation-dependent internalization and recycling of OPRD1, and in degrading cAMP by recruiting phosphodiesterases to activated receptors. ARRB1 acts as a multivalent adapter, switching GPCRs from G-protein signaling (short-lived signals) to ARRB1 signaling (distinct signals initiated during internalization). It serves as a scaffold for MAPK pathways, particularly MAPK1/3 (ERK1/2), which are confined to cytoplasmic locations like endocytic vesicles. ARRB1 recruits c-Src to ADRB2, activating ERK. For some GPCRs, ARRB1 and ARRB2 cooperate in signaling (codependent regulation), while for others, they exhibit reciprocal regulation, with one inhibiting the other. ARRB1 inhibits ERK signaling in AGTR1- and AVPR2-mediated activation. It's essential for SP-stimulated endocytosis of NK1R, recruiting c-Src to internalized NK1R, leading to ERK activation, crucial for SP's antiapoptotic effects. ARRB1 participates in F2RL1-mediated ERK activity. It acts as a scaffold for the AKT1 pathway, involved in alpha-thrombin- and IGF1-stimulated AKT1 signaling, promoting protection against apoptosis. ARRB1 activates the p38 MAPK signaling pathway and actin bundle formation, contributing to F2RL1-mediated cytoskeletal rearrangement and chemotaxis. It works with GNAQ to activate RHOA, leading to AGTR1-mediated stress fiber formation. ARRB1 appears to function as a signaling scaffold in MIP-1-beta-stimulated CCR5-dependent chemotaxis. It attenuates NF-kappa-B-dependent transcription in response to GPCR or cytokine stimulation by stabilizing CHUK. ARRB1 may serve as a nuclear messenger for GPCRs. It participates in OPRD1-stimulated transcriptional regulation by translocating to promoter regions and recruiting EP300, leading to histone acetylation. ARRB1 regulates LEF1 transcriptional activity through interactions with DVL1 and/or DVL2. Additionally, it's involved in regulating receptors other than GPCRs. ARRB1 participates in Toll-like receptor and IL-1 receptor signaling by interacting with TRAF6, preventing its autoubiquitination and oligomerization, required for NF-kappa-B and JUN activation. ARRB1 binds phosphoinositides, including inositolhexakisphosphate (InsP6). It's involved in IL8-mediated granule release in neutrophils. ARRB1 is crucial for ACKR2-induced RAC1-LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for ACKR2 up-regulation from endosomes to the cell membrane, enhancing chemokine uptake and degradation. It participates in the internalization of ACKR3. ARRB1 negatively regulates the NOTCH signaling pathway by mediating NOTCH1 ubiquitination and degradation by ITCH, recruiting the ubiquitin-protein ligase to the receptor. It exists as a monomer, homodimer, homooligomer (mediated by InsP6 binding), and heterooligomer with ARRB2 (mediated by InsP6 binding). ARRB1 interacts with various proteins, including GPR143, ADRB2, CHRM2, LHCGR, CYTH2, CASR, AP2B1, CLTC, CCR2, GRK2, CRR5, PTAFR, MAP2K3, CREB1, TRAF6, IGF1R, MDM2, C5AR1, PDE4D, SRC, TACR1, RAF1, CHUK, IKBKB, MAP3K14, DVL1, DVL2, MAPK4/MKK4, HCK, CXCR1, ACKR3, ACKR4, and ARRDC1.

ARRB1 is also known as ARB1, ARR1.

Associated Diseases

WES Whole Exome Sequencing