Arrb1 (rat beta-arrestin-1, arrestin-2; UniProt P29066): manual literature synthesis

No deep-research provider was available for this review. This file is a manual synthesis
from the cached publications (publications/PMID_*.md) and the UniProt record
(genes/rat/Arrb1/Arrb1-uniprot.txt). Every claim carries inline provenance.

Identity and family

• Rat Arrb1 encodes beta-arrestin-1 (also called arrestin-2), a 418-aa member of the arrestin
  family with arrestin N- and C-domains (Pfam PF00339, PF02752; PANTHER PTHR11792:SF22
  BETA-ARRESTIN-1) [file:rat/Arrb1/Arrb1-uniprot.txt "Belongs to the arrestin family."].
• The rat cDNA was cloned together with beta-arrestin-2 from a rat brain library
  PMID:1517224.
• Expression: neuronal tissues and spleen, low elsewhere
  PMID:1517224.

Core activity 1: binding phosphorylated, activated GPCRs and desensitization

• Purified beta-arrestin-1 quenches coupling of GRK-phosphorylated beta2-adrenergic receptor
  to Gs in reconstituted systems PMID:1517224.
• A phosphorylated V2 vasopressin receptor C-tail peptide (V2Rpp) binds and conformationally
  activates rat beta-arrestin-1, releasing its C-terminus and enhancing clathrin binding
  PMID:17513300.
• Crystal structure of active beta-arrestin-1 with V2Rpp PMID:23604254; the protein used was rat beta-arrestin-1 PMID:23604254.
• Cryo-EM structures with C5aR1, CXCR4, M2R and D6R phosphopeptides/receptors define a
  P-X-P-P phospho-motif recognised by a K-K-R-R-K-K N-domain groove
  PMID:37209686;
  rat beta-arrestin-1 was used PMID:37209686.
  Atypical engagement through M2R ICL3 PMID:38175886.
• Receptor-specific binding in rat systems: FSH receptor in Sertoli cells
  PMID:16899567;
  alpha1A/alpha1B adrenergic receptors PMID:18523139.
• Physiological desensitization: in rat mesenteric arterial smooth muscle, arrestin2
  (beta-arrestin-1) is needed for P2Y2 receptor desensitization
  PMID:20705669.
• PDE4 recruitment limits cAMP at activated beta2AR
  PMID:12399592.

Core activity 2: clathrin/AP-2 cargo adaptor for receptor endocytosis

• UniProt summary [file:rat/Arrb1/Arrb1-uniprot.txt "The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin-associated sorting proteins)"].
• beta-arrestin is a beta2-appendage-selective AP-2 adaptor
  PMID:15728179.
• Clathrin binding increases on activation PMID:17513300.
• Endosomal receptor/beta-arrestin-1 complexes (bradykinin B2R)
  PMID:25016018.
• PAR2 endocytosis and signalosome PMID:10725339.

Core activity 3: signaling scaffold (ERK and others)

• mGlu1 receptor-driven MAPK activation in Purkinje cells requires beta-arrestin
  PMID:12519791.
• Adrenal AT1R-driven sustained ERK and aldosterone production (rat in vivo)
  PMID:19289825.
• Reciprocal regulation: in rat VSMCs, beta-arrestin-1 knockdown increases early AngII-ERK
  PMID:19254952;
  and opposes beta-arrestin-2 anti-apoptotic signaling [PMID:19171933 "We have also found that β-arrestin-1 functionally opposes this signaling (33)."; "knocking-down β-arrestin-1 leads to decreases in apoptotic reagent-induced caspase-3 cleavage even in the absence of stimulation with AngII"].
• Cofilin pathway scaffolding downstream of PAR2 PMID:17500066.
• Estrogen receptor-alpha/beta-arrestin-1 complex in neurons
  PMID:19339617.
• Insulin downregulates beta-arrestin-1 and impairs IGF-1/GPCR MAPK signaling
  PMID:12167719.

Core activity 4: E3 ubiquitin ligase adaptor

• TRPV4 down-regulation in rat VSMCs PMID:20650893.
• Notch degradation via ARRDC1-ITCH PMID:23886940.
• MDM2-p53 scaffold PMID:21857681.

Nuclear / transcriptional roles (non-core)

• Delta-opioid-induced nuclear translocation; p300 recruitment at p27/c-fos promoters
  PMID:16325578.
• Dishevelled/LEF PMID:11742073.
• CREB complex for GDNF (C6 glioma) PMID:21223624.

Localization

• Postsynaptic sites in rat brain PMID:1517224.
• Recruited from cytoplasm to plasma membrane PMID:16899567.
• Peripheral sensory terminals PMID:14519533.

Expression responses and phenotypes (peripheral)

• Morphine lowers Arrb1 mRNA in locus coeruleus PMID:12614678.
• Astrocyte survival PMID:24378649.
• Thioredoxin-1 interaction in PC12 cells PMID:25486571.
• Sevoflurane neurotoxicity PMID:26621121.

Problems found in source annotations

• The mouse phototransduction annotation (PMID:11853756, propagated to rat by ISO) comes from a
  paper on rod arrestin (Sag) knockout mice, not beta-arrestin-1
  PMID:11853756.
• The mouse "cysteine-type endopeptidase inhibitor activity" (PMID:19915011, propagated by ISO)
  is a phenotype-to-function mapping; the paper describes an ERK1/2-p90RSK-Bad mechanism
  PMID:19915011.