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beta-arrestin-2; arrestin beta-2 (ARRB2 ARB2 ARR2)

Function: - regulates beta-adrenergic receptor function - beta- arrestins seem to bind phosphorylated beta-adrenergic receptors, thereby causing a significant impairment of their capacity to activate Gs proteins - binds to phosphorylated C-terminus of TGF-beta receptor 3, promotes endocytosis of TGFBR3 & downregulates TGF-beta signaling [2] - Frizzled 4 binding to protein kinase C phosphorylated dishevelled 2 recruits beta-arrestin 2; further stimulation by wnt5A is required for endocytosis via clathrin coated pits [1] Structure: belongs to the arrestin family Compartment: cytoplasm (putative), nucleus Alternative splicing: named isoforms=3 Comparative biology: - mice without functional beta-arrestin-2 are 3 times more sensitive to the analgesic effect of morphine than normal mice - additionally the effects of morphine last 3 times as long - these effects are mediated via the mu-opioid receptor (as they are nullified by naloxone)

General

beta-arrestin phosphoprotein

Properties

SIZE: entity length = 409 aa MW = 46 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: Tyr phosphorylation site {Y48} peptide motif {389-399}

Database Correlations

OMIM 107941 UniProt P32121 PFAM correlations Entrez Gene 409 Kegg hsa:409

References

  1. Chen W et al Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4. Science 301:1391-4, 2003 PMID: 12958364
  2. Chen W et al Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor and down-regulation of its signaling. Science 301:1394-7, 2003 PMID: 12958365
  3. Journal Watch 20(3):27, 2000
  4. Bohn LM et al Enhanced morphine analgesia in mice lacking beta-arrestin 2. Science 286:2495, 1999 PMID: 10617462
  5. Entrez Gene :accession 409