Arrestin beta 2

ARRB2
Identifiers
Aliases	ARRB2, ARB2, ARR2, BARR2, Arrestin beta 2
External IDs	MGI: 99474 HomoloGene: 3183 GeneCards: ARRB2
Gene ontology Molecular function • type 2A serotonin receptor binding • protein domain specific binding • type 1 angiotensin receptor binding • platelet activating factor receptor binding • protein complex binding • alpha-1B adrenergic receptor binding • 14-3-3 protein binding • protein kinase B binding • mitogen-activated protein kinase binding • follicle-stimulating hormone receptor binding • protein binding • enzyme binding • angiotensin receptor binding • protein complex scaffold • D1 dopamine receptor binding • receptor binding • G-protein coupled receptor binding • ubiquitin protein ligase binding • alpha-1A adrenergic receptor binding Cellular component • cytoplasm • cytosol • postsynaptic membrane • postsynaptic density • membrane • plasma membrane • endocytic vesicle • dendritic spine • intracellular • cytoplasmic, membrane-bounded vesicle • basolateral plasma membrane • clathrin-coated pit • cytoplasmic vesicle • nucleus Biological process • proteasome-mediated ubiquitin-dependent protein catabolic process • positive regulation of calcium ion transport • G-protein coupled receptor internalization • regulation of protein phosphorylation • G-protein coupled receptor signaling pathway • negative regulation of interleukin-1 beta production • negative regulation of protein kinase B signaling • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process • positive regulation of protein kinase B signaling • positive regulation of protein phosphorylation • endocytosis • regulation of G-protein coupled receptor protein signaling pathway • positive regulation of receptor internalization • chemical synaptic transmission, postsynaptic • negative regulation of release of cytochrome c from mitochondria • negative regulation of interleukin-6 production • receptor internalization • transcription from RNA polymerase II promoter • positive regulation of peptidyl-serine phosphorylation • detection of temperature stimulus involved in sensory perception of pain • follicle-stimulating hormone signaling pathway • platelet activation • dopamine receptor signaling pathway • negative regulation of protein ubiquitination • brain development • negative regulation of GTPase activity • negative regulation of toll-like receptor signaling pathway • protein ubiquitination • positive regulation of DNA biosynthetic process • positive regulation of ERK1 and ERK2 cascade • transport • positive regulation of peptidyl-tyrosine phosphorylation • cell chemotaxis • protein transport • negative regulation of natural killer cell mediated cytotoxicity • regulation of androgen receptor signaling pathway • positive regulation of synaptic transmission, dopaminergic • negative regulation of tumor necrosis factor production • negative regulation of signal transduction • positive regulation of protein ubiquitination • transforming growth factor beta receptor signaling pathway • negative regulation of NF-kappaB transcription factor activity • negative regulation of smooth muscle cell apoptotic process • desensitization of G-protein coupled receptor protein signaling pathway by arrestin • signal transduction • adult walking behavior • negative regulation of interleukin-12 production • Wnt signaling pathway, planar cell polarity pathway Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	409	216869
Ensembl	ENSG00000141480	ENSMUSG00000060216
UniProt	P32121	Q91YI4
RefSeq (mRNA)	NM_001257328 NM_001257329 NM_001257330 NM_001257331 NM_004313 NM_199004	NM_001271358 NM_001271359 NM_001271360 NM_145429
RefSeq (protein)	NP_001244257.1 NP_001244258.1 NP_001244259.1 NP_001244260.1 NP_004304.1 NP_945355.1	NP_001258287.1 NP_001258288.1 NP_001258289.1 NP_663404.1
Location (UCSC)	Chr 17: 4.71 – 4.72 Mb	Chr 11: 70.43 – 70.44 Mb
PubMed search	[1]	[2]
Wikidata

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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,^[3][4][5] as well as having signalling roles in their own right.^{[6][7][8][9][10]} 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.^[11]

The protein may interact with the agonist DOI in 5-HT_2A receptor signaling.^[12][13]

Interactions

Arrestin beta 2 has been shown to interact with

• AP2B1,^[14][15]
• PSCD2,^[16]
• Mdm2,^[17][18][19] and
• RALGDS.^[20]

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Breivogel CS, Lambert JM, Gerfin S, Huffman JW, Razdan RK (July 2008). "Sensitivity to delta9-tetrahydrocannabinol is selectively enhanced in beta-arrestin2 -/- mice". Behavioural Pharmacology. 19 (4): 298–307. doi:10.1097/FBP.0b013e328308f1e6. PMC 2751575. PMID 18622177.
4. Li Y, Liu X, Liu C, Kang J, Yang J, Pei G, Wu C (March 2009). "Improvement of morphine-mediated analgesia by inhibition of β-arrestin2 expression in mice periaqueductal gray matter". International Journal of Molecular Sciences. 10 (3): 954–63. doi:10.3390/ijms10030954. PMC 2672012. PMID 19399231.
5. Zheng H, Loh HH, Law PY (January 2008). "Beta-arrestin-dependent mu-opioid receptor-activated extracellular signal-regulated kinases (ERKs) Translocate to Nucleus in Contrast to G protein-dependent ERK activation". Molecular Pharmacology. 73 (1): 178–90. doi:10.1124/mol.107.039842. PMC 2253657. PMID 17947509.
6. Ma L, Pei G (January 2007). "Beta-arrestin signaling and regulation of transcription". Journal of Cell Science. 120 (Pt 2): 213–8. doi:10.1242/jcs.03338. PMID 17215450.
7. Defea K (March 2008). "Beta-arrestins and heterotrimeric G-proteins: collaborators and competitors in signal transduction". British Journal of Pharmacology. 153 Suppl 1 (S1): S298–309. doi:10.1038/sj.bjp.0707508. PMC 2268080. PMID 18037927.
8. Barki-Harrington L, Rockman HA (February 2008). "Beta-arrestins: multifunctional cellular mediators". Physiology. 23: 17–22. doi:10.1152/physiol.00042.2007. PMID 18268361.
9. Patel PA, Tilley DG, Rockman HA (March 2009). "Physiologic and cardiac roles of beta-arrestins". Journal of Molecular and Cellular Cardiology. 46 (3): 300–8. doi:10.1016/j.yjmcc.2008.11.015. PMID 19103204.
10. Golan M, Schreiber G, Avissar S (2009). "Antidepressants, beta-arrestins and GRKs: from regulation of signal desensitization to intracellular multifunctional adaptor functions". Current Pharmaceutical Design. 15 (14): 1699–708. doi:10.2174/138161209788168038. PMID 19442183.
11. "Entrez Gene: ARRB2 arrestin, beta 2".
12. Schmid CL, Raehal KM, Bohn LM (January 2008). "Agonist-directed signaling of the serotonin 2A receptor depends on beta-arrestin-2 interactions in vivo". Proceedings of the National Academy of Sciences of the United States of America. 105 (3): 1079–84. doi:10.1073/pnas.0708862105. PMC 2242710. PMID 18195357.
13. Abbas A, Roth BL (January 2008). "Arresting serotonin". Proceedings of the National Academy of Sciences of the United States of America. 105 (3): 831–2. doi:10.1073/pnas.0711335105. PMC 2242676. PMID 18195368.
14. Laporte SA, Oakley RH, Zhang J, Holt JA, Ferguson SS, Caron MG, Barak LS (March 1999). "The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis". Proceedings of the National Academy of Sciences of the United States of America. 96 (7): 3712–7. doi:10.1073/pnas.96.7.3712. PMC 22359. PMID 10097102.
15. Kim YM, Benovic JL (August 2002). "Differential roles of arrestin-2 interaction with clathrin and adaptor protein 2 in G protein-coupled receptor trafficking". The Journal of Biological Chemistry. 277 (34): 30760–8. doi:10.1074/jbc.M204528200. PMID 12070169.
16. Claing A, Chen W, Miller WE, Vitale N, Moss J, Premont RT, Lefkowitz RJ (November 2001). "beta-Arrestin-mediated ADP-ribosylation factor 6 activation and beta 2-adrenergic receptor endocytosis". The Journal of Biological Chemistry. 276 (45): 42509–13. doi:10.1074/jbc.M108399200. PMID 11533043.
17. Wang P, Gao H, Ni Y, Wang B, Wu Y, Ji L, Qin L, Ma L, Pei G (February 2003). "Beta-arrestin 2 functions as a G-protein-coupled receptor-activated regulator of oncoprotein Mdm2". The Journal of Biological Chemistry. 278 (8): 6363–70. doi:10.1074/jbc.M210350200. PMID 12488444.
18. Wang P, Wu Y, Ge X, Ma L, Pei G (March 2003). "Subcellular localization of beta-arrestins is determined by their intact N domain and the nuclear export signal at the C terminus". The Journal of Biological Chemistry. 278 (13): 11648–53. doi:10.1074/jbc.M208109200. PMID 12538596.
19. Shenoy SK, Xiao K, Venkataramanan V, Snyder PM, Freedman NJ, Weissman AM (August 2008). "Nedd4 mediates agonist-dependent ubiquitination, lysosomal targeting, and degradation of the beta2-adrenergic receptor". The Journal of Biological Chemistry. 283 (32): 22166–76. doi:10.1074/jbc.M709668200. PMC 2494938. PMID 18544533.
20. Bhattacharya M, Anborgh PH, Babwah AV, Dale LB, Dobransky T, Benovic JL, Feldman RD, Verdi JM, Rylett RJ, Ferguson SS (August 2002). "Beta-arrestins regulate a Ral-GDS Ral effector pathway that mediates cytoskeletal reorganization". Nature Cell Biology. 4 (8): 547–55. doi:10.1038/ncb821. PMID 12105416.

Further reading

• Lefkowitz RJ (July 1998). "G protein-coupled receptors. III. New roles for receptor kinases and beta-arrestins in receptor signaling and desensitization". The Journal of Biological Chemistry. 273 (30): 18677–80. doi:10.1074/jbc.273.30.18677. PMID 9668034.
• Attramadal H, Arriza JL, Aoki C, Dawson TM, Codina J, Kwatra MM, Snyder SH, Caron MG, Lefkowitz RJ (September 1992). "Beta-arrestin2, a novel member of the arrestin/beta-arrestin gene family". The Journal of Biological Chemistry. 267 (25): 17882–90. PMID 1517224.
• Rapoport B, Kaufman KD, Chazenbalk GD (April 1992). "Cloning of a member of the arrestin family from a human thyroid cDNA library". Molecular and Cellular Endocrinology. 84 (3): R39–43. doi:10.1016/0303-7207(92)90038-8. PMID 1587386.
• Calabrese G, Sallese M, Stornaiuolo A, Stuppia L, Palka G, De Blasi A (September 1994). "Chromosome mapping of the human arrestin (SAG), beta-arrestin 2 (ARRB2), and beta-adrenergic receptor kinase 2 (ADRBK2) genes". Genomics. 23 (1): 286–8. doi:10.1006/geno.1994.1497. PMID 7695743.
• Parruti G, Peracchia F, Sallese M, Ambrosini G, Masini M, Rotilio D, De Blasi A (May 1993). "Molecular analysis of human beta-arrestin-1: cloning, tissue distribution, and regulation of expression. Identification of two isoforms generated by alternative splicing". The Journal of Biological Chemistry. 268 (13): 9753–61. PMID 8486659.
• Le Gouill C, Parent JL, Rola-Pleszczynski M, Stanková J (February 1997). "Role of the Cys90, Cys95 and Cys173 residues in the structure and function of the human platelet-activating factor receptor". FEBS Letters. 402 (2-3): 203–8. doi:10.1016/S0014-5793(96)01531-1. PMID 9037196.
• Barak LS, Ferguson SS, Zhang J, Caron MG (October 1997). "A beta-arrestin/green fluorescent protein biosensor for detecting G protein-coupled receptor activation". The Journal of Biological Chemistry. 272 (44): 27497–500. doi:10.1074/jbc.272.44.27497. PMID 9346876.
• Laporte SA, Oakley RH, Zhang J, Holt JA, Ferguson SS, Caron MG, Barak LS (March 1999). "The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis". Proceedings of the National Academy of Sciences of the United States of America. 96 (7): 3712–7. doi:10.1073/pnas.96.7.3712. PMC 22359. PMID 10097102.
• Cheng ZJ, Zhao J, Sun Y, Hu W, Wu YL, Cen B, Wu GX, Pei G (January 2000). "beta-arrestin differentially regulates the chemokine receptor CXCR4-mediated signaling and receptor internalization, and this implicates multiple interaction sites between beta-arrestin and CXCR4". The Journal of Biological Chemistry. 275 (4): 2479–85. doi:10.1074/jbc.275.4.2479. PMID 10644702.
• Lin F, Wang Hy, Malbon CC (June 2000). "Gravin-mediated formation of signaling complexes in beta 2-adrenergic receptor desensitization and resensitization". The Journal of Biological Chemistry. 275 (25): 19025–34. doi:10.1074/jbc.275.25.19025. PMID 10858453.
• McDonald PH, Chow CW, Miller WE, Laporte SA, Field ME, Lin FT, Davis RJ, Lefkowitz RJ (November 2000). "Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3". Science. 290 (5496): 1574–7. doi:10.1126/science.290.5496.1574. PMID 11090355.
• Luttrell LM, Roudabush FL, Choy EW, Miller WE, Field ME, Pierce KL, Lefkowitz RJ (February 2001). "Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds". Proceedings of the National Academy of Sciences of the United States of America. 98 (5): 2449–54. doi:10.1073/pnas.041604898. PMC 30158. PMID 11226259.
• Cen B, Yu Q, Guo J, Wu Y, Ling K, Cheng Z, Ma L, Pei G (March 2001). "Direct binding of beta-arrestins to two distinct intracellular domains of the delta opioid receptor". Journal of Neurochemistry. 76 (6): 1887–94. doi:10.1046/j.1471-4159.2001.00204.x. PMID 11259507.
• Oakley RH, Laporte SA, Holt JA, Barak LS, Caron MG (June 2001). "Molecular determinants underlying the formation of stable intracellular G protein-coupled receptor-beta-arrestin complexes after receptor endocytosis*". The Journal of Biological Chemistry. 276 (22): 19452–60. doi:10.1074/jbc.M101450200. PMID 11279203.
• Miller WE, McDonald PH, Cai SF, Field ME, Davis RJ, Lefkowitz RJ (July 2001). "Identification of a motif in the carboxyl terminus of beta -arrestin2 responsible for activation of JNK3". The Journal of Biological Chemistry. 276 (30): 27770–7. doi:10.1074/jbc.M102264200. PMID 11356842.
• Claing A, Chen W, Miller WE, Vitale N, Moss J, Premont RT, Lefkowitz RJ (November 2001). "beta-Arrestin-mediated ADP-ribosylation factor 6 activation and beta 2-adrenergic receptor endocytosis". The Journal of Biological Chemistry. 276 (45): 42509–13. doi:10.1074/jbc.M108399200. PMID 11533043.
• Hilairet S, Bélanger C, Bertrand J, Laperrière A, Foord SM, Bouvier M (November 2001). "Agonist-promoted internalization of a ternary complex between calcitonin receptor-like receptor, receptor activity-modifying protein 1 (RAMP1), and beta-arrestin". The Journal of Biological Chemistry. 276 (45): 42182–90. doi:10.1074/jbc.M107323200. PMID 11535606.
• Shenoy SK, McDonald PH, Kohout TA, Lefkowitz RJ (November 2001). "Regulation of receptor fate by ubiquitination of activated beta 2-adrenergic receptor and beta-arrestin". Science. 294 (5545): 1307–13. doi:10.1126/science.1063866. PMID 11588219.
• Chen Z, Dupré DJ, Le Gouill C, Rola-Pleszczynski M, Stanková J (March 2002). "Agonist-induced internalization of the platelet-activating factor receptor is dependent on arrestins but independent of G-protein activation. Role of the C terminus and the (D/N)PXXY motif". The Journal of Biological Chemistry. 277 (9): 7356–62. doi:10.1074/jbc.M110058200. PMID 11729201.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.