Recombinant Human Beta-arrestin-2 (ARRB2), partial

Code CSB-YP002135HU1
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Source Yeast
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Code CSB-EP002135HU1
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Source E.coli
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Code CSB-EP002135HU1-B
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Source E.coli
Conjugate Avi-tag Biotinylated
E. coli biotin ligase (BirA) is highly specific in covalently attaching biotin to the 15 amino acid AviTag peptide. This recombinant protein was biotinylated in vivo by AviTag-BirA technology, which method is BriA catalyzes amide linkage between the biotin and the specific lysine of the AviTag.
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Code CSB-BP002135HU1
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Source Baculovirus
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Code CSB-MP002135HU1
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Source Mammalian cell
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Product Details

Purity
>85% (SDS-PAGE)
Target Names
ARRB2
Uniprot No.
Alternative Names
ARB 2; ARB2; ARR 2; ARR2; ARRB 2; ARRB2; ARRB2_HUMAN; Arrestin 3; Arrestin beta 2; Arrestin beta-2; BARR2; Beta-arrestin-2; DKFZp686L0365; HGNC:712
Species
Homo sapiens (Human)
Protein Length
Partial
Tag Info
Tag type will be determined during the manufacturing process.
The tag type will be determined during production process. If you have specified tag type, please tell us and we will develop the specified tag preferentially.
Form
Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
Buffer before Lyophilization
Tris/PBS-based buffer, 6% Trehalose, pH 8.0
Reconstitution
We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20℃/-80℃. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting and FAQs
Storage Condition
Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life
The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time
Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Note: All of our proteins are default shipped with normal blue ice packs, if you request to ship with dry ice, please communicate with us in advance and extra fees will be charged.
Notes
Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet
Please contact us to get it.

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Target Background

Function
Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. During homologous desensitization, beta-arrestins bind to the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G-protein; the binding appears to require additional receptor determinants exposed only in the active receptor conformation. The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin-associated sorting proteins) and recruiting the GPRCs to the adapter protein 2 complex 2 (AP-2) in clathrin-coated pits (CCPs). However, the extent of beta-arrestin involvement appears to vary significantly depending on the receptor, agonist and cell type. Internalized arrestin-receptor complexes traffic to intracellular endosomes, where they remain uncoupled from G-proteins. Two different modes of arrestin-mediated internalization occur. Class A receptors, like ADRB2, OPRM1, ENDRA, D1AR and ADRA1B dissociate from beta-arrestin at or near the plasma membrane and undergo rapid recycling. Class B receptors, like AVPR2, AGTR1, NTSR1, TRHR and TACR1 internalize as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptors, for extended periods of time. Receptor resensitization then requires that receptor-bound arrestin is removed so that the receptor can be dephosphorylated and returned to the plasma membrane. Mediates endocytosis of CCR7 following ligation of CCL19 but not CCL21. Involved in internalization of P2RY1, P2RY4, P2RY6 and P2RY11 and ATP-stimulated internalization of P2RY2. Involved in phosphorylation-dependent internalization of OPRD1 and subsequent recycling or degradation. Involved in ubiquitination of IGF1R. Beta-arrestins function as multivalent adapter proteins that can switch the GPCR from a G-protein signaling mode that transmits short-lived signals from the plasma membrane via small molecule second messengers and ion channels to a beta-arrestin signaling mode that transmits a distinct set of signals that are initiated as the receptor internalizes and transits the intracellular compartment. Acts as signaling scaffold for MAPK pathways such as MAPK1/3 (ERK1/2) and MAPK10 (JNK3). ERK1/2 and JNK3 activated by the beta-arrestin scaffold are largely excluded from the nucleus and confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Acts as signaling scaffold for the AKT1 pathway. GPCRs for which the beta-arrestin-mediated signaling relies on both ARRB1 and ARRB2 (codependent regulation) include ADRB2, F2RL1 and PTH1R. For some GPCRs the beta-arrestin-mediated signaling relies on either ARRB1 or ARRB2 and is inhibited by the other respective beta-arrestin form (reciprocal regulation). Increases ERK1/2 signaling in AGTR1- and AVPR2-mediated activation (reciprocal regulation). Involved in CCR7-mediated ERK1/2 signaling involving ligand CCL19. Is involved in type-1A angiotensin II receptor/AGTR1-mediated ERK activity. Is involved in type-1A angiotensin II receptor/AGTR1-mediated MAPK10 activity. Is involved in dopamine-stimulated AKT1 activity in the striatum by disrupting the association of AKT1 with its negative regulator PP2A. Involved in AGTR1-mediated chemotaxis. Appears to function as signaling scaffold involved in regulation of MIP-1-beta-stimulated CCR5-dependent chemotaxis. Involved in attenuation of NF-kappa-B-dependent transcription in response to GPCR or cytokine stimulation by interacting with and stabilizing CHUK. Suppresses UV-induced NF-kappa-B-dependent activation by interacting with CHUK. The function is promoted by stimulation of ADRB2 and dephosphorylation of ARRB2. Involved in p53/TP53-mediated apoptosis by regulating MDM2 and reducing the MDM2-mediated degradation of p53/TP53. May serve as nuclear messenger for GPCRs. Upon stimulation of OR1D2, may be involved in regulation of gene expression during the early processes of fertilization. Also involved in regulation of receptors other than GPCRs. Involved in endocytosis of TGFBR2 and TGFBR3 and down-regulates TGF-beta signaling such as NF-kappa-B activation. Involved in endocytosis of low-density lipoprotein receptor/LDLR. Involved in endocytosis of smoothened homolog/Smo, which also requires GRK2. Involved in endocytosis of SLC9A5. Involved in endocytosis of ENG and subsequent TGF-beta-mediated ERK activation and migration of epithelial cells. Involved in Toll-like receptor and IL-1 receptor signaling through the interaction with TRAF6 which prevents TRAF6 autoubiquitination and oligomerization required for activation of NF-kappa-B and JUN. Involved in insulin resistance by acting as insulin-induced signaling scaffold for SRC, AKT1 and INSR. Involved in regulation of inhibitory signaling of natural killer cells by recruiting PTPN6 and PTPN11 to KIR2DL1. Involved in IL8-mediated granule release in neutrophils. Involved in the internalization of the atypical chemokine receptor ACKR3. Acts as an adapter protein coupling FFAR4 receptor to specific downstream signaling pathways, as well as mediating receptor endocytosis. During the activation step of NLRP3 inflammasome, directly associates with NLRP3 leading to inhibition of proinflammatory cytokine release and inhibition of inflammation.
Gene References into Functions
  1. Pre-treatment with beta-arrestin2 agonists was shown to inhibit the AMPK/mTOR signaling pathway, and to inhibit autophagy by restoring the levels of beta-arrestin2 in BEAS-2B cells. These changes were reversed with the knockdown of beta-arrestin2, indicating that beta-arrestin2 suppressed autophagy through the AMPK-mTOR signaling pathway. PMID: 30355935
  2. Extracellular alpha-synuclein induces sphingosine S1P1R uncoupled from inhibitory G-protein leaving beta-arrestin signal intact. PMID: 28300069
  3. Results showed that significantly higher expression of betaarrestin2 was observed in colorectal cancer tissues compared with normal colon tissues. PMID: 29620228
  4. overexpression of beta-arrestin2 can inhibit the growth of renal cell carcinoma (RCC) cells in vitro, and beta-arrestin2 acts as a tumor suppressor gene in RCC; the main mechanism may directly suppress the phosphorylation of IkBa and indirectly suppress NFkB PMID: 28485809
  5. Study investigated the association between five ARRB2 single nucleotide polymorphisms (SNPs): rs1045280, rs2036657, rs4790694, rs3786047 and rs452246, and response to antidepressant treatment in a sample of 569 patients with a major depressive episode treated for 6months: GG/GT patients for rs4522461 and AA/AC patients for rs4790694 had a lower response. PMID: 29031912
  6. Itch/beta-arrestin2 complex binds SuFu and induces its Lys63-linked polyubiquitylation without affecting its stability. PMID: 29515120
  7. USP33 may indirectly regulate the degradation and recycling of CXCR4 through deubiquitinating beta-arrestin2, promoting colorectal tumor cell metastasis. PMID: 27835898
  8. Antihistamines displayed similar kinetic signatures on antagonizing histamine-induced beta-arrestin2 recruitment as compared to displacing radioligand binding from the H1R. PMID: 27468652
  9. the internalization motif for the human neuropeptide Y4 receptor, which regulates arrestin-3 recruitment and receptor endocytosis, was identified. PMID: 27818291
  10. Collectively, these data show that beta-arrestin2 phosphorylation at Thr(383) underlies beta-arrestin-dependent Erk1/2 activation by G protein-coupled receptors. PMID: 28169830
  11. Data indicate that a constitutively monomeric CXCL12 variant reproduced the G protein-dependent and beta-arrestin-dependent responses that are associated with normal CXCR4 signaling and lead to cell migration. PMID: 28325822
  12. EPCR occupancy recruits G-protein coupled receptor kinase 5, thereby inducing beta-arrestin-2 biased PAR1 signaling by both APC and thrombin. In PMID: 27561318
  13. CCR5 is highly expressed in active inflammatory bowel disease, and it has positive correlation with lymphocyte grade and negative correlation with expression of beta-arrestin2. PMID: 28140695
  14. Data suggest that PAR4 and P2Y12 heterodimer internalization/endocytosis is required for beta-arrestin-2 recruitment to endosomes and up-regulation of Akt signaling; activation of PAR4 but not of P2Y12 drives internalization of the PAR4-P2Y12 heterodimer. (PAR4 = protease-activated receptor 4; P2Y12 = purinergic receptor P2Y, G-protein coupled, 12 protein; Akt = proto-oncogene protein c-akt) PMID: 28652403
  15. Heterodimerization of the kappa opioid receptor and neurotensin receptor 1 contributes to a novel beta-arrestin-2-signaling pathway. PMID: 27523794
  16. RACK1 and beta-arrestin2 inhibit the dimerization of PDE4D5. PMID: 26257302
  17. Suggest that fenoterol inhibited AICAR-induced AMPK alpha1 activation and TNF-alpha release through beta-arrestin-2 in THP-1 cells. PMID: 27657826
  18. Results demonstrate that betaArr2 signaling may be an important pathway for TAAR1 function and that the activation of the TAAR1-D2R complex negatively modulates GSK3b signaling PMID: 26372541
  19. Role for engagement of BARR2 by the transactivated EGFR in agonist-specific regulation of delta receptor activation of ERK1/2 PMID: 26211551
  20. Data suggest that thrombin can directly activate PAR2 vasorelaxation, signal transduction (stimulating both calcium and MAP kinase responses), and triggering beta-arrestin recruitment (both beta-arrestin 1 and 2). PMID: 26957205
  21. a beta-arrestin signalling cycle that is catalytically activated by the GPCR and energetically coupled to the endocytic machinery PMID: 26829388
  22. The rare variants in ARRB2 were significantly associated with smoking status. PMID: 25450229
  23. analysis of the crystal structure of the rhodopsin-arrestin complex PMID: 26467309
  24. In this study, we aimed to exploit an in vitro model system of BPH in order to better understand the mechanisms of alpha-AR signaling in prostatic hyperplasia. PMID: 26850854
  25. interaction of beta-arrestin with GPCRs, and the beta-arrestin conformational changes in real time and in living human cells, using a series of fluorescence resonance energy transfer (FRET)-based beta-arrestin2 biosensors PMID: 27007855
  26. ARRB2 is not upregulated in inflammation-associated hepatocellular carcinoma (HCC) and paracancerous tissues. PMID: 26077142
  27. Beta-arrestin 2 promotes inflammation-induced intestinal epithelial apoptosis through endoplasmic reticulum stress/PUMA in colitis. PMID: 25354317
  28. MTS assay revealed that silencing of beta-arrestin 2 increased the sensitivity to anti-cancer drugs to some extent. On the other hand, overexpression of beta-arrestin 2 had the opposite effects. PMID: 25973019
  29. In a mouse model of Marfan syndrome, BARR2 contributes to thoracic aortic aneurysm formation by regulating ERK1/2-dependent expression of proaneurysmal genes and proteins downstream of the AT1aR. PMID: 26371162
  30. GPCR cell-surface expression is regulated by receptor sequestration in response to beta-arrestin-2 phosphorylation by ERK1/2 PMID: 26324936
  31. GPR40 functions via both G protein-mediated and beta-arrestin-mediated mechanisms; endogenous and synthetic ligands differentially engage these pathways to promote insulin secretion. PMID: 26157145
  32. identified a novel role for beta-arrestin2 in the modulation of the castration-resistant prostate cancer progress through FOXO1 PMID: 25752515
  33. Study demonstrates that the minor allele of rs1045280, the tSNP of ARRB2, significantly increases late-onset Alzheimer's disease risk in a Northern Han Chinese population, implying that ARRB2 may represent a susceptibility gene PMID: 24635845
  34. arrestin-3 and GRK2 play an essential role in the regulation of agonist-mediated GPR40 internalization, but are not involved in the regulation of constitutive GPR40 internalization. PMID: 25038452
  35. SUMOylation is a novel mechanism in the regulation of beta-arrestin 2-mediated IL-1R/TRAF6 signaling PMID: 25425640
  36. The stem cell-expressed receptor Lgr5 possesses canonical and functionally active molecular determinants critical to beta-arrestin-2 recruitment. PMID: 24386388
  37. Decreased beta-arrestin expression is associated with breast cancer. PMID: 24568448
  38. Phosphorylation and structural elements within the C-terminal tail of FFA4 allow for the recruitment of arrestin-3. PMID: 24817122
  39. a novel adaptor beta-arrestin 2 that associates with phosphorylated TIGIT for further recruitment of SHIP1 (SH2-containing inositol phosphatase 1) through the ITT-like motif. PMID: 24817116
  40. GPR43 modulates NF-kappaB activity via beta-arrestin 2. PMID: 23985900
  41. CRF2(a) receptor desensitization is dependent on beta-arrestin2 recruitment. PMID: 23820308
  42. CCR1.beta-arrestin-2 complex may be related to a potential scavenging function of the receptor, which may be important for maintenance of chemokine gradients and receptor responsiveness in complex fields of chemokines during inflammation. PMID: 24056371
  43. Taken together, the participation of 5-HT1A and FGFR1 homodimers and recruitment of beta-arrestin2 was demonstrated in the FGFR1-5-HT1A heteroreceptor complexes upon agonist treatments. PMID: 24157794
  44. Beta-arr2 binding is only required for agonist-induced internalization of the CB1 receptor. PMID: 23541635
  45. beta-arrestin 2 and CCR7 and PI3K phosphorylation have a role in bisoprolol reversed epinephrine-mediated inhibition of cell migration, in dendritic cells loaded with cholesterol PMID: 23290307
  46. Social anhedonia mutant DISC-1 mouse model has reduced levels of beta-arrestin-1,2 in the nucleus accumbens. PMID: 23011268
  47. beta-arrestin2-PDE4D5 complex allowed the recruitment of Epac1 to beta2AR and induced a switch from beta2AR non-hypertrophic signaling to a beta1AR-like pro-hypertrophic signaling cascade. PMID: 23266473
  48. Arf (ADP-ribosylation factor) GAP (GTPase-activating protein) AGAP2 plays a role in the signalling and recycling of beta2-adrenergic receptors, co-localizing with overexpressed beta2AR and trapping beta2AR in the perinuclear region. PMID: 23527545
  49. Beta 2 adrenergic receptor endocytosis requires beta-arrestin2 but not ARRDC3. PMID: 23208550
  50. The interaction of TbetaRII with betaarrestin2 is involved in modulating TGFbeta signal transduction, as loss of betaarrestin2 increases the phosphorylation of p38 and modestly affects pSmad levels. PMID: 23069267

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Subcellular Location
Cytoplasm. Nucleus. Cell membrane. Membrane, clathrin-coated pit. Cytoplasmic vesicle. Note=Translocates to the plasma membrane and colocalizes with antagonist-stimulated GPCRs.
Protein Families
Arrestin family
Database Links

HGNC: 712

OMIM: 107941

KEGG: hsa:409

STRING: 9606.ENSP00000269260

UniGene: Hs.435811

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