Affinage

SAG

S-arrestin · UniProt P10523

Round 2 corrected
Length
405 aa
Mass
45.1 kDa
Annotated
2026-04-28
130 papers in source corpus 15 papers cited in narrative 15 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SAG (S-arrestin/arrestin-1) is the principal terminator of rod phototransduction, binding light-activated, rhodopsin kinase–phosphorylated rhodopsin to sterically block transducin coupling and shield the receptor from PP2A-mediated dephosphorylation (PMID:3040978, PMID:2550422). Phosphorylated rhodopsin's C-tail disrupts arrestin's buried polar core (Arg175–Asp30–Asp296–Asp303–Arg382), releasing the autoinhibitory C-tail and triggering an ~21° inter-domain rotation that extends the finger loop and loop-139 into the receptor cavity while C-edge loops anchor to the membrane (PMID:10206946, PMID:23604253, PMID:28220785, PMID:33159335). Arrestin binding slows retinal chromophore release from rhodopsin, coupling arrestin dissociation to all-trans-retinal reduction and visual-cycle recycling (PMID:1386362, PMID:15591052). In vivo, SAG is essential for cone photoreceptor survival and light adaptation, and enhanced-binding arrestin-1 mutants can partially rescue rhodopsin kinase deficiency (PMID:20019357, PMID:19361994).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1987 High

    Established that rhodopsin shut-off requires two sequential steps — phosphorylation by rhodopsin kinase followed by SAG binding — resolving how transducin activation is quenched after photon absorption.

    Evidence Biochemical reconstitution measuring transducin-stimulated PDE activity in rod outer segments with purified components

    PMID:3040978

    Open questions at the time
    • Stoichiometry of phosphorylation sites required for arrestin binding was undefined
    • Mechanism of arrestin selectivity for phosphorylated vs. unphosphorylated receptor was unknown
  2. 1989 High

    Revealed a second regulatory function of arrestin — shielding phosphorhodopsin from PP2A-mediated dephosphorylation — explaining how the deactivated state is maintained until the receptor is recycled.

    Evidence In vitro phosphatase assays with purified rod outer segment extracts and substrate specificity controls

    PMID:2550422

    Open questions at the time
    • Identity of the in vivo opsin phosphatase was not settled
    • Whether arrestin shielding is relieved by retinal release was untested
  3. 1992 High

    Linked arrestin dissociation from rhodopsin to all-trans-retinal reduction, establishing that visual-cycle chromophore recycling cannot proceed while arrestin remains bound.

    Evidence Spectrophotometric analysis of rhodopsin photoproducts and arrestin binding to M380 pseudo-photoproduct

    PMID:1386362

    Open questions at the time
    • Kinetic coupling between retinal reduction and arrestin release was not quantified at physiological temperature
    • Enzyme identity for retinal reduction in situ was not addressed
  4. 1999 High

    Identified the polar core (Arg175, Asp30, Asp296, Asp303, Arg382) as the phosphosensor whose disruption switches arrestin from the basal to the receptor-binding conformation, answering how arrestin discriminates phosphorylated from unphosphorylated receptor.

    Evidence Site-directed and second-site suppressor mutagenesis with in vitro rhodopsin binding assays, interpreted alongside the crystal structure

    PMID:10206946

    Open questions at the time
    • Full structural view of the activated state was lacking
    • Which phosphorylation sites on rhodopsin contact the polar core was unresolved
  5. 1999 Medium

    Mapped the primary rhodopsin-contact surface of arrestin to residues 90–140, narrowing the receptor-binding interface and highlighting the finger-loop region.

    Evidence Phage display, synthetic peptide competition of arrestin binding, and GST-fusion pulldowns

    PMID:10052946

    Open questions at the time
    • Peptide-based mapping cannot capture conformational contributions
    • Residue-level resolution within the 90–140 segment was not achieved
  6. 2004 High

    Quantified that arrestin slows retinal release ~2-fold and that arrestin and retinal dissociation share similar activation energies, mechanistically coupling receptor desensitization to chromophore recycling kinetics.

    Evidence Fluorescence spectroscopy with monobromobimane-labeled arrestin mutants; kinetic and thermodynamic analysis

    PMID:15591052

    Open questions at the time
    • Whether the coupling is direct or mediated by conformational intermediates was unresolved
    • In vivo relevance of the ~2-fold slowing was not tested
  7. 2009 High

    Demonstrated in vivo that SAG is essential for cone survival and light adaptation, and that enhanced-binding arrestin-1 mutants can partly rescue rhodopsin kinase deficiency, establishing the physiological sufficiency of arrestin for single-step receptor shut-off.

    Evidence Arrestin-1 and arrestin-4 knockout mice; transgenic rescue; ERG light-adaptation and flicker protocols; photoreceptor morphometry

    PMID:19361994 PMID:20019357

    Open questions at the time
    • Mechanism by which SAG promotes cone survival independent of rod desensitization was unclear
    • Whether enhanced mutants cause long-term toxicity in vivo was not assessed
  8. 2012 High

    DEER/EPR distance measurements on receptor-bound arrestin-1 showed that the finger loop and loop-139 move toward the receptor upon binding but the inter-domain arrangement is more subtle than a simple clam-shell opening, revising the structural model of arrestin activation.

    Evidence Double electron-electron resonance (DEER) EPR with multiple spin-label pairs on arrestin-1 free and bound to P-Rh*

    PMID:23091036

    Open questions at the time
    • Full atomic-resolution model of the rhodopsin–arrestin complex was still missing
    • Contribution of membrane lipids to the bound-state conformation was not addressed
  9. 2013 High

    Crystal structure of the pre-activated arrestin-1 (p44 splice variant) at 3.0 Å revealed the ~21° inter-domain rotation, polar-core breakage, and central-crest loop rearrangements triggered by C-tail displacement, providing the first high-resolution view of the activated arrestin conformation.

    Evidence X-ray crystallography of arrestin-1 p44; site-directed fluorescence spectroscopy validation

    PMID:23604253

    Open questions at the time
    • Structure was of a C-tail-truncated variant, not of the full-length receptor-bound complex
    • Dynamics of the transition from basal to activated state were not captured
  10. 2016 High

    Comprehensive scanning mutagenesis showed that arrestin-1 engages phosphorylated agonist-bound (Meta II-P) and phosphorylated apo-receptor (Ops-P) rhodopsin through structurally distinct binding modes, with different contributions of phosphosensors, inter-domain interface, and C-edge loops.

    Evidence Systematic mutagenesis of all arrestin residues; quantitative in vitro binding to Meta II-P vs. Ops-P

    PMID:27350090

    Open questions at the time
    • Structural basis of the distinct binding modes at atomic resolution was not available
    • Physiological significance of the Ops-P complex in dark adaptation was unclear
  11. 2017 High

    Identified C-edge loops as a phosphorylation-dependent membrane anchor that adopts different orientations in the pre-complex versus the high-affinity complex, adding a lipid-engagement step to the arrestin activation model.

    Evidence Molecular dynamics simulations validated by site-directed fluorescence spectroscopy of arrestin-1 on rhodopsin-containing membranes

    PMID:28220785

    Open questions at the time
    • Lipid specificity of C-edge engagement was not defined
    • Whether C-edge membrane anchoring is required in vivo was untested
  12. 2020 High

    Comprehensive finger-loop mutagenesis established this element as the primary activation sensor of arrestin-1, with six residues selectively required for binding only to the light-activated receptor form, separating the activation-sensing and phosphosensing functions of arrestin.

    Evidence Site-directed mutagenesis of all finger-loop residues; binding assays to four distinct rhodopsin functional forms in WT and C-tail-truncated backgrounds

    PMID:33159335

    Open questions at the time
    • Whether these residues insert into the receptor transmembrane core was structurally unconfirmed for visual arrestin
    • Energetic contribution of individual finger-loop contacts was not measured
  13. 2021 High

    Crystal structures of arrestin-1 with inositol phosphates showed that InsPs displace the C-tail by binding the N-domain basic patch but leave the polar core intact, defining a priming mechanism distinct from full activation and potentially regulating arrestin translocation in photoreceptors.

    Evidence X-ray crystallography of bovine Arr1 ligand-free (with near-complete C-tail) and InsP-bound states

    PMID:34678158

    Open questions at the time
    • In vivo role of InsP-mediated priming in arrestin translocation is undemonstrated
    • Whether InsP priming synergizes with partial receptor phosphorylation was untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of full-length mammalian arrestin-1 bound to native phosphorylated rhodopsin in a lipid bilayer, capturing the complete binding interface including C-edge membrane contacts, remains to be determined.
  • No cryo-EM or crystal structure of the full-length mammalian Arr1–P-Rh* complex in a membrane environment
  • Kinetic pathway of arrestin activation (order of polar-core disruption, C-tail release, finger-loop insertion, membrane anchoring) is not resolved in real time
  • In vivo role of InsP-mediated priming in photoreceptor arrestin translocation lacks direct evidence

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 3
Localization
GO:0005829 cytosol 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-9709957 Sensory Perception 4
Partners
GRK1PPP2CARHOSAG
Complex memberships
Rhodopsin–arrestin-1 complex

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 Photoactivated rhodopsin is deactivated by a two-step mechanism: first, rhodopsin kinase phosphorylates light-activated rhodopsin at multiple sites, partially suppressing its ability to activate transducin; second, the 48 kDa S-antigen (arrestin/SAG) binds specifically to the phosphorylated, light-activated rhodopsin and potentiates the inhibitory effect, most likely by competing with transducin for binding to phosphorylated rhodopsin. Biochemical reconstitution assay measuring transducin-mediated phosphodiesterase activation in rod outer segment preparations; competitive binding experiments Journal of receptor research High 3040978
1989 Arrestin (SAG) specifically inhibits the dephosphorylation of freshly photolyzed (light-activated) phosphorhodopsin by protein phosphatase 2A (PP2A), but does not inhibit dephosphorylation of unbleached rhodopsin nor dephosphorylation of phosphorylase a, indicating substrate-directed protection. This reveals a novel regulatory mechanism by which arrestin binding prevents PP2A access to phosphorhodopsin. In vitro phosphatase activity assay with purified rod outer segment extracts, okadaic acid inhibition, DEAE-Sepharose chromatography co-elution of opsin phosphatase with PP2A The Journal of biological chemistry High 2550422
1992 Reduction of the photolyzed chromophore all-trans-retinal to all-trans-retinol is essential for recycling of photoactivated rhodopsin: once reduction occurs, arrestin dissociates from the receptor and the chromophore site becomes accessible for regeneration. When reduction does not occur, free all-trans-retinal can form a Meta II-like pseudo-photoproduct (M380) that binds arrestin tightly and blocks rhodopsin regeneration. Spectrophotometric analysis of rhodopsin photoproducts; binding assays of arrestin and rhodopsin kinase to M380 vs native metarhodopsin species; biochemical manipulation of retinal reduction in rod outer segment preparations The Journal of biological chemistry High 1386362
1999 The transition of arrestin from its inactive (basal) conformation to the high-affinity receptor-binding state is triggered by the phosphorylated C-terminal tail of rhodopsin disrupting a hydrogen-bonded network of buried charged residues called the 'polar core' (involving Arg175, Asp30, Asp296, Asp303, Arg382). Mutations that disrupt polar core interactions (e.g., R175E, D296R) bypass the requirement for receptor phosphorylation, enabling arrestin to bind activated, unphosphorylated rhodopsin. Site-directed mutagenesis of arrestin residues; in vitro binding assays to light-activated phosphorylated and unphosphorylated rhodopsin; second-site suppressor mutagenesis restoring critical interactions; interpreted in conjunction with crystal structure The Journal of biological chemistry High 10206946
1999 The principal region of arrestin that mediates binding to photoactivated phosphorhodopsin is contained within residues 90–140, with the minimal inhibitory peptide mapping to residues 109–130 (IC50 ~1.1 mM). A GST fusion of residues 95–140 binds rhodopsin regardless of activation or phosphorylation state, indicating this is a primary contact region. Phage display of arrestin fragments panned against phosphorylated rhodopsin; synthetic peptide competition assay measuring inhibition of arrestin binding and cGMP phosphodiesterase activation; GST fusion protein pulldown Biochemistry Medium 10052946
2000 Peptide competition assays identified two regions of arrestin (residues 11–30 and 51–70 in the N-terminal domain; residues 231–260 in the C-terminal domain) that interact with metarhodopsin II (MII), with arrestin peptide 11–30 showing selectivity for phosphorylated MII over the transducin-stabilized form. Both the N- and C-terminal domains of arrestin contact rhodopsin, and these sites overlap with transducin-binding surfaces. Spectrophotometric extra-MII stabilization assay; synthetic peptide competition of arrestin- and transducin-dependent MII stabilization using native disc membranes The Journal of biological chemistry Medium 10969086
2004 Arrestin release from rhodopsin and retinal (chromophore) release are directly linked events with similar activation energies. Arrestin slows the rate of retinal release approximately 2-fold at physiological temperatures and abolishes the pH dependence of retinal release. Fluorescence labeling at I72C and S251C reveals these sites are buried at the rhodopsin-arrestin or phospholipid-arrestin interface upon binding. Evidence also indicates arrestin can bind a post-Meta II photodecay product (possibly Meta III). Fluorescence spectroscopy using monobromobimane-labeled arrestin mutants; kinetic analysis of arrestin and retinal release; EPR and biochemical approaches The Journal of biological chemistry High 15591052
2009 Arrestin-1 mutants with enhanced ability to bind active, unphosphorylated rhodopsin (bypassing the need for rhodopsin kinase phosphorylation) partially compensate for defects in rhodopsin phosphorylation in rod photoreceptors in vivo, promoting photoreceptor survival, improving functional ERG responses, and facilitating photoresponse recovery in rhodopsin kinase-deficient mice. Transgenic mouse model expressing enhanced arrestin-1 mutant in rhodopsin kinase (RK)-deficient rods; electroretinography; photoreceptor cell counting; functional photoresponse recovery measurements Current biology : CB High 19361994
2009 Arrestin-1 (SAG) is essential for cone photoreceptor survival and light adaptation. In Arr1-knockout mice reared in darkness, viable cone density diminishes over time, and cone ERG b-wave amplitudes fail to increase during light adaptation (3–15 min background illumination), a defect rescued by restoration of Arr1 expression. Either Arr1 or Arr4 is sufficient to maintain normal cone flicker responses. Arrestin-1 and arrestin-4 knockout mice; quantitative retinal morphology; TUNEL apoptosis assay; immunohistochemistry; electroretinography (ERG) light adaptation and flicker protocols; transgenic rescue Investigative ophthalmology & visual science High 20019357
2012 Upon binding to light-activated phosphorylated rhodopsin (P-Rh*), the 'finger loop' (residues 67–79) of arrestin-1 moves toward the expected location of P-Rh*, but does not adopt a fully extended conformation. A striking movement of the loop containing residue 139 away from the adjacent finger loop facilitates receptor binding. The relative position of the N and C domains remains largely unchanged (contra the 'clam-shell' model). Loops at residues 139, 157, and 344 show high flexibility in both free and receptor-bound arrestin-1. Double electron-electron resonance (DEER) EPR spectroscopy with spin-labeled arrestin-1 pairs; distance measurements in free vs. P-Rh*-bound arrestin-1 Proceedings of the National Academy of Sciences of the United States of America High 23091036
2013 The crystal structure of bovine arrestin-1 splice variant p44 (C-tail truncation mimicking activation) at 3.0 Å reveals the pre-activated arrestin conformation: breakage of the polar core and other interlobe hydrogen-bond networks leads to ~21° rotation of the two lobes. Key receptor-binding loops in the central crest region (finger loop, loop 139, gate loop Asp296–Asn305) rearrange from restricted to extended conformations. C-tail displacement releases these loops and enables receptor binding, confirmed by site-directed fluorescence spectroscopy. X-ray crystallography at 3.0 Å; site-directed fluorescence spectroscopy validating conformational changes; comparison with basal arrestin-1 structure Nature High 23604253
2016 Scanning mutagenesis of all arrestin-1 residues reveals that binding to phosphorylated agonist-bound rhodopsin (Meta II-P) and phosphorylated apo-receptor (Ops-P) both require arrestin activation (polar core disruption or C-tail displacement), but the two complexes are structurally distinct: phosphate-binding residues (phosphosensors), inter-domain interface residues, receptor-binding loops, and C-edge residues contribute differently to the two receptor forms, indicating different binding modes. Unbiased scanning mutagenesis of all arrestin residues; in vitro binding assays to Meta II-P and Ops-P; quantitative comparison of mutant effects across both receptor forms Scientific reports High 27350090
2017 Molecular dynamics simulations and site-directed fluorescence spectroscopy demonstrate that C-edge loops of arrestin-1 function as a membrane anchor during rhodopsin interaction. Activation of arrestin by receptor-attached phosphates is necessary for C-edge engagement of the membrane. The C-edge conformation and orientation differ between the pre-complex (arrestin interacting with phosphorylated receptor C-terminus only) and the high-affinity complex. Molecular dynamics simulations; site-directed fluorescence spectroscopy experiments on arrestin-1 interactions with rhodopsin in membranes Nature communications High 28220785
2020 Comprehensive mutagenesis of the finger loop in bovine visual arrestin-1 demonstrates that the finger loop is the key element of the activation sensor: the majority of finger loop residues are important for binding to light-activated rhodopsin, with six mutations affecting binding exclusively to the light-activated form (not phosphorylated dark rhodopsin or unphosphorylated active rhodopsin). This establishes the finger loop as the structural element that detects the active conformation of the receptor. Comprehensive site-directed mutagenesis of finger loop residues in arrestin-1; cell-free translation of radiolabeled mutant proteins; in vitro binding assays to multiple rhodopsin functional forms (P-Rh*, Rh*, P-Rh, Rh); tested in both WT and C-terminally truncated arrestin-1 backgrounds Journal of neurochemistry High 33159335
2021 Inositol phosphates (InsPs) bind to the N-domain basic patch of visual arrestin-1 (Arr1), displacing the C-tail, suggesting they prime Arr1 for rhodopsin interaction and may direct Arr1 translocation from inner to outer photoreceptor segments. Crystal structures show that C-tail removal by InsP binding leaves the polar core intact, indicating InsP binding is insufficient to fully activate Arr1 but acts as a priming step. X-ray crystallography of bovine Arr1 in ligand-free state (near-complete C-tail model) and InsP-bound states; structural comparison Structure (London, England : 1993) High 34678158

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
1990 beta-Arrestin: a protein that regulates beta-adrenergic receptor function. Science (New York, N.Y.) 1024 2163110
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2011 β-Arrestin-mediated receptor trafficking and signal transduction. Trends in pharmacological sciences 587 21680031
1992 Beta-arrestin2, a novel member of the arrestin/beta-arrestin gene family. The Journal of biological chemistry 433 1517224
1997 DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3-26.1 is deleted in malignant brain tumours. Nature genetics 402 9288095
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2018 Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis. Theranostics 309 29556344
2010 Beyond desensitization: physiological relevance of arrestin-dependent signaling. Pharmacological reviews 300 20427692
2004 The molecular acrobatics of arrestin activation. Trends in pharmacological sciences 276 15102497
2009 Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). Journal of proteome research 237 19199708
2008 Beta-blockers alprenolol and carvedilol stimulate beta-arrestin-mediated EGFR transactivation. Proceedings of the National Academy of Sciences of the United States of America 233 18787115
2007 beta-arrestin-biased agonism at the beta2-adrenergic receptor. The Journal of biological chemistry 219 18086673
2007 Beta-arrestin signaling and regulation of transcription. Journal of cell science 214 17215450
2008 On the origins of arrestin and rhodopsin. BMC evolutionary biology 194 18664266
1995 Chromosome 10 deletion mapping in human gliomas: a common deletion region in 10q25. Oncogene 191 7784070
2000 Salivary agglutinin, which binds Streptococcus mutans and Helicobacter pylori, is the lung scavenger receptor cysteine-rich protein gp-340. The Journal of biological chemistry 180 11007786
1999 Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D. Proceedings of the National Academy of Sciences of the United States of America 177 10485905
1997 Isolation and characterization of a new member of the scavenger receptor superfamily, glycoprotein-340 (gp-340), as a lung surfactant protein-D binding molecule. The Journal of biological chemistry 177 9153228
2013 The protein interaction landscape of the human CMGC kinase group. Cell reports 174 23602568
2006 Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry. Journal of proteome research 173 16740002
2018 Molecular mechanism of GPCR-mediated arrestin activation. Nature 167 29720655
2018 Catalytic activation of β-arrestin by GPCRs. Nature 167 29720660
2005 Seven-transmembrane receptor signaling through beta-arrestin. Science's STKE : signal transduction knowledge environment 153 16267056
1999 How does arrestin respond to the phosphorylated state of rhodopsin? The Journal of biological chemistry 153 10206946
2003 Comprehensive proteomic analysis of human Par protein complexes reveals an interconnected protein network. The Journal of biological chemistry 152 14676191
2008 How does arrestin assemble MAPKs into a signaling complex? The Journal of biological chemistry 144 19001375
2004 Differential beta-arrestin trafficking and endosomal sorting of somatostatin receptor subtypes. The Journal of biological chemistry 143 15001578
2005 A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease. American journal of human genetics 137 16385451
1993 Polypeptide variants of beta-arrestin and arrestin3. The Journal of biological chemistry 137 8340388
2007 Regulation of DMBT1 via NOD2 and TLR4 in intestinal epithelial cells modulates bacterial recognition and invasion. Journal of immunology (Baltimore, Md. : 1950) 135 17548659
1994 Cone arrestin identified by targeting expression of a functional family. The Journal of biological chemistry 135 8308033
2013 Crystal structure of pre-activated arrestin p44. Nature 134 23604253
2016 Functional competence of a partially engaged GPCR-β-arrestin complex. Nature communications 131 27827372
2010 Review: Gp-340/DMBT1 in mucosal innate immunity. Innate immunity 130 20418254
1992 The role of arrestin and retinoids in the regeneration pathway of rhodopsin. The Journal of biological chemistry 130 1386362
2002 Identification of the bacteria-binding peptide domain on salivary agglutinin (gp-340/DMBT1), a member of the scavenger receptor cysteine-rich superfamily. The Journal of biological chemistry 127 12050164
2020 How GPCR Phosphorylation Patterns Orchestrate Arrestin-Mediated Signaling. Cell 126 33296703
1989 Regulation of rhodopsin dephosphorylation by arrestin. The Journal of biological chemistry 120 2550422
2015 Emerging Functional Divergence of β-Arrestin Isoforms in GPCR Function. Trends in endocrinology and metabolism: TEM 116 26471844
2005 Arrestin times for compartmentalised cAMP signalling and phosphodiesterase-4 enzymes. Current opinion in cell biology 109 15780588
2011 A novel role for interleukin-27 (IL-27) as mediator of intestinal epithelial barrier protection mediated via differential signal transducer and activator of transcription (STAT) protein signaling and induction of antibacterial and anti-inflammatory proteins. The Journal of biological chemistry 108 22069308
1999 Regulation of muscarinic acetylcholine receptor sequestration and function by beta-arrestin. The Journal of biological chemistry 107 10212203
2004 Bacteria binding by DMBT1/SAG/gp-340 is confined to the VEVLXXXXW motif in its scavenger receptor cysteine-rich domains. The Journal of biological chemistry 106 15355985
2017 Structural basis of arrestin-3 activation and signaling. Nature communications 105 29127291
2005 The StcE protease contributes to intimate adherence of enterohemorrhagic Escherichia coli O157:H7 to host cells. Infection and immunity 103 15731026
1993 X-arrestin: a new retinal arrestin mapping to the X chromosome. FEBS letters 100 8224247
2017 Mammalian APE1 controls miRNA processing and its interactome is linked to cancer RNA metabolism. Nature communications 99 28986522
1987 Deactivation of photoactivated rhodopsin by rhodopsin-kinase and arrestin. Journal of receptor research 97 3040978
2001 Beta-arrestin- and dynamin-dependent endocytosis of the AT1 angiotensin receptor. Molecular pharmacology 95 11160859
1999 Lack of DMBT1 expression in oesophageal, gastric and colon cancers. British journal of cancer 95 9888459
1999 Glycoprotein-340 binds surfactant protein-A (SP-A) and stimulates alveolar macrophage migration in an SP-A-independent manner. American journal of respiratory cell and molecular biology 94 10101009
2007 Salivary agglutinin/glycoprotein-340/DMBT1: a single molecule with variable composition and with different functions in infection, inflammation and cancer. Biological chemistry 93 18020944
2017 CHD3 and CHD4 form distinct NuRD complexes with different yet overlapping functionality. Nucleic acids research 91 28977666
2007 DMBT1 confers mucosal protection in vivo and a deletion variant is associated with Crohn's disease. Gastroenterology 91 17983803
2010 Morphine-like opiates selectively antagonize receptor-arrestin interactions. The Journal of biological chemistry 90 20189994
2003 The new face of active receptor bound arrestin attracts new partners. Structure (London, England : 1993) 88 12962621
2018 Molecular mechanism of modulating arrestin conformation by GPCR phosphorylation. Nature structural & molecular biology 87 29872229
2017 C-edge loops of arrestin function as a membrane anchor. Nature communications 84 28220785
2012 Conformation of receptor-bound visual arrestin. Proceedings of the National Academy of Sciences of the United States of America 84 23091036
2014 Inactivation of SAG/RBX2 E3 ubiquitin ligase suppresses KrasG12D-driven lung tumorigenesis. The Journal of clinical investigation 81 24430184
2012 Functional characterization of SAG/RBX2/ROC2/RNF7, an antioxidant protein and an E3 ubiquitin ligase. Protein & cell 80 23136067
2008 Beta-arrestin-mediated signaling regulates protein synthesis. The Journal of biological chemistry 80 18276584
2004 Alternative, nonapoptotic programmed cell death: mediation by arrestin 2, ERK2, and Nur77. The Journal of biological chemistry 78 14769794
2001 Agonist-induced internalization of the metabotropic glutamate receptor 1a is arrestin- and dynamin-dependent. Journal of neurochemistry 76 11483657
2018 Structural Basis of Arrestin-Dependent Signal Transduction. Trends in biochemical sciences 68 29636212
2009 Enhanced arrestin facilitates recovery and protects rods lacking rhodopsin phosphorylation. Current biology : CB 67 19361994
2004 Dynamics of arrestin-rhodopsin interactions: arrestin and retinal release are directly linked events. The Journal of biological chemistry 67 15591052
2000 Interactions of metarhodopsin II. Arrestin peptides compete with arrestin and transducin. The Journal of biological chemistry 67 10969086
2023 Plasma membrane preassociation drives β-arrestin coupling to receptors and activation. Cell 62 37146613
2021 Receptor-Arrestin Interactions: The GPCR Perspective. Biomolecules 61 33557162
2017 Understanding the GPCR biased signaling through G protein and arrestin complex structures. Current opinion in structural biology 60 28558341
2014 Arrestin interactions with G protein-coupled receptors. Handbook of experimental pharmacology 60 24292823
2000 Arrestin isoforms dictate differential kinetics of A2B adenosine receptor trafficking. Biochemistry 58 11041847
2017 Structural mechanism of arrestin activation. Current opinion in structural biology 56 28600951
2018 Arrestin recruitment to dopamine D2 receptor mediates locomotion but not incentive motivation. Molecular psychiatry 54 30120413
2013 Structural determinants of arrestin functions. Progress in molecular biology and translational science 54 23764050
2002 Regulation of arrestin-3 phosphorylation by casein kinase II. The Journal of biological chemistry 52 11877451
2009 Diversity in arrestin function. Cellular and molecular life sciences : CMLS 51 19597700
2023 Tail engagement of arrestin at the glucagon receptor. Nature 48 37558880
2023 Signal transduction at GPCRs: Allosteric activation of the ERK MAPK by β-arrestin. Proceedings of the National Academy of Sciences of the United States of America 45 37844230
2019 Arrestin-β-1 Physically Scaffolds TSH and IGF1 Receptors to Enable Crosstalk. Endocrinology 45 31127272
1993 Beta-arrestin and arrestin are recognized by autoantibodies in sera from multiple sclerosis patients. Proceedings of the National Academy of Sciences of the United States of America 45 8475065
2020 SnapShot: β-Arrestin Functions. Cell 44 32888497
2017 FPR2 signaling without β-arrestin recruitment alters the functional repertoire of neutrophils. Biochemical pharmacology 44 28855087
2020 Allosteric interactions in the parathyroid hormone GPCR-arrestin complex formation. Nature chemical biology 43 32632293
2014 Overview of different mechanisms of arrestin-mediated signaling. Current protocols in pharmacology 43 25446289
2013 True arrestins and arrestin-fold proteins: a structure-based appraisal. Progress in molecular biology and translational science 42 23764049
2019 Therapeutic Potential of Targeting ß-Arrestin. Frontiers in pharmacology 40 30894814
2014 Role for β-arrestin in mediating paradoxical β2AR and PAR2 signaling in asthma. Current opinion in pharmacology 40 24907413
1992 Cloning and expression of SAG: a novel marker of cellular senescence. Experimental cell research 39 1544376
2013 Progastrin stimulates colonic cell proliferation via CCK2R- and β-arrestin-dependent suppression of BMP2. Gastroenterology 38 23891976
2005 Beta-arrestin goes nuclear. Cell 38 16325568
2020 Exploring GPCR-arrestin interfaces with genetically encoded crosslinkers. EMBO reports 36 32929862
2010 Transduced Tat-SAG fusion protein protects against oxidative stress and brain ischemic insult. Free radical biology & medicine 36 20100567
2017 β-arrestin signalling and bias in hormone-responsive GPCRs. Molecular and cellular endocrinology 35 28174117
2019 The structural basis of the arrestin binding to GPCRs. Molecular and cellular endocrinology 34 30703488
2016 β-Arrestin-2 Counters CXCR7-Mediated EGFR Transactivation and Proliferation. Molecular cancer research : MCR 34 26921391
2021 Differential Involvement of ACKR3 C-Tail in β-Arrestin Recruitment, Trafficking and Internalization. Cells 32 33799570
2019 β-Arrestin-2 BRET Biosensors Detect Different β-Arrestin-2 Conformations in Interaction with GPCRs. ACS sensors 31 31849219
2014 Ubiquitination by SAG regulates macrophage survival/death and immune response during infection. Cell death and differentiation 31 24786833
2014 Differential regulation of endosomal GPCR/β-arrestin complexes and trafficking by MAPK. The Journal of biological chemistry 31 25016018
2012 Arrestin scaffolds NHERF1 to the P2Y12 receptor to regulate receptor internalization. The Journal of biological chemistry 31 22610101
2016 SAG/Rbx2-Dependent Neddylation Regulates T-Cell Responses. The American journal of pathology 29 27543965
2009 Visual Arrestin 1 contributes to cone photoreceptor survival and light adaptation. Investigative ophthalmology & visual science 29 20019357
2007 Rod1, an arrestin-related protein, is phosphorylated by Snf1-kinase in Saccharomyces cerevisiae. Biochemical and biophysical research communications 29 17949685
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