ARRB1_RABIT
ID ARRB1_RABIT Reviewed; 410 AA.
AC Q95223;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Beta-arrestin-1;
DE AltName: Full=Arrestin beta-1;
GN Name=ARRB1;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New Zealand white;
RX PubMed=9301482; DOI=10.1006/exer.1997.0298;
RA Wan X.L., Sears J., Chen S., Sears M.;
RT "Circadian aqueous flow mediated by beta-arrestin induced homologous
RT desensitization.";
RL Exp. Eye Res. 64:1005-1011(1997).
CC -!- FUNCTION: Functions in regulating agonist-mediated G-protein coupled
CC receptor (GPCR) signaling by mediating both receptor desensitization
CC and resensitization processes. During homologous desensitization, beta-
CC arrestins bind to the GPRK-phosphorylated receptor and sterically
CC preclude its coupling to the cognate G-protein; the binding appears to
CC require additional receptor determinants exposed only in the active
CC receptor conformation. The beta-arrestins target many receptors for
CC internalization by acting as endocytic adapters (CLASPs, clathrin-
CC associated sorting proteins) and recruiting the GPRCs to the adapter
CC protein 2 complex 2 (AP-2) in clathrin-coated pits (CCPs). However, the
CC extent of beta-arrestin involvement appears to vary significantly
CC depending on the receptor, agonist and cell type. Internalized
CC arrestin-receptor complexes traffic to intracellular endosomes, where
CC they remain uncoupled from G-proteins. Two different modes of arrestin-
CC mediated internalization occur. Class A receptors, like ADRB2, OPRM1,
CC ENDRA, D1AR and ADRA1B dissociate from beta-arrestin at or near the
CC plasma membrane and undergo rapid recycling. Class B receptors, like
CC AVPR2, AGTR1, NTSR1, TRHR and TACR1 internalize as a complex with
CC arrestin and traffic with it to endosomal vesicles, presumably as
CC desensitized receptors, for extended periods of time. Receptor
CC resensitization then requires that receptor-bound arrestin is removed
CC so that the receptor can be dephosphorylated and returned to the plasma
CC membrane. Involved in internalization of P2RY4 and UTP-stimulated
CC internalization of P2RY2. Involved in phosphorylation-dependent
CC internalization of OPRD1 ands subsequent recycling. Involved in the
CC degradation of cAMP by recruiting cAMP phosphodiesterases to ligand-
CC activated receptors. Beta-arrestins function as multivalent adapter
CC proteins that can switch the GPCR from a G-protein signaling mode that
CC transmits short-lived signals from the plasma membrane via small
CC molecule second messengers and ion channels to a beta-arrestin
CC signaling mode that transmits a distinct set of signals that are
CC initiated as the receptor internalizes and transits the intracellular
CC compartment. Acts as signaling scaffold for MAPK pathways such as
CC MAPK1/3 (ERK1/2). ERK1/2 activated by the beta-arrestin scaffold is
CC largely excluded from the nucleus and confined to cytoplasmic locations
CC such as endocytic vesicles, also called beta-arrestin signalosomes.
CC Recruits c-Src/SRC to ADRB2 resulting in ERK activation. GPCRs for
CC which the beta-arrestin-mediated signaling relies on both ARRB1 and
CC ARRB2 (codependent regulation) include ADRB2, F2RL1 and PTH1R. For some
CC GPCRs the beta-arrestin-mediated signaling relies on either ARRB1 or
CC ARRB2 and is inhibited by the other respective beta-arrestin form
CC (reciprocal regulation). Inhibits ERK1/2 signaling in AGTR1- and AVPR2-
CC mediated activation (reciprocal regulation). Is required for SP-
CC stimulated endocytosis of NK1R and recruits c-Src/SRC to internalized
CC NK1R resulting in ERK1/2 activation, which is required for the
CC antiapoptotic effects of SP. Is involved in proteinase-activated F2RL1-
CC mediated ERK activity. Acts as signaling scaffold for the AKT1 pathway.
CC Is involved in alpha-thrombin-stimulated AKT1 signaling. Is involved in
CC IGF1-stimulated AKT1 signaling leading to increased protection from
CC apoptosis. Involved in activation of the p38 MAPK signaling pathway and
CC in actin bundle formation. Involved in F2RL1-mediated cytoskeletal
CC rearrangement and chemotaxis. Involved in AGTR1-mediated stress fiber
CC formation by acting together with GNAQ to activate RHOA. Appears to
CC function as signaling scaffold involved in regulation of MIP-1-beta-
CC stimulated CCR5-dependent chemotaxis. Involved in attenuation of NF-
CC kappa-B-dependent transcription in response to GPCR or cytokine
CC stimulation by interacting with and stabilizing CHUK. May serve as
CC nuclear messenger for GPCRs. Involved in OPRD1-stimulated
CC transcriptional regulation by translocating to CDKN1B and FOS promoter
CC regions and recruiting EP300 resulting in acetylation of histone H4.
CC Involved in regulation of LEF1 transcriptional activity via interaction
CC with DVL1 and/or DVL2 Also involved in regulation of receptors other
CC than GPCRs. Involved in Toll-like receptor and IL-1 receptor signaling
CC through the interaction with TRAF6 which prevents TRAF6
CC autoubiquitination and oligomerization required for activation of NF-
CC kappa-B and JUN. Involved in IL8-mediated granule release in
CC neutrophils. Binds phosphoinositides. Binds inositolhexakisphosphate
CC (InsP6) (By similarity). Required for atypical chemokine receptor
CC ACKR2-induced RAC1-LIMK1-PAK1-dependent phosphorylation of cofilin
CC (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to
CC cell membrane, increasing its efficiency in chemokine uptake and
CC degradation. Involved in the internalization of the atypical chemokine
CC receptor ACKR3 (By similarity). Negatively regulates the NOTCH
CC signaling pathway by mediating the ubiquitination and degradation of
CC NOTCH1 by ITCH. Participates in the recruitment of the ubiquitin-
CC protein ligase to the receptor (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P49407}.
CC -!- SUBUNIT: Monomer. Homodimer. Homooligomer; the self-association is
CC mediated by InsP6-binding. Heterooligomer with ARRB2; the association
CC is mediated by InsP6-binding. Interacts with ADRB2 (phosphorylated).
CC Interacts with CHRM2 (phosphorylated). Interacts with LHCGR. Interacts
CC with CYTH2 and CASR. Interacts with AP2B1 (dephosphorylated);
CC phosphorylation of AP2B1 disrupts the interaction. Interacts
CC (dephosphorylated at Ser-404) with CLTC. Interacts with CCR2 and GRK2.
CC Interacts with CRR5. Interacts with PTAFR (phosphorylated on serine
CC residues). Interacts with CLTC and MAP2K3. Interacts with CREB1.
CC Interacts with TRAF6. Interacts with IGF1R and MDM2. Interacts with
CC C5AR1. Interacts with PDE4D. Interacts with SRC (via the SH3 domain and
CC the protein kinase domain); the interaction is independent of the
CC phosphorylation state of SRC C-terminus. Interacts with TACR1.
CC Interacts with RAF1. Interacts with CHUK, IKBKB and MAP3K14. Interacts
CC with DVL1; the interaction is enhanced by phosphorylation of DVL1.
CC Interacts with DVL2; the interaction is enhanced by phosphorylation of
CC DVL2. Interacts with IGF1R. Associates with MAP kinase p38. Part of a
CC MAPK signaling complex consisting of TACR1, ARRB1, SRC, MAPK1
CC (activated) and MAPK3 (activated). Part of a MAPK signaling complex
CC consisting of F2RL1, ARRB1, RAF1, MAPK1 (activated) and MAPK3
CC (activated). Interacts with GPR143 (By similarity). Interacts with
CC MAP2K4/MKK4. Interacts with HCK and CXCR1 (phosphorylated) (By
CC similarity). Interacts with ACKR3 and ACKR4 (By similarity). Interacts
CC with ARRDC1; the interaction is direct. Interacts with GPR61, GPR62 and
CC GPR135 (By similarity). {ECO:0000250|UniProtKB:P49407}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Cell membrane {ECO:0000250}. Membrane, clathrin-coated pit
CC {ECO:0000305}. Cell projection, pseudopodium {ECO:0000250}. Cytoplasmic
CC vesicle {ECO:0000250}. Note=Translocates to the plasma membrane and
CC colocalizes with antagonist-stimulated GPCRs. The monomeric form is
CC predominantly located in the nucleus. The oligomeric form is located in
CC the cytoplasm. Translocates to the nucleus upon stimulation of OPRD1
CC (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction
CC the AP-2 complex subunit AP2B1. Binding to phosphorylated GPCRs induces
CC a conformationanl change that exposes the motif to the surface (By
CC similarity). {ECO:0000250}.
CC -!- DOMAIN: The N-terminus binds InsP6 with low affinity. {ECO:0000250}.
CC -!- DOMAIN: The C-terminus binds InsP6 with high affinity. {ECO:0000250}.
CC -!- PTM: Constitutively phosphorylated at in the cytoplasm. At the plasma
CC membrane, is rapidly dephosphorylated, a process that is required for
CC clathrin binding and ADRB2 endocytosis but not for ADRB2 binding and
CC desensitization. Once internalized, is rephosphorylated (By
CC similarity). {ECO:0000250}.
CC -!- PTM: The ubiquitination status appears to regulate the formation and
CC trafficking of beta-arrestin-GPCR complexes and signaling.
CC Ubiquitination appears to occur GPCR-specific. Ubiquitinated by MDM2;
CC the ubiquitination is required for rapid internalization of ADRB2.
CC Deubiquitinated by USP33; the deubiquitination leads to a dissociation
CC of the beta-arrestin-GPCR complex. Stimulation of a class A GPCR, such
CC as ADRB2, induces transient ubiquitination and subsequently promotes
CC association with USP33 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the arrestin family. {ECO:0000305}.
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DR EMBL; U75838; AAC48753.1; -; mRNA.
DR AlphaFoldDB; Q95223; -.
DR SMR; Q95223; -.
DR STRING; 9986.ENSOCUP00000019641; -.
DR BindingDB; Q95223; -.
DR InParanoid; Q95223; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0031143; C:pseudopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0002092; P:positive regulation of receptor internalization; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR Gene3D; 2.60.40.640; -; 1.
DR Gene3D; 2.60.40.840; -; 1.
DR InterPro; IPR000698; Arrestin.
DR InterPro; IPR014752; Arrestin-like_C.
DR InterPro; IPR011021; Arrestin-like_N.
DR InterPro; IPR011022; Arrestin_C-like.
DR InterPro; IPR017864; Arrestin_CS.
DR InterPro; IPR014753; Arrestin_N.
DR InterPro; IPR014756; Ig_E-set.
DR PANTHER; PTHR11792; PTHR11792; 1.
DR Pfam; PF02752; Arrestin_C; 1.
DR Pfam; PF00339; Arrestin_N; 1.
DR PRINTS; PR00309; ARRESTIN.
DR SMART; SM01017; Arrestin_C; 1.
DR SUPFAM; SSF81296; SSF81296; 2.
DR PROSITE; PS00295; ARRESTINS; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cell projection; Coated pit; Cytoplasm; Cytoplasmic vesicle;
KW Membrane; Nucleus; Phosphoprotein; Protein transport; Reference proteome;
KW Signal transduction inhibitor; Transcription; Transcription regulation;
KW Transport; Ubl conjugation.
FT CHAIN 1..410
FT /note="Beta-arrestin-1"
FT /id="PRO_0000205196"
FT REGION 1..163
FT /note="Interaction with SRC"
FT /evidence="ECO:0000250"
FT REGION 45..86
FT /note="Interaction with CHRM2"
FT /evidence="ECO:0000250"
FT REGION 318..410
FT /note="Interaction with TRAF6"
FT /evidence="ECO:0000250"
FT REGION 345..367
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 389..410
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 345..361
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 250
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250"
FT BINDING 255
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250"
FT BINDING 324
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250"
FT BINDING 326
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250"
FT MOD_RES 47
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWG8"
FT MOD_RES 404
FT /note="Phosphoserine; by GRK5"
FT /evidence="ECO:0000250|UniProtKB:P49407"
SQ SEQUENCE 410 AA; 46360 MW; A8AB781CF089B65A CRC64;
MGDKGTRVFK KASPNGKLTV YLGKRGFVDH IDLVDPVDGV VLVDPEYLKE RRVYVTLTCA
FRYGREDLDV LGLTFRKDLF VANVQSFPPA PEDKKPLTRL QERLIKKLGE HAYPFTFEIP
PKLPCSVTLQ PGPEDTGKAC GVDYEVKAFC AENLEEKIHK RNSVRLVIRK VQYAPERPGP
HPTAETTRLF LMSDKPLHLE ASLDKEIYYH GEPIIVNVHV TNNTNKTVKK IKISVRQYAD
ICLFNTAQYK CPVAMEEADD TVAPSSTFCK VYTLTPFLAN NREKRGLALD GKLKHEDTNL
ASSTLMREGA NREILGIIVS YKVKVKLVVS RGGDVAVELP FTLMHPKPKE EPPHREVPEN
ETPVDTNLIE LDTNDDDIVF EDFARQRLKG MKDDKEEEDD VTGSPRLNDR
