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P49407

- ARRB1_HUMAN

UniProt

P49407 - ARRB1_HUMAN

Protein

Beta-arrestin-1

Gene

ARRB1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 138 (01 Oct 2014)
      Sequence version 2 (05 Mar 2002)
      Previous versions | rss
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    Functioni

    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. Involved in internalization of P2RY4 and UTP-stimulated internalization of P2RY2. Involved in phosphorylation-dependent internalization of OPRD1 ands subsequent recycling. Involved in the degradation of cAMP by recruiting cAMP phosphodiesterases to ligand-activated receptors. 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). ERK1/2 activated by the beta-arrestin scaffold is largely excluded from the nucleus and confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Recruits c-Src/SRC to ADRB2 resulting in ERK activation. 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). Inhibits ERK1/2 signaling in AGTR1- and AVPR2-mediated activation (reciprocal regulation). Is required for SP-stimulated endocytosis of NK1R and recruits c-Src/SRC to internalized NK1R resulting in ERK1/2 activation, which is required for the antiapoptotic effects of SP. Is involved in proteinase-activated F2RL1-mediated ERK activity. Acts as signaling scaffold for the AKT1 pathway. Is involved in alpha-thrombin-stimulated AKT1 signaling. Is involved in IGF1-stimulated AKT1 signaling leading to increased protection from apoptosis. Involved in activation of the p38 MAPK signaling pathway and in actin bundle formation. Involved in F2RL1-mediated cytoskeletal rearrangement and chemotaxis. Involved in AGTR1-mediated stress fiber formation by acting together with GNAQ to activate RHOA. 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. May serve as nuclear messenger for GPCRs. Involved in OPRD1-stimulated transcriptional regulation by translocating to CDKN1B and FOS promoter regions and recruiting EP300 resulting in acetylation of histone H4. Involved in regulation of LEF1 transcriptional activity via interaction with DVL1 and/or DVL2 Also involved in regulation of receptors other than GPCRs. 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. Binds phosphoinositides. Binds inositolhexakisphosphate (InsP6) By similarity. Involved in IL8-mediated granule release in neutrophils. Required for atypical chemokine receptor ACKR2-induced RAC1-LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. Involved in the internalization of the atypical chemokine receptor ACKR3.By similarity18 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei250 – 2501Inositol hexakisphosphateBy similarity
    Binding sitei255 – 2551Inositol hexakisphosphateBy similarity
    Binding sitei324 – 3241Inositol hexakisphosphateBy similarity
    Binding sitei326 – 3261Inositol hexakisphosphateBy similarity

    GO - Molecular functioni

    1. angiotensin receptor binding Source: UniProtKB
    2. cysteine-type endopeptidase inhibitor activity involved in apoptotic process Source: Ensembl
    3. enzyme inhibitor activity Source: ProtInc
    4. GTPase activator activity Source: UniProtKB
    5. insulin-like growth factor receptor binding Source: UniProtKB
    6. protein binding Source: UniProtKB
    7. transcription factor binding Source: UniProtKB
    8. transcription regulatory region DNA binding Source: BHF-UCL
    9. ubiquitin protein ligase binding Source: UniProtKB

    GO - Biological processi

    1. activation of MAPK activity Source: Ensembl
    2. apoptotic DNA fragmentation Source: Ensembl
    3. blood coagulation Source: Reactome
    4. follicle-stimulating hormone signaling pathway Source: Ensembl
    5. G-protein coupled receptor internalization Source: UniProtKB
    6. membrane organization Source: Reactome
    7. negative regulation of apoptotic process Source: Ensembl
    8. negative regulation of ERK1 and ERK2 cascade Source: Ensembl
    9. negative regulation of GTPase activity Source: Ensembl
    10. negative regulation of interleukin-6 production Source: UniProtKB
    11. negative regulation of interleukin-8 production Source: UniProtKB
    12. negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
    13. negative regulation of protein phosphorylation Source: Ensembl
    14. negative regulation of protein ubiquitination Source: UniProtKB
    15. Notch signaling pathway Source: Reactome
    16. phototransduction Source: Ensembl
    17. platelet activation Source: Reactome
    18. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
    19. positive regulation of GTPase activity Source: GOC
    20. positive regulation of histone acetylation Source: BHF-UCL
    21. positive regulation of histone H4 acetylation Source: UniProtKB
    22. positive regulation of insulin secretion involved in cellular response to glucose stimulus Source: Ensembl
    23. positive regulation of peptidyl-serine phosphorylation Source: Ensembl
    24. positive regulation of protein binding Source: Ensembl
    25. positive regulation of protein phosphorylation Source: UniProtKB
    26. positive regulation of protein ubiquitination Source: Ensembl
    27. positive regulation of receptor internalization Source: UniProtKB
    28. positive regulation of Rho protein signal transduction Source: UniProtKB
    29. positive regulation of smooth muscle cell apoptotic process Source: Ensembl
    30. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    31. post-Golgi vesicle-mediated transport Source: Reactome
    32. proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
    33. protein transport Source: UniProtKB-KW
    34. protein ubiquitination Source: UniProtKB
    35. stress fiber assembly Source: UniProtKB
    36. transcription from RNA polymerase II promoter Source: UniProtKB

    Keywords - Molecular functioni

    Signal transduction inhibitor

    Keywords - Biological processi

    Protein transport, Transcription, Transcription regulation, Transport

    Enzyme and pathway databases

    ReactomeiREACT_118614. Activated NOTCH1 Transmits Signal to the Nucleus.
    REACT_19287. Lysosome Vesicle Biogenesis.
    REACT_19400. Golgi Associated Vesicle Biogenesis.
    REACT_21384. Thrombin signalling through proteinase activated receptors (PARs).
    SignaLinkiP49407.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Beta-arrestin-1
    Alternative name(s):
    Arrestin beta-1
    Gene namesi
    Name:ARRB1
    Synonyms:ARR1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:711. ARRB1.

    Subcellular locationi

    Cytoplasm. Nucleus. Cell membrane. Membraneclathrin-coated pit Curated. Cell projectionpseudopodium By similarity. Cytoplasmic vesicle
    Note: Translocates to the plasma membrane and colocalizes with antagonist-stimulated GPCRs. The monomeric form is predominantly located in the nucleus. The oligomeric form is located in the cytoplasm. Translocates to the nucleus upon stimulation of OPRD1 By similarity.By similarity

    GO - Cellular componenti

    1. basolateral plasma membrane Source: Ensembl
    2. chromatin Source: BHF-UCL
    3. coated pit Source: UniProtKB-SubCell
    4. cytoplasm Source: UniProtKB
    5. cytoplasmic vesicle Source: UniProtKB
    6. cytoplasmic vesicle membrane Source: Reactome
    7. cytosol Source: Reactome
    8. dendritic spine Source: Ensembl
    9. Golgi membrane Source: Reactome
    10. lysosomal membrane Source: Reactome
    11. nucleus Source: UniProtKB
    12. plasma membrane Source: ProtInc
    13. postsynaptic density Source: Ensembl
    14. postsynaptic membrane Source: Ensembl
    15. pseudopodium Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cell projection, Coated pit, Cytoplasm, Cytoplasmic vesicle, Membrane, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi169 – 1691R → E: Constitutive active; enables phosphorylation-independent binding to GPCRs. 1 Publication
    Mutagenesisi388 – 3881F → A: Abolishes interaction with AP2B1. 1 Publication
    Mutagenesisi390 – 3901D → P: Abolishes interaction with AP2B1. 1 Publication
    Mutagenesisi393 – 3931R → A: Abolishes interaction with AP2B1. 1 Publication

    Organism-specific databases

    PharmGKBiPA59.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 418418Beta-arrestin-1PRO_0000205194Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei47 – 471PhosphotyrosineBy similarity
    Modified residuei412 – 4121Phosphoserine; by GRK53 Publications

    Post-translational modificationi

    Constitutively phosphorylated at Ser-412 in the cytoplasm. At the plasma membrane, is rapidly dephosphorylated, a process that is required for clathrin binding and ADRB2 endocytosis but not for ADRB2 binding and desensitization. Once internalized, is rephosphorylated.3 Publications
    The ubiquitination status appears to regulate the formation and trafficking of beta-arrestin-GPCR complexes and signaling. Ubiquitination appears to occur GPCR-specific. Ubiquitinated by MDM2; the ubiquitination is required for rapid internalization of ADRB2. Deubiquitinated by USP33; the deubiquitination leads to a dissociation of the beta-arrestin-GPCR complex. Stimulation of a class A GPCR, such as ADRB2, induces transient ubiquitination and subsequently promotes association with USP33.1 Publication

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP49407.
    PaxDbiP49407.
    PRIDEiP49407.

    2D gel databases

    OGPiP49407.

    PTM databases

    PhosphoSiteiP49407.

    Expressioni

    Gene expression databases

    ArrayExpressiP49407.
    BgeeiP49407.
    CleanExiHS_ARRB1.
    GenevestigatoriP49407.

    Organism-specific databases

    HPAiCAB003763.

    Interactioni

    Subunit structurei

    Monomer. Homodimer. Homooligomer; the self-association is mediated by InsP6-binding. Heterooligomer with ARRB2; the association is mediated by InsP6-binding. Interacts with GPR143. Interacts with ADRB2 (phosphorylated). Interacts with CHRM2 (phosphorylated). Interacts with LHCGR. Interacts with CYTH2 and CASR. Interacts with AP2B1 (dephosphorylated at 'Tyr-737'); phosphorylation of AP2B1 at 'Tyr-737' disrupts the interaction. Interacts (dephosphorylated at Ser-412) with CLTC. Interacts with CCR2 and ADRBK1. Interacts with CRR5. Interacts with PTAFR (phosphorylated on serine residues). Interacts with CLTC and MAP2K3. Interacts with CREB1. Interacts with TRAF6. Interacts with IGF1R and MDM2. Interacts with C5AR1. Interacts with PDE4D. Interacts with SRC (via the SH3 domain and the protein kinase domain); the interaction is independent of the phosphorylation state of SRC C-terminus. Interacts with TACR1. Interacts with RAF1. Interacts with CHUK, IKBKB and MAP3K14. Interacts with DVL1; the interaction is enhanced by phosphorylation of DVL1. Interacts with DVL2; the interaction is enhanced by phosphorylation of DVL2. Interacts with IGF1R. Associates with MAP kinase p38. Part of a MAPK signaling complex consisting of TACR1, ARRB1, SRC, MAPK1 (activated) and MAPK3 (activated). Part of a MAPK signaling complex consisting of F2RL1, ARRB1, RAF1, MAPK1 (activated) and MAPK3 (activated) By similarity. Interacts with MAP2K4/MKK4. Interacts with HCK and CXCR1 (phosphorylated). Interacts with ACKR3 and ACKR4.By similarity17 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CALM3P621583EBI-743313,EBI-397435
    GNAQP501482EBI-743313,EBI-3909604
    GNASQ5JWF25EBI-743313,EBI-4400880
    GNMTQ147495EBI-743313,EBI-744239
    GSNP063963EBI-743313,EBI-351506
    HIF1AQ166653EBI-743313,EBI-447269
    HSPA8P111424EBI-743313,EBI-351896
    MAP3K5Q996833EBI-743313,EBI-476263
    MAPK10P537792EBI-743313,EBI-713543
    NCLP193383EBI-743313,EBI-346967
    NOLC1Q149783EBI-743313,EBI-396155
    PKMP146183EBI-743313,EBI-353408
    PPM1AP358134EBI-743313,EBI-989143
    PPM1BO756884EBI-743313,EBI-1047039
    PRPF4BQ135232EBI-743313,EBI-395940
    S100A9P067022EBI-743313,EBI-1055001
    STK38Q152083EBI-743313,EBI-458376
    TCOF1Q134283EBI-743313,EBI-396105
    YWHAQP273483EBI-743313,EBI-359854
    YY1P254904EBI-743313,EBI-765538
    ZRANB2O952184EBI-743313,EBI-1051583

    Protein-protein interaction databases

    BioGridi106901. 243 interactions.
    DIPiDIP-29979N.
    IntActiP49407. 204 interactions.
    MINTiMINT-128176.
    STRINGi9606.ENSP00000377141.

    Structurei

    Secondary structure

    1
    418
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi384 – 39411

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2IV8X-ray2.80P/Q383-402[»]
    ProteinModelPortaliP49407.
    SMRiP49407. Positions 5-393.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP49407.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 163163Interaction with SRCBy similarityAdd
    BLAST
    Regioni45 – 8642Interaction with CHRM2By similarityAdd
    BLAST
    Regioni318 – 418101Interaction with TRAF6Add
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi385 – 39511[DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motifAdd
    BLAST

    Domaini

    The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction the AP-2 complex subunit AP2B1 By similarity. Binding to phosphorylated GPCRs induces a conformationanl change that exposes the motif to the surface.By similarity
    The N-terminus binds InsP6 with low affinity.By similarity
    The C-terminus binds InsP6 with high affinity.By similarity

    Sequence similaritiesi

    Belongs to the arrestin family.Curated

    Phylogenomic databases

    eggNOGiNOG302111.
    HOGENOMiHOG000231319.
    HOVERGENiHBG002399.
    InParanoidiP49407.
    KOiK04439.
    OMAiEAPIDTN.
    OrthoDBiEOG79W954.
    PhylomeDBiP49407.
    TreeFamiTF314260.

    Family and domain databases

    Gene3Di2.60.40.640. 1 hit.
    2.60.40.840. 1 hit.
    InterProiIPR000698. Arrestin.
    IPR011021. Arrestin-like_N.
    IPR014752. Arrestin_C.
    IPR011022. Arrestin_C-like.
    IPR017864. Arrestin_CS.
    IPR014753. Arrestin_N.
    IPR014756. Ig_E-set.
    [Graphical view]
    PANTHERiPTHR11792. PTHR11792. 1 hit.
    PfamiPF02752. Arrestin_C. 1 hit.
    PF00339. Arrestin_N. 1 hit.
    [Graphical view]
    PRINTSiPR00309. ARRESTIN.
    SMARTiSM01017. Arrestin_C. 1 hit.
    [Graphical view]
    SUPFAMiSSF81296. SSF81296. 2 hits.
    PROSITEiPS00295. ARRESTINS. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1A (identifier: P49407-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MGDKGTRVFK KASPNGKLTV YLGKRDFVDH IDLVDPVDGV VLVDPEYLKE    50
    RRVYVTLTCA FRYGREDLDV LGLTFRKDLF VANVQSFPPA PEDKKPLTRL 100
    QERLIKKLGE HAYPFTFEIP PNLPCSVTLQ PGPEDTGKAC GVDYEVKAFC 150
    AENLEEKIHK RNSVRLVIRK VQYAPERPGP QPTAETTRQF LMSDKPLHLE 200
    ASLDKEIYYH GEPISVNVHV TNNTNKTVKK IKISVRQYAD ICLFNTAQYK 250
    CPVAMEEADD TVAPSSTFCK VYTLTPFLAN NREKRGLALD GKLKHEDTNL 300
    ASSTLLREGA NREILGIIVS YKVKVKLVVS RGGLLGDLAS SDVAVELPFT 350
    LMHPKPKEEP PHREVPENET PVDTNLIELD TNDDDIVFED FARQRLKGMK 400
    DDKEEEEDGT GSPQLNNR 418
    Length:418
    Mass (Da):47,066
    Last modified:March 5, 2002 - v2
    Checksum:i0A3C135092338D10
    GO
    Isoform 1B (identifier: P49407-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         334-341: Missing.

    Show »
    Length:410
    Mass (Da):46,309
    Checksum:i4FBA2B09E6C2D236
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti146 – 1461V → A in AAA35559. (PubMed:8486659)Curated
    Sequence conflicti146 – 1461V → A in AAA35558. (PubMed:8486659)Curated
    Sequence conflicti165 – 1651R → G in AAA35559. (PubMed:8486659)Curated
    Sequence conflicti165 – 1651R → G in AAA35558. (PubMed:8486659)Curated
    Sequence conflicti229 – 2291K → E in AAA35559. (PubMed:8486659)Curated
    Sequence conflicti229 – 2291K → E in AAA35558. (PubMed:8486659)Curated
    Sequence conflicti329 – 3291V → E in AAC33295. 1 PublicationCurated
    Sequence conflicti329 – 3291V → E in AAC34123. 1 PublicationCurated
    Sequence conflicti400 – 4001K → E in AAA35559. (PubMed:8486659)Curated
    Sequence conflicti400 – 4001K → E in AAA35558. (PubMed:8486659)Curated
    Sequence conflicti414 – 4141Q → R in AAA35559. (PubMed:8486659)Curated
    Sequence conflicti414 – 4141Q → R in AAA35558. (PubMed:8486659)Curated
    Sequence conflicti417 – 4171N → D in AAA35559. (PubMed:8486659)Curated
    Sequence conflicti417 – 4171N → D in AAA35558. (PubMed:8486659)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei334 – 3418Missing in isoform 1B. 3 PublicationsVSP_000322

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L04685 mRNA. Translation: AAA35559.1.
    L04685 mRNA. Translation: AAA35558.1.
    AF084040 mRNA. Translation: AAC33295.1.
    AF084940 mRNA. Translation: AAC34123.1.
    DQ314865 Genomic DNA. Translation: ABC40724.1.
    FJ348262 mRNA. Translation: ACI96306.1.
    CH471076 Genomic DNA. Translation: EAW74962.1.
    BC003636 mRNA. Translation: AAH03636.1.
    CCDSiCCDS31640.1. [P49407-2]
    CCDS44684.1. [P49407-1]
    PIRiB46682.
    RefSeqiNP_004032.2. NM_004041.4. [P49407-1]
    NP_064647.1. NM_020251.3. [P49407-2]
    UniGeneiHs.503284.
    Hs.625320.

    Genome annotation databases

    EnsembliENST00000360025; ENSP00000353124; ENSG00000137486. [P49407-2]
    ENST00000420843; ENSP00000409581; ENSG00000137486. [P49407-1]
    GeneIDi408.
    KEGGihsa:408.
    UCSCiuc001owe.2. human. [P49407-1]
    uc001owf.2. human. [P49407-2]

    Polymorphism databases

    DMDMi20141238.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Web resourcesi

    Wikipedia

    Arrestin entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L04685 mRNA. Translation: AAA35559.1 .
    L04685 mRNA. Translation: AAA35558.1 .
    AF084040 mRNA. Translation: AAC33295.1 .
    AF084940 mRNA. Translation: AAC34123.1 .
    DQ314865 Genomic DNA. Translation: ABC40724.1 .
    FJ348262 mRNA. Translation: ACI96306.1 .
    CH471076 Genomic DNA. Translation: EAW74962.1 .
    BC003636 mRNA. Translation: AAH03636.1 .
    CCDSi CCDS31640.1. [P49407-2 ]
    CCDS44684.1. [P49407-1 ]
    PIRi B46682.
    RefSeqi NP_004032.2. NM_004041.4. [P49407-1 ]
    NP_064647.1. NM_020251.3. [P49407-2 ]
    UniGenei Hs.503284.
    Hs.625320.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2IV8 X-ray 2.80 P/Q 383-402 [» ]
    ProteinModelPortali P49407.
    SMRi P49407. Positions 5-393.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 106901. 243 interactions.
    DIPi DIP-29979N.
    IntActi P49407. 204 interactions.
    MINTi MINT-128176.
    STRINGi 9606.ENSP00000377141.

    Chemistry

    BindingDBi P49407.
    ChEMBLi CHEMBL1795088.

    PTM databases

    PhosphoSitei P49407.

    Polymorphism databases

    DMDMi 20141238.

    2D gel databases

    OGPi P49407.

    Proteomic databases

    MaxQBi P49407.
    PaxDbi P49407.
    PRIDEi P49407.

    Protocols and materials databases

    DNASUi 408.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000360025 ; ENSP00000353124 ; ENSG00000137486 . [P49407-2 ]
    ENST00000420843 ; ENSP00000409581 ; ENSG00000137486 . [P49407-1 ]
    GeneIDi 408.
    KEGGi hsa:408.
    UCSCi uc001owe.2. human. [P49407-1 ]
    uc001owf.2. human. [P49407-2 ]

    Organism-specific databases

    CTDi 408.
    GeneCardsi GC11M074976.
    HGNCi HGNC:711. ARRB1.
    HPAi CAB003763.
    MIMi 107940. gene.
    neXtProti NX_P49407.
    PharmGKBi PA59.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG302111.
    HOGENOMi HOG000231319.
    HOVERGENi HBG002399.
    InParanoidi P49407.
    KOi K04439.
    OMAi EAPIDTN.
    OrthoDBi EOG79W954.
    PhylomeDBi P49407.
    TreeFami TF314260.

    Enzyme and pathway databases

    Reactomei REACT_118614. Activated NOTCH1 Transmits Signal to the Nucleus.
    REACT_19287. Lysosome Vesicle Biogenesis.
    REACT_19400. Golgi Associated Vesicle Biogenesis.
    REACT_21384. Thrombin signalling through proteinase activated receptors (PARs).
    SignaLinki P49407.

    Miscellaneous databases

    EvolutionaryTracei P49407.
    GeneWikii Arrestin_beta_1.
    GenomeRNAii 408.
    NextBioi 1713.
    PROi P49407.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P49407.
    Bgeei P49407.
    CleanExi HS_ARRB1.
    Genevestigatori P49407.

    Family and domain databases

    Gene3Di 2.60.40.640. 1 hit.
    2.60.40.840. 1 hit.
    InterProi IPR000698. Arrestin.
    IPR011021. Arrestin-like_N.
    IPR014752. Arrestin_C.
    IPR011022. Arrestin_C-like.
    IPR017864. Arrestin_CS.
    IPR014753. Arrestin_N.
    IPR014756. Ig_E-set.
    [Graphical view ]
    PANTHERi PTHR11792. PTHR11792. 1 hit.
    Pfami PF02752. Arrestin_C. 1 hit.
    PF00339. Arrestin_N. 1 hit.
    [Graphical view ]
    PRINTSi PR00309. ARRESTIN.
    SMARTi SM01017. Arrestin_C. 1 hit.
    [Graphical view ]
    SUPFAMi SSF81296. SSF81296. 2 hits.
    PROSITEi PS00295. ARRESTINS. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular analysis of human beta-arrestin-1: cloning, tissue distribution, and regulation of expression. Identification of two isoforms generated by alternative splicing."
      Parruti G., Peracchia F., Sallese M., Ambrosini G., Masini M., Rotilio D., de Blasi A.
      J. Biol. Chem. 268:9753-9761(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1A AND 1B).
      Tissue: Peripheral blood.
    2. "Molecular cloning of two isoforms of human beta-arrestin 1."
      Yu Q.M., Zhou T.H., Cheng Z.J., Ma L., Pei G.
      Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1A AND 1B).
      Tissue: Brain.
    3. NHLBI resequencing and genotyping service (RS&G)
      Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    4. "Isolation of cDNA coding for Homo sapiens arrestin, beta 1 (ARRB1), transcript variant 2."
      Kaighin V.A., Martin A.L., Aronstam R.S.
      Submitted (OCT-2008) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1B).
      Tissue: Lung.
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1A).
      Tissue: Uterus.
    7. "Monocyte chemoattractant protein-1-induced CCR2B receptor desensitization mediated by the G protein-coupled receptor kinase 2."
      Aragay A.M., Mellado M., Frade J.M., Martin A.M., Jimenez-Sainz M.C., Martinez-A C., Mayor F. Jr.
      Proc. Natl. Acad. Sci. U.S.A. 95:2985-2990(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CCR2 AND ADRBK1.
    8. "Targeted construction of phosphorylation-independent beta-arrestin mutants with constitutive activity in cells."
      Kovoor A., Celver J., Abdryashitov R.I., Chavkin C., Gurevich V.V.
      J. Biol. Chem. 274:6831-6834(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF ARG-169.
    9. Cited for: INTERACTION WITH ADRB2, SUBCELLULAR LOCATION.
    10. "Differential affinities of visual arrestin, beta arrestin1, and beta arrestin2 for G protein-coupled receptors delineate two major classes of receptors."
      Oakley R.H., Laporte S.A., Holt J.A., Caron M.G., Barak L.S.
      J. Biol. Chem. 275:17201-17210(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, ASSOCIATION WITH ANTAGONIST-STIMULATED GPCRS.
    11. "Regulation of tyrosine kinase activation and granule release through beta-arrestin by CXCRI."
      Barlic J., Andrews J.D., Kelvin A.A., Bosinger S.E., DeVries M.E., Xu L., Dobransky T., Feldman R.D., Ferguson S.S., Kelvin D.J.
      Nat. Immunol. 1:227-233(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HCK AND CXCR1.
    12. "Phosphorylation of key serine residues is required for internalization of the complement 5a (C5a) anaphylatoxin receptor via a beta-arrestin, dynamin, and clathrin-dependent pathway."
      Braun L., Christophe T., Boulay F.
      J. Biol. Chem. 278:4277-4285(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN INTERNALIZATION OF C5AR1, SUBCELLULAR LOCATION, INTERACTION WITH C5AR1.
    13. "{beta}-Arrestin is crucial for ubiquitination and down-regulation of the insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 ligase."
      Girnita L., Shenoy S.K., Sehat B., Vasilcanu R., Girnita A., Lefkowitz R.J., Larsson O.
      J. Biol. Chem. 280:24412-24419(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN UBIQUITINATION OF IGF1R, INTERACTION WITH IGF1R AND MDM2.
    14. "Reciprocal regulation of angiotensin receptor-activated extracellular signal-regulated kinases by beta-arrestins 1 and 2."
      Ahn S., Wei H., Garrison T.R., Lefkowitz R.J.
      J. Biol. Chem. 279:7807-7811(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN AGTR1-MEDIATED ERK SIGNALING.
    15. "A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription."
      Kang J., Shi Y., Xiang B., Qu B., Su W., Zhu M., Zhang M., Bao G., Wang F., Zhang X., Yang R., Fan F., Chen X., Pei G., Ma L.
      Cell 123:833-847(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEAR FUNCTION IN TRANSCRIPTIONAL REGULATION, SUBCELLULAR LOCATION, INTERACTION WITH CREB1.
    16. "beta-Arrestin 1 and Galphaq/11 coordinately activate RhoA and stress fiber formation following receptor stimulation."
      Barnes W.G., Reiter E., Violin J.D., Ren X.-R., Milligan G., Lefkowitz R.J.
      J. Biol. Chem. 280:8041-8050(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CYTOSKELETAL REARRANGEMENT, SUBCELLULAR LOCATION.
    17. "G protein-coupled receptor kinases promote phosphorylation and beta-arrestin-mediated internalization of CCR5 homo- and hetero-oligomers."
      Huettenrauch F., Pollok-Kopp B., Oppermann M.
      J. Biol. Chem. 280:37503-37515(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN IN INTERNALIZATION OF CCR5, INTERACTION WITH CCR5.
    18. "Multiple independent functions of arrestins in the regulation of protease-activated receptor-2 signaling and trafficking."
      Stalheim L., Ding Y., Gullapalli A., Paing M.M., Wolfe B.L., Morris D.R., Trejo J.
      Mol. Pharmacol. 67:78-87(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN F2LR1-MEDIATED ERK SIGNALING, SUBCELLULAR LOCATION.
    19. "Different G protein-coupled receptor kinases govern G protein and beta-arrestin-mediated signaling of V2 vasopressin receptor."
      Ren X.-R., Reiter E., Ahn S., Kim J., Chen W., Lefkowitz R.J.
      Proc. Natl. Acad. Sci. U.S.A. 102:1448-1453(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN AVPR2-MEDIATED ERK SIGNALING.
    20. "Molecular switches involving the AP-2 beta2 appendage regulate endocytic cargo selection and clathrin coat assembly."
      Edeling M.A., Mishra S.K., Keyel P.A., Steinhauser A.L., Collins B.M., Roth R., Heuser J.E., Owen D.J., Traub L.M.
      Dev. Cell 10:329-342(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AP2B1, MUTAGENESIS OF PHE-388; ASP-390 AND ARG-393.
    21. "beta-arrestin-dependent, G protein-independent ERK1/2 activation by the beta2 adrenergic receptor."
      Shenoy S.K., Drake M.T., Nelson C.D., Houtz D.A., Xiao K., Madabushi S., Reiter E., Premont R.T., Lichtarge O., Lefkowitz R.J.
      J. Biol. Chem. 281:1261-1273(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN ADRB2-MEDIATED ERK SIGNALING, SUBCELLULAR LOCATION.
    22. "Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation."
      Gesty-Palmer D., Chen M., Reiter E., Ahn S., Nelson C.D., Wang S., Eckhardt A.E., Cowan C.L., Spurney R.F., Luttrell L.M., Lefkowitz R.J.
      J. Biol. Chem. 281:10856-10864(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PTH1R-MEDIATED ERK SIGNALING.
    23. "Platelet-activating factor-induced clathrin-mediated endocytosis requires beta-arrestin-1 recruitment and activation of the p38 MAPK signalosome at the plasma membrane for actin bundle formation."
      McLaughlin N.J., Banerjee A., Kelher M.R., Gamboni-Robertson F., Hamiel C., Sheppard F.R., Moore E.E., Silliman C.C.
      J. Immunol. 176:7039-7050(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN INTERNALIZATION OF PTAFR, FUNCTION IN THE P38 MAPK SIGNALING PATHWAY, FUNCTION IN ACTIN BUNDLE FORMATION, SUBCELLULAR LOCATION, INTERACTION WITH PTAFR AND MAP2K3.
    24. "Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling."
      Wang Y., Tang Y., Teng L., Wu Y., Zhao X., Pei G.
      Nat. Immunol. 7:139-147(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN TLR/IL-1 RECEPTOR SIGNALING, INTERACTION WITH TRAF6.
    25. "The melanosomal/lysosomal protein OA1 has properties of a G protein-coupled receptor."
      Innamorati G., Piccirillo R., Bagnato P., Palmisano I., Schiaffino M.V.
      Pigment Cell Res. 19:125-135(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH GPR143.
    26. "Src-dependent phosphorylation of beta2-adaptin dissociates the beta-arrestin-AP-2 complex."
      Fessart D., Simaan M., Zimmerman B., Comeau J., Hamdan F.F., Wiseman P.W., Bouvier M., Laporte S.A.
      J. Cell Sci. 120:1723-1732(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AP2B1.
    27. "Beta-arrestins specifically constrain beta2-adrenergic receptor signaling and function in airway smooth muscle."
      Deshpande D.A., Theriot B.S., Penn R.B., Walker J.K.
      FASEB J. 22:2134-2141(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN BETA-ADRENERGIC RECEPTOR REGULATION.
    28. "Post-endocytic fates of delta-opioid receptor are regulated by GRK2-mediated receptor phosphorylation and distinct beta-arrestin isoforms."
      Zhang X., Wang F., Chen X., Chen Y., Ma L.
      J. Neurochem. 106:781-792(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN INTERNALIZATION OF OPRD1.
    29. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    30. "Inhibition of dynamin prevents CCL2-mediated endocytosis of CCR2 and activation of ERK1/2."
      Garcia Lopez M.A., Aguado Martinez A., Lamaze C., Martinez-Alonso C., Fischer T.
      Cell. Signal. 21:1748-1757(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN INTERNALIZATION OF CCR2.
    31. Cited for: PHOSPHORYLATION AT SER-412.
    32. "A scanning peptide array approach uncovers association sites within the JNK/beta arrestin signalling complex."
      Li X., MacLeod R., Dunlop A.J., Edwards H.V., Advant N., Gibson L.C., Devine N.M., Brown K.M., Adams D.R., Houslay M.D., Baillie G.S.
      FEBS Lett. 583:3310-3316(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MAP2K4/MKK4.
    33. "An arrestin-dependent multi-kinase signaling complex mediates MIP-1beta/CCL4 signaling and chemotaxis of primary human macrophages."
      Cheung R., Malik M., Ravyn V., Tomkowicz B., Ptasznik A., Collman R.G.
      J. Leukoc. Biol. 86:833-845(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN MIP-1-BETA-STIMULATED CHEMOTAXIS.
    34. "Beta-arrestin-dependent signaling and trafficking of 7-transmembrane receptors is reciprocally regulated by the deubiquitinase USP33 and the E3 ligase Mdm2."
      Shenoy S.K., Modi A.S., Shukla A.K., Xiao K., Berthouze M., Ahn S., Wilkinson K.D., Miller W.E., Lefkowitz R.J.
      Proc. Natl. Acad. Sci. U.S.A. 106:6650-6655(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP33, INTERACTION WITH USP33.
    35. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    36. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    37. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
      Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
      Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    38. Cited for: FUNCTION, INTERACTION WITH ACKR3.
    39. "Beta-arrestin recruitment and G protein signaling by the atypical human chemokine decoy receptor CCX-CKR."
      Watts A.O., Verkaar F., van der Lee M.M., Timmerman C.A., Kuijer M., van Offenbeek J., van Lith L.H., Smit M.J., Leurs R., Zaman G.J., Vischer H.F.
      J. Biol. Chem. 288:7169-7181(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH ACKR4.
    40. "Beta-arrestin-dependent activation of the cofilin pathway is required for the scavenging activity of the atypical chemokine receptor D6."
      Borroni E.M., Cancellieri C., Vacchini A., Benureau Y., Lagane B., Bachelerie F., Arenzana-Seisdedos F., Mizuno K., Mantovani A., Bonecchi R., Locati M.
      Sci. Signal. 6:RA30-RA30(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    41. "Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly."
      Schmid E.M., Ford M.G.J., Burtey A., Praefcke G.J.K., Peak-Chew S.-Y., Mills I.G., Benmerah A., McMahon H.T.
      PLoS Biol. 4:E262-E262(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 383-402 IN COMPLEX WITH AP2B1.

    Entry informationi

    Entry nameiARRB1_HUMAN
    AccessioniPrimary (citable) accession number: P49407
    Secondary accession number(s): B6V9G8
    , O75625, O75630, Q2PP20, Q9BTK8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: March 5, 2002
    Last modified: October 1, 2014
    This is version 138 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3