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ARRB1 Gene

protein-coding   GIFtS: 63
GCID: GC11M074976

Arrestin, Beta 1


(Previous symbol: ARR1)
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Arrestin, Beta 11 2
ARR11 2 3
Arrestin 21 2
ARB12
beta-arrestin-12
Arrestin Beta-13

External Ids:    HGNC: 7111   Entrez Gene: 4082   Ensembl: ENSG000001374867   OMIM: 1079405   UniProtKB: P494073   

Export aliases for ARRB1 gene to outside databases

Previous GC identifers: GC11M077303 GC11M076515 GC11M075199 GC11M074702 GC11M074654 GC11M071275


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for ARRB1 Gene:
Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of
G-protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones,
neurotransmitters, or sensory signals. Arrestin beta 1 is a cytosolic protein and acts as a cofactor in the
beta-adrenergic receptor kinase (BARK) mediated desensitization of beta-adrenergic receptors. Besides the central
nervous system, it is expressed at high levels in peripheral blood leukocytes, and thus the BARK/beta-arrestin
system is believed to play a major role in regulating receptor-mediated immune functions. Alternatively spliced
transcripts encoding different isoforms of arrestin beta 1 have been described. (provided by RefSeq, Jan 2011)

GeneCards Summary for ARRB1 Gene:
ARRB1 (arrestin, beta 1) is a protein-coding gene. Diseases associated with ARRB1 include whim syndrome, and mood disorder. GO annotations related to this gene include transcription factor binding and ubiquitin protein ligase binding. An important paralog of this gene is SAG.

UniProtKB/Swiss-Prot: ARRB1_HUMAN, P49407
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. 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

Gene Wiki entry for ARRB1 (Arrestin beta 1) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000011.10  NT_167190.2  NC_018922.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the ARRB1 gene promoter:
         ER-alpha   GR   HFH-3   Elk-1   AML1a   GR-beta   FOXI1   SRY   GR-alpha   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): ARRB1 promoter sequence
   Search Chromatin IP Primers for ARRB1

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat ARRB1


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 11q13   Ensembl cytogenetic band:  11q13.4   HGNC cytogenetic band: 11q13

ARRB1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ARRB1 gene location

GeneLoc information about chromosome 11         GeneLoc Exon Structure

GeneLoc location for GC11M074976:  view genomic region     (about GC identifiers)

Start:
74,971,166 bp from pter      End:
75,062,875 bp from pter
Size:
91,710 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: ARRB1_HUMAN, P49407 (See protein sequence)
Recommended Name: Beta-arrestin-1  
Size: 418 amino acids; 47066 Da
Subunit: 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
1 PDB 3D structure from and Proteopedia for ARRB1:
2IV8 (3D)    
Secondary accessions: B6V9G8 O75625 O75630 Q2PP20 Q9BTK8
Alternative splicing: 2 isoforms:  P49407-1   P49407-2   

Explore the universe of human proteins at neXtProt for ARRB1: NX_P49407

Explore proteomics data for ARRB1 at MOPED

Post-translational modifications: 

  • 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 rephosphorylated1
  • 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 USP331
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See ARRB1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_004032.2  NP_064647.1  

    ENSEMBL proteins: 
     ENSP00000409581   ENSP00000353124   ENSP00000436530   ENSP00000433171   ENSP00000434196  
     ENSP00000436352   ENSP00000433137   ENSP00000377141  
    Reactome Protein details: P49407

    ARRB1 Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
    Browse R&D Systems for human recombinant proteins
    Browse recombinant and purified proteins available from Enzo Life Sciences
    OriGene Purified Proteins for ARRB1
    OriGene Protein Over-expression Lysate for ARRB1
    OriGene Custom MassSpec
    OriGene Custom Protein Services for ARRB1
    GenScript Custom Purified and Recombinant Proteins Services for ARRB1
    Novus Biologicals ARRB1 Proteins
    Novus Biologicals ARRB1 Lysates
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp.

    ARRB1 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of ARRB1
    R&D Systems Antibodies for ARRB1 (beta-Arrestin 1)
    Cell Signaling Technology (CST) Antibodies for ARRB1 
    OriGene Antibodies for ARRB1
    OriGene Custom Antibody Services for ARRB1
    Novus Biologicals ARRB1 Antibodies
    Abcam antibodies for ARRB1 (P32121, P49407)
    Browse Antibodies at Cloud-Clone Corp.
    ThermoFisher Antibodies for ARRB1
    LSBio Antibodies in human, mouse, rat for ARRB1

    ARRB1 Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for ARRB1
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for ARRB1
    Browse Enzo Life Sciences for kits & assays
    Browse ELISAs at Cloud-Clone Corp.
    Browse CLIAs at Cloud-Clone Corp.


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    Selected InterPro protein domains (see all 7):
     IPR014756 Ig_E-set
     IPR011022 Arrestin_C-like
     IPR014753 Arrestin_N
     IPR000698 Arrestin
     IPR014752 Arrestin_C

    Graphical View of Domain Structure for InterPro Entry P49407

    ProtoNet protein and cluster: P49407

    1 Blocks protein domain: IPB000698 Arrestin

    UniProtKB/Swiss-Prot: ARRB1_HUMAN, P49407
    Domain: 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
    Domain: The N-terminus binds InsP6 with low affinity (By similarity)
    Domain: The C-terminus binds InsP6 with high affinity (By similarity)
    Similarity: Belongs to the arrestin family


    ARRB1 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
    About This Section

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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: ARRB1_HUMAN, P49407
    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. 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

         Genatlas biochemistry entry for ARRB1:
    beta-arrestin 1,Ca2+ binding protein of the retinal red outer segments,widely expressed,binding to P-rhodopsin and
    inhibiting further G protein activation desensitized receptor-arrestin complex and sequestered through clathrin
    coated pits,also regulator of beta-adrenergic receptor A and involved in synaptic transmission in photoreceptor
    cells

         Gene Ontology (GO): Selected molecular function terms (see all 21):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004402NOT histone acetyltransferase activity IDA16325578
    GO:0004857enzyme inhibitor activity TAS2163110
    GO:0005096GTPase activator activity IMP15611106
    GO:0005159insulin-like growth factor receptor binding IPI15878855
    GO:0005515protein binding IPI16189514
         
    ARRB1 for ontologies           About GeneDecksing


    Phenotypes:
         8 MGI mutant phenotypes (inferred from 1 allele(MGI details for Arrb1):
     behavior/neurological  cardiovascular system  cellular  growth/size/body  homeostasis/metabolism 
     mortality/aging  muscle  respiratory system 

    ARRB1 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-out Arrb1tm1Jse for ARRB1

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for ARRB1
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for ARRB1

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for ARRB1
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for ARRB1

    miRNA
    Products:
        
    miRTarBase miRNAs that target ARRB1:
    hsa-mir-92a-3p (MIRT049191), hsa-mir-335-5p (MIRT016808), hsa-mir-186-5p (MIRT045162), hsa-mir-26b-5p (MIRT028751), hsa-mir-98-5p (MIRT027412)

    Block miRNA regulation of human, mouse, rat ARRB1 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate ARRB1 (see all 56):
    hsa-miR-579 hsa-miR-642a hsa-miR-29a hsa-miR-374a hsa-miR-624 hsa-miR-218 hsa-miR-1304 hsa-miR-649
    SwitchGear 3'UTR luciferase reporter plasmidARRB1 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for ARRB1
    Predesigned siRNA for gene silencing in human, mouse, rat ARRB1

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for ARRB1

    Clone
    Products:
         
    OriGene clones in human, mouse for ARRB1 (see all 12)
    OriGene ORF clones in mouse, rat for ARRB1
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 2): ARRB1 (NM_004041)
    Sino Biological Human cDNA Clone for ARRB1
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for ARRB1
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat ARRB1

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for ARRB1
    Browse ESI BIO Cell Lines and PureStem Progenitors for ARRB1 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ARRB1


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    ARRB1_HUMAN, P49407: Cytoplasm. Nucleus. Cell membrane. Membrane, clathrin-coated pit (Probable). Cell
    projection, pseudopodium (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)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus5
    plasma membrane5
    cytosol4
    golgi apparatus4
    lysosome4
    vacuole4
    endosome2
    cytoskeleton1
    mitochondrion1

    Gene Ontology (GO): Selected cellular component terms (see all 17):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000139Golgi membrane TAS--
    GO:0000785chromatin IDA16325578
    GO:0005622intracellular ----
    GO:0005634nucleus IDA16325578
    GO:0005737cytoplasm IDA10823817

    ARRB1 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
    About This Section

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    SuperPaths for ARRB1 About   (see all 21)  
    See pathways by source

    SuperPathContained pathways About
    1ADP signalling through P2Y purinoceptor 12
    Thrombin signalling through proteinase activated receptors (PARs)0.69
    Beta-agonist/Beta-blocker Pathway, Pharmacodynamics0.34
    Development Angiotensin signaling via beta Arrestin0.39
    2MAPK signaling pathway
    MAPK signaling pathway0.50
    MAPK signaling pathway0.50
    3Chemokine Signaling
    Chemokine signaling pathway0.33
    Chemokine Signaling0.33
    4Signaling by NOTCH1 PEST Domain Mutants in Cancer
    Signaling by NOTCH1 PEST Domain Mutants in Cancer0.79
    Signaling by NOTCH1 t(7;9)(NOTCH1-M1580 K2555) Translocation Mutant0.79
    Signaling by NOTCH1 HD Domain Mutants in Cancer0.79
    FBXW7 Mutants and NOTCH1 in Cancer0.79
    Signaling by NOTCH1 in Cancer0.79
    Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer0.79
    Signaling by NOTCH10.79
    Signaling by NOTCH0.64
    5Clathrin derived vesicle budding
    Clathrin derived vesicle budding0.89
    Lysosome Vesicle Biogenesis0.41
    Golgi Associated Vesicle Biogenesis0.89
    Membrane Trafficking0.32
    trans-Golgi Network Vesicle Budding0.89

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    3 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for ARRB1
        Chemokine Signaling
    cAMP Pathway
    Colorectal Cancer Metastasis

    2 Cell Signaling Technology (CST) Pathways for ARRB1
        Wnt / Hedgehog / Notch
    Tyrosine Kinases / Adaptors

    2 GeneGo (Thomson Reuters) Pathways for ARRB1
        Development Angiotensin signaling via beta-Arrestin
    Cytoskeleton remodeling RalA regulation pathway

    Selected BioSystems Pathways for ARRB1 (see all 6)
        Myometrial Relaxation and Contraction Pathways
    MAPK signaling pathway
    Calcium Regulation in the Cardiac Cell
    Wnt Signaling Pathway NetPath
    Corticotropin-releasing hormone


    4 Reactome Pathways for ARRB1
        Golgi Associated Vesicle Biogenesis
    Lysosome Vesicle Biogenesis
    Thrombin signalling through proteinase activated receptors (PARs)
    Activated NOTCH1 Transmits Signal to the Nucleus

    1 PharmGKB Pathway for ARRB1
        Beta-agonist/Beta-blocker Pathway, Pharmacodynamics

    5 Kegg Pathways  (Kegg details for ARRB1):
        MAPK signaling pathway
    Chemokine signaling pathway
    Endocytosis
    Phototransduction
    Morphine addiction


    ARRB1 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including ARRB1: 
              G-Protein-Coupled Receptor Signaling PathwayFinder in human mouse rat
              Neurotoxicity in human mouse rat

    Interactions:

        Search GeneGlobe Interaction Network for ARRB1

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for ARRB1 (P494071, 2, 3 ENSP000003771414) via UniProtKB, MINT, STRING, and/or I2D (see all 402)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    HIST1H4AP628053I2D: score=1 
    HIST1H4BP628053I2D: score=1 
    HIST1H4CP628053I2D: score=1 
    HIST1H4DP628053I2D: score=1 
    HIST1H4EP628053I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 41):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000187activation of MAPK activity IEA--
    GO:0001933negative regulation of protein phosphorylation IEA--
    GO:0001934positive regulation of protein phosphorylation IMP--
    GO:0002031G-protein coupled receptor internalization IMP10521508
    GO:0002092positive regulation of receptor internalization IMP--

    ARRB1 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
    About This Section

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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for ARRB1

    9 Novoseek inferred chemical compound relationships for ARRB1 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    etorphine 56.8 1 16115983 (1)
    serine 36.4 2 11579203 (1), 15893521 (1)
    tyrosine 31.4 3 17664271 (2), 15456867 (1)
    threonine 30.3 1 11579203 (1)
    phosphoinositide 29.8 1 17680774 (1)
    isoproterenol 29.6 6 12020767 (1), 18678875 (1), 12552097 (1), 12167719 (1)
    calcium 5.04 4 17623778 (1), 16912040 (1), 17023422 (1)
    glutamate 0 1 12519791 (1)
    morphine 0 1 16115983 (1)



    ARRB1 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
    About This Section

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    REFSEQ mRNAs for ARRB1 gene (2 alternative transcripts): 
    NM_004041.4  NM_020251.3  

    Unigene Cluster for ARRB1:

    Arrestin, beta 1
    Hs.503284  [show with all ESTs]
    Unigene Representative Sequence: NM_004041
    13 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000420843(uc001owe.2 uc001owf.2) ENST00000360025 ENST00000532447
    ENST00000531012 ENST00000529741 ENST00000532525 ENST00000524400 ENST00000533609
    ENST00000527385 ENST00000530086 ENST00000529280 ENST00000533255 ENST00000393505

    miRNA
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    hsa-miR-579 hsa-miR-642a hsa-miR-29a hsa-miR-374a hsa-miR-624 hsa-miR-218 hsa-miR-1304 hsa-miR-649
    SwitchGear 3'UTR luciferase reporter plasmidARRB1 3' UTR sequence
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    Additional mRNA sequence: 

    AF084040.1 AF084940.1 AK074660.1 AK289718.1 AK293758.1 AL157484.1 BC003636.2 FJ348262.1 
    L04685.1 

    18 DOTS entries:

    DT.97839794  DT.95290767  DT.95077272  DT.100777614  DT.406001  DT.113437  DT.95239975  DT.120727057 
    DT.40297036  DT.85104858  DT.100688168  DT.120727023  DT.120727040  DT.120727066  DT.120727076  DT.120727079 
    DT.40193048  DT.40246233 

    Selected AceView cDNA sequences (see all 265):

    BC003636 CB852390 AI379151 AL693356 BM663566 CA313548 BF115243 BI489948 
    BE207758 F03091 BM681392 AL547951 AL699165 CR604447 BM924952 AA991658 
    AI991686 BX282347 AI857697 AI401658 CD516701 CR596009 BM727743 BM905866 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for ARRB1 (see all 6)    About this scheme

    ExUns: 1 ^ 2 ^ 3a · 3b ^ 4 ^ 5a · 5b · 5c · 5d ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12 ^ 13 ^ 14 ^ 15
    SP1:              -                 -           -     -           -                                   -                           
    SP2:              -                 -           -     -           -                                   -     -                     
    SP3:              -                 -                                                                                             
    SP4:                                -                                                                                             
    SP5:                                                                                                                              


    ECgene alternative splicing isoforms for ARRB1

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

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    ARRB1 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AGGGCTTGGA
    ARRB1 Expression
    About this image


    ARRB1 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 2) fully expand
     
     Lung (Respiratory System)
             Alveolar type II cells
     
     Liver (Hepatobiliary System)
             Liver Lobule
    ARRB1 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    ARRB1 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.503284
        Pathway & Disease-focused RT2 Profiler PCR Arrays including ARRB1: 
              G-Protein-Coupled Receptor Signaling PathwayFinder in human mouse rat
              Neurotoxicity in human mouse rat

    Primer
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    In Situ
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ARRB1

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for ARRB1 gene from Selected species (see all 14)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Arrb11 , 5 arrestin, beta 11, 5 89.79(n)1
    98.56(a)1
      7 (54.09 cM)5
    1096891  NM_177231.21  NP_796205.11 
     995354665 
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia LOC1004863491 beta-arrestin-1-like 82.16(n)
    94.16(a)
      100486349  XM_004912226.1  XP_004912283.1 
    zebrafish
    (Danio rerio)
    Actinopterygii arrb11 arrestin, beta 1 76.63(n)
    90.67(a)
      553266  NM_001159822.1  NP_001153294.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta krz1 , 3 kurtz1 65(a)
    (best of 3)3
    63.07(n)1
    66.58(a)1
      100E33
    535541  NM_001260471.21  NP_001247400.11 
    worm
    (Caenorhabditis elegans)
    Secernentea arr-11 , 3 beta-arrestin3
    arr-11
    54(a)3
    58.86(n)1
    59.29(a)1
      1804461  NM_075782.41  NP_508183.11 


    ENSEMBL Gene Tree for ARRB1 (if available)
    TreeFam Gene Tree for ARRB1 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for ARRB1 gene
    SAG2  ARR32  ARRB22  
    6 SIMAP similar genes for ARRB1 using alignment to 7 protein entries:     ARRB1_HUMAN (see all proteins):
    ARRB2    DKFZp686L0365    ARR3    SAG    DKFZp686J1593    DKFZp686I1383

    ARRB1 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for ARRB1 (see all 1952)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 11 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs5640111,2
    C,F,A--71333727(+) TGGTTG/ATCAGG 2 -- int17Minor allele frequency- A:0.37MN WA NA EA 548
    rs2007572801,2
    C--71338580(+) AAGCA-/C/TTAAGC 2 -- int10--------
    rs112843671,2
    C,F--71343217(+) GAAGG-/TTTTTT 2 -- int1 trp33Minor allele frequency- T:0.33NA CSA 6
    rs351376141,2
    C--71343878(+) AAAAA-/AGAAGC 2 -- int11Minor allele frequency- A:0.50NA 2
    rs1449163611,2
    --74835801(+) GAACAA/GGAACC 2 -- ds50010--------
    rs1490529851,2
    --74835805(+) AAGAAC/TCAGGG 2 -- ds50010--------
    rs1929204811,2
    --74835904(+) GTCACA/GAAATC 2 -- ds50010--------
    rs613245081,2
    C,F--74835980(+) GAAGAG/AGGACA 2 -- ds50014Minor allele frequency- A:0.11WA CSA 124
    rs612651421,2
    C,F--74836112(+) AGGGAG/AGCATT 2 -- ds50017Minor allele frequency- A:0.14WA CSA NA EA 365
    rs1847471931,2
    --74836502(+) CACTTC/TCTATG 2 -- ut310--------

    HapMap Linkage Disequilibrium report for ARRB1 (74971166 - 75062875 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 2 variations for ARRB1:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv522447CNV Loss19592680
    nsv832211CNV Loss17160897

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing ARRB1
    DNA2.0 Custom Variant and Variant Library Synthesis for ARRB1

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

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    OMIM gene information: 107940    OMIM disorders: --

    Selected diseases for ARRB1 (see all 21):    
    About MalaCards
    whim syndrome    mood disorder    nicotine dependence    primary biliary cirrhosis
    multiple sclerosis    pertussis    lymphoblastic leukemia    asthma
    colorectal cancer    retinitis    ovarian cancer    leukemia
    thyroiditis    arthritis    lung cancer    pancreatitis
    adenocarcinoma    endotheliitis    breast cancer    malaria


    ARRB1 for disorders           About GeneDecksing

    7 Novoseek inferred disease relationships for ARRB1 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    heart failure 23.6 1 8293560 (1)
    multiple sclerosis 9.83 4 17618287 (1), 17965263 (1)
    mood disorders 0.557 1 15514408 (1)
    autoimmunity 0 3 17618287 (2), 17641656 (1)
    metastasis 0 9 19202075 (1), 16432186 (1)
    tumors 0 2 19202075 (1)
    cancer 0 2 19202075 (1)

    Genetic Association Database (GAD): ARRB1
    Human Genome Epidemiology (HuGE) Navigator: ARRB1 (6 documents)

    Export disorders for ARRB1 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

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    PubMed articles for ARRB1 gene, integrated from 10 sources (see all 259):
    (articles sorted by number of sources associating them with ARRB1)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Molecular analysis of human beta-arrestin-1: cloning, tissue distribution, and regulation of expression. Identification of two isoforms generated by alternative splicing. (PubMed id 8486659)1, 2, 3, 9 Parruti G.... de Blasi A. (J. Biol. Chem. 1993)
    2. 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. (PubMed id 16709866)1, 2, 9 McLaughlin N.J.... Silliman C.C. (J. Immunol. 2006)
    3. Beta-arrestins 1 and 2 are associated with nicotine dependence in European American smokers. (PubMed id 17579607)1, 4, 9 Sun D....Li M.D. (Mol. Psychiatry 2008)
    4. beta-Arrestin 1 and Galphaq/11 coordinately activate RhoA and stress fiber formation following receptor stimulation. (PubMed id 15611106)1, 2, 9 Barnes W.G....Lefkowitz R.J. (J. Biol. Chem. 2005)
    5. {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. (PubMed id 15878855)1, 2, 9 Girnita L.... Larsson O. (J. Biol. Chem. 2005)
    6. A scanning peptide array approach uncovers association sites within the JNK/beta arrestin signalling complex. (PubMed id 19782076)1, 2, 9 Li X.... Baillie G.S. (FEBS Lett. 2009)
    7. Reciprocal regulation of angiotensin receptor-activated extracellular signal-regulated kinases by beta-arrestins 1 and 2. (PubMed id 14711824)1, 2, 9 Ahn S.... Lefkowitz R.J. (J. Biol. Chem. 2004)
    8. A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription. (PubMed id 16325578)1, 2, 9 Kang J.... Ma L. (Cell 2005)
    9. 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. (PubMed id 12464600)1, 2, 9 Braun L.... Boulay F. (J. Biol. Chem. 2003)
    10. Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation. (PubMed id 16492667)1, 2, 9 Gesty-Palmer D....Lefkowitz R.J. (J. Biol. Chem. 2006)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section

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    Entrez Gene: 408 HGNC: 711 AceView: ARRB1 Ensembl:ENSG00000137486 euGenes: HUgn408
    ECgene: ARRB1 Kegg: 408 H-InvDB: ARRB1

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for ARRB1 Pharmacogenomics, SNPs, Pathways
    Wikipedia http://en.wikipedia.org/wiki/Arrestin

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for ARRB1 gene:
    Search GeneIP for patents involving ARRB1

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, and ESI BIO, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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    GeneCards Homepage - Last full update: 7 May 2014 - Incrementals: 9 May 2014 , 2 Jun 2014 , 26 Jun 2014 , 30 Jun 2014

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