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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

ARRB2 Gene

protein-coding   GIFtS: 64
GCID: GC17P004613

Arrestin, Beta 2


(Previous symbol: ARR2)
  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)
About This Section

Aliases
Arrestin, Beta 21 2     ARB22 3
ARR21 2 3     BARR22
Arrestin 31 2     beta-arrestin-22
Arrestin Beta-22 3     

External Ids:    HGNC: 7121   Entrez Gene: 4092   Ensembl: ENSG000001414807   OMIM: 1079415   UniProtKB: P321213   

Export aliases for ARRB2 gene to outside databases

Previous GC identifers: GC17P005040 GC17P004959 GC17P004564 GC17P004820 GC17P004560 GC17P004502


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for ARRB2 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 2, like arrestin beta 1, was shown to inhibit
beta-adrenergic receptor function in vitro. It is expressed at high levels in the central nervous system and may
play a role in the regulation of synaptic receptors. Besides the brain, a cDNA for arrestin beta 2 was isolated
from thyroid gland, and thus it may also be involved in hormone-specific desensitization of TSH receptors.
Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene.
(provided by RefSeq, Mar 2012)

GeneCards Summary for ARRB2 Gene: 
ARRB2 (arrestin, beta 2) is a protein-coding gene. Diseases associated with ARRB2 include pain agnosia, and whim syndrome, and among its related super-pathways are Thromboxane signalling through TP receptor and MAPK signaling pathway. GO annotations related to this gene include ubiquitin protein ligase binding and receptor binding. An important paralog of this gene is SAG.

UniProtKB/Swiss-Prot: ARRB2_HUMAN, P32121
Function: Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both
receptor desensitization and resensitization processes. During homologous desensitization, beta-arrestins bind to
the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G-protein; the binding
appears to require additional receptor determinants exposed only in the active receptor conformation. The
beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs,
clathrin-associated sorting proteins) and recruiting the GPRCs to the adapter protein 2 complex 2 (AP-2) in
clathrin-coated pits (CCPs). However, the extent of beta-arrestin involvement appears to vary significantly
depending on the receptor, agonist and cell type. Internalized arrestin-receptor complexes traffic to
intracellular endosomes, where they remain uncoupled from G-proteins. Two different modes of arrestin-mediated
internalization occur. Class A receptors, like ADRB2, OPRM1, ENDRA, D1AR and ADRA1B dissociate from beta-arrestin
at or near the plasma membrane and undergo rapid recycling. Class B receptors, like AVPR2, AGTR1, NTSR1, TRHR and
TACR1 internalize as a complex with arrestin and traffic with it to endosomal vesicles, presumably as
desensitized receptors, for extended periods of time. Receptor resensitization then requires that receptor-bound
arrestin is removed so that the receptor can be dephosphorylated and returned to the plasma membrane. Mediates
endocytosis of CCR7 following ligation of CCL19 but not CCL21. Involved in internalization of P2RY1, P2RY4, P2RY6
and P2RY11 and ATP-stimulated internalization of P2RY2. Involved in phosphorylation-dependent internalization of
OPRD1 and subsequent recycling or degradation. Involved in ubiquitination of IGF1R. Beta-arrestins function as
multivalent adapter proteins that can switch the GPCR from a G-protein signaling mode that transmits short-lived
signals from the plasma membrane via small molecule second messengers and ion channels to a beta-arrestin
signaling mode that transmits a distinct set of signals that are initiated as the receptor internalizes and
transits the intracellular compartment. Acts as signaling scaffold for MAPK pathways such as MAPK1/3 (ERK1/2) and
MAPK10 (JNK3). ERK1/2 and JNK3 activated by the beta-arrestin scaffold are largely excluded from the nucleus and
confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Acts as
signaling scaffold for the AKT1 pathway. GPCRs for which the beta-arrestin-mediated signaling relies on both
ARRB1 and ARRB2 (codependent regulation) include ADRB2, F2RL1 and PTH1R. For some GPCRs the
beta-arrestin-mediated signaling relies on either ARRB1 or ARRB2 and is inhibited by the other respective
beta-arrestin form (reciprocal regulation). Increases ERK1/2 signaling in AGTR1- and AVPR2-mediated activation
(reciprocal regulation). Involved in CCR7-mediated ERK1/2 signaling involving ligand CCL19. Is involved in
type-1A angiotensin II receptor/AGTR1-mediated ERK activity. Is involved in type-1A angiotensin II
receptor/AGTR1-mediated MAPK10 activity. Is involved in dopamine-stimulated AKT1 activity in the striatum by
disrupting the association of AKT1 with its negative regulator PP2A. Involved in AGTR1-mediated chemotaxis.
Appears to function as signaling scaffold involved in regulation of MIP-1-beta-stimulated CCR5-dependent
chemotaxis. Involved in attenuation of NF-kappa-B-dependent transcription in response to GPCR or cytokine
stimulation by interacting with and stabilizing CHUK. Suppresses UV-induced NF-kappa-B-dependent activation by
interacting with CHUK. The function is promoted by stimulation of ADRB2 and dephosphorylation of ARRB2. Involved
in p53/TP53-mediated apoptosis by regulating MDM2 and reducing the MDM2-mediated degradation of p53/TP53. May
serve as nuclear messenger for GPCRs. Upon stimulation of OR1D2, may be involved in regulation of gene expression
during the early processes of fertilization. Also involved in regulation of receptors others than GPCRs. Involved
in endocytosis of TGFBR2 and TGFBR3 and down-regulates TGF-beta signaling such as NF-kappa-B activation. Involved
in endocytosis of low-density lipoprotein receptor/LDLR. Involved in endocytosis of smoothened homolog/Smo, which
also requires ADRBK1. Involved in endocytosis of SLC9A5. Involved in endocytosis of ENG and subsequent
TGF-beta-mediated ERK activation and migration of epithelial cells. Involved in Toll-like receptor and IL-1
receptor signaling through the interaction with TRAF6 which prevents TRAF6 autoubiquitination and oligomerization
required for activation of NF-kappa-B and JUN. Involved in insulin resistance by acting as insulin-induced
signaling scaffold for SRC, AKT1 and INSR. Involved in regulation of inhibitory signaling of natural killer cells
by recruiting PTPN6 and PTPN11 to KIR2DL1. Involved in IL8-mediated granule release in neutrophils

Gene Wiki entry for ARRB2 (Arrestin beta 2) 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 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000017.10  NC_018928.2  NT_010718.16  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the ARRB2 gene promoter:
         COUP-TF1   COUP-TF   AP-1   ATF-2   COUP   c-Jun   HNF-4alpha1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidARRB2 promoter sequence
   Search SABiosciences Chromatin IP Primers for ARRB2

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat ARRB2


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

Entrez Gene cytogenetic band: 17p13   Ensembl cytogenetic band:  17p13.2   HGNC cytogenetic band: 17p13

ARRB2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ARRB2 gene location

GeneLoc information about chromosome 17         GeneLoc Exon Structure

GeneLoc location for GC17P004613:  view genomic region     (about GC identifiers)

Start:
4,613,784 bp from pter      End:
4,624,795 bp from pter
Size:
11,012 bases      Orientation:
plus strand

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB 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., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: ARRB2_HUMAN, P32121 (See protein sequence)
Recommended Name: Beta-arrestin-2  
Size: 409 amino acids; 46106 Da
Subunit: Homooligomer; the self-association is mediated by InsP6-binding (Probable). Heterooligomer with ARRB1;
the association is mediated by InsP6-binding. Interacts with ADRB2 AND CHRM2. Interacts with PDE4A. Interacts
with PDE4D. Interacts with MAPK10, MAPK1 and MAPK3. Interacts with DRD2. Interacts with FSHR. Interacts with
CLTC. Interacts with HTR2C. Interacts with CCR5. Interacts with CXCR4. Interacts with SRC. Interacts with DUSP16;
the interaction is interrupted by stimulation of AGTR1 and activation of MAPK10. Interacts with CHUK; the
interaction is enhanced stimulation of ADRB2. Interacts with RELA. Interacts with MDM2; the interaction is
enhanced by activation of GPCRs. Interacts with SLC9A5. Interacts with TRAF6. Interacts with IGF1R. Interacts
with ENG. Interacts with KIR2DL1, KIR2DL3 and KIR2DL4. Interacts with LDLR. Interacts with AP2B1. Interacts with
C5AR1. Interacts with RAF1. Interacts with MAP2K1. Interacts with MAPK1. Interacts with MAPK10; the interaction
enhances MAPK10 activation by MAP3K5. Interacts with MAP2K4; the interaction is enhanced by presence of MAP3K5
and MAPK10. Interacts with MAP3K5. Interacts with AKT1. Interacts with IKBKB and MAP3K14. Interacts with SMO
(activated). Interacts with GSK3A and GSK3B. Associates with protein phosphatase 2A (PP2A) (By similarity).
Interacts with DHX8; the interaction is detected in the nucleus upon OR1D2 stimulation. Interacts with GAPDHS;
the interaction is detected in the nucleus upon OR1D2 stimulation. Interacts with H2AFX; the interaction is
detected in the nucleus upon OR1D2 stimulation. Interacts with KIF14; the interaction is detected in the nucleus
upon OR1D2 stimulation. Interacts with RCC1; the interaction is detected in the nucleus upon OR1D2 stimulation.
Interacts with CXCR4; the interaction is dependent on C-terminal phosphorylation of CXCR4 and allows activation
of MAPK1 and MAPK3. Interacts with GPR143. Interacts with HCK and CXCR1 (phosphorylated)
Subcellular location: Cytoplasm. Nucleus. Cell membrane. Membrane, clathrin-coated pit (By similarity).
Cytoplasmic vesicle. Note=Translocates to the plasma membrane and colocalizes with antagonist-stimulated GPCRs
Secondary accessions: B4DLW0 B5B0C0 B7WPL3 D3DTK2 H0Y688 Q0Z8D3 Q2PP19 Q6ICT3 Q8N7Y2 Q9UEQ6
Alternative splicing: 5 isoforms:  P32121-1   P32121-3   P32121-2   P32121-4   P32121-5   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for ARRB2: NX_P32121

Explore proteomics data for ARRB2 at MOPED 

Post-translational modifications:

  • UniProtKB: Phosphorylated at Thr-382 in the cytoplasm; probably dephosphorylated at the plasma membrane. The phosphorylation
    does not regulate internalization and recycling of ADRB2, interaction with clathrin or AP2B1
  • UniProtKB: The ubiquitination status appears to regulate the formation and trafficking of beta-arrestin-GPCR complexes and
    signaling. Ubiquitination appears to occurr GPCR-specifc. 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. Stimulation of a class B GPCR promotes a sustained ubiquitination
  • UniProtKB: Hydroxylation by PHD2 modulates the rate of internalization by slowing down recruitment to the plasma membrane and
    inhibiting subsequent co-internalization with class A receptors
  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_P32121

  • ARRB2 Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    ARRB2 Protein Expression
    REFSEQ proteins (6 alternative transcripts): 
    NP_001244257.1  NP_001244258.1  NP_001244259.1  NP_001244260.1  NP_004304.1  NP_945355.1  

    ENSEMBL proteins: 
     ENSP00000269260   ENSP00000458371   ENSP00000466344   ENSP00000341895   ENSP00000465296  
     ENSP00000458946   ENSP00000370898   ENSP00000403701   ENSP00000465877   ENSP00000466857  
     ENSP00000460879   ENSP00000460607  
    Reactome Protein details: P32121
    Human Recombinant Protein Products for ARRB2: 
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    OriGene Protein Over-expression Lysate for ARRB2
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    Novus Biologicals ARRB2 Proteins
    Novus Biologicals ARRB2 Lysates
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates 
    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp. 

    Gene Ontology (GO): 5/12 cellular component terms (GO ID links to tree view) (see all 12):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005622intracellular ----
    GO:0005634nucleus IDA16820410
    GO:0005737cytoplasm IDA12958365
    GO:0005829cytosol TAS--
    GO:0005886plasma membrane TAS--

    ARRB2 for ontologies           About GeneDecksing



    ARRB2 Antibody Products: 
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    Assay Products for ARRB2: 
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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    5/7 InterPro protein domains (see all 7):
     IPR000698 Arrestin
     IPR014756 Ig_E-set
     IPR014752 Arrestin_C
     IPR011022 Arrestin_C-like
     IPR011021 Arrestin-like_N

    Graphical View of Domain Structure for InterPro Entry P32121

    ProtoNet protein and cluster: P32121

    1 Blocks protein domain: IPB000698 Arrestin

    UniProtKB/Swiss-Prot: ARRB2_HUMAN, P32121
    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)
    Similarity: Belongs to the arrestin family


    ARRB2 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,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    Molecular Function:

         UniProtKB/Swiss-Prot Summary: ARRB2_HUMAN, P32121
    Function: Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both
    receptor desensitization and resensitization processes. During homologous desensitization, beta-arrestins bind to
    the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G-protein; the binding
    appears to require additional receptor determinants exposed only in the active receptor conformation. The
    beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs,
    clathrin-associated sorting proteins) and recruiting the GPRCs to the adapter protein 2 complex 2 (AP-2) in
    clathrin-coated pits (CCPs). However, the extent of beta-arrestin involvement appears to vary significantly
    depending on the receptor, agonist and cell type. Internalized arrestin-receptor complexes traffic to
    intracellular endosomes, where they remain uncoupled from G-proteins. Two different modes of arrestin-mediated
    internalization occur. Class A receptors, like ADRB2, OPRM1, ENDRA, D1AR and ADRA1B dissociate from beta-arrestin
    at or near the plasma membrane and undergo rapid recycling. Class B receptors, like AVPR2, AGTR1, NTSR1, TRHR and
    TACR1 internalize as a complex with arrestin and traffic with it to endosomal vesicles, presumably as
    desensitized receptors, for extended periods of time. Receptor resensitization then requires that receptor-bound
    arrestin is removed so that the receptor can be dephosphorylated and returned to the plasma membrane. Mediates
    endocytosis of CCR7 following ligation of CCL19 but not CCL21. Involved in internalization of P2RY1, P2RY4, P2RY6
    and P2RY11 and ATP-stimulated internalization of P2RY2. Involved in phosphorylation-dependent internalization of
    OPRD1 and subsequent recycling or degradation. Involved in ubiquitination of IGF1R. Beta-arrestins function as
    multivalent adapter proteins that can switch the GPCR from a G-protein signaling mode that transmits short-lived
    signals from the plasma membrane via small molecule second messengers and ion channels to a beta-arrestin
    signaling mode that transmits a distinct set of signals that are initiated as the receptor internalizes and
    transits the intracellular compartment. Acts as signaling scaffold for MAPK pathways such as MAPK1/3 (ERK1/2) and
    MAPK10 (JNK3). ERK1/2 and JNK3 activated by the beta-arrestin scaffold are largely excluded from the nucleus and
    confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Acts as
    signaling scaffold for the AKT1 pathway. GPCRs for which the beta-arrestin-mediated signaling relies on both
    ARRB1 and ARRB2 (codependent regulation) include ADRB2, F2RL1 and PTH1R. For some GPCRs the
    beta-arrestin-mediated signaling relies on either ARRB1 or ARRB2 and is inhibited by the other respective
    beta-arrestin form (reciprocal regulation). Increases ERK1/2 signaling in AGTR1- and AVPR2-mediated activation
    (reciprocal regulation). Involved in CCR7-mediated ERK1/2 signaling involving ligand CCL19. Is involved in
    type-1A angiotensin II receptor/AGTR1-mediated ERK activity. Is involved in type-1A angiotensin II
    receptor/AGTR1-mediated MAPK10 activity. Is involved in dopamine-stimulated AKT1 activity in the striatum by
    disrupting the association of AKT1 with its negative regulator PP2A. Involved in AGTR1-mediated chemotaxis.
    Appears to function as signaling scaffold involved in regulation of MIP-1-beta-stimulated CCR5-dependent
    chemotaxis. Involved in attenuation of NF-kappa-B-dependent transcription in response to GPCR or cytokine
    stimulation by interacting with and stabilizing CHUK. Suppresses UV-induced NF-kappa-B-dependent activation by
    interacting with CHUK. The function is promoted by stimulation of ADRB2 and dephosphorylation of ARRB2. Involved
    in p53/TP53-mediated apoptosis by regulating MDM2 and reducing the MDM2-mediated degradation of p53/TP53. May
    serve as nuclear messenger for GPCRs. Upon stimulation of OR1D2, may be involved in regulation of gene expression
    during the early processes of fertilization. Also involved in regulation of receptors others than GPCRs. Involved
    in endocytosis of TGFBR2 and TGFBR3 and down-regulates TGF-beta signaling such as NF-kappa-B activation. Involved
    in endocytosis of low-density lipoprotein receptor/LDLR. Involved in endocytosis of smoothened homolog/Smo, which
    also requires ADRBK1. Involved in endocytosis of SLC9A5. Involved in endocytosis of ENG and subsequent
    TGF-beta-mediated ERK activation and migration of epithelial cells. Involved in Toll-like receptor and IL-1
    receptor signaling through the interaction with TRAF6 which prevents TRAF6 autoubiquitination and oligomerization
    required for activation of NF-kappa-B and JUN. Involved in insulin resistance by acting as insulin-induced
    signaling scaffold for SRC, AKT1 and INSR. Involved in regulation of inhibitory signaling of natural killer cells
    by recruiting PTPN6 and PTPN11 to KIR2DL1. Involved in IL8-mediated granule release in neutrophils

         Genatlas biochemistry entry for ARRB2:
    beta-arrestin 2,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): 5/17 molecular function terms (GO ID links to tree view) (see all 17):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001664G-protein coupled receptor binding IPI10644702
    GO:0005102receptor binding IPI18604210
    GO:0005515protein binding IPI12958365
    GO:0019904protein domain specific binding IEA--
    GO:0031625ubiquitin protein ligase binding IPI15878855
         
    ARRB2 for ontologies           About GeneDecksing


    Phenotypes:
         9 MGI mutant phenotypes (inferred from 2 alleles(MGI details for Arrb2):
     behavior/neurological  cellular  growth/size  homeostasis/metabolism  immune system 
     integument  mortality/aging  nervous system  respiratory system 

    ARRB2 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-out Arrb2tm1Rjl for ARRB2

       inGenious Targeting Laboratory - Custom generated mouse model solutions for ARRB2 
       inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for ARRB2

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for ARRB2 
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for ARRB2 

    miRNA
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    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat ARRB2
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    SwitchGear 3'UTR luciferase reporter plasmidARRB2 3' UTR sequence
    Inhib. RNA
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    (Pathways according to EMD Millipore, 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 SABiosciences, 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 Oct 2013 via Entrez Gene).
    About This Section

    SuperPaths for ARRB2 About   (see all 32)                                                                                              See pathways by source

    SuperPathContained pathways About
    1Thromboxane signalling through TP receptor
    Thrombin signalling through proteinase activated receptors (PARs)0.67
    Development Angiotensin signaling via beta-Arrestin0.40
    2MAPK signaling pathway
    MAPK signaling pathway0.50
    MAPK signaling pathway0.50
    3Chemokine Signaling
    Chemokine Signaling0.33
    Chemokine signaling pathway0.33
    4Signaling by NOTCH1 t(7 9)(NOTCH1:M1580 K2555) Translocation Mutant
    Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer0.79
    Signaling by NOTCH1 in Cancer0.79
    Signaling by NOTCH1 PEST Domain Mutants in Cancer0.79
    Signaling by NOTCH10.79
    FBXW7 Mutants and NOTCH1 in Cancer0.79
    Signaling by NOTCH1 t(7 9)(NOTCH1:M1580 K2555) Translocation Mutant0.79
    Signaling by NOTCH1 HD Domain Mutants in Cancer0.79
    Signaling by NOTCH0.74
    5Platelet activation, signaling and aggregation
    Platelet activation, signaling and aggregation0.43
    Hemostasis0.43

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    2 EMD Millipore Pathways for ARRB2
        Development Angiotensin signaling via beta-Arrestin
    Cytoskeleton remodeling RalA regulation pathway

    3 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for ARRB2
        Chemokine Signaling
    NK1R-mediated Non-Apoptotic PCD
    cAMP Pathway

    2 Cell Signaling Technology (CST) Pathways for ARRB2
        Wnt / Hedgehog / Notch
    Tyrosine Kinases / Adaptors

    2 GeneGo (Thomson Reuters) Pathways for ARRB2
        Development Angiotensin signaling via beta-Arrestin
    Cytoskeleton remodeling RalA regulation pathway

    5/15 BioSystems Pathways for ARRB2 (see all 15)
        MAPK signaling pathway
    Myometrial Relaxation and Contraction Pathways
    Calcium Regulation in the Cardiac Cell
    TGF-beta Receptor Signaling Pathway
    Wnt Signaling Pathway NetPath


    5/14        Reactome Pathways for ARRB2 (see all 14)
        Hemostasis
    Signaling by NOTCH
    FBXW7 Mutants and NOTCH1 in Cancer
    Signaling by NOTCH1 HD Domain Mutants in Cancer
    Signaling by NOTCH1 in Cancer

    2 PharmGKB Pathways for ARRB2
        Beta-agonist/Beta-blocker Pathway, Pharmacodynamics
    Diuretics Pathway, Pharmacodynamics

    5/7         Kegg Pathways  (Kegg details for ARRB2) (see all 7):
        MAPK signaling pathway
    Chemokine signaling pathway
    Endocytosis
    Dopaminergic synapse
    Olfactory transduction


    ARRB2 for pathways           About GeneDecksing

    Interactions:

        Search SABiosciences Gene Network CentralTM Interacting Genes and Proteins Networks for ARRB2

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

    5/758 Interacting proteins for ARRB2 (P321211, 2, 3 ENSP000002692604) via UniProtKB, MINT, STRING, and/or I2D (see all 758)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    ENSG00000212866P081073I2D: score=1 
    ENSG00000215328P081073I2D: score=1 
    ENSG00000224501P081073I2D: score=1 
    ENSG00000231555P081073I2D: score=1 
    ENSG00000232804P081073I2D: score=1 
    About this table

    Gene Ontology (GO): 5/40 biological process terms (GO ID links to tree view) (see all 40):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001932regulation of protein phosphorylation ----
    GO:0001934positive regulation of protein phosphorylation ----
    GO:0002031G-protein coupled receptor internalization IMP12582207
    GO:0002032desensitization of G-protein coupled receptor protein signaling pathway by arrestin IMP12582207
    GO:0002092positive regulation of receptor internalization IEA--

    ARRB2 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    ARRB2 for compounds           About GeneDecksing

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

    Browse Tocris compounds for ARRB2

    10 Novoseek inferred chemical compound relationships for ARRB2 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    etorphine 54.6 3 12860981 (1), 16115983 (1)
    threonine 32.2 3 17363685 (2), 19846537 (1)
    serine 31 4 17363685 (2), 18096696 (1), 19846537 (1)
    morphine 28.9 14 19071087 (4), 19477204 (2), 16115983 (1), 15849022 (1)
    isoproterenol 19.9 2 16051698 (2)
    opiate 14.9 4 14969742 (3)
    dopamine 8.2 2 15849022 (1), 18768802 (1)
    glycogen 4.88 1 19366991 (1)
    tyrosine 4.86 1 19828694 (1)
    atp 0 3 15728711 (2)

    Search CenterWatch for drugs/clinical trials and news about ARRB2

    (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,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    REFSEQ mRNAs for ARRB2 gene (6 alternative transcripts): 
    NM_001257328.1  NM_001257329.1  NM_001257330.1  NM_001257331.1  NM_004313.3  NM_199004.1  

    Unigene Cluster for ARRB2:

    Arrestin, beta 2
    Hs.435811  [show with all ESTs]
    Unigene Representative Sequence: NM_001257328
    18/20 Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 20):
    ENST00000269260(uc002fyj.3 uc002fyk.3 uc002fyl.3 uc010vsg.2 uc002fym.3 uc002fyn.3)
    ENST00000574502 ENST00000574954 ENST00000570718 ENST00000570739 ENST00000346341
    ENST00000572457 ENST00000574888 ENST00000575131 ENST00000571791 ENST00000572497
    ENST00000573886 ENST00000381488 ENST00000412477 ENST00000571428 ENST00000575877
    ENST00000576235 ENST00000572782
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    Additional mRNA sequence: 

    AB209786.1 AF106941.1 AK097542.1 AK290951.1 AK297059.1 AK297181.1 BC007427.2 BC039066.1 
    BC067368.1 BC095450.1 CR450310.1 CR749218.1 DQ664180.1 EU883572.1 NR_047516.1 Z11501.1 

    20 DOTS entries:

    DT.446214  DT.100795649  DT.100029380  DT.95260342  DT.95260334  DT.95260335  DT.120918219  DT.100029379 
    DT.101975712  DT.91826805  DT.92439000  DT.92439012  DT.100834184  DT.120918187  DT.120918230  DT.120918276 
    DT.92439001  DT.95260344  DT.40131620  DT.91690247 

    24/275 AceView cDNA sequences (see all 275):

    AW339626 AI198368 AA948189 AA002119 AA357190 CR609288 BQ437671 CA428342 
    CR618545 BI039218 BM987156 BU681734 BX091880 CR620652 CA448696 BQ212507 
    NM_004313 BQ438853 AI300602 BU626617 BI021272 BQ213860 AA331076 BQ882891 

    GeneLoc Exon Structure

    5/8 Alternative Splicing Database (ASD) splice patterns (SP) for ARRB2 (see all 8)    About this scheme

    ExUns: 1a · 1b ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b · 6c ^ 7 ^ 8 ^ 9 ^ 10a · 10b · 10c ^ 11 ^ 12 ^ 13a · 13b ^ 14 ^ 15 ^ 16
    SP1:                                                                                -           -                                             
    SP2:                          -                                                                                                               
    SP3:              -     -     -                                                                                                               
    SP4:              -     -     -     -     -     -     -     -                                                                                 
    SP5:                    -     -                                                                                                               


    ECgene alternative splicing isoforms for ARRB2

    (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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    ARRB2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    ARRB2 Expression
    About this image


    See ARRB2 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for ARRB2

    SOURCE GeneReport for Unigene cluster: Hs.435811
        SABiosciences Expression via Pathway-Focused PCR Array including ARRB2: 
              G-Protein-Coupled Receptor Signaling PathwayFinder in human mouse rat

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    (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)
    About This Section

    This gene was present in the common ancestor of animals.

    Orthologs for ARRB2 gene from 5/13 species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Arrb21 , 5 arrestin, beta 21, 5 89.98(n)1
    96.82(a)1
      11 (42.99 cM)5
    2168691  NM_145429.41  NP_663404.11 
     704326355 
    African clawed frog
    (Xenopus laevis)
    Amphibia LOC3980462 cone arrestin 72.97(n)    L40463.1 
    zebrafish
    (Danio rerio)
    Actinopterygii zgc640072 similar to arrestin, beta 2 79.36(n)   394099  BC054595.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta krz3   -- 56(a)
    (best of 3)
      100E3   --
    worm
    (Caenorhabditis elegans)
    Secernentea arr-13 beta-arrestin 52(a)     --


    ENSEMBL Gene Tree for ARRB2 (if available)
    TreeFam Gene Tree for ARRB2 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for ARRB2 gene
    SAG2  ARR32  ARRB12  
    6 SIMAP similar genes for ARRB2 using alignment to 7 protein entries:     ARRB2_HUMAN (see all proteins):
    DKFZp686L0365    ARRB1    ARR3    DKFZp686J1593    SAG    DKFZp686I1383

    ARRB2 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/423 SNPs in ARRB2 are shown (see all 423)    About this table     
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 17 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs20894801,2
    C,F,H--4611799(+) TACTAC/G/TAGCTC 7 -- us2k122NS EA NA 2644
    rs770019781,2
    C,F--4611801(+) CTACAG/ACTCAT 7 -- us2k12Minor allele frequency- A:0.10CSA WA 120
    rs786087531,2
    C,F--4611810(+) ATAAAG/AGCAGT 7 -- us2k11Minor allele frequency- A:0.01NA 120
    rs762804131,2
    C,F--4611812(+) AAAGGC/AAGTGT 7 -- us2k12Minor allele frequency- A:0.07WA 120
    rs1470246001,2
    --4611813(+) AAGGCA/GGTGTA 7 -- us2k10--------
    rs1476738371,2
    --4611818(+) AGTGTA/TGACCC 7 -- us2k10--------
    rs1849792511,2
    --4611830(+) AAAAAC/GGAGCA 7 -- us2k10--------
    rs1422413641,2
    C--4611835(+) GGAGCA/CGCAGC 7 -- us2k10--------
    rs23261171,2
    C,F,H--4611839(+) CAGCAG/ACAAGA 7 -- us2k110Minor allele frequency- A:0.07NS EA NA WA CSA 663
    rs1461164221,2
    --4611843(+) AGCAAA/GATTTA 7 -- us2k10--------

    HapMap Linkage Disequilibrium report for ARRB2 (4613784 - 4624795 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 5 variations for ARRB2:    About this table     
    Variant IDTypeSubtypePubMed ID
    esv2328716CNV Deletion18987734
    esv2715557CNV Deletion23290073
    esv995819CNV Deletion20482838
    nsv833346CNV Loss17160897
    nsv111849CNV Loss16902084

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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    OMIM gene information: 107941    OMIM disorders: --

    20/29 diseases for ARRB2 (see all 29):    About MalaCards
    pain agnosia    whim syndrome    tardive dyskinesia    agnosia
    cocaine dependence    nicotine dependence    choroiditis    allergic asthma
    retinal degeneration    attention deficit hyperactivity disorder    thyroiditis    alcohol dependence
    asthma    meningitis    hyperglycemia    retinitis
    alcoholism    cystic fibrosis    insulin resistance    schizophrenia

    1 disease from the University of Copenhagen DISEASES database for ARRB2:
    Pain agnosia

    ARRB2 for disorders           About GeneDecksing

    6 Novoseek inferred disease relationships for ARRB2 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    retinal degeneration 42.3 3 16835270 (3)
    retinopathy 19.5 2 8733141 (1)
    asthma allergic 15 1 12925697 (1)
    asthma 0 1 12925697 (1)
    tumors 0 1 12488444 (1)
    heart failure 0 2 8293560 (2)

    Genetic Association Database (GAD): ARRB2
    Human Genome Epidemiology (HuGE) Navigator: ARRB2 (19 documents)

    Export disorders for ARRB2 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

    PubMed articles for ARRB2 gene, integrated from 9 sources (see all 307):
    (articles sorted by number of sources associating them with ARRB2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Chromosome mapping of the human arrestin (SAG), beta-arrestin 2 (ARRB2), and beta-adrenergic receptor kinase 2 (ADRBK2) genes. (PubMed id 7695743)1, 3, 9 Calabrese G....De Blasi A. (1994)
    2. Beta-arrestin 2 functions as a G-protein-coupled receptor-activated regulator of oncoprotein Mdm2. (PubMed id 12488444)1, 2, 9 Wang P....Pei G. (2003)
    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. (2008)
    4. The coding-synonymous polymorphism rs1045280 (Ser280Ser) in beta-arrestin 2 (ARRB2) gene is associated with tardive dyskinesia in Chinese patients with schizophrenia. (PubMed id 19049562)1, 4, 9 Liou Y.J....Lai I.C. (2008)
    5. Possible association of beta-arrestin 2 gene with methamphetamine use disorder, but not schizophrenia. (PubMed id 17233643)1, 4, 9 Ikeda M....Iwata N. (2007)
    6. Activity-dependent internalization of smoothened mediated by beta- arrestin 2 and GRK2. (PubMed id 15618519)1, 2, 9 Chen W.... Lefkowitz R.J. (2004)
    7. Dynamic interaction between the dual specificity phosphatase MKP7 and the JNK3 scaffold protein beta-arrestin 2. (PubMed id 15888437)1, 2, 9 Willoughby E.A. and Collins M.K. (2005)
    8. A scanning peptide array approach uncovers associatio n sites within the JNK/beta arrestin signalling complex. (PubMed id 19782076)1, 2, 9 Li X....Baillie G.S. (2009)
    9. Beta-arrestin 2-dependent angiotensin II type 1A receptor-mediated pathway of chemotaxis. (PubMed id 15635042)1, 2, 9 Hunton D.L.... Lefkowitz R.J. (2005)
    10. {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. (2005)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     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
    Entrez Gene: 409 HGNC: 712 AceView: ARRB2 Ensembl:ENSG00000141480 euGenes: HUgn409
    ECgene: ARRB2 Kegg: 409 H-InvDB: ARRB2

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for ARRB2 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for ARRB2 Genetics and Cytogenetics in Oncology and Haematology
    Wikipedia http://en.wikipedia.org/wiki/Arrestin

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    Patent Information for ARRB2 gene:
    Search GeneIP for patents involving ARRB2

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



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    About This Section

     
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     Search LifeMap BioReagents cell lines for ARRB2
     Gene Synthesis
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     Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ARRB2
     SwitchGear 3'UTR luciferase reporter plasmids for ARRB2
     SwitchGear Promoter luciferase reporter plasmids for ARRB2
     ThermoFisher Antibodies for ARRB2
     Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat ARRB2
     inGenious Targeting Laboratory - Custom generated mouse model solutions for ARRB2
     inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for ARRB2
    Customized:
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     LSBio Antibodies in human, mouse, rat for ARRB2
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    GeneCards Homepage - Last full update: 23 Oct 2013 - Incrementals: 4 Nov 2013 , 7 Nov 2013 , 23 Jan 2014

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    Category
    (GIFtS: 73)
    transforming growth factor, beta 1
    GIFtS Group
    The GeneCards human gene database gene index: 1 3 5 6 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z 


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