FB2025_01 , released February 20, 2025
Gene: Dmel\Arr2
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General Information
Symbol
Dmel\Arr2
Species
D. melanogaster
Name
Arrestin 2
Annotation Symbol
CG5962
Feature Type
FlyBase ID
FBgn0000121
Gene Model Status
Stock Availability
Gene Summary
Arrestin 2 (Arr2) encodes a protein involved in rhodopsin inactivation that contributes to photoreceptor maintenance and smell and sound perception. [Date last reviewed: 2019-03-07] (FlyBase Gene Snapshot)
Also Known As

arrestin, PRI, phosrestin I, Β-Arrestin, ArrB

Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
3-26
RefSeq locus
NT_037436 REGION:8647261..8648936
Sequence
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
Gene Ontology (GO) Annotations (14 terms)
Molecular Function (3 terms)
Terms Based on Experimental Evidence (1 term)
CV Term
Evidence
References
inferred from physical interaction with FLYBASE:ninaE; FB:FBgn0002940
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN001370087
traceable author statement
Biological Process (8 terms)
Terms Based on Experimental Evidence (6 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
Cellular Component (3 terms)
Terms Based on Experimental Evidence (3 terms)
CV Term
Evidence
References
located_in cytoplasm
inferred from direct assay
colocalizes_with rhabdomere
inferred from direct assay
inferred from direct assay
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
is_active_in cytoplasm
inferred from biological aspect of ancestor with PANTHER:PTN001370087
Gene Group (FlyBase)
Protein Family (UniProt)
Belongs to the arrestin family. (P19107)
Summaries
Gene Snapshot
Arrestin 2 (Arr2) encodes a protein involved in rhodopsin inactivation that contributes to photoreceptor maintenance and smell and sound perception. [Date last reviewed: 2019-03-07]
Protein Function (UniProtKB)
Regulates photoreceptor cell deactivation (PubMed:36994075, PubMed:8316831). Arr1 and Arr2 proteins are mediators of rhodopsin inactivation and are essential for the termination of the phototransduction cascade (PubMed:8316831). Involved in regulating normal cycles of per nuclear accumulation in brain circadian neurons and thus is important for normal circadian behavior (PubMed:36994075). In the dark, functions with Arr1 to promote the formation of cytosolic Bdbt foci, which are required for dco localization to photoreceptor nuclei where it phosphorylates and activates degradation of per (PubMed:36994075).
(UniProt, P19107)
Phenotypic Description (Red Book; Lindsley and Zimm 1992)
Arr2
Encodes a second Drosophila homologue of mammalian arrestin, a 49-kd (or 46-kd) protein that is phosphorylated by exposure to light in wild type but not in ninaE flies which lack rhodopsin in photoreceptor cells 1-6, nor norpA flies which are deficient in phospholipase C activity. Phosphorylation dependent on the presence of Ca++, whose intracellular levels are regulated by phospholipase C. Expression first detected in late pupae, when other genes involved in phototransduction are also first expressed. Arr2 expression is approximately seven times that of Arr1. In the adult, transcript localized to photoreceptor cells of the compound eye and the ocelli.
Summary (Interactive Fly)

a protein that interacts stoichiometrically with activated rhodopsin, inhibiting its ability to interact with the G protein, transducin, thus terminating the visual response

Gene Model and Products
Number of Transcripts
1
Number of Unique Polypeptides
1

Please see the JBrowse view of Dmel\Arr2 for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)
Isoform displayed:
Pfam protein domains
InterPro name
classification
start
end
Protein Domains (via SMART)
Isoform displayed:
SMART protein domains
InterPro name
classification
start
end
Structure
Protein 3D structure   (Predicted by AlphaFold)   (AlphaFold entry P19107)

If you don't see a structure in the viewer, refresh your browser.
Model Confidence:
  • Very high (pLDDT > 90)
  • Confident (90 > pLDDT > 70)
  • Low (70 > pLDDT > 50)
  • Very low (pLDDT < 50)

AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Some regions with low pLDDT may be unstructured in isolation.

Experimentally Determined Structures
Crossreferences
Comments on Gene Model

Gene model reviewed during 5.46

Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0076599
1547
401
Additional Transcript Data and Comments
Reported size (kB)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
FBpp0076326
45.0
401
8.87
Polypeptides with Identical Sequences

There is only one protein coding transcript and one polypeptide associated with this gene

Additional Polypeptide Data and Comments
Reported size (kDa)
Comments
External Data
Post Translational Modification

Phosphorylated upon light exposure.

(UniProt, P19107)
Linkouts
Sequences Consistent with the Gene Model
Nucleotide / Polypeptide Records
 
Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Arr2 using the Feature Mapper tool.

External Data
Crossreferences
Linkouts
Expression Data
Testis-specificity index

The testis specificity index was calculated from modENCODE tissue expression data by Vedelek et al., 2018 to indicate the degree of testis enrichment compared to other tissues. Scores range from -2.52 (underrepresented) to 5.2 (very high testis bias).

-0.61

Transcript Expression
expression microarray
Stage
Tissue/Position (including subcellular localization)
Reference
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

Eye-enriched transcripts determined by ratio of expression level in wild-type heads. versus expression level in so heads.

Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
immunolocalization
Stage
Tissue/Position (including subcellular localization)
Reference
mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
western blot
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

In flies reared in the dark, ~20-30% of Arr2 is immunolocalized to the rhabdomere, whilst the remaining ~70-80% localizes in the cell body cytoplasm.

Arr2 protein localization is light dependent. In dark conditions, Arr2 is localized throughout the photoreceptor cell, but in response to light, the protein becomes concentrated in the rhabdomeres.

Arr2 protein is detected in all rhabdomeres of the adult visual system.

Marker for
 
Subcellular Localization
CV Term
Evidence
References
located_in cytoplasm
inferred from direct assay
colocalizes_with rhabdomere
inferred from direct assay
inferred from direct assay
Expression Deduced from Reporters
Reporter: P{arr2-lacZ}
Stage
Tissue/Position (including subcellular localization)
Reference
High-Throughput Expression Data
Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\Arr2 in JBrowse
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
Reference
See Gelbart and Emmert, 2013 for analysis details and data files for all genes.
Developmental Proteome: Life Cycle
Developmental Proteome: Embryogenesis
External Data and Images
Linkouts
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
Images
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 13 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 19 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of Arr2
Transgenic constructs containing regulatory region of Arr2
Aberrations (Deficiencies and Duplications) ( 1 )
Inferred from experimentation ( 1 )
Inferred from location ( 4 )
Variants
Variant Molecular Consequences
Alleles Representing Disease-Implicated Variants
Phenotypes
Orthologs
Human Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Homo sapiens (Human) (10)
5 of 14
Yes
No
5 of 14
Yes
No
2  
5 of 14
Yes
No
2  
5 of 14
Yes
No
1  
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
2  
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (10)
5 of 14
Yes
No
5 of 14
Yes
No
4 of 14
No
No
2 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Mus musculus (laboratory mouse) (10)
5 of 14
Yes
No
5 of 14
Yes
No
5 of 14
Yes
No
4 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Xenopus tropicalis (Western clawed frog) (7)
2 of 13
Yes
No
2 of 13
Yes
No
2 of 13
Yes
No
2 of 13
Yes
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
Danio rerio (Zebrafish) (17)
5 of 14
Yes
No
5 of 14
Yes
No
5 of 14
Yes
No
4 of 14
No
No
4 of 14
No
No
4 of 14
No
No
4 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Caenorhabditis elegans (Nematode, roundworm) (23)
5 of 14
Yes
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Anopheles gambiae (African malaria mosquito) (14)
12 of 12
Yes
Yes
3 of 12
No
No
Arabidopsis thaliana (thale-cress) (0)
Saccharomyces cerevisiae (Brewer's yeast) (0)
Schizosaccharomyces pombe (Fission yeast) (0)
Escherichia coli (enterobacterium) (0)
Other Organism Orthologs (via OrthoDB)
Data provided directly from OrthoDB:Arr2. Refer to their site for version information.
Paralogs
Paralogs (via DIOPT v9.1)
Drosophila melanogaster (Fruit fly) (17)
5 of 13
5 of 13
5 of 13
1 of 13
1 of 13
1 of 13
1 of 13
1 of 13
1 of 13
1 of 13
1 of 13
1 of 13
1 of 13
1 of 13
1 of 13
1 of 13
1 of 13
Human Disease Associations
FlyBase Human Disease Model Reports
    Disease Ontology (DO) Annotations
    Models Based on Experimental Evidence ( 1 )
    Allele
    Disease
    Evidence
    References
    Potential Models Based on Orthology ( 2 )
    Human Ortholog
    Disease
    Evidence
    References
    Modifiers Based on Experimental Evidence ( 2 )
    Allele
    Disease
    Interaction
    References
    Disease Associations of Human Orthologs (via DIOPT v9.1 and OMIM)
    Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.
    Functional Complementation Data
    Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.
    Interactions
    Summary of Physical Interactions
    esyN Network Diagram
    Show neighbor-neighbor interactions:
    Show/hide secondary interactors 
    (data from AllianceMine provided by esyN)
    Select Layout:
    Legend:
    Protein
    RNA
    Selected Interactor(s)
    Other Interaction Browsers

    Please see the Physical Interaction reports below for full details
    protein-protein
    Physical Interaction
    Assay
    References
    Summary of Genetic Interactions
    esyN Network Diagram
    Show/hide secondary interactors 
    (data from AllianceMine provided by esyN)
    esyN Network Key:
    Suppression
    Enhancement
    Other Interaction Browsers

    Please look at the allele data for full details of the genetic interactions
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    External Data
    Linkouts
    BioGRID - A database of protein and genetic interactions.
    DroID - A comprehensive database of gene and protein interactions.
    MIST (genetic) - An integrated Molecular Interaction Database
    MIST (protein-protein) - An integrated Molecular Interaction Database
    Pathways
    Signaling Pathways (FlyBase)
    Metabolic Pathways
    FlyBase
    External Links
    External Data
    Class of Gene
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    3L
    Recombination map
    3-26
    Cytogenetic map
    Sequence location
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    66D9-66D9
    Limits computationally determined from genome sequence between P{lacW}foij8E8 and P{PZ}SrpRβrK561&P{lacW}l(3)j5B6j5B6
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    66D10-66D11
    (determined by in situ hybridisation)
    Experimentally Determined Recombination Data
    Location
    Left of (cM)
    Right of (cM)
    Notes
    Stocks and Reagents
    Stocks (11)
    Genomic Clones (14)
     

    Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete

    cDNA Clones (992)
     

    Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see JBrowse for alignment of the cDNAs and ESTs to the gene model.

    cDNA clones, fully sequenced
    BDGP DGC clones
    Other clones
    Drosophila Genomics Resource Center cDNA clones

    For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

    cDNA Clones, End Sequenced (ESTs)
    Other clones
    RNAi and Array Information
    Linkouts
    DRSC - Results frm RNAi screens
    Antibody Information
    Laboratory Generated Antibodies
    Commercially Available Antibodies
     
    Cell Line Information
    Publicly Available Cell Lines
     
      Other Stable Cell Lines
       
        Other Comments

        Light-dependent translocation of Arr2 protein into the rhabdomere requires ninaC protein (the ninaC p132 isoform is the primary isoform needed). The interaction between the Arr2 and ninaC proteins is phosphoinositide (PI) dependent and ninaC protein binds PIs directly.

        Light-dependent trafficking of Arr2 protein is regulated by direct interaction with phosphoinositides and is required for light adaptation in the photoreceptor cells.

        Area matching Drosophila EST AI297861. This EST forms a contig with ESTs AA697916 and AI063366 which overlap 5' end of Drosophila 49KDa phosphoprotein gene, Acc. No. M32141.

        Arr2 mediates photoreceptor apoptosis in rdgC306 mutants and long-lived internalised complexes of phosphorylated M-arrestin complexes are the triggering agents for apoptotic death of photoreceptor cells.

        Phosphorylation of Arr2 protein is necessary for its release from rhodopsin.

        Phosrestin 1 is phosphorylated by the CaMKII kinase. The earliest light induced phosphorylation in the photoreceptor is the phosphorylation of a single site of Arr2 by a kinase dependent on both Ca2+ and calmodulin. The kinase that is responsible for the phosphorylation of Arr2 is CaMKII. Results suggest CaMKII may play a role in regulating light adaptation in photoreceptors.

        In disrupted photoreceptor cells metarhodopsin is not stabilised until arrestin is present. In intact photoreceptor cels significant metarhodopsin stabilisation occurs even in the absence of bound arrestin.

        Comparison of upstream DNA of Dmir\Arr2 and Arr2 genes identifies regions that could be involved in retina-specific transcription and dosage compensation.

        A model for metarhodopsin inactivation has been formalised in which the stochiometric binding of arrestin determines the receptor inactivation rate. This model is supported by electrophysiological measurements of metarhodopsin inactivation in dissociated photoreceptors where cytosolic arrestin levels are genetically and physiologically manipulated.

        Arr2 is localised to the photoreceptor cells where the Arr2 gene product undergoes light-dependent phosphorylation.

        Arr2 undergoes light-induced phosphorylation on a subsecond time scale, which is faster than that of any other protein in vivo. Phosphorylation is dependent upon the activation of phosphoinositide-specific phospholipase (PI-PLC), norpA. inaC is dispensible for phosphorylation. Phosphorylation is catalysed by a class of calmodulin-dependent kinase (CaMK) in vitro and Arr2 has a unique phosphorylation site at S366.

        Arr1 and Arr2 proteins have a similar function in regulating photoreceptor cell deactivation. The deactivation of the visual response in Arr2 mutants is primarily determined by Arr1 protein. Although the termination of the phototransduction cascade in wild type photoreceptors is determined by the concerted action of several feedback regulatory steps, in the absence of arrestins the termination of the phototransduction process becomes rate-limited by the slow decay of metarhodopsin.

        Encodes a Drosophila homologue of mammalian arrestin, a protein that is phosphorylated by exposure to light in wild-type but not in ninaE flies which lack rhodopsin in photoreceptor cells 1-6, nor norpA flies which are deficient in phospholipase C activity. Phosphorylation dependent on the presence of Ca++, whose intracellular levels are regulated by phospholipase C.

        Arr1 and Arr2 follow different time courses of phosphorylation in vivo: when 43% of Arr2 is phosphorylated Arr1 remains unchanged (from nonilluminated flies).

        Arr1 and Arr2 have different functional roles in the photoreceptor.

        Phosphorylation of retina-specific polypeptides 80 and 49 may be involved in some early stages of photoreceptor excitation or its modulation.

        Relationship to Other Genes
        Source for database merge of
        Additional comments
        Nomenclature History
        Source for database identify of
        Nomenclature comments
        Etymology
        Synonyms and Secondary IDs (30)
        Reported As
        Symbol Synonym
        AH
        DmArrestin-2
        Dro.-Arr.II
        Phosrestin-1
        Β-Arrestin
        Secondary FlyBase IDs
          Datasets (0)
          Study focus (0)
          Experimental Role
          Project
          Project Type
          Title
          Study result (0)
          Result
          Result Type
          Title
          External Crossreferences and Linkouts ( 53 )
          Sequence Crossreferences
          NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
          GenBank Nucleotide - A collection of sequences from several sources, including GenBank, RefSeq, TPA, and PDB.
          GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.
          RefSeq - A comprehensive, integrated, non-redundant, well-annotated set of reference sequences including genomic, transcript, and protein.
          UniProt/GCRP - The gene-centric reference proteome (GCRP) provides a 1:1 mapping between genes and UniProt accessions in which a single 'canonical' isoform represents the product(s) of each protein-coding gene.
          UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information
          UniProt/TrEMBL - Automatically annotated and unreviewed records of protein sequence and functional information
          Other crossreferences
          AlphaFold DB - AlphaFold provides open access to protein structure predictions for the human proteome and other key proteins of interest, to accelerate scientific research.
          BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
          DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
          EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
          FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
          FlyMine - An integrated database for Drosophila genomics
          KEGG Genes - Molecular building blocks of life in the genomic space.
          MARRVEL_MODEL - MARRVEL (model organism gene)
          Linkouts
          BioGRID - A database of protein and genetic interactions.
          Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
          DroID - A comprehensive database of gene and protein interactions.
          DRSC - Results frm RNAi screens
          FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
          FlyCyc Genes - Genes from a BioCyc PGDB for Dmel
          Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
          Flygut - An atlas of the Drosophila adult midgut
          FlyMet - A comprehensive tissue-specific metabolomics resource for Drosophila.
          iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
          Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
          KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.
          MIST (genetic) - An integrated Molecular Interaction Database
          MIST (protein-protein) - An integrated Molecular Interaction Database
          References (197)