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General Information
Symbol
Dmel\fzr
Species
D. melanogaster
Name
fizzy-related
Annotation Symbol
CG3000
Feature Type
FlyBase ID
FBgn0262699
Gene Model Status
Stock Availability
Gene Summary
fizzy-related (fzr) encodes a protein that binds to the Anaphase-Promoting Complex/Cyclosome (APC/C) ubiquitin ligase to stimulate its activity during G1 phase. [Date last reviewed: 2019-03-07] (FlyBase Gene Snapshot)
Also Known As

Cdh1, rap, retina aberrant in pattern, Rap/Fzr, redax

Key Links
Genomic Location
Cytogenetic map
Sequence location
X:4,667,290..4,679,537 [-]
Recombination map
1-8
RefSeq locus
NC_004354 REGION:4667290..4679537
Sequence
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
GO Summary Ribbons
Gene Ontology (GO) Annotations (19 terms)
Molecular Function (2 terms)
Terms Based on Experimental Evidence (0 terms)
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000460086
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000460086
(assigned by GO_Central )
Biological Process (11 terms)
Terms Based on Experimental Evidence (9 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from mutant phenotype
inferred from direct assay
inferred from mutant phenotype
inferred from mutant phenotype
inferred from direct assay
inferred from mutant phenotype
NOT involved_in exit from mitosis
inferred from mutant phenotype
Terms Based on Predictions or Assertions (3 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000460086
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000460086
(assigned by GO_Central )
inferred from electronic annotation with InterPro:IPR033010
(assigned by InterPro )
Cellular Component (6 terms)
Terms Based on Experimental Evidence (6 terms)
CV Term
Evidence
References
inferred from direct assay
located_in axon
inferred from direct assay
located_in centriole
inferred from direct assay
located_in centrosome
inferred from direct assay
located_in cytoplasm
inferred from direct assay
located_in spindle
inferred from direct assay
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000460086
(assigned by GO_Central )
Gene Group (FlyBase)
Protein Family (UniProt)
-
Summaries
Gene Snapshot
fizzy-related (fzr) encodes a protein that binds to the Anaphase-Promoting Complex/Cyclosome (APC/C) ubiquitin ligase to stimulate its activity during G1 phase. [Date last reviewed: 2019-03-07]
Gene Group (FlyBase)
ANAPHASE-PROMOTING COMPLEX -
Anaphase-promoting complex/cyclosome (APC/C) is a multisubunit E3 ubiquitin ligase. Active during mitosis and G1 phases of the cell cycle, it mediates the degradation of cyclins and other key cell cycle regulators triggering the metaphase to anaphase transition and the exit from mitosis. (Adapted from PMID:12208841).
Phenotypic Description (Red Book; Lindsley and Zimm 1992)
rap: retina aberrant in pattern (J.C. Hall)
Eyes grossly abnormal: rough surface texture, and deep pseudopupil (DPP) has anomalous appearance; finer level observations show ommatidia to be aberrant in size, shape, and alignment; in sections, numbers of photoreceptor cells per ommatidium vary greatly, and positions of such cells plus rhabdomere arrangements are altered. Developmentally, recruitment of presumptive photoreceptors behind morphogenetic furrow in third larval instar eye disc is abnormal: e.g., arrangement of five-cell preclusters is very disorganized, and the normal increase in numbers of cells within clusters does not occur, so that, in regions where eight-cell clusters are found in wild-type, there are small clusters in rap, intermingled with others than can have >8 cells; cell bodies of developing photoreceptor cells do not become apically positioned in the disc, as in wild-type. Temperature-shift experiments on rap4 show a temperature-sensitive period for roughened eye is in third larval instar. Mosaic experiments, involving induced mitotic recombination in rap1/+ larvae, showed that normal adult ommatidia always had a rap+ R8 cell, whereas R1-7 could readily be genotypically rap1 in such facets; also, certain phenotypically mutant ommatidia, near borders separating mutant and wild-type tissue, contained all rap+ cells (in clusters of 3, 4, 6, or 8 photoreceptor cells).
Summary (Interactive Fly)

Trp-Asp repeat (WD-repeat) protein - negatively regulates the levels of cyclins A, B and B3 thus promoting mitosis - Notch-dependent Fizzy-related expression is required for the mitotic-to-endocycle transition in follicle cells

Gene Model and Products
Number of Transcripts
2
Number of Unique Polypeptides
1

Please see the JBrowse view of Dmel\fzr 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
Comments on Gene Model

Gene model reviewed during 5.52

Low-frequency RNA-Seq exon junction(s) not annotated.

Gene model reviewed during 5.55

Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0070686
2610
478
FBtr0070687
2516
478
Additional Transcript Data and Comments
Reported size (kB)

2.6 (longest cDNA)

Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
RefSeq ID
GenBank
FBpp0070654
53.5
478
9.24
FBpp0070655
53.5
478
9.24
Polypeptides with Identical Sequences

The group(s) of polypeptides indicated below share identical sequence to each other.

478 aa isoforms: fzr-PA, fzr-PB
Additional Polypeptide Data and Comments
Reported size (kDa)
Comments
External Data
Linkouts
Sequences Consistent with the Gene Model
Mapped Features

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

External Data
Crossreferences
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Linkouts
Expression Data
Expression Summary Ribbons
Colored tiles in ribbon indicate that expression data has been curated by FlyBase for that anatomical location. Colorless tiles indicate that there is no curated data for that location.
For complete stage-specific expression data, view the modENCODE Development RNA-Seq section under High-Throughput Expression below.
Transcript Expression
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

fzr expression is detected in the testis in the subapical region containing primary spermatocyte clusters that have recently completed the last mitotic division.

Maternal fzr transcripts are detected during early syncytial stages but not in the late syncytial blastoderm. Zygotic expression initiates after the 13th embryonic mitosis and is detectable during gastrulation. Strong expression is observed at stage 11 in the salivary gland placodes and in the anterior and posterior midgut primordia. This is followed by expression at lower levels throughout the embryo. It appears that fzr is expressed in tissues during the stages when the cells become postmitotic.

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

fzr protein and loco protein are strongly co-localized along the ventral edge of the larval brain near the margin between the brain and ventral ganglion but not in deeper regions of the brain. Both proteins are expressed within glial cells and are also expressed early in neuroblasts in third instar larvae.

Marker for
 
Subcellular Localization
CV Term
Evidence
References
inferred from direct assay
located_in axon
inferred from direct assay
located_in centriole
inferred from direct assay
located_in centrosome
inferred from direct assay
located_in cytoplasm
inferred from direct assay
located_in spindle
inferred from direct assay
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\fzr in GBrowse 2
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
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Images
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 29 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 17 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of fzr
Transgenic constructs containing regulatory region of fzr
Aberrations (Deficiencies and Duplications) ( 10 )
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
eye disc & mitotic cell cycle
follicle cell & nucleus | somatic clone, with Scer\GAL4Act5C.PP
Orthologs
Human Orthologs (via DIOPT v8.0)
Homo sapiens (Human) (3)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
15 of 15
Yes
Yes
4 of 15
No
No
3 of 15
No
No
Model Organism Orthologs (via DIOPT v8.0)
Mus musculus (laboratory mouse) (3)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
15 of 15
Yes
Yes
3 of 15
No
No
3 of 15
No
No
2  
Rattus norvegicus (Norway rat) (3)
12 of 13
Yes
Yes
4 of 13
No
No
2 of 13
No
Yes
Xenopus tropicalis (Western clawed frog) (4)
9 of 12
Yes
Yes
3 of 12
No
No
2 of 12
No
Yes
1 of 12
No
Yes
Danio rerio (Zebrafish) (3)
13 of 15
Yes
Yes
12 of 15
No
Yes
4 of 15
No
No
Caenorhabditis elegans (Nematode, roundworm) (2)
13 of 15
Yes
Yes
2 of 15
No
No
Arabidopsis thaliana (thale-cress) (9)
9 of 9
Yes
Yes
8 of 9
No
Yes
8 of 9
No
Yes
2 of 9
No
No
2 of 9
No
No
2 of 9
No
No
2 of 9
No
No
2 of 9
No
No
1 of 9
No
No
Saccharomyces cerevisiae (Brewer's yeast) (3)
13 of 15
Yes
Yes
5 of 15
No
Yes
3 of 15
No
No
Schizosaccharomyces pombe (Fission yeast) (5)
9 of 12
Yes
Yes
8 of 12
No
Yes
2 of 12
No
Yes
2 of 12
No
No
2 of 12
No
No
Ortholog(s) in Drosophila Species (via OrthoDB v9.1) ( EOG091906AQ )
Organism
Common Name
Gene
AAA Syntenic Ortholog
Multiple Dmel Genes in this Orthologous Group
Drosophila suzukii
Spotted wing Drosophila
Drosophila simulans
Drosophila sechellia
Drosophila erecta
Drosophila yakuba
Drosophila ananassae
Drosophila pseudoobscura pseudoobscura
Drosophila persimilis
Drosophila willistoni
Drosophila virilis
Drosophila mojavensis
Drosophila grimshawi
Orthologs in non-Drosophila Dipterans (via OrthoDB v9.1) ( EOG0915046W )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Musca domestica
House fly
Lucilia cuprina
Australian sheep blowfly
Mayetiola destructor
Hessian fly
Aedes aegypti
Yellow fever mosquito
Anopheles darlingi
American malaria mosquito
Anopheles gambiae
Malaria mosquito
Culex quinquefasciatus
Southern house mosquito
Orthologs in non-Dipteran Insects (via OrthoDB v9.1) ( EOG090W04BD )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Bombyx mori
Silkmoth
Danaus plexippus
Monarch butterfly
Heliconius melpomene
Postman butterfly
Apis florea
Little honeybee
Apis mellifera
Western honey bee
Bombus impatiens
Common eastern bumble bee
Bombus terrestris
Buff-tailed bumblebee
Linepithema humile
Argentine ant
Megachile rotundata
Alfalfa leafcutting bee
Nasonia vitripennis
Parasitic wasp
Dendroctonus ponderosae
Mountain pine beetle
Dendroctonus ponderosae
Mountain pine beetle
Tribolium castaneum
Red flour beetle
Pediculus humanus
Human body louse
Rhodnius prolixus
Kissing bug
Rhodnius prolixus
Kissing bug
Cimex lectularius
Bed bug
Cimex lectularius
Bed bug
Zootermopsis nevadensis
Nevada dampwood termite
Zootermopsis nevadensis
Nevada dampwood termite
Zootermopsis nevadensis
Nevada dampwood termite
Zootermopsis nevadensis
Nevada dampwood termite
Zootermopsis nevadensis
Nevada dampwood termite
Zootermopsis nevadensis
Nevada dampwood termite
Zootermopsis nevadensis
Nevada dampwood termite
Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( EOG090X0480 )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Ixodes scapularis
Black-legged tick
Stegodyphus mimosarum
African social velvet spider
Tetranychus urticae
Two-spotted spider mite
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Orthologs in non-Arthropod Metazoa (via OrthoDB v9.1) ( EOG091G06FJ )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strongylocentrotus purpuratus
Purple sea urchin
Strongylocentrotus purpuratus
Purple sea urchin
Strongylocentrotus purpuratus
Purple sea urchin
Ciona intestinalis
Vase tunicate
Ciona intestinalis
Vase tunicate
Gallus gallus
Domestic chicken
Gallus gallus
Domestic chicken
Paralogs
Paralogs (via DIOPT v8.0)
Drosophila melanogaster (Fruit fly) (3)
7 of 10
6 of 10
2 of 10
Human Disease Associations
FlyBase Human Disease Model Reports
    Disease Model Summary Ribbon
    Disease Ontology (DO) Annotations
    Models Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Evidence
    References
    Potential Models Based on Orthology ( 0 )
    Human Ortholog
    Disease
    Evidence
    References
    Modifiers Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Interaction
    References
    Disease Associations of Human Orthologs (via DIOPT v8.0 and OMIM)
    Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.
    Homo sapiens (Human)
    Gene name
    Score
    OMIM
    OMIM Phenotype
    DO term
    Complementation?
    Transgene?
    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:
    Select Layout:
    Legend:
    Protein
    RNA
    Selected Interactor(s)
    Interactions Browser

    Please see the Physical Interaction reports below for full details
    protein-protein
    Physical Interaction
    Assay
    References
    Summary of Genetic Interactions
    esyN Network Diagram
    esyN Network Key:
    Suppression
    Enhancement

    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
    suppressible
    External Data
    Linkouts
    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
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    X
    Recombination map
    1-8
    Cytogenetic map
    Sequence location
    X:4,667,290..4,679,537 [-]
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    4C11-4C12
    Limits computationally determined from genome sequence between P{EP}CG2930EP1352 and P{EP}EP425
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    4C11-4C16
    (determined by in situ hybridisation) 4C7--8 (determined by in situ hybridisation)
    4C7-4C8
    (determined by in situ hybridisation)
    Experimentally Determined Recombination Data
    Left of (cM)
    Right of (cM)
    Notes
    Stocks and Reagents
    Stocks (14)
    Genomic Clones (14)
     

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

    cDNA Clones (103)
     

    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 GBrowse 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)
    RNAi and Array Information
    Linkouts
    GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
    Antibody Information
    Laboratory Generated Antibodies
     
    Commercially Available Antibodies
     
    Other Information
    Relationship to Other Genes
    Source for database identify of

    Source for identity of: fzr CG3000

    Source for identity of: rap wex

    Source for identity of: fzr rap

    Source for database merge of

    Source for merge of: rap fzr

    Source for merge of: l(1)G0326 rap

    Source for merge of: rap anon-WO03040301.193

    Source for merge of: rap redax

    Additional comments

    The 'rap' locus was first phenotypically characterized and named by Karpilow et al., 1989 (FBrf0049809). Later Sigrist and Lehner, 1997 (FBrf0098351) molecularly & functionally characterized a gene and named it as 'fzr'. 4- 5 years later, the connection between the 'rap' locus and the 'fzr' gene was made (FBrf0134170, FBrf0151839), at which point FlyBase kept 'rap' as the 'merged' gene symbol. However, it's clear that 'fzr' is the preferred symbol in the published literature, and so the gene has now (FB2016_06) been renamed from 'rap' to 'fzr' to FlyBase to reflect this. This change is supported by Christian Lehner and Tadmiri Venkatesh.

    Source for merge of rap anon-WO03040301.193 was sequence comparison ( date:051113 ).

    Other Comments

    rap is required for cell cycle-dependent degradation of the CycB product during eye development.

    In rap mutant embryos glial cells are not found at the normal positions but instead fail to migrate as far as in the wildtype embryonic nervous system.

    dsRNA made from templates generated with primers directed against this gene tested in RNAi screen for effects on Kc167 and S2R+ cell morphology.

    rap is not required for completion of mitosis, though is required during G1.

    Identification: screen for mutations affecting commissure formation in the CNS of the embryo.

    rap negatively regulates the levels of CycA, CycB and CycB3 proteins. rap is required for cyclin removal during G1 when the embryonic epidermal cell proliferation stops and during G2 preceding salivary gland endoreduplication.

    In rap mutants, although some of the R8-specific markers show normal expression patterns, other aspects of the R8 cell differentiation are abnormal. R1, R6 and R7 cells fail to differentiate properly. These results suggest rap gene encodes an R8-specific function that plays a role in the determination of the photoreceptor cells R1, R6 and R7.

    The interaction of rap and rg with S is synergistic and dosage sensitive.

    Eyes grossly abnormal: rough surface texture and deep pseudopupil (DPP) has anomalous appearance; finer level observations show ommatidia to be aberrant in size, shape, and alignment; in sections, numbers of photoreceptor cells per ommatidium vary greatly and positions of such cells plus rhabdomere arrangements are altered. Developmentally, recruitment of presumptive photoreceptors behind morphogenetic furrow in third larval instar eye disc is abnormal: e.g., arrangement of five-cell preclusters is very disorganized and the normal increase in numbers of cells within clusters does not occur, so that, in regions where eight-cell clusters are found in wild-type, there are small clusters in rap, intermingled with others than can have >8 cells; cell bodies of developing photoreceptor cells do not become apically positioned in the disc, as in wild-type.

    Origin and Etymology
    Discoverer
    Etymology
    Identification
    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/TrEMBL - Automatically annotated and unreviewed records of protein sequence and functional information
    Other crossreferences
    BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
    Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
    Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
    Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
    GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
    iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
    KEGG Genes - Molecular building blocks of life in the genomic space.
    SignaLink - A signaling pathway resource with multi-layered regulatory networks.
    Synonyms and Secondary IDs (35)
    Reported As
    Symbol Synonym
    anon-WO03040301.193
    rap/fizzy-related
    Secondary FlyBase IDs
    • FBgn0003200
    • FBgn0020547
    • FBgn0029059
    • FBgn0040176
    • FBgn0066831
    • FBgn0026624
    Datasets (0)
    Study focus (0)
    Experimental Role
    Project
    Project Type
    Title
    References (198)