FB2025_01 , released February 20, 2025
Gene: Dmel\insc
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General Information
Symbol
Dmel\insc
Species
D. melanogaster
Name
inscuteable
Annotation Symbol
CG11312
Feature Type
FlyBase ID
FBgn0011674
Gene Model Status
Stock Availability
Gene Summary
inscuteable (insc) encodes an adaptor protein required for asymmetric cell division. It interacts with the microtubule binding protein encoded by mud and the adaptor encoded by pins. It also binds to the apical complex proteins encoded by baz, par-6 and aPKC and may recruit microtubule binding proteins to the apical cell cortex to induce apical-basal spindle orientation. [Date last reviewed: 2019-03-07] (FlyBase Gene Snapshot)
Also Known As

nem, fam, l(2)05475

Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
2-92
RefSeq locus
NT_033778 REGION:20821262..20836028
Sequence
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
Gene Ontology (GO) Annotations (20 terms)
Molecular Function (2 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from physical interaction with FLYBASE:corn; FB:FBgn0259173
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000483397
Biological Process (14 terms)
Terms Based on Experimental Evidence (12 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from physical interaction with FLYBASE:corn; FB:FBgn0259173
inferred from genetic interaction with FLYBASE:Gαi; FB:FBgn0001104
inferred from genetic interaction with FLYBASE:pins; FB:FBgn0040080
inferred from mutant phenotype
inferred from mutant phenotype
inferred from direct assay
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
involved_in RNA localization
inferred from mutant phenotype
inferred from mutant phenotype
Terms Based on Predictions or Assertions (4 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000483397
inferred from electronic annotation with InterPro:IPR039921
inferred from biological aspect of ancestor with PANTHER:PTN000483397
traceable author statement
Cellular Component (4 terms)
Terms Based on Experimental Evidence (4 terms)
CV Term
Evidence
References
located_in cell cortex
inferred from direct assay
located_in cytoplasm
inferred from direct assay
inferred from direct assay
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
is_active_in apical cortex
inferred from biological aspect of ancestor with PANTHER:PTN000483397
Gene Group (FlyBase)
Protein Family (UniProt)
-
Summaries
Gene Snapshot
inscuteable (insc) encodes an adaptor protein required for asymmetric cell division. It interacts with the microtubule binding protein encoded by mud and the adaptor encoded by pins. It also binds to the apical complex proteins encoded by baz, par-6 and aPKC and may recruit microtubule binding proteins to the apical cell cortex to induce apical-basal spindle orientation. [Date last reviewed: 2019-03-07]
Gene Group (FlyBase)
RAPS-INSC COMPLEX -
The raps-insc complex is an adaptor complex involved in organisation of the mitotic spindle in asymmetric cell division. (Adapted from FBrf0217064.)
Summary (Interactive Fly)

novel protein - SH3 binding domain, ankyrin repeats and cytoskeletal attachment domain - controller of cell fate during asymmetric cell division

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

Please see the JBrowse view of Dmel\insc 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 Q9W2R4)

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
PDB - An information portal to biological macromolecular structures
Comments on Gene Model

Gene model reviewed during 5.51

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

Shares 5' UTR with upstream gene.

Gene model reviewed during 5.53

Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0071562
3887
859
Additional Transcript Data and Comments
Reported size (kB)

4.3 (northern blot)

4.2 (northern blot)

Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
FBpp0071490
95.0
859
6.68
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)

767 (aa); 84 (kD predicted)

Comments
External Data
Crossreferences
PDB - An information portal to biological macromolecular structures
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\insc 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
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).

-0.70

Transcript Expression
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
antennal anlage in statu nascendi

Comment: reported as procephalic ectoderm anlage in statu nascendi

dorsal head epidermis anlage in statu nascendi

Comment: reported as procephalic ectoderm anlage in statu nascendi

visual anlage in statu nascendi

Comment: reported as procephalic ectoderm anlage in statu nascendi

antennal anlage

Comment: reported as procephalic ectoderm anlage

central brain anlage

Comment: reported as procephalic ectoderm anlage

dorsal head epidermis anlage

Comment: reported as procephalic ectoderm anlage

visual anlage

Comment: reported as procephalic ectoderm anlage

antennal primordium

Comment: reported as procephalic ectoderm primordium

central brain primordium

Comment: reported as procephalic ectoderm primordium

visual primordium

Comment: reported as procephalic ectoderm primordium

dorsal head epidermis primordium

Comment: reported as procephalic ectoderm primordium

lateral head epidermis primordium

Comment: reported as procephalic ectoderm primordium

ventral head epidermis primordium

Comment: reported as procephalic ectoderm primordium

northern blot
Stage
Tissue/Position (including subcellular localization)
Reference

Comment: reference states 3-12 hr AEL

Comment: reference states 4-20 hr AEL

Additional Descriptive Data

insc transcript is detected in 4-20 hr embryos, and in adult male and female flies. insc transcript is first detected during the cellular blastoderm stage within the procephalic neurogenic region. The region of expression extends dorsally at stage 6/7. Expression is subsequently detected in individual cells within the embryonic brain until late embryogenesis. During germ band extension, insc transcript expression is detected in the neurectoderm, and in early germ band extended embryos, the full wave of delaminating neuroblasts express insc transcript. In the developing CNS, most, if not all, neuroblasts express insc. Transient expression in some putative PNS precursors (external sense organ precursors and Ich5 precursor) is detected in 5 hr embryos. No CNS expression is detected after stage 14 of embryogenesis.

insc RNA is localized to the apical cortex of neuroblasts during interphase. During mitosis, it is located in the cytoplasm.

Marker for
 
Subcellular Localization
CV Term

plasma membrane | apical & proximal to

cytoplasm

Polypeptide Expression
immunolocalization
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

insc protein localizes to the apical end of GMC1-1.

raps protein and insc protein colocalize during the neuroblast cell cycle except in delaminating neuroblasts at which time insc protein is detected in the apical stalks of neuroblasts and raps protein is not detected.

insc protein is first detected at stage 6 in the procephalic neurectoderm and later in the delaminating neuroblasts of the ventral nerve cord. At late stage 10, insc protein is detected in two cells per segment in the lateral epidermis that are thought to be the first two cells that will give rise to the larval peripheral sense organs. Expression is lost in developing sense organs by the time of dorsal closure but remains in the CNS until after it has condensed. In stages 10-13, expression is seen in mesodermal cells presumed to be muscle precursors and in the posterior midgut primordia. Strong expression is seen at stage 15 in the pharynx, gastric caecae, hindgut, tracheal branches, and Malpighian tubules. insc protein is also detected in pupal wing discs older than about 20hr after puparium formation. It is present in the intervein spaces and is excluded from the veins themselves.

Marker for
 
Subcellular Localization
CV Term
Evidence
References
located_in cell cortex
inferred from direct assay
located_in cytoplasm
inferred from direct assay
inferred from direct assay
Expression Deduced from Reporters
Reporter: P{GawB}inscMz1407
Stage
Tissue/Position (including subcellular localization)
Reference
Reporter: P{lacZ}inscAB44
Stage
Tissue/Position (including subcellular localization)
Reference
High-Throughput Expression Data
Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\insc 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
Flygut - An atlas of the Drosophila adult midgut
Images
FlyExpress - Embryonic expression images (BDGP data)
  • Stages(s) 1-3
  • Stages(s) 4-6
  • Stages(s) 7-8
  • Stages(s) 9-10
  • Stages(s) 11-12
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 40 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 40 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of insc
Transgenic constructs containing regulatory region of insc
Aberrations (Deficiencies and Duplications) ( 12 )
Variants
Variant Molecular Consequences
Alleles Representing Disease-Implicated Variants
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
Sterility
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
abdominal ventral sensillum campaniformium vc1 & thecogen cell
abdominal ventral sensillum campaniformium vc2 & thecogen cell
abdominal ventral sensillum campaniformium vc3 & thecogen cell
abdominal ventral sensillum campaniformium vc4a & thecogen cell
abdominal ventral sensillum campaniformium vc4b & thecogen cell
embryonic neuroblast & spindle
mitotic domain 9 & spindle
Orthologs
Human Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Homo sapiens (Human) (1)
6 of 14
Yes
Yes
 
4  
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (1)
6 of 14
Yes
Yes
Mus musculus (laboratory mouse) (1)
7 of 14
Yes
Yes
Xenopus tropicalis (Western clawed frog) (2)
1 of 13
Yes
No
1 of 13
Yes
Yes
Danio rerio (Zebrafish) (0)
Caenorhabditis elegans (Nematode, roundworm) (1)
3 of 14
Yes
Yes
Anopheles gambiae (African malaria mosquito) (0)
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:insc. Refer to their site for version information.
Paralogs
Paralogs (via DIOPT v9.1)
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 ( 0 )
Human Ortholog
Disease
Evidence
References
Modifiers Based on Experimental Evidence ( 1 )
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.
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.
Dmel gene
Ortholog showing functional complementation
Supporting References
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
RNA-protein
Physical Interaction
Assay
References
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
Linkouts
Class of Gene
Genomic Location and Detailed Mapping Data
Chromosome (arm)
2R
Recombination map
2-92
Cytogenetic map
Sequence location
FlyBase Computed Cytological Location
Cytogenetic map
Evidence for location
57B3-57B3
Limits computationally determined from genome sequence between P{lacW}l(2)k06409k06409&P{PZ}insc05475 and P{PZ}l(2)0780607806
Experimentally Determined Cytological Location
Cytogenetic map
Notes
References
57B1-57B4
(determined by in situ hybridisation)
57B1-57B4
57B1-57B20
57B1-57B5
(determined by in situ hybridisation)
57B-57B
(determined by in situ hybridisation)
57B-57B
57B1--3 57B1--5 57B2--3 57B3--5
Experimentally Determined Recombination Data
Left of (cM)
Right of (cM)
Notes
Stocks and Reagents
Stocks (32)
Genomic Clones (22)
cDNA Clones (24)
 

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)
    BDGP DGC 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

        insc has a role in augmenting metaphase spindle length in embryonic neuroblasts.

        insc regulates the apical-basal polarity of the pIIb division in the vp1-vp4a lineages in the embryo.

        mira and insc are required for the correct cortical location of pros protein in NB6-4T.

        The central third of the insc coding region is sufficient for the normal glia-neuron cell-fate choice of the NB6-4T daughter cell.

        Embryos deficient for insc function show failure of spindle rotation in neuroblasts.

        raps and insc might orient asymmetric cell divisions by localising or locally modulating a heterotrimeric G-protein signalling cascade at the apical cell cortex.

        Apical localisation of insc protein in embryonic neuroblasts requires baz.

        Localisation of insc protein depends on baz.

        The correct positioning of numb protein and proper orientation of division in ganglion mother cells requires insc.

        Asymmetrical segregation of numb protein into one of the sibling cells produced by division of muscle progenitor cells depends on insc, and is essential for the specification of distinct sibling cell fates.

        Extrinsic and intrinsic cues and microfilaments regulate the subcellular localisation of the pros, insc and stau proteins in neuroblasts.

        insc and stau mediate asymmetric localization and segregation of pros RNA during neuroblast cell divisions. insc nucleates an apical complex and is required for protein localization, spindle orientation and RNA localization.

        Mutant embryos show lack of muscles without disturbance of myoblast fusion or epidermis pattern.

        insc is a neural precursor gene and encodes a candidate for a cytoskeletal adaptor protein.

        Ectopic expression of insc in other epithelial cells leads to spindle reorientation.

        Orientation of the mitotic spindle and correct localisation of numb and pros in basal daughter cells requires insc.

        insc may be required for the development of the somatic musculature and the chordotonal organs of the PNS, but it is not involved in the development of the visceral mesoderm and the dorsal vessel.

        The CNS and PNS of insc mutants are morphologically abnormal, resulting from general disorganization of the neuroblast array and defective neuroblast morphology and abnormal sense organ morphology. The numbers of particular neuroblasts, and their ganglion mother cell progeny, are also faulty.

        The insc product may affect cytoskeletal organization and/or asymmetric division of neuronal precursors.

        Relationship to Other Genes
        Source for database merge of
        Additional comments

        The complementation group previously identified as 'fam' corresponds to the sktl/insc locus. Until it is demonstrated to be otherwise, all alleles previously represented as alleles of 'fam' are now recorded as alleles of both insc and sktl.

        Nomenclature History
        Source for database identify of
        Nomenclature comments
        Etymology
        Synonyms and Secondary IDs (17)
        Reported As
        Symbol Synonym
        l(2)k12405
        Secondary FlyBase IDs
        • FBgn0010601
        • FBgn0013468
        • FBgn0015387
        Datasets (0)
        Study focus (0)
        Experimental Role
        Project
        Project Type
        Title
        Study result (0)
        Result
        Result Type
        Title
        External Crossreferences and Linkouts ( 50 )
        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/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)
        PDB - An information portal to biological macromolecular structures
        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
        Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
        FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
        FlyCyc Genes - Genes from a BioCyc PGDB for Dmel
        Flygut - An atlas of the Drosophila adult midgut
        iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
        Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
        MIST (genetic) - An integrated Molecular Interaction Database
        MIST (protein-protein) - An integrated Molecular Interaction Database
        References (373)