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General Information
Symbol
Dmel\how
Species
D. melanogaster
Name
held out wings
Annotation Symbol
CG10293
Feature Type
FlyBase ID
FBgn0264491
Gene Model Status
Stock Availability
Gene Snapshot
held out wings (how) encodes an RNA-binding protein highly expressed in the mesoderm and tendon cells. It is spliced into two isoforms: how(L) and how(S). how(L) induces RNA destabilization, whereas How(S) stabilizes the RNA targets. [Date last reviewed: 2019-03-07]
Also Known As
who, struthio, l(3)j5B5, sci, stru
Key Links
Genomic Location
Cytogenetic map
Sequence location
3R:22,042,191..22,079,321 [+]
Recombination map
3-74
Sequence
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
GO Summary Ribbons
Protein Family (UniProt)
-
Molecular Function (GO)
[Detailed GO annotations]
Experimental Evidence
Predictions / Assertions
Summaries
Protein Function (UniProtKB)
Required for integrin-mediated cell-adhesion in wing blade. Vital role in steroid regulation of muscle development and to control heart rate. Required during embryogenesis, in late stages of somatic muscle development, for myotube migration and during metamorphosis for muscle reorganization.
(UniProt, O01367)
Summary (Interactive Fly)
KH motif - putative RNA-binding protein - functions in the migration and attachment of somatic muscle cells - targets Dpp mRNA - cell divisions in the embryonic mesoderm are repressed via posttranscriptional regulation of string/cdc25 by How - repression of the Drosophila midkine and pleiotrophin homolog miple by HOW is essential for correct mesoderm spreading
Gene Model and Products
Number of Transcripts
6
Number of Unique Polypeptides
5

Please see the GBrowse view of Dmel\how or the JBrowse view of Dmel\how 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
Annotated transcripts do not represent all possible combinations of alternative exons and/or alternative promoters.
Low-frequency RNA-Seq exon junction(s) not annotated.
Gene model reviewed during 5.47
Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0084177
3964
405
FBtr0084178
1759
375
FBtr0100514
2181
380
FBtr0301401
3884
405
FBtr0301402
3103
404
FBtr0335195
4003
418
Additional Transcript Data and Comments
Reported size (kB)
4.0 (northern blot)
4.5, 4.0, 3.5 (northern blot)
4.4, 3.6 (northern blot)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
RefSeq ID
GenBank
FBpp0083575
44.3
405
8.10
FBpp0083576
40.9
375
6.96
FBpp0099954
41.5
380
7.02
FBpp0290615
44.3
405
8.10
FBpp0290616
44.2
404
8.10
FBpp0307182
45.6
418
8.00
Polypeptides with Identical Sequences

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

405 aa isoforms: how-PA, how-PD
Additional Polypeptide Data and Comments
Reported size (kDa)
405 (aa)
404 (aa); 44 (kD predicted)
Comments
how protein binds homopolymeric RNA (poly(A)) in vitro. A Myc-epitope-tagged how protein expressed in HeLa cells migrates with a molecular mass of about 55 kD.
External Data
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\how using the Feature Mapper tool.

External Data
Crossreferences
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Linkouts
Gene Ontology (24 terms)
Molecular Function (3 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000129650
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000129548
(assigned by GO_Central )
Biological Process (19 terms)
Terms Based on Experimental Evidence (18 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from mutant phenotype
(assigned by UniProt )
inferred from mutant phenotype
(assigned by UniProt )
inferred from mutant phenotype
inferred from expression pattern
inferred from mutant phenotype
(assigned by UniProt )
inferred from direct assay
(assigned by UniProt )
inferred from mutant phenotype
(assigned by UniProt )
inferred from mutant phenotype
inferred from high throughput mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
(assigned by UniProt )
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
traceable author statement
Cellular Component (2 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
inferred from direct assay
inferred from direct assay
inferred from direct assay
(assigned by UniProt )
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000129548
(assigned by GO_Central )
inferred by curator from GO:0000381
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
organism

Comment: maternally deposited

northern blot
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
No Assay Recorded
Stage
Tissue/Position (including subcellular localization)
Reference
immunolocalization
Stage
Tissue/Position (including subcellular localization)
Reference
mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
how protein expression was detected in vas-expressing GSCs, their immediate daughter cells (gonialblasts), and 2-cell spermatogonial cysts. Expression is downregulated at the 4-cell stage. how protein expression is also detected in somatic hub cells and in the nuclei of mature cyst cells but not in somatic stem cells.
A GFPFBtr0091350:pb-XRhow fusion protein localizes to the nucleus of mouse NIH 3T3 and Drosophila S2 cells.
how protein is first detected in the cells of the ventral furrow and the staining extends beyond the cephalic furrow. In the early stages of gastrulation, staining is mostly in the ventral furrow but is also seen in head mesoderm and around the cephalic furrow. Later, expression becomes restricted to myogenic cells. Expression is observed in precursors of the somatic muscles, pharyngeal muscles, visceral muscles and cardiac cells. Expression is also seen in muscle attachment sites. In larvae, expression is observed in the nuclei of muscle fibers and in adepithelial cells of the imaginal discs. In adults, expression occurs in the tendon cells that attach the flight muscle fibers to the dorsal cuticle of the thorax. During oogenesis, expression is observed in follicular stalk cells that join the different egg chambers in the ovary.
Marker for
Subcellular Localization
CV Term
Evidence
References
inferred from direct assay
inferred from direct assay
inferred from direct assay
(assigned by UniProt )
Expression Deduced from Reporters
Reporter: P{GawB}how24B
Stage
Tissue/Position (including subcellular localization)
Reference
Reporter: P{lacW}B1-93F
Stage
Tissue/Position (including subcellular localization)
Reference
Reporter: P{lArB}how1A122
Stage
Tissue/Position (including subcellular localization)
Reference
High-Throughput Expression Data
Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\how 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, and Transgenic Constructs
Classical and Insertion Alleles ( 44 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 12 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of how
Transgenic constructs containing regulatory region of how
Deletions and Duplications ( 11 )
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
Orthologs
Human Orthologs (via DIOPT v7.1)
Homo sapiens (Human) (4)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
13 of 15
Yes
Yes
2 of 15
No
No
2 of 15
No
No
2 of 15
No
No
Model Organism Orthologs (via DIOPT v7.1)
Mus musculus (laboratory mouse) (4)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
13 of 15
Yes
Yes
2 of 15
No
No
2 of 15
No
No
1 of 15
No
No
Rattus norvegicus (Norway rat) (5)
8 of 13
Yes
Yes
2 of 13
No
No
2 of 13
No
No
1 of 13
No
No
1 of 13
No
Yes
Xenopus tropicalis (Western clawed frog) (4)
8 of 12
Yes
Yes
2 of 12
No
No
1 of 12
No
No
1 of 12
No
No
Danio rerio (Zebrafish) (6)
12 of 15
Yes
Yes
12 of 15
Yes
Yes
7 of 15
No
Yes
2 of 15
No
No
2 of 15
No
No
2 of 15
No
No
Caenorhabditis elegans (Nematode, roundworm) (7)
13 of 15
Yes
Yes
5 of 15
Yes
No
5 of 15
No
Yes
3 of 15
No
Yes
3 of 15
No
Yes
3 of 15
No
Yes
2 of 15
No
Yes
Arabidopsis thaliana (thale-cress) (5)
7 of 9
Yes
Yes
6 of 9
No
Yes
5 of 9
No
Yes
5 of 9
No
Yes
5 of 9
No
Yes
Saccharomyces cerevisiae (Brewer's yeast) (1)
1 of 15
Yes
No
Schizosaccharomyces pombe (Fission yeast) (0)
No records found.
Orthologs in Drosophila Species (via OrthoDB v9.1) ( EOG09190B1R )
Organism
Common Name
Gene
AAA Syntenic Ortholog
Multiple Dmel Genes in this Orthologous Group
Drosophila melanogaster
fruit fly
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) ( EOG0915073L )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Musca domestica
House fly
Glossina morsitans
Tsetse 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) ( EOG090W07C4 )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Danaus plexippus
Monarch butterfly
Heliconius melpomene
Postman butterfly
Apis florea
Little honeybee
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
Tribolium castaneum
Red flour beetle
Pediculus humanus
Human body louse
Rhodnius prolixus
Kissing bug
Cimex lectularius
Bed bug
Acyrthosiphon pisum
Pea aphid
Zootermopsis nevadensis
Nevada dampwood termite
Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( EOG090X0778 )
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
Orthologs in non-Arthropod Metazoa (via OrthoDB v9.1) ( EOG091G0EED )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
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
Gallus gallus
Domestic chicken
Gallus gallus
Domestic chicken
Paralogs
Paralogs (via DIOPT v7.1)
Drosophila melanogaster (Fruit fly) (9)
6 of 10
5 of 10
5 of 10
4 of 10
4 of 10
4 of 10
4 of 10
3 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 ( 1 )
    Allele
    Disease
    Interaction
    References
    Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
     
    Disease Associations of Human Orthologs (via DIOPT v7.1 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.
    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
    RNA-protein
    Physical Interaction
    Assay
    References
    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
    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
    Gene Group - Pathway Membership (FlyBase)
    External Data
    Linkouts
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    3R
    Recombination map
    3-74
    Cytogenetic map
    Sequence location
    3R:22,042,191..22,079,321 [+]
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    94A1-87F10
    Limits computationally determined from genome sequence between P{PZ}tsl00617 and P{lacW}howj5B5&P{EP}EP738; Left limit from in situ hybridisation (FBrf0099762) Right limit from in situ hybridisation (FBrf0099762)
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    94A1-94A2
    (determined by in situ hybridisation)
    87F3-87F10
    (determined by in situ hybridisation)
    93F-93F
    (determined by in situ hybridisation)
    93F13-93F13
    (determined by in situ hybridisation)
    Experimentally Determined Recombination Data
    Left of (cM)
    Right of (cM)
    Notes
    Located on 3R.
    Stocks and Reagents
    Stocks (29)
    Genomic Clones (33)
    cDNA Clones (391)
     

    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 sequences
    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
      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: how CG10293
      Source for database merge of
      Source for merge of: how anon- EST:Liang-2 .39
      Source for merge of: how l(3)j5B5
      Source for merge of: how sci
      Source for merge of: how l(3)S090417 l(3)S053606
      Additional comments
      Other Comments
      The balance between two distinct forms of how protein maintains low levels of sr protein at the precursor stage in future tendon cells and high levels in the mature tendon.
      Identification: Genetic screen for mutations that produce blisters in somatic wing clones.
      how encodes a member of the KH RNA binding protein family that functions during muscle development.
      Cloning and partial characterisation of how, defined by the Scer\GAL4 24B transposant. Four cDNAs (2-9, 4-2, D-11 and D-5) that contain a KH domain are isolated and sequence compared to how : a family of proteins having closely related KH domains is discovered.
      how appears to regulate some aspects of integrin functioning.
      Identification: Genetic screen for autosomal mutations that produce blisters in somatic wing clones. 1 allele of how has been isolated.
      how function is required late in embryogenesis to control heart rate and muscular activity.
      Origin and Etymology
      Discoverer
      Etymology
      Identification
      External Crossreferences and Linkouts ( 78 )
      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 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/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
      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.
      Linkouts
      ApoDroso - Functional genomic database for photoreceptor development, survival and function
      DroID - A comprehensive database of gene and protein interactions.
      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
      Synonyms and Secondary IDs (34)
      Reported As
      Symbol Synonym
      KH93F
      anon-EST:Liang-2.39
      l(3)S053606
      l(3)S090417
      l(3)j5D5
      l(3)s2612
      Secondary FlyBase IDs
      • FBgn0028068
      • FBgn0082187
      • FBgn0017397
      • FBgn0011379
      • FBgn0011385
      • FBgn0015249
      • FBgn0020779
      • FBgn0025731
      • FBgn0025956
      Datasets (0)
      Study focus (0)
      Experimental Role
      Project
      Project Type
      Title
      References (173)