Open Close
General Information
Symbol
Dmel\mle
Species
D. melanogaster
Name
maleless
Annotation Symbol
CG11680
Feature Type
FlyBase ID
FBgn0002774
Gene Model Status
Stock Availability
Enzyme Name (EC)
DNA helicase (3.6.4.12)
Gene Summary
maleless (mle) encodes a helicase and a member of the Male-Specific-Lethal dosage compensation complex, which increases male X chromosome transcription approximately two-fold. mle homozygous mutant males die as larvae, while females are viable. [Date last reviewed: 2019-03-14] (FlyBase Gene Snapshot)
Also Known As

nap, napts, no-action-potential, male lethal, no action potential

Key Links
Genomic Location
Cytogenetic map
Sequence location
2R:5,974,857..5,980,778 [-]
Recombination map
2-55
RefSeq locus
NT_033778 REGION:5974857..5980778
Sequence
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
GO Summary Ribbons
Gene Ontology (GO) Annotations (35 terms)
Molecular Function (12 terms)
Terms Based on Experimental Evidence (5 terms)
CV Term
Evidence
References
inferred from mutant phenotype
(assigned by CACAO )
inferred from direct assay
inferred from direct assay
inferred from direct assay
(assigned by UniProt )
enables RNA binding
inferred from physical interaction with FLYBASE:lncRNA:roX2; FB:FBgn0019660
Terms Based on Predictions or Assertions (8 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN001053532
(assigned by GO_Central )
inferred from electronic annotation with InterPro:IPR044447
(assigned by InterPro )
enables ATP binding
inferred from electronic annotation with InterPro:IPR002464, InterPro:IPR011545
(assigned by InterPro )
inferred from sequence or structural similarity with UniProtKB:Q08211
(assigned by UniProt )
inferred from sequence or structural similarity with UniProtKB:Q08211
(assigned by UniProt )
inferred from sequence or structural similarity with UniProtKB:Q08211
(assigned by UniProt )
inferred from sequence or structural similarity
inferred from sequence or structural similarity
traceable author statement
enables RNA binding
inferred from biological aspect of ancestor with PANTHER:PTN000433338
(assigned by GO_Central )
Biological Process (11 terms)
Terms Based on Experimental Evidence (6 terms)
CV Term
Evidence
References
involved_in axon extension
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from direct assay
inferred from genetic interaction with FLYBASE:Su(var)3-7; FB:FBgn0003598
Terms Based on Predictions or Assertions (7 terms)
CV Term
Evidence
References
inferred from sequence or structural similarity with UniProtKB:Q08211
(assigned by UniProt )
traceable author statement
inferred from sequence or structural similarity with UniProtKB:Q08211
(assigned by UniProt )
inferred from biological aspect of ancestor with PANTHER:PTN001053532
(assigned by GO_Central )
inferred from sequence or structural similarity with UniProtKB:Q08211
(assigned by UniProt )
inferred from sequence or structural similarity with UniProtKB:Q08211
(assigned by UniProt )
inferred from biological aspect of ancestor with PANTHER:PTN001053532
(assigned by GO_Central )
Cellular Component (12 terms)
Terms Based on Experimental Evidence (8 terms)
CV Term
Evidence
References
located_in chromatin
inferred from direct assay
located_in chromosome
inferred from direct assay
located_in cytosol
inferred from direct assay
part_of MSL complex
inferred from direct assay
inferred from direct assay
located_in nucleus
inferred from direct assay
inferred from direct assay
located_in X chromosome
inferred from direct assay
Terms Based on Predictions or Assertions (5 terms)
CV Term
Evidence
References
is_active_in cytoplasm
inferred from biological aspect of ancestor with PANTHER:PTN002707150
(assigned by GO_Central )
is_active_in nucleolus
inferred from biological aspect of ancestor with PANTHER:PTN001053532
(assigned by GO_Central )
is_active_in nucleus
inferred from biological aspect of ancestor with PANTHER:PTN000717298
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN001053532
(assigned by GO_Central )
inferred from sequence or structural similarity with UniProtKB:Q08211
(assigned by UniProt )
Protein Family (UniProt)
Belongs to the DEAD box helicase family. DEAH subfamily. (P24785)
Catalytic Activity (EC)
Experimental Evidence
-
Predictions / Assertions
ATP + H(2)O = ADP + phosphate (3.6.4.12)
Summaries
Gene Snapshot
maleless (mle) encodes a helicase and a member of the Male-Specific-Lethal dosage compensation complex, which increases male X chromosome transcription approximately two-fold. mle homozygous mutant males die as larvae, while females are viable. [Date last reviewed: 2019-03-14]
Gene Group (FlyBase)
MALE SPECIFIC LETHAL COMPLEX -
The Male Specific Lethal (MSL) complex is a chromatin modifying complex composed of five protein subunits and two non-coding RNAs. MSL is involved in X chromosome dosage compensation in males. (Adapted from FBrf0228243).
DEAH-BOX RNA HELICASES -
DEAH-box RNA helicases belong to helicase superfamily 2 (SF2). They are characterized by the presence of nine conserved helicase motifs, including the DEAH sequence in motif II. (Adapted from PMID:21509200.)
OTHER DNA HELICASES -
The 'other DNA helicases' group comprises DNA helicases that do not fit into any of the other major DNA helicase groups.
Protein Function (UniProtKB)
Required in males for dosage compensation of X chromosome linked genes. Mle, msl-1 and msl-3 are colocalized on X chromosome. Each of the msl proteins requires all the other msls for wild-type X-chromosome binding. Probably unwinds double-stranded DNA and RNA in a 3' to 5' direction.
(UniProt, P24785)
Phenotypic Description (Red Book; Lindsley and Zimm 1992)
mle: maleless
Homozygous males die, but homozygous females survive. Males produced by homozygous females die during the third larval instar, whereas those produced by heterozygous females are late pupal lethals. Females transformed into phenotypic males (tra) or intersexes (dsx) unaffected by mle, i.e. mle acts only upon single-X-bearing flies. No interaction with msl-1 or msl-2 (Belote, 1983, Genetics 96: 165-86). mle4 males surviving at 18 are sterile, small, and slow developing. Concluded to be defective in dosage compensation in males based on decreased levels of X-linked-enzyme activities (G6PD, 6GPD, FUM, β-HAD) but not autosomally encoded enzymes (ADH, AO, GPDH, IDH) in homozygous mle4 male larvae and escaping adults, e.g. β-HAD. The incorporation of labeled uridine by the polytene X chromosome relative to that of 2R is lower than normal in mle4 males (Belote and Lucchesi, 1980, Nature 285: 573-75); steady-rate level of Sgs4 mRNA incompletely compensated in mle4 and mle4/mle6 male larvae (Breen and Lucchesi, 1986, Genetics 112: 483-91). Polytene X chromosome of mle males appears narrower and more densely stained than that of control males. Few homozygous mle gynandromorphs survive; XO patches small, with small bristles, and mostly confined to abdomen (Uenoyama, Uchida, Fukunaga, and Oishi, 1982, Genetics 102: 223-31). mle pole cell transplanted into wild-type hosts incapable of undergoing normal spermatogenesis (Bachiller and Sanchez, 1986, Dev. Biol. 118: 379-84). Homozygous (and to a lesser extent heterozygous) mle females that are heterozygous for SxlF1 (Uenoyama, Fukunaga, and Oishi, 1982, Genetics 102: 233-43; Skripsky and Lucchesi, 1982, Dev. Biol. 94: 153-64) or are the surviving progeny raised at 17 of homozygous da mothers (Cline, 1982, Genetics 100: 641-63) develop as intersexes.
napts: no action potential (J.C. Hall; M. Kernan)
Larvae or adults become rapidly paralyzed when exposed to 37 and rapidly recover on return to lower temperatures. Rearing stocks chronically at room temperature or above causes napts to "adapt" such that higher temperatures (> 40) are required for paralysis (Kyriacou and Hall, 1985). Experiments involving one-time rearing at low temperature caused napts to paralyze at relatively low temperatures (Nelson and Wyman, 1990). Axonal conduction (but not synaptic transmission) fails in larvae at high temperatures (Wu et al., 1978; Wu and Ganetzky, 1980), but action potentials in the giant fiber (GF) pathway of adults are not blocked at temperatures up to 43 (Elkins and Ganetzky, 1990; Nelson and Wyman, 1990), though the latency from brain stimulation to response of thoracic muscles are aberrantly long, even at low temperatures (Nelson and Wyman, 1990), and this long-latency disappears as the temperature is raised to 35 (Elkins and Ganetzky, 1990). "Following frequency" of napts thoracic muscle responses (re. GF pathway stimulation) reduced at elevated temperatures, an effect which can be reversed by injection of 4-amino-pyridine (Nelson and Wyman, 1990). At permissive temperatures, refractory period for elicitation of a series of action potentials is abnormally long (Ganetzky and Wu, 1980); at these low temperatures, napts suppresses effects of "hyperexcitability" mutations such as Sh, bas, bss, eas, Hk, kdn, and tko (Ganetzky and Wu, 1982, Genetics 100: 597-614). napts is unconditionally lethal (Ganetzky and Wu, 1980) in a double mutant with parats1 (death occurring during 1st larval instar) and the viability of other para; napts combinations is poor (Ganetzky, 1984); two doses of para+ (in males) suppresses high-temperature paralysis of napts (Stern et al., 1990). In mosaic experiments, cuticular clones of parats1 in a napts background (after low-temperature development) have non-functioning sensory cells, probably due to lack of nerve conduction which, however, did not cause any anatomical abnormalities involving the central projections of these sensory neurons (Burg and Wu, 1986). Another developmental study, examining larval nerve terminal innervating body-wall muscles (Budnik et al., 1990), showed slight reduction in the extent of branching caused by napts at permissive temperature; the increase in branching (and higher than normal number of varicosities on motor-neurites) induced by an eag Sh double mutant was suppressed by napts (re. low-temperature rearing). napts in combination with tipE leads to poor viability at permissive temperature for both mutants (Ganetzky, 1986, J. Neurogenet. 3: 19-31; Jackson, Wilson, and Hall, 1986, J. Neurogenet. 3: 1-17). napts is, at permissive temperature, hypersensitive to blocking effects of tetrodotoxin (TTX) on action potentials (Ganetzky and Wu, 1980); brain membrane extracts of napts, assayed at low or high temperatures, have subnormal levels of tetrodotoxin (Kauvar, 1982) or saxitoxin (Jackson et al., 1984) binding activity; the latter study reports that there are no qualitative alterations of this binding activity (kd is normal). Cultured neurons from napts larvae are 4 to 5-fold more resistant than wild-type cells to killing effects of veratridine, irrespective of temperature (22 vs 35) (Suzuki and Wu 1984, J. Neurogenet. 1: 225-38), but TTX has no effects on these mutant cells, whose general growth characteristics are also normal (Wu, Suzuki and Poo, 1983, J. Neurosci. 3: 1888-99). The mutation does not seem to modify the expression of sodium currents in embryonic neurons (O'Dowd and Aldrich, 1988, J. Neurosci. 8: 3633-43). Exposure of napts males to high temperature causes arrest of oscillator underlying rhythmic component of courtship song (Kyriacou and Hall, 1985); in experiments on conditioned courtship, napts males learn normally but have shortened memory spans, and napts suppresses Sh-induced decrements in courtship learning (Cowan and Siegel, 1984, J. Neurogenet. 1: 333-44; 1986, J. Neurogenet. 3: 187-201).
Summary (Interactive Fly)

DEAH-box subfamily ATP-dependent helicase - Mle plays an early role in dosage compensations, perhaps in packaging RNA into growing dosage compensation protein complexes - remodels the roX lncRNAs, enabling the long noncoding RNA-mediated assembly of the dosage compensation complex

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

Please see the JBrowse view of Dmel\mle 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 5.47

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

Gene model reviewed during 5.48

Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0086031
4062
1293
FBtr0100576
4023
936
Additional Transcript Data and Comments
Reported size (kB)

4.0 (northern blot)

Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
RefSeq ID
GenBank
FBpp0085367
143.7
1293
7.23
FBpp0100031
104.1
936
7.15
Polypeptides with Identical Sequences

None of the polypeptides share 100% sequence identity.

Additional Polypeptide Data and Comments
Reported size (kDa)

1293, 226 (aa); 140 (kD observed); 144 (kD predicted)

Comments

The truncated form of mle protein is predicted

by one of the cDNAs. It has 198aa in common with the larger form of mle

and has 28 distinct amino acids at its carboxy terminus.

External Data
Subunit Structure (UniProtKB)

Interacts with Top2.

(UniProt, P24785)
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\mle 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
northern blot
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

mle transcripts are detected throughout development and are found in males and females.

mle transcripts are not sex-specific.

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

mle protein is detected in nuclear extracts from adult males and females.

Strong anti-mle protein staining is observed at hundreds of sites along the length of the male X chromosome. Weak staining of the autosomes and the female X is also observed.

Marker for
 
Subcellular Localization
CV Term
Evidence
References
located_in chromatin
inferred from direct assay
located_in chromosome
inferred from direct assay
located_in cytosol
inferred from direct assay
part_of MSL complex
inferred from direct assay
inferred from direct assay
located_in nucleus
inferred from direct assay
inferred from direct assay
located_in X chromosome
inferred from direct assay
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\mle 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
EMBL-EBI Single Cell Expression Atlas
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
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 ( 38 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 24 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of mle
Transgenic constructs containing regulatory region of mle
Aberrations (Deficiencies and Duplications) ( 18 )
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
abdomen & macrochaeta
axon & motor neuron | conditional ts
chromosome
neuromuscular junction & synapse | conditional ts
Orthologs
Human Orthologs (via DIOPT v8.0)
Homo sapiens (Human) (21)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
15 of 15
Yes
Yes
4 of 15
No
Yes
4 of 15
No
No
4 of 15
No
No
3 of 15
No
No
2 of 15
No
No
2 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
Yes
1 of 15
No
No
1 of 15
No
No
1 of 15
No
Yes
Model Organism Orthologs (via DIOPT v8.0)
Mus musculus (laboratory mouse) (20)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
14 of 15
Yes
Yes
4 of 15
No
Yes
4 of 15
No
No
4 of 15
No
No
3 of 15
No
No
2 of 15
No
No
2 of 15
No
No
2 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
Yes
1 of 15
No
Yes
Rattus norvegicus (Norway rat) (19)
11 of 13
Yes
Yes
4 of 13
No
Yes
4 of 13
No
No
3 of 13
No
No
2 of 13
No
No
2 of 13
No
No
2 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
Yes
Xenopus tropicalis (Western clawed frog) (16)
9 of 12
Yes
Yes
3 of 12
No
Yes
3 of 12
No
No
3 of 12
No
No
2 of 12
No
No
2 of 12
No
No
2 of 12
No
No
2 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
Yes
Danio rerio (Zebrafish) (19)
12 of 15
Yes
Yes
4 of 15
No
No
4 of 15
No
No
3 of 15
No
Yes
3 of 15
No
No
2 of 15
No
No
2 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
Yes
1 of 15
No
No
Caenorhabditis elegans (Nematode, roundworm) (12)
14 of 15
Yes
Yes
2 of 15
No
No
2 of 15
No
No
2 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
Arabidopsis thaliana (thale-cress) (8)
5 of 9
Yes
No
5 of 9
Yes
No
5 of 9
Yes
No
4 of 9
No
No
4 of 9
No
Yes
3 of 9
No
Yes
1 of 9
No
No
1 of 9
No
No
Saccharomyces cerevisiae (Brewer's yeast) (7)
5 of 15
Yes
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
Schizosaccharomyces pombe (Fission yeast) (2)
4 of 12
Yes
No
4 of 12
Yes
No
Ortholog(s) in Drosophila Species (via OrthoDB v9.1) ( EOG0919011A )
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) ( EOG091500PQ )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Musca domestica
House fly
Glossina morsitans
Tsetse fly
Lucilia cuprina
Australian sheep blowfly
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) ( EOG090W00JU )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Bombyx mori
Silkmoth
Danaus plexippus
Monarch butterfly
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
Tribolium castaneum
Red flour beetle
Pediculus humanus
Human body louse
Rhodnius prolixus
Kissing bug
Cimex lectularius
Bed bug
Acyrthosiphon pisum
Pea aphid
Acyrthosiphon pisum
Pea aphid
Acyrthosiphon pisum
Pea aphid
Acyrthosiphon pisum
Pea aphid
Zootermopsis nevadensis
Nevada dampwood termite
Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( EOG090X00IZ )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strigamia maritima
European centipede
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) ( EOG091G0PKT )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strongylocentrotus purpuratus
Purple sea urchin
Ciona intestinalis
Vase tunicate
Ciona intestinalis
Vase tunicate
Paralogs
Paralogs (via DIOPT v8.0)
Drosophila melanogaster (Fruit fly) (13)
6 of 10
6 of 10
4 of 10
4 of 10
4 of 10
3 of 10
3 of 10
3 of 10
3 of 10
3 of 10
3 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 ( 1 )
    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
    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.
    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
    Subunit Structure (UniProtKB)
    Interacts with Top2.
    (UniProt, P24785 )
    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
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    2R
    Recombination map
    2-55
    Cytogenetic map
    Sequence location
    2R:5,974,857..5,980,778 [-]
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    42A6-42A6
    Limits computationally determined from genome sequence between P{PZ}l(2)0985109851&P{lacW}Src42Ak10108 and P{lacW}l(2)k09848k09848&P{EP}EP407
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    42A-42A
    (determined by in situ hybridisation)
    Experimentally Determined Recombination Data
    Location
    Left of (cM)
    Notes

    Maps just distal to ap based on deficiency mapping.

    Stocks and Reagents
    Stocks (11)
    Genomic Clones (18)
     

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

    cDNA Clones (18)
     

    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
      DRSC - Results frm RNAi screens
      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: mle CG11680

      Source for database merge of
      Additional comments

      The paralysis of 'nap' is not complemented by mle alleles.

      "mle" alleles fail to complement the paralysis caused by "nap" alleles, indicating that "nap" and "mle" are allelic.

      Molecular analysis demonstrated that "mle" mutants are allelic to "nap" mutants.

      Other Comments

      The mle protein interacts with the most prominent transcriptionally active regions of chromosomes independently of other MSL proteins.

      More than 80% of para transcripts in a mlenap-ts1 background are aberrant, owing to internal deletions that include the edited para exon.

      The mlenap-ts1 mutation results in the occurrence of a "splicing catastrophe" of the para transcript in the region of the RNA editing site.

      Gene products of the male specific lethal (msl) group of genes including msl-1, msl-2, msl-3, mle, and mof are associated with all female chromosomes at a low level but are sequestered to the X chromosome in males. There is evidence for the presence of nucleation sites for association of msl proteins with the X chromosome rather than individual gene binding sites.

      Gene products of the male specific lethal (msl) group of genes preferentially associate with the male X chromosome and may have a role in dosage compensation. This may be achieved by regulating an inverse dosage effect, which would be maintained on the male X and nullified on the autosomes.

      Used as a 'bait' in the yeast two-hybrid system to screen for interactors from an imaginal disc cDNA library: Dbp80 is identified.

      mof colocalises with the MSL complex on the X chromosome: a sequence of binding events results in the formation of the MSL complex on the X chromosome in males and in the targeting of mof to its presumed site of action. mle is necessary but only as a structural component for the recruitment of mof to the X chromosome.

      In the germline mle is not involved in chromosomal dosage compensation but may be involved in post-transcriptional gene regulation. Loss of mle has no detectable effect on expression or localisation of acetylated His4.

      mle has NTPase and both RNA and DNA helicase activities.

      The NTPase/helicase activities of mle are essential for dosage compensation.

      Loss of mle NTPase and helicase activities results in male lethality without elimination of the localisation of the mle-msl-1 complex to the male X chromosome.

      msl-2 and msl-1 colocalise to a reproducible subset of their wild-type X chromosome sites in the absence of either mle or msl-3.

      The roX1 gene is positively regulated by genes of the dosage compensation system such as mle.

      X chromosome proteins associated with dosage compensation in melanogaster are sufficiently conserved to allow significant antibody cross-reaction to D.simulans, D.virilis, D.americana.americana and D.pseudoobscura.pseudoobscura chromosomes. Cross reaction is also observed in the X chromosome and the X2 chromosome (2 copies in females and 1 in males) of D.miranda. These results provide evidence that the male-specific lethal proteins can be acquired on previously unrelated chromosome arms during evolution.

      Male-specific lethal (MSL) proteins accumulate in a subregion of male nuclei (the X chromosome) beginning at late blastoderm stage. X chromosomal binding of the MSLs is observed throughout embryonic and larval development in both diploid and polytene tissues. His4 colocalises with the MSLs in embryos. Binding of the MSLs is interdependent in diploid cells and is prevented in female embryonic cells by Sxl.

      Mutations in Khc enhance the para and mel and suppress the Sh and eag mutant phenotypes.

      Association of mle with the polytene X chromosome is RNase sensitive and mutations in the ATPase motifs affect mle function. The carboxyl terminus of mle may have a potential role in general affinity to RNA.

      The products of msl-1, msl-2, mle and msl-3 loci specifically associate with hundreds of sites along the X chromosome in males, but not in females. The binding of each of the four proteins requires the functional products from the other three. 2X3A individuals are mosaic for both Sxl expression and msl-1, msl-2, mle and msl-3 binding to the X chromosome, with a perfect inverse correlation at the cellular level between Sxl expression and msl-1, msl-2, mle and msl-3 X chromosome binding.

      Heartbeat of mlenap-ts1 individuals is seriously impaired, becoming arrhythmic at elevated temperatures.

      Immunostaining of embryonic and larval stages demonstrates that His4, msl-1 and msl-3 are associated with the male X chromosome as early as gastrulation, while mle binding is not detected until the late embryonic/late larval stages.

      The msl-3, mle and msl-1 gene products may associate with one another in a male-specific heteromeric complex on the X chromosome to achieve its hyperactivation.

      The expression pattern of mle suggests mle has a maternal component that appears at the beginning of embryogenesis and localises to the male X chromosome at stage 8.

      Elements needed for dosage compensation are localised to the X chromosome only after blastoderm and msl-dependent dosage compensation is not necessary during the first part of embryogenesis. This suggest the existance of an additional msl-independent dosage compensation mechanism; dosage compensation of run expression at blastoderm is not dependent on male specific lethal genes.

      The binding of mle, msl-1, msl-2 and His4 proteins to the X chromosome are interdependent from early embryogenesis.

      The msl-2 primary transcript may play a role in male specific binding of mle, msl-3 and msl-1 to the X chromosome.

      The gene products of mle, msl-1 bind to the male X chromosome in an identical pattern, and the binding sites of H4Ac16 acetylated form of the His4 product are largely coincident with the mle/msl-1 binding sites. Association of H4Ac16 protein with the male X chromosome requires wild type function of msl-1, msl-2, mle and msl-3.

      The four msl gene products interact to form a multiprotein complex.

      Antisera to mle protein label the euchromatic X chromosome through mitosis, but neither the X heterochromatin nor autosomes.

      msl-1, like mle and H4Ac16 (an acetylated form of the His4 product), exhibits a wild type male localisation pattern in Sxl- XX nuclei.

      In females, the Sxl product functions to prevent mle from binding to the two X chromosomes. The X chromosome binding of mle requires wild type msl-1, msl-2 and msl-3 functions.

      mle was identified by two very different mutant phenotypes, male-lethality ('mle') and rapid paralysis of larvae or adults when exposed to 37oC ('napts').

      The 'mle' group phenotype: Mutants are defective for dosage compensation in males. Homozygous males die, but homozygous females survive. Males produced by homozygous females die during the third larval instar, whereas those produced by heterozygous females are late pupal lethals. Females transformed into phenotypic males (tra1) or intersexes (dsx1) unaffected by mle1, i.e. mle acts only upon single-X-bearing flies. mle4 males surviving at 18oC are sterile, small and slow developing. Polytene X chromosome of mle1 males appears narrower and more densely stained than that of control males. The 'nap' group phenotype: Larvae or adults become rapidly paralyzed when exposed to 37oC and rapidly recover on return to lower temperatures.

      mle plays a direct role in dosage compensation of the X chromosome.

      Slight reduction in the extent of branching caused by mlenap-ts1 at permissive temperature; the increase in branching (and higher than normal number of varicosities on motor-neurites) induced by an eag Sh double mutant was suppressed by mlenap-ts1 (re. low-temperature rearing).

      Action potentials in the giant fiber (GF) pathway of adults are not blocked at temperatures up to 43oC. The long-latency phenotype disappears as the temperature is raised to 35oC.

      Experiments involving one-time rearing at low temperature caused mlenap-ts1 to paralyze at relatively low temperatures. Action potentials in the giant fiber (GF) pathway of adults are not blocked at temperatures up to 43oC, though the latency from brain stimulation to response of thoracic muscles are aberrantly long, even at low temperatures. 'Following frequency' of mlenap-ts1 thoracic muscle responses (re. GF pathway stimulation) is reduced at elevated temperatures, an effect which can be reversed by injection of 4-amino-pyridine.

      Two doses of para+ (in males) suppresses high-temperature paralysis of mlenap-ts1.

      Mutation does not seem to modify the expression of sodium currents in embryonic neurons.

      mle1 pole cell transplanted into wild-type hosts are incapable of undergoing normal spermatogenesis.

      Steady-rate level of Sgs4 mRNA incompletely compensated in mle4 and mle4/mle6 male larvae.

      In mosaic experiments, cuticular clones of parats1 in a mlenap-ts1 background (after low-temperature development) have non-functioning sensory cells, probably due to lack of nerve conduction which, however, did not cause any anatomical abnormalities involving the central projections of these sensory neurons.

      In experiments on conditioned courtship, mlenap-ts1 males learn normally but have shortened memory spans and mlenap-ts1 suppresses Sh-induced decrements in courtship learning.

      mlenap-ts1 in combination with tipE1 leads to poor viability at permissive temperature.

      Rearing stocks chronically at room temperature or above causes mlenap-ts1 to 'adapt' such that higher temperatures (> 40oC) are required for paralysis. Exposure of mlenap-ts1 males to high temperature causes arrest of oscillator underlying rhythmic component of courtship song.

      mle and para are involved in the function of sodium channels.

      Genetic, electrophysiological, behavioral and pharmacological studies of mlenap and para mutants suggest that they effect sodium channels.

      Brain membrane extracts of mlenap-ts1, assayed at low or high temperatures, have subnormal levels of saxitoxin, though there are no qualitative alterations of this binding activity (kD is normal).

      Cultured neurons from mlenap-ts1 larvae are 4 to 5-fold more resistant than wild-type cells to killing effects of veratridine, irrespective of temperature (22oC vs 35oC).

      Mutants show no interaction with msl-11 or msl-21.

      Cultured neurons from mlenap-ts1 larvae are not affected by TTX, their general growth characteristics are normal.

      Brain membrane extracts of mlenap-ts1, assayed at low or high temperatures, have subnormal levels of tetrodotoxin.

      Few homozygous mle1 gynandromorphs survive; X0 patches small, with small bristles, and mostly confined to abdomen.

      mle is involved in dosage compensation in males.

      Mutants show decreased levels of X-linked-enzyme activities (G6PD, 6GPD, FUM) but not autosomally encoded enzymes (ADH, AO, GPDH, IDH) in homozygous mle4 male larvae when compared with non-msl controls.

      The incorporation of labeled uridine by the polytene X chromosome relative to that of 2R is lower than normal in mle4 males.

      Axonal conduction (but not synaptic transmission) fails in mutant larvae at high temperatures. At permissive temperatures, refractory period for elicitation of a series of action potentials is abnormally long and mutants are hypersensitive to blocking effects of tetrodotoxin (TTX) on action potentials. mlenap-ts1 is unconditionally lethal in a double mutant with parats1 (death occurring during 1st larval instar).

      Axonal conduction (but not synaptic transmission) fails in larvae at high temperatures.

      Origin and Etymology
      Discoverer
      Etymology
      Identification
      External Crossreferences and Linkouts ( 56 )
      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/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information
      Other crossreferences
      Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
      EMBL-EBI Single Cell Expression Atlas
      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
      Flygut - An atlas of the Drosophila adult midgut
      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.
      MARRVEL_MODEL
      modMine - A data warehouse for the modENCODE project
      Linkouts
      BioGRID - A database of protein and genetic interactions.
      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
      FlyMine - An integrated database for Drosophila genomics
      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 (18)
      Reported As
      Symbol Synonym
      mak
      mll
      Secondary FlyBase IDs
        Datasets (1)
        Study focus (1)
        Experimental Role
        Project
        Project Type
        Title
        • bait_protein
        Genome-wide localization of chromosomal proteins in cell lines by ChIP-chip and ChIP-Seq.
        References (411)