General Information
Symbol
Dmel\Sxl
Species
D. melanogaster
Name
Sex lethal
Annotation Symbol
CG43770
Feature Type
FlyBase ID
FBgn0264270
Gene Model Status
Stock Availability
Gene Snapshot
Sex-lethal is an RNA-binding protein, member of the RNA recognition motif (RRM) family. It is a master-feminizing switch contributing to all aspects of sexual dimorphism. [Date last reviewed: 2016-06-30]
Also Known As
fs(1)M106, Sx1, SxlPe
Genomic Location
Cytogenetic map
Sequence location
X:7,074,550..7,098,053 [-]
Recombination map
1-19
Sequence
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
GO Summary Ribbons
Families, Domains and Molecular Function
Gene Group Membership (FlyBase)
Protein Family (UniProt, Sequence Similarities)
-
Summaries
Gene Group Membership
Positive Regulators of Hedgehog Signaling Pathway -
Positive regulators of hedgehog signaling down-regulation the pathway, enhancing the activation of transcription of hh-responsive genes.
UniProt Contributed Function Data
Sex determination switch protein which controls sexual development by sex-specific splicing. Regulates dosage compensation in females by suppressing hyperactivation of X-linked genes. Expression of the embryo-specific isoform is under the control of primary sex-determining signal, which depends on the ratio of X chromosomes relative to autosomes ( X:A ratio). Expression occurs in 2X:2A cells, but not in X:2A cells. The X:A ratio seems to be signaled by the relative concentration of the X-linked transcription factors SIS-A and SIS-B. As a result, the embryo-specific product is expressed early only in female embryos and specifies female-adult specific splicing; in the male where it is not expressed, the default splicing gives rise to a truncated non-functional protein. The female-specific isoform specifies the splicing of its own transcript, thereby initiating a positive autoregulatory feedback loop leading to female development pathway. The female-specific isoform controls the sex-specific splicing of transformer (TRA); acts as a translational repressor for male-specific lethal-2 (MSL-2) and prevents male-less (MLE), MSL-1 and MSL-3 proteins from associating with the female X chromosome.
(UniProt, P19339)
Phenotypic Description from the Red Book (Lindsley and Zimm 1992)
fs(1)K1274
Viability good at 29 but ovaries of homozygous females severely atrophied, probably with tumorous follicles. At 25 cysts contain 16 nurse cells and no oocyte; females fertile when raised at 23. Mosaic studies indicate germ-line function of gene (Perrimon and Gans, 1983, Dev. Biol. 100: 365-73).
Sxl: Sex lethal (T.W. Cline)
Sxl+ is a switch gene that acts throughout development to control all aspects of sexual dimorphism. Its products are required for female and must be absent for male development. Uniquely among sex-determination genes, after responding early in development to the primary sex-determination signal (the X:A ratio), Sxl maintains its own activity state as well as that of the downstream genes with which it interacts. It is required in a cell-autonomous fashion for both germ-line and somatic female development. It controls dosage compensation in females by suppressing hyperactivation of X-linked genes. Mutations of Sxl fall into two general classes: (1) recessive loss-of-function alleles that are deleterious to homozygous females, but viable and without phenotypic consequences in males, and (2) dominant gain-of-function alleles that behave as constitutive mutations, dominant and deleterious in males but without adverse effect in females, either heterozygous or homozygous. The variety of functions of the Sxl gene can be affected differentially by mutations, accounting in part for the complex complementation pattern observed for the large array of diverse mutant alleles. It is important to be aware that phenotypic parameters of mutant alleles and allele combinations can be very sensitive to culture conditions and genetic background. A number of positive regulators of Sxl are known, including the genes da, fs(1)A1621, sis-a, and sis-b. The female-specific lethal or sterile effects of mutations in these genes are suppressed by gain-of-function Sxl alleles. Throughout all but the very earliest period of development, female-specific expression of Sxl is known to be achieved by female-specific splicing of mRNA. The translation products from these female-spliced RNAs appear to help maintain the female-specific (productive) RNA processing mode which generates them, thereby establishing a positive feedback loop that maintains the female state throughout development.
Sxlf1
Homozygous females invariably die as embryos but hemizygous males are fully viable and fertile. In most wildtype genetic backgrounds, heterozygous females exhibit normal viability and fertility, although occasionally display morphological defects characteristic of early cell death; however, can be dominant semilethal for females in some wild-type genetic backgrounds and under suboptimal growth conditions. In doubly heterozygous combination with otherwise recessive mutations in positive regulators of Sxl, this allele can behave as a dominant: heterozygote viability is reduced for daughters of da/+ females, as well as for females that are also heterozygotes for either sis-a, sis-b or fs(1)A1621. In some such doubly heterozygous situations, escaper females may be incompletely masculinized (mosaic intersex). Homozygosity for mutations in the autosomal male-specific lethal loci does not suppress recessive Sxlf1 lethality, but it does partially masculinize Sxlf1/+ females (generating mosaic intersexes) and suppresses cell-death-related morphological defects. Homozygous moribund embryos show sex-specific alterations in the phenotypic expression of hypomorphic X-linked alleles such as run25, a reflection of upsets in dosage compensation (female hyperactivation). Depending on the time of induction, Sxlf1/Sxlf1 clones induced in Sxlf1/+ females can be phenotypically male and reduced in size. 2X:3A animals homozygous or heterozygous for Sxlf1 are viable but masculinized. In genetic mosaics and chimeras, Sxlf1 homozygous germ cells develop abnormally and fail to generate functional gametes. In some situations, the mutant female tissue displays masculine traits. Sxlf1 rescues males from the otherwise lethal effects of a simultaneous duplication of sis-a+ and sis-b+.
Sxlf2
Homozygous females are either inviable or very poorly viable, depending on genetic background. Escapers are invariably sterile but otherwise display no obvious sexual abnormalities. Complements Sxlf2593. Homozygotes defective in dosage compensation as indicated by hyperincorporation of uridine by their polytene chromosomes. Allele fails to support oogenesis in germ-line clones induced by mitotic recombination.
Sxlf3
A hypomorphic allele selected as an intragenic suppressor of SxlM1 male lethality; maps 0.0065 cM to the right of SxlM1. Only characterized in cis combination with SxlM1. The double mutant is fully viable in males and poorly viable in homozygous females, with escapers being phenotypically male and sterile. Hemizygous females are lethal. Partially complements Sxlf2593, generating true intersexes. Partially complements Sxlf7,M1 with escapers phenotypically male and sterile. Fully complements Sxlfhv1. By itself, double mutant fails to bypass maternal da+ requirement for activation, but can complement Sxlf7,M1 in this regard. Double heterozygote with fs(1)A1621 is fertile.
Sxlf7
A hypomorphic allele selected as an intragenic suppressor of SxlM1 male lethality; maps 0.0099 cM to the left of SxlM1. Only characterized in cis combination with SxlM1. The double mutant is male viable and semiviable in homozygous females. Escaper females are phenotypically male and sterile. Hemizygous females are inviable. Double heterozygote with fs(1)A1621 is sterile, like Sxlf1 but unlike SxlM1,f3. The double-mutant allele retains some ability to rescue daughters from the otherwise lethal maternal effect of da; however, lowering maternal da+ activity appears to decrease Sxlf7,M1 functioning, consistent with other evidence that the parental allele, SxlM1, is not fully constitutive. In the absence of a wild-type Sxl allele, Sxlf7,M1 daughters that survive the da maternal effect are phenotypically male and sterile; in contrast, the addition to this genotype of a wild-type Sxl allele in trans renders survivors phenotypically female, but still sterile with masculinized gonads. The latter genotype of female is fertile provided mothers carry at least one da+ allele. The ability of Sxlf7,M1 to rescue daughters is greatly enhanced by mutations in the autosomal, male-specific-lethal loci, genes involved in hyperactivation of X-linked genes in males. The basis for this enhancement is related to the ability of these same mutations to enhance the survival of Sxlf7,M1 hemizygous females. Although Sxlf7,M1 was used to demonstrate the ability of Sxl gene products to activate Sxl+ alleles in trans, it can be inferred that this allele is far below wild type in this activity. Sxlf7,M1 is a dominant suppressor of sis-a female-specific lethality, generating sterile females remarkably similar to those described above rescued from the da maternal effect. Unlike SxlM1,f3, fails to complement Sxlf2593; yet partially complements SxlM1,f3 and SxlfPb, generating sterile phenotypic males. Allele supports oogenesis in homozygous mutant germ-line clones induced by mitotic recombination. In males, mutant allele suppresses the otherwise lethal effect of a duplication of region 3C2-5A2; addition of Sxl+ to this aneuploid genotype generates mosaic intersexes indicating that the positive autoregulatory activity of Sxl products can bypass the X/A signal. Double heterozygote with fs(1)A1621 is sterile (like Sxlf1 and unlike SxlM1,f3).
Sxlf9
A lethal hypomorphic allele defective in some very early steps in the sex-determination process, but which has no adverse effect on the growth or sexual development of homozygous mutant diplo-X clones induced by mitotic recombination. Rare escapers at 18 are phenotypically female; nevertheless, it has a dominant masculinizing effect on the phenotype of triploid intersexes (2X:3A) and interacts in a dominant-lethal fashion with mutations in da or sis-a, both early acting positive regulators of Sxl. Fully complements SxlfPR class (partial deletions of Sxl information that impair later functions of the gene more than earlier). Complements SxlM1,fPa-ra.
Sxlf2593
A hypomorphic allele that is temperature sensitive for most Sxl functions. Perhaps most notable for the fact that homozygote viability can be quite high, with the females developing as true intersexes (their specific grade of inter-sexuality depends on temperature). Lethal over a deficiency, a null allele, or Sxlf7,M1 at any temperature; at permissive temperatures, weakly complements SxlM1,f3 and hypomorphic alleles of the SxlfPR class, generating (true) intersexual escapers; complementation better with SxlfPb, generating sterile females; fully complements Sxlf2, Sxlf9, and Sxlfhv1.
Sxlfhv1
A subliminal allele, viable and fertile as homozygous females, but with greatly reduced viability in trans to nulls. Polytene chromosomes of Sxlfhv1/Sxlf1 larvae that survive to third instar hyperincorporate uridine, revealing female dosage compensation upsets. Mutation of mle appears to partially masculinize this heteroallelic combination and may slightly increase viability under some conditions. Sxlfhv1 homozygotes and heterozygotes display an increased requirement for maternal da+ activity, suggestive of defects in early Sxl regulation.
SxlfLS
A lethal hypomorphic allele that is able to initiate female development, but is defective in its ability to maintain the female developmental commitment and/or to elicit female sexual differentiation. It is masculinizing in homozygous mutant somatic clones induced by mitotic recombination, and it causes the tissue in such clones to grow poorly; nevertheless, it has no dominant effect on the sexual phenotype of triploid intersexes, nor does it interact in a dominant fashion with mutations in da or sis-a, both early acting positive regulators of Sxl. Fully complements Sxlf9, which appears to have a very different set of defects.
SxlfP7BO
Female-lethal null allele that appears to be deleted for the entire Sxl transcription unit. Males are fully viable, fertile, and display normal male sexual behavior.
SxlfPa
A hybrid-dysgenesis-induced apparent null allele selected as an intragenic suppressor of SxlM1 male lethality. Only characterized in cis combination with SxlM1. A P-element insertion 5' to the site of the DNA insertion in SxlM1 but still within the region of Sxl transcribed at all stages. Revertible.
SxlfPa-ra
A hybrid-dysgenesis-induced derivative of SxlM1,fPa selected for having regained the ability to complement Sxlf9. This complex allele disrupts both male and female development, with the magnitude of the effects in either sex depending on culture temperature in a reciprocal fashion: high temperature is more permissive for females and less permissive (more feminizing) for males. Intersexual males show little male sexual behavior and stimulate courtship from other males. Dominant male-lethal effects are greatly enhanced by the presence of a duplication of Sxl+ in trans; male escapers with both alleles exhibit an unusual dorsalization of the abdomen, their sternites being variably transformed into tergites.
SxlfPb
A P-insertion-induced lethal hypomorphic allele with the unusual distinction of displaying a mosaic intersex phenotype in homozygous mutant diplo-X clones induced by mitotic recombination; hence, appears to be defective in the cellular maintenance of the female sexual commitment. Under dysgenic conditions, can mutate further to less extreme or to more extreme condition. Partially complements Sxlf7,M1, generating masculinized individuals; partially complements Sxlf2593, generating sterile females; fully complements Sxlf9.
SxlM1
Unconditionally lethal to males, even in the presence of a Sxl+ duplication. Retains normal level of female function as evidenced by full viability and fertility of homozygous and hemizygous mutant females. Recovered by virtue of ability to bypass the normal requirement by females for maternally supplied da+ product, a positive regulator of Sxl+; however, bypass is incomplete at higher temperatures. Phenotype in both sexes results from expression of Sxl+ female sex determination and dosage compensation functions largely (though not completely) independently of the normal controls. This is shown by the observation that induction of mutations in cis that suppress dominant, male-specific lethality is invariably associated with a corresponding reduction in Sxl+ female-specific activities and the dominant da maternal-effect bypass phenotype. SxlM1 is lethal to most gynandromorphs by the pharate-adult stage, disrupting the development of their haplo-X tissue in a cell-autonomous fashion; mutant haplo-X tissue in gynandromorphs is often, but not always, feminized. This variable penetrance of the sex transformation suggests a residual level of control by the X/A balance. SxlM1 feminizes triploid intersexes, killing them as pharate adults, while suppressing B and Hw alleles in a fashion consistent with expectations for constitutive expression of normal female dosage-compensation functions. Analysis of effects on the dosage compensation of the very early acting segmentation gene, run, suggests that constitutive expression of female functions is not observed prior to the time when the later Sxl promoter is required and RNA processing control is known to be operating. Since run dosage compensation during this period does require functioning of maternal da+, zygotic Sxl+, and the X/A balance, the ability of SxlM1 to bypass these controls during later stages of development would seem to indicate that the effect of the mutant lesion it carries is on Sxl-RNA splicing, a process that these other Sxl+ regulators may only affect indirectly. The position of the SxlM1 mutant lesion in the vicinity of the male-specific exon is suggestive in this connection. Variable expressivity of this mutant allele may underlie two additional observations: (1) SxlM1 male lethality can be suppressed by fs(1)A1621, yet fs(1)A1621 female sterility can be suppressed by SxlM1, and (2) transplants of SxlM1/Y and SxlM1/+ germ cells show that although the allele does not appear to interfere with spermatogenesis in testes, it blocks the otherwise masculinizing effect of testicular somatic tissue on diplo-X (female) germ cells.
Gene Model and Products
Number of Transcripts
25
Number of Unique Polypeptides
15

Please see the GBrowse view of Dmel\Sxl or the JBrowse view of Dmel\Sxl 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 6.02
Stop-codon suppression (UAA) postulated; FBrf0216884.
Annotated transcripts do not represent all possible combinations of alternative exons and/or alternative promoters
Gene model reviewed during 6.06
Tissue-specific extension of 3' UTRs observed during later stages (FBrf0218523, FBrf0219848); all variants may not be annotated
Annotated transcripts do not represent all supported alternative splices within 5' UTR.
Gene model reviewed during 5.44
Gene model reviewed during 5.48
Gene model reviewed during 5.45
Gene model reviewed during 5.43
Gene model reviewed during 5.39
gene_with_stop_codon_read_through ; SO:0000697
Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0331259
2933
314
FBtr0336728
2068
48
FBtr0336729
1800
322
FBtr0346796
1776
331
FBtr0331260
2020
48
FBtr0331261
1515
344
FBtr0331262
3097
354
FBtr0331263
2863
314
FBtr0331249
3263
48
FBtr0331250
3227
346
FBtr0331251
5164
366
FBtr0331253
1886
346
FBtr0331254
2130
42
FBtr0331255
1854
354
FBtr0331256
4309
48
FBtr0331257
2758
344
FBtr0331258
5964
364
FBtr0331264
4077
352
FBtr0331265
2112
42
FBtr0331266
3738
342
FBtr0331268
1910
354
FBtr0331247
2892
344
FBtr0331270
5164
722
FBtr0331271
4077
708
FBtr0336727
3317
42
Additional Transcript Data and Comments
Reported size (kB)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
RefSeq ID
GenBank
FBpp0303701
34.3
314
9.71
FBpp0307709
5.6
48
10.11
FBpp0307710
35.2
322
9.79
FBpp0312374
36.2
331
9.95
FBpp0303702
5.6
48
10.11
FBpp0303703
37.6
344
9.53
FBpp0303704
38.5
354
9.84
FBpp0303705
34.3
314
9.71
FBpp0303691
5.6
48
10.11
FBpp0303692
37.6
346
9.79
FBpp0303693
39.8
366
8.63
FBpp0303695
37.6
346
9.79
FBpp0303696
4.8
42
9.84
FBpp0303697
38.5
354
9.84
FBpp0303698
5.6
48
10.11
FBpp0303699
37.6
344
9.53
FBpp0303700
39.8
364
8.11
FBpp0303706
38.4
352
9.39
FBpp0303707
4.8
42
9.84
FBpp0303708
37.4
342
8.84
FBpp0303710
38.5
354
9.84
FBpp0303689
37.4
344
9.28
FBpp0303712
78.0
722
8.44
FBpp0303713
76.5
708
9.09
FBpp0307708
4.8
42
9.84
Polypeptides with Identical Sequences

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

48 aa isoforms: Sxl-PAA, Sxl-PB, Sxl-PF, Sxl-PM
346 aa isoforms: Sxl-PG, Sxl-PJ
42 aa isoforms: Sxl-PK, Sxl-PQ, Sxl-PZ
354 aa isoforms: Sxl-PD, Sxl-PL, Sxl-PT
344 aa isoforms: Sxl-PC, Sxl-PN
314 aa isoforms: Sxl-PA, Sxl-PE
Additional Polypeptide Data and Comments
Reported size (kDa)
Comments
Sxl protein binds to the non-sex specific pyrimidine tract/3\' splice site of tra pre-mRNA blocking the binding of the U2AF splicing factor. It does not bind to the female specific splice site.
The female specific form of the Sxl protein was shown to bind to the uridine rich sequences of the Sxl pre-mRNA by UV crosslinking experiments.
Sxl expression is derepressed in dpn null male embryos while the female embryo expression pattern is unchanged. Sxl was also misexpressed in embryos with altered dosage of the dpn and sc genes.
External Data
Subunit Structure (UniProtKB)
Part of a complex containing fl(2)d, Sxl and vir (PubMed:12444081). Intreracts with nito (PubMed:26324914).
(UniProt, P19339)
Domain
The Gly-Asn rich domain is required for the cooperative interaction with RNA and for regulating the splicing activity.
(UniProt, P19339)
Crossreferences
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\Sxl 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 (36 terms)
Molecular Function (10 terms)
Terms Based on Experimental Evidence (6 terms)
CV Term
Evidence
References
inferred from direct assay
inferred from direct assay
inferred from direct assay
inferred from direct assay
inferred from physical interaction with FLYBASE:Sin; FB:FBgn0028402
inferred from physical interaction with FLYBASE:snf; FB:FBgn0003449
Terms Based on Predictions or Assertions (6 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000610044
(assigned by GO_Central )
inferred from sequence or structural similarity
traceable author statement
inferred from biological aspect of ancestor with PANTHER:PTN000610044
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000610044
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN002768817
(assigned by GO_Central )
Biological Process (21 terms)
Terms Based on Experimental Evidence (8 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from direct assay
inferred from direct assay
inferred from direct assay
Terms Based on Predictions or Assertions (13 terms)
CV Term
Evidence
References
Cellular Component (5 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
inferred from direct assay
Terms Based on Predictions or Assertions (4 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000610044
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000610044
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000610044
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN002768817
(assigned by GO_Central )
Expression Data
Transcript Expression
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
organism | ubiquitous

Comment: Probe hits exons common to all Sxl transcripts

Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
immunolocalization
Stage
Tissue/Position (including subcellular localization)
Reference
mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
Sxl is expressed in female germline stem cells and in the adjacent two to three cells where the bam-898+133.GFP cyst cell marker is first expressed.
Sxl is normally expressed uniformly in female embryos starting from early blastoderm stages and is not expressed in male embryos. In hhb.P embryos, the ectopic h protein suppresses Sxl in the anterior of the embryo resulting in its expression only at the posterior end in female embryos. In schb.P embryos, ectopic sc protein causes ectopic Sxl expression in the anterior end of male embryos.
Marker for
 
Subcellular Localization
CV Term
Evidence
References
inferred from direct assay
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\Sxl 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
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Images
Alleles, Insertions, Transgenic Constructs and Phenotypes
Classical and Insertion Alleles ( 99 )
For All Classical and Insertion Alleles Show
 
Allele of Sxl
Class
Mutagen
Associated Insertion
Stocks
Known lesion
    0
    Yes
    Other relevant insertions
    miscellaneous insertions
    Name
    Expression Data
    Transgenic Constructs ( 50 )
    For All Alleles Carried on Transgenic Constructs Show
    Transgenic constructs containing/affecting coding region of Sxl
    Allele of Sxl
    Mutagen
    Associated Transgenic Construct
    Stocks
    Transgenic constructs containing regulatory region of Sxl
    characterization construct
    Name
    Expression Data
    Deletions and Duplications ( 34 )
    Partially duplicated in
    Summary of 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 sternite 2 & abdominal sternite bristle | male
    abdominal sternite 3 & abdominal sternite bristle | male
    abdominal sternite 4 & abdominal sternite bristle | male
    abdominal sternite 5 & abdominal sternite bristle | male
    abdominal sternite 6 & abdominal sternite bristle | ectopic | male
    intercalary heterochromatin & polytene chromosome | female (with Sxlf1)
    intercalary heterochromatin & polytene chromosome | female (with Sxlfhv1)
    oocyte & spindle
    Orthologs
    Human Orthologs (via DIOPT v7.1)
    Homo sapiens (Human) (7)
    Species\Gene Symbol
    Score
    Best Score
    Best Reverse Score
    Alignment
    Complementation?
    Transgene?
    2 of 15
    Yes
    No
    2 of 15
    Yes
    No
    2 of 15
    Yes
    No
    1 of 15
    No
    No
     
    1 of 15
    No
    No
     
    1 of 15
    No
    No
     
    1 of 15
    No
    No
     
    Model Organism Orthologs (via DIOPT v7.1)
    Mus musculus (laboratory mouse) (6)
    Species\Gene Symbol
    Score
    Best Score
    Best Reverse Score
    Alignment
    Complementation?
    Transgene?
    2 of 15
    Yes
    No
    2 of 15
    Yes
    No
    1 of 15
    No
    No
    1 of 15
    No
    No
    1 of 15
    No
    No
    1 of 15
    No
    No
    Rattus norvegicus (Norway rat) (7)
    2 of 13
    Yes
    No
    2 of 13
    Yes
    No
    1 of 13
    No
    No
    1 of 13
    No
    No
    1 of 13
    No
    No
    1 of 13
    No
    No
    1 of 13
    No
    No
    Xenopus tropicalis (Western clawed frog) (1)
    1 of 12
    Yes
    No
    Danio rerio (Zebrafish) (9)
    2 of 15
    Yes
    No
    2 of 15
    Yes
    No
    2 of 15
    Yes
    No
    2 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
    Yes
    Caenorhabditis elegans (Nematode, roundworm) (3)
    2 of 15
    Yes
    No
    1 of 15
    No
    No
    1 of 15
    No
    No
    Arabidopsis thaliana (thale-cress) (8)
    1 of 9
    Yes
    No
    1 of 9
    Yes
    No
    1 of 9
    Yes
    No
    1 of 9
    Yes
    No
    1 of 9
    Yes
    No
    1 of 9
    Yes
    Yes
    1 of 9
    Yes
    No
    1 of 9
    Yes
    No
    Saccharomyces cerevisiae (Brewer's yeast) (2)
    2 of 15
    Yes
    No
    1 of 15
    No
    No
    Schizosaccharomyces pombe (Fission yeast) (2)
    2 of 12
    Yes
    No
    1 of 12
    No
    Yes
    Orthologs in Drosophila Species (via OrthoDB v9.1) ( EOG09190CBN )
    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) ( EOG0915097F )
    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) ( EOG090W0EOR )
    Organism
    Common Name
    Gene
    Multiple Dmel Genes in this Orthologous Group
    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
    Acyrthosiphon pisum
    Pea aphid
    Zootermopsis nevadensis
    Nevada dampwood termite
    Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( EOG090X07KE )
    Organism
    Common Name
    Gene
    Multiple Dmel Genes in this Orthologous Group
    Strigamia maritima
    European centipede
    Ixodes scapularis
    Black-legged tick
    Ixodes scapularis
    Black-legged tick
    Stegodyphus mimosarum
    African social velvet spider
    Stegodyphus mimosarum
    African social velvet spider
    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) ( EOG091G0G9L )
    Organism
    Common Name
    Gene
    Multiple Dmel Genes in this Orthologous Group
    Strongylocentrotus purpuratus
    Purple sea urchin
    Ciona intestinalis
    Vase tunicate
    Gallus gallus
    Domestic chicken
    Gallus gallus
    Domestic chicken
    Gallus gallus
    Domestic chicken
    Human Disease Model Data
    FlyBase Human Disease Model Reports
      Alleles Reported to Model Human Disease (Disease Ontology)
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      Models ( 0 )
      Allele
      Disease
      Evidence
      References
      Interactions ( 0 )
      Allele
      Disease
      Interaction
      References
      Comments ( 0 )
       
      Human Orthologs (via DIOPT v7.1)
      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
      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:
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      Selected Interactor(s)
      Interactions Browser

      Please look at the Interaction Group reports for full details of the physical interactions
      protein-protein
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      References
      RNA-protein
      Interacting group
      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
      Subunit Structure (UniProtKB)
      Part of a complex containing fl(2)d, Sxl and vir (PubMed:12444081). Intreracts with nito (PubMed:26324914).
      (UniProt, P19339 )
      Linkouts
      DroID - A comprehensive database of gene and protein interactions.
      Pathways
      Gene Group - Pathway Membership (FlyBase)
      Positive Regulators of Hedgehog Signaling Pathway -
      Positive regulators of hedgehog signaling down-regulation the pathway, enhancing the activation of transcription of hh-responsive genes.
      External Data
      Linkouts
      Genomic Location and Detailed Mapping Data
      Chromosome (arm)
      X
      Recombination map
      1-19
      Cytogenetic map
      Sequence location
      X:7,074,550..7,098,053 [-]
      FlyBase Computed Cytological Location
      Cytogenetic map
      Evidence for location
      6F3-6F5
      Limits computationally determined from genome sequence between P{EP}inx7EP1641 and P{EP}CG9650EP1340&P{EP}CG9650EP1617
      Experimentally Determined Cytological Location
      Cytogenetic map
      Notes
      References
      Determined by deficiency mapping (details unspecified).
      6F5-6F5
      (determined by in situ hybridisation) 6F (determined by in situ hybridisation)
      Experimentally Determined Recombination Data
      Notes
      Recombination distance between Sxlf9 and 'f3' of SxlM1,f3 is 0.015cM. Recombination distance between Sxlf9 and SxlM1 is 0.007cM.
      Sxl lies in the middle of a 0.6cM stretch that appears to contain no genes vital to both sexes.
      Stocks and Reagents
      Stocks (64)
      Genomic Clones (16)
       

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

      cDNA Clones (223)
       

      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
      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
         
        Developmental Studies Hybridoma Bank - Monoclonal antibodies for use in research
        Other Information
        Relationship to Other Genes
        Source for database identify of
        Source for database merge of
        Source for merge of: Sxl CG18350
        Source for merge of: Sxl CG14425
        Additional comments
        Annotations CG18350 and CG14425 merged as CG43770 in release 5.44 of the genome annotation. Merge supported by stop codon read-through analysis (FBrf0216884).
        Dicistronic annotation CG33070 split out into separate annotations for each open reading frame, CG18350 and CG14425, in release 4.2 of the genome annotation. CG18350 corresponds to Sxl.
        The current convention for this gene is that alleles specifically disrupting female development (generally recessive loss of function) are designated Sxlf, followed by a number, whereas those specifically disrupting male development (generally dominant gain of function) are designated "SxlM", followed by a number. In cases where a single lesion might have both characters, the "SxlM" designation would prevail. P in the designation indicates that the allele (and sometimes the stock as well) is likely to harbor P-element sequences. For new alleles selected as changes in the functioning of pre-existing mutant alleles, the original allele designation is followed by a d (for 'derivative'), then a number. If and when such derivatives are shown to carry more than one lesion within the gene, the mutant designation will change to reflect the presence and order on the chromosome of the multiple lesions, individual mutations being separated by commas. For the most part, alleles in common use before these conventions were adopted were renamed only if the changes were relatively minor and self evident.
        Other Comments
        The repression of nos protein expression seen in the daughter cells of the germline stem cells in the female germarium is dependent on the presence of Sxl protein binding site in the nos 3' UTR.
        Sxl protein requires the obligatory cofactor Unr protein for 3'-UTR mediated translational repression of msl-2 in females. Sxl protein recruits Unr protein to the 3' UTR of msl-2 mRNA specifically in female cells.
        Sxl function in the female germline is required for the generation of the female-specific e(r) transcript.
        Sxl protein inhibits translation of msl-2 mRNA using a dual mechanism. The protein binds to both the 5' UTR and 3' UTR of the mRNA, thus preventing both the recruitment of 43S ribosomal preinitiation complexes and ribosomal scanning to the downstream initiation codon of msl-2 mRNA.
        Infection by Wolbachia restores fertility to D.melanogaster females that do not produce eggs because they have protein-coding lesions in Sxl. This suppression is allele specific.
        Exon 3 repression in Sxl pre-mRNA splicing requires competition between the 5' splice sites of exons 2 and 3 but is independent of their relative strength. The distal 3' splice site preceeding exon 3 plays a critical role in defining the exon, while the proximal 3' splice site is preferentially used for the actual splicing reaction, suggesting a switch in 3' splice site recognition between the two processes of exon definition and splicing catalysis.
        Recombination and disjunction in female germ cells depend on the germline activity of Sxl.
        Sxl is an important target for repression by nos in germ cells. Sxl protein is ectopically expressed in the pole cells of nos- embryos.
        msl-2 mRNA translation is inhibited by the Sxl gene product. Sxl binding sites in both the 5' and 3' UTRs of msl-2 RNA cooperate in this translational repression.
        The crystal structure has been determined at 2.6A resolution of the complex formed between two tandemly arranged RNA-binding domains of the Sxl protein and a 12 nucleotide, single stranded RNA derived from the tra polypyrimidine tract. The two RNA-binding domains have their β-sheet platforms facing each other to form a V-shaped cleft. The RNA is bound in this cleft, where the tra UGUUUUUUU sequence is specifically recognized by the Sxl protein.
        run directly activates Sxl transcription.
        Candidate gene for sex comb tooth number and testicular atrophy quantitative trait loci.
        The splicing and translational regulatory activities of the Sxl protein are separable. Sxl is controlled by both positive and negative autoregulation. Sxl protein binds to the 3' UTRs of msl-2 and Sxl mRNAs in vivo.
        Expression of sisA and Sxl is as tightly coupled as Dvir\sisA and Dvir\Sxl, suggesting that the same primary sex determination mechanism exists throughout the genus Drosophila.
        Sxl acts as a translational repressor as well as a splicing regulator.
        4.1kb, 3.1kb and 1.9kb transcript 3' UTRs contain 14, 8 and 1 consensus Rbp9 binding sites, respectively.
        The two RRM (RNA recognition motif) domains of Sxl are responsible for RNA binding. Specificity in the recognition of target RNAs requires both RRM domains. The two RRM domains mediate Sxl :Sxl protein interactions, and these interactions probably occur both in cis and in trans. The interaction of Sxl protein with snf protein is mediated by the R1 RRM domain of Sxl.
        Analysis of msl-2 deletion constructs and msl-2-Ecol\lacZ regulatory constructs suggests that Sxl acts synergistically through sequences in both the 5' and 3' untranslated regions of msl-2 to mediate repression of msl-2 protein expression.
        Sxl has multiple and separable activities in the regulation of pre-mRNA splicing.
        An increase in the dose of snf+ can trigger the female Sxl RNA splicing mode in male germ cells and can feminise triploid intersex (2X3A) germ cells. Female specific regulation of Sxl in the germline involves a position autoregulatory feedback loop on RNA splicing. Sxl-positive male germ cells make female Sxl protein isoforms. Somatic feminisation does not feminise Sxl-positive male germ cells.
        The amino terminal RNA binding domain (RBD1) fragment of Sxl is prepared on the basis of a limited proteolysis analysis and the solution structure of RBD1 is determined by NMR. Analysis reveals RBD1 has non-consensus types of amino acid residues at several key positions near and inside the RNP2/RNP1 motifs.
        Association of Sxl protein with multiple sites in the 5' and 3' untranslated regions of msl-2 transcript represses its translation in females.
        NMR analysis of Sxl fragment indicates the A/G, U1, U2, U5 and U6 residues in the target sequence of tra are specifically recognised by the two RNA-binding domains of the Sxl protein.
        The Sxl RBD1+2/tra PPT interaction is analysed by chemical shift perturbation mapping of the protein backbone. Data suggests the two domains respond quite differently to the presence of tra PPT RNA.
        The roX1 gene shows a male-specific expression pattern in adult flies. roX1 expression is dependent on Sxl, but is independent of tra activity, and is positively regulated by genes of the dosage compensation system such as mle.
        The glycine-rich N-terminus of the Sxl protein influences interactions with hnRNP proteins containing RNA binding and glycine-rich domains.
        The early (embryo) splicing pattern is not regulated by stage- or sex-specific trans-acting factors. The early splicing pattern is dependent on whether the 5' splice site region originates from exon E1 or exon 2.
        Anti-Sxl monoclonal antibody detected Sxl-like proteins in species of the D.melanogaster and D.virilis radiation that migrate with the same size range as the two most prominent Sxl protein isoforms of D.melanogaster.
        Sxl protein is associated with snf protein in vitro and in vivo.
        Male-specific lethal (MSL) proteins accumulate in a subregion of male nuclei (the X chromosome) beginning at late blastoderm stage. Binding of the MSLs is interdependent in diploid cells and is prevented in female embryonic cells by Sxl.
        Female-specific tra pre-mRNA splicing requires not only Sxl function but fl(2)d function.
        Reporter constructs used to examine the splicing of Sxl-Pe transcripts indicate that neither specific maternal products, Sxl protein, nor an X chromosome to autosome ratio of 1 are required for the processing of the embryonic mRNAs. Skipping two intervening exons to generate an open reading frame that will encode the Sxl early proteins appears to be an intrinsic property of initiating the early Sxl RNAs within the first intron of the Sxl-Pm maintenance transcription unit.
        Expression of activated h in early blastoderm embryos causes ectopic Sxl expression and male-specific lethality, implying that the h-related denominator element dpn represses Sxl during sex-determination by directly recognising the early Sxl promoter.
        msl-1 binding to the X chromosome is prevented in females by the Sxl products derived from the activation of the early Sxl promoter.
        Dsub\Sxl is cloned, characterised and compared to the gene organisation, early and late expression patterns, 5' regulatory sequences and alternative splicing mechanisms of Sxl.
        Both of the RNA-binding domains (RBDs) of Sxl are required for efficient and specific binding of Sxl protein to the tra cis-acting element. In addition the RBDs mediate homodimerisation of the Sxl protein, which is enhanced by the addition of RNA containing the Sxl binding site.
        snf protein cooperates with the female-specific Sxl protein to block utilisation of the male-specific exon of the Sxl pre-mRNA.
        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.
        The time course of expression of dpn and Sxl in dpn mutant backgrounds suggests that dpn is required for sex determination only during the later stages of X:A signalling in males, to prevent inappropriate expression of SxlPe in the face of increasing sis gene product levels.
        Sxl sex-specifically regulates msl-2 expression.
        Molecular analysis of the SxlM alleles has been undertaken to address the question of what is responsible for their constitutive behavior. The constitutive character of the SxlM alleles is a consequence of an alteration of the structure of the pre-mRNA that allows some level of female splicing to occur even in the absence of functional Sxl gene product. Most of the constitutive character of SxlM alleles appears to depend on the mutant alleles' responsiveness, perhaps greater than wild type, to the autoregulatory splicing activity of the wild type Sxl proteins they produce.
        In contrast to somatic cells, the action of Sxl in XY germ cells has no sex-transforming effect. Sxl is more likely to perform a subordinate function in oogenesis.
        In vitro binding assays demonstrate an RNA-dependent interaction between Sxl and snf proteins, crosslinking experiments demonstrate that this association has significance in vivo.
        In the early embryo the activity of Sxl-Pe is controlled in a highly dose-sensitive fashion by the genes on the X chromosome that function as denominator elements (sc, sisA, da and run). Functional dissection of Sxl-Pe indicates that activating the promoter in females requires the cumulative action of multiple numerator genes which appear to exert their effects through reiterated cis-acting target sites in the promoter. Conversely, maintaining the promoter silent in males requires the repressive activities of denominator genes, and at least one of the denominator genes also appears to function through target sequences within the promoter.
        Genetic and molecular analyses suggest that vir is required for female-specific splicing of Sxl and of tra pre-mRNA.
        Female-specific expression of genes in the germline is dependent on a somatic signalling pathway whose primary target is not Sxl.
        Transfection assays and in vitro DNA binding experiments indicate that da/sc heterodimers directly activate the Sxl early promoter by binding to both high and low affinity sites. dpn protein represses this activation by specific binding to a unique site within the Sxl early promoter.
        To initiate biophysical studies of the Sxl-polypyrimidine tract (PPT) complex minimal protein and RNA sequence elements have been identified that retain a specific high-affinity interaction.
        vir is necessary for female-specific expression of Sxl as well as for vital processes unrelated to sex.
        Alleles of Sxl can partially suppress the mutant phenotype of ovoD2/+ heterozygous ovaries.
        The maternal effects of her are mediated through effects on Sxl expression, maternal her function is needed for the initiation of Sxl function. her- intersexuality cannot be rescued by constitutive Sxl expression.
        Expression of Sxl recombinant genes demonstrate that neither RRM repeat alone can support strong specific Sxl RNA binding but two RRM repeats together with other N- and C-terminal sequences deleted binds RNA as tightly and specifically as the full length protein. The regions required for self interaction can now be identified using in vitro binding assays.
        The Sxl splice site consensus is a highly specific sequence, explaining why it can regulate splicing of tra pre-mRNA and autoregulate splicing of its own mRNA.
        ovo, otu, snf and Sxl are not involved in the early events of germline sex determination, but are required later, during metamorphosis or in the adult for oogenesis.
        Female-specific functions of Sxl regulate sexual behaviour and synthesis of the three major sex pheromones that have been identified in normal sexually mature males and virgin females.
        In vitro RNA binding has been used to demonstrate a cooperative interaction between the N-termini of two Sxl monomers when binding to adjacent U-rich binding sites on the Sxl pre-mRNA. Transient infections into Schneider cells and germline transformations also demonstrate the importance of the Sxl N-terminus.
        The msl-2 primary transcript may be the target of Sxl sex specific regulation and may play a role in male specific binding of mle, msl-3 and msl-1 to the X chromosome.
        Tumorous cells produced by Sxl mutants are capable of female-specific transcription and RNA processing indicating the ovarian cells retain some female identity. It is proposed that mutations do not cause male transformation of the female germ line but instead either cause an ambiguous sexual identity or block specific stages of oogenesis. Germ line function of Sxl depends on the activity of a specific otu isoform.
        The "male specific lethals" that function downstream of Sxl do not control all aspects of dosage compensation either at the blastoderm stage or later in development. Sxl functions in early dosage compensation are controlled from the Pe promoter.
        Sxl prevents the accumulation of H4Ac16, acetylated form of His4, on the X chromosomes in females.
        The four msl gene products interact to form a multiprotein complex. Results suggest that the presence of Sxl is necessary to prevent the association of msl-1 with the X chromosome in females, as is the case for mle and msl-3.
        Resonance assignments and solution structure of a portion of Sxl containing the second RNA-binding domain has been determined using multidimensional heteronuclear NMR.
        Levels of msl-1 expression in Sxl mutants demonstrates that Sxl negatively regulates the level of msl-1 protein. msl-1, like mle and H4Ac16 (an acetylated form of the His4 product), exhibits a wild type male localisation pattern in Sxl- XX nuclei.
        A fragment of the D.melanogaster Sxl gene has been used as a probe for in situ hybridisation of Chrysomya rufifacies polytene chromosomes.
        Splicing of Sxl RNA has been studied in B5228 mutant embryos.
        RNA binding specificity of Sxl protein is examined by applying an in vitro selection and amplification of ligand RNAs from a random sequence pool. Sequence and in vitro binding analyses of the selected RNAs showed that Sxl preferentially binds to a polyuridine stretch surrounded by purine residues and the binding may be facilitated by an AG sequence downstream of the polyuridine stretch.
        Sxl protein can be targeted to specific polytene chromosome sites containing regulatory splicing signals. Sxl-containing RNP complexes in embryonic nuclear extracts have been identified that appear to be quantitatively different from general heterogeneous nuclear RNPs (hnRNPs).
        The tra gene is regulated by Sxl-dependent 3' splice site blockage. 40 nucleotides immediately upstream of the regulated splice site are sufficient to direct sex-specific regulated splicing.
        tra product present in somatic cells of XY animals, or in backgrounds lacking the sex-determining function of Sxl, is sufficient to support developing XX germ cells through oogenesis.
        Sxl binds its own pre-mRNA at the 3' splice site of the male exon (exon 3) and at additional binding sites surrounding the male exon. The amino terminus of the Sxl protein has cooperative binding properties, this portion shares amino acid similarity with other RNA-binding proteins and is essential for Sxl's function as a splicing regulator in vivo.
        Partial germline sex transformation occurs in otu, snf, Sxl and bam ovarian tumors.
        The wild type product of snf plays an important role in establishing female-specific RNA splicing of Sxl.
        Sex-specific processing of nascent Sxl RNA operates in the germ line as well as in the soma. One class of female sterile mutations is defective in germ-line sex-specific splicing of Sxl, another (including mutations at Sxl itself) is defective in the changes of Sxl protein distribution observed in wild type germ cells. During the final stages of oogenesis several mechanisms apparently operate to prevent progeny from inheriting Sxl protein.
        sisA is required in all somatic nuclei for the proper activation of Sxl. Sxl is the only significant target of the somatic sex determination signal. An increased sisA dose equivalent to that in females causes male lethal effects and cannot activate the construct P{SxlPe-lacZ}, which carries the embryonic promoter of Sxl, to the female expression level in all tissues. Male lethality can be completely suppressed by a Sxl null mutation.
        In females, the Sxl product functions to prevent mle from binding to the two X chromosomes.
        In the soma, the sex of the cells is autonomously determined by the X:A signal, while in the germ line, the sex is determined by cell autonomous and somatic inductive signals. The genes sc, sisA, run are required to activate Sxl in the soma but not in the germ line. Transplantation studies support a somatic positive feminizing signal for germ-line development. Activation of Sxl in the germ line may be controlled by the X:A ratio and a positive feminizing signal from the soma.
        Three exons and two introns around the regulated splice sites are sufficient for sex-specific splicing. The male exon 3' splice site is not the primary target for Sxl autoregulation, the 5' splice site of the male exon may be a target. Multiple upstream cis-acting elements are required for Sxl autoregulation.
        The male Sxl exon is subject to Sxl regulation when a fragment containing the exon plus flanking intron sequences is placed in the introns of two different genes, ftz and w. A very small fragment of the male intron containing only the male intron plus 3' and 5' splice signals optimised to fit the consensus is sufficient for regulation in a heterologous context. The poly(U) run in the Sxl 3' splice site is also required for the sex-specific splicing. Results suggest a blockage mechanism is probably used in Sxl autoregulation, in support of Sosnowski et al (FBrf0049361).
        A sequence comparison and numerical analysis of the RRM-containing (RNA recognition motif) proteins suggests that functionally related RRM-containing proteins have significant sequence similarities in their RRMs.
        The region of the Sxl+ premRNA bearing the key regulatory stop codons is spliced in the same sex-specific manner in the germ line as in the soma. The genetic hierarchy regulating female germ-line sex determination includes tra, tra2, dsx, fu, otu, ovo, snf and Sxl itself. fu, otu, ovo and snf function upstream of Sxl.
        Female cells may be viable in the absence of detectable Sxl protein expression.
        Mutant germ cells in otu ovaries have a morphology similar to primary spermatocytes and express male-specific reporter genes and have male-type Sxl splicing. otu acts upstream of Sxl in germline sex determination.
        Sxl function may not be sufficient to direct germ cells into the female pathway, and, in the germ line, Sxl may not be regulated by the X:A ratio.
        In vitro system that recapitulates the regulation by Sxl of tra sex-specific splicing developed. Sxl blocks splicing to the non-sex specific, default site in tra by specifically binding to its polypyrimidine tract, blocking the binding of the essential splicing factor U2AF: U2AF then acivates the lower-affinity female-specific site. U2AF has a splicing effector domain that Sxl lacks: addition of this effector domain converts Sxl from a splicing repressor to a splicing activator, rendering it unable to mediate splice-site switching.
        Sxl activity is initially controlled by the female-specific expression of early Sxl transcripts. The proteins encoded by these transcripts set up the autoregulatory feedback loop in motion by directing female specific splicing of late Sxl RNAs derived from the late Sxl promoter.
        Cotransfection experiments in Kc cells show that the female-specific Sxl product induces the synthesis of its own female-specific mRNA by negative control of male-specific splicing. Deletion, substitution and binding experiments demonstrated that multiple uridine-rich sequences in the introns around the male-specific third exon are involved in the splicing regulation of Sxl pre-mRNA.
        snf is a positive regulator of Sxl in the germline and soma.
        Sxl function directs the development of sexually dimorphic skeletal muscles.
        run gene product is required for the initial step of Sxl activation but does not have a major role as an X-counting element.
        Dosage studies suggest balance of sc, dpn and Sxl involved in sex-specific lethality.
        Ectopic expression of a female Sxl cDNA can induce the female-specific splicing of Sxl transcripts, independently of the X/A ratio. This trans-activation can occur at late stages of development and once initiated the female splicing mode can stably maintained through a positive feedback loop.
        The sex-, stage-, and tissue-specific expression of Sxl protein has been determined.
        Sxl promoter is uniquely sensitive to the dose of a small set of specific X/A numerator genes, including sisA and sc.
        sc is a component of the X:A ratio and is required in females for the initiation of Sxl expression. Failure to activate Sxl expression in females results in lethality due to improper gene dosage compensation.
        Dose-sensitive cooperative interactions in the assembly or binding of sis-dependent transcription factors may directly determine the activity of the female-specific promoter of Sxl.
        Mutations in zygotic gene Sxl interact with RpII140wimp.
        The structure of a number of late Sxl transcripts has been analysed.
        The role of sc in generating the X:A signal that controls Sxl activity has been studied.
        Co-transfection experiments in which Sxl cDNA and the tra gene are expressed in Kc cells demonstrate that the female Sxl-encoded protein binds specifically to the tra transcript at or near the non-sex-specific acceptor site. This implies that the female Sxl gene product is the trans-acting factor that regulates alternative splicing.
        da and sc are both required for the induction of Sxl expression.
        The mechanism of sex determination in the germ line has been analysed.
        The lack of interaction between Tpl and Sxl or da suggests that Tpl does not function in measuring the X/A ratio in Drosophila.
        The interaction between snf and Sxl mutations reduces the viability of females heterozygous for Sxl. The mosaicism exhibited by flies heterozygous for snf and Sxl- suggests that the transformation of diplo-X tissues to male morphology is due to the interaction of snf and Sxl in the zygote: failure to maintain Sxl expression in some somatic cells.
        There is an interaction between snf and Sxl mutants indicating both gene products are involved in the regulation of the same pathway.
        Genetic analysis of rearrangements within Sxl has allowed correlation of changes in specific functions with DNA alterations.
        The X/A ratio is believed to act through an X-linked control gene, Sxl (Cline, 1978, Genetics 90, 683--698, Cline, 1983, Dev. Biol. 95, 260--274). High levels of Sxl expression dictate the female path of sexual differentiation and a low transcription rate for X-linked genes, low expression levels result in the male pathway and high levels of X-linked gene transcription (Cline, 1978, Genetics 90, 683--698, Cline, 1983, Dev. Biol. 95, 260--274). A model has been formulated on how the activity of the Sxl locus can be related to the X/A ratio (Gadagkar, 1982, J. Biosci.4, 377--390).
        da+ zygotic function is not involved in Sxl+ regulation: lowered da+ zygotic dose does not reduce Sxl+ expression of sex determination functions.
        The interaction between Sxl and da in triploids has been studied.
        Interactions between Sxl and msl-1, msl-2 and mle mutants have been studied.
        Sxl+ is a switch gene that acts throughout development to control all aspects of sexual dimorphism. Its products are required for female and must be absent for male development. Uniquely among sex-determination genes, after responding early in development to the primary sex-determination signal (the X:A ratio), Sxl maintains its own activity state as well as that of the downstream genes with which it interacts. It is required in a cell-autonomous fashion for both germ-line and somatic female development. It controls dosage compensation in females by suppressing hyperactivation of X-linked genes. Mutations of Sxl fall into two general classes: (1) recessive loss-of-function alleles that are deleterious to homozygous females, but viable and without phenotypic consequences in males, and (2) dominant gain-of-function alleles that behave as constitutive mutations, dominant and deleterious in males but without adverse effect in females, either heterozygous or homozygous. The variety of functions of the Sxl gene can be affected differentially by mutations, accounting in part for the complex complementation pattern observed for the large array of diverse mutant alleles. It is important to be aware that phenotypic parameters of mutant alleles and allele combinations can be very sensitive to culture conditions and genetic background. A number of positive regulators of Sxl are known, including the genes da, snf, sis-a and sis-b. The female-specific lethal or sterile effects of mutations in these genes are suppressed by gain-of-function Sxl alleles. Throughout all but the very earliest period of development, female-specific expression of Sxl is known to be achieved by female-specific splicing of mRNA. The translation products from these female-spliced RNAs appear to help maintain the female-specific (productive) RNA processing mode which generates them, thereby establishing a positive feedback loop that maintains the female state throughout development.
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        External Crossreferences and Linkouts ( 446 )
        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.
        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
        Linkouts
        Drosophila Genomics Resource Center - Drosophila Genomics Resource Center cDNA clones
        DroID - A comprehensive database of gene and protein interactions.
        Developmental Studies Hybridoma Bank - Monoclonal antibodies for use in research
        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
        Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
        KEGG Genes - Molecular building blocks of life in the genomic space.
        Synonyms and Secondary IDs (31)
        Reported As
        Symbol Synonym
        CG14425/CG18350
        Fl
        Mex156
        Su(da)
        Sxl
        (Cho et al., 2018, Guo et al., 2018, Harumoto and Lemaitre, 2018, Knuckles et al., 2018, Moschall et al., 2018, Dutta et al., 2017, Forés et al., 2017, Kan et al., 2017, Malik et al., 2017, Mohr et al., 2017, Moschall et al., 2017, Salz et al., 2017, Erickson, 2016, Gibilisco et al., 2016, Haussmann et al., 2016, Lence et al., 2016, Sawanth et al., 2016, Brooks et al., 2015, Fear et al., 2015, Forés et al., 2015, Lucchesi and Kuroda, 2015, Tower, 2015, Yan and Perrimon, 2015, Zaharieva et al., 2015, Ashwal-Fluss et al., 2014, Cline, 2014.11.10, Cline, 2014.11.10, Cline, 2014.11.11, Clough et al., 2014, Harumoto et al., 2014, Hennig et al., 2014, Lee et al., 2014, Ma et al., 2014, Stern et al., 2014, Zhang et al., 2014, Chen et al., 2013, Evans and Cline, 2013, Fernández and Kravitz, 2013, Fuse et al., 2013, Hombría and Sotillos, 2013, Li et al., 2013, Manoli et al., 2013, Ruiz et al., 2013, Vicoso and Bachtrog, 2013, Xin et al., 2013, Alekseyenko et al., 2012, Chau et al., 2012, Japanese National Institute of Genetics, 2012.5.21, Sun et al., 2012, Tarone et al., 2012, Venables et al., 2012, Whitworth et al., 2012, Barbaro and Lukacsovich, 2011.3.8, Barry et al., 2011, Gempe and Beye, 2011, Graham et al., 2011, Graveley et al., 2011, Hartmann et al., 2011, Hashiyama et al., 2011, Jungreis et al., 2011, Kappes et al., 2011, Kimura, 2011, Li et al., 2011, Lott et al., 2011, Tsurumi et al., 2011, Vargas et al., 2011, Yao and Fox, 2011, Cline et al., 2010, Gladstein et al., 2010, Harrison et al., 2010, Johnson et al., 2010, Mourikis et al., 2010, Pospisilik et al., 2010, Robinett et al., 2010, Suissa et al., 2010, Tastan et al., 2010, Casper and Van Doren, 2009, Chau et al., 2009, Graham et al., 2009, Graze et al., 2009, Hu et al., 2009, Kalifa et al., 2009, Lebo et al., 2009, Shen et al., 2009, Sun and Birchler, 2009, Sun and Cline, 2009, Buchler and Louis, 2008, Chau et al., 2008, González et al., 2008, Hartmann et al., 2008, Horabin and Olcese, 2008, Kalamegham and Oliver, 2008, Kpebe and Rabinow, 2008, Liang et al., 2008, Lu et al., 2008, Matyunina et al., 2008, McDermott and Kliman, 2008, Penn et al., 2008, Siera and Cline, 2008, Smith and Oliver, 2008, Avila and Erickson, 2007, Buszczak et al., 2007, Corona et al., 2007, Deshpande et al., 2007, Deshpande et al., 2007, Erickson and Quintero, 2007, Evans and Cline, 2007, Garbe and Bashaw, 2007, Gonzalez and Erickson, 2007, Hempel and Oliver, 2007, Jones et al., 2007, Kadrmas et al., 2007, Nurminsky, 2007, Penn and Schedl, 2007, Quinones-Coello, 2007, Reiter et al., 2007, Robida et al., 2007, Siera and Cline, 2007, Sun and Cline, 2007, Vanderzwan-Butler et al., 2007, Vied et al., 2007, Walthall et al., 2007, Wang and Lin, 2007, Yokoyama et al., 2007, Billeter et al., 2006, Casper and Van Doren, 2006, Chaouki and Salz, 2006, Deng and Meller, 2006, Deshpande et al., 2006, Gawande et al., 2006, Graham et al., 2006, Jolly and Lakhotia, 2006, Kadener et al., 2006, McIntyre et al., 2006, Mendjan et al., 2006, Pal Bhadra et al., 2006, ten Bosch et al., 2006, Traut et al., 2006, Burnette et al., 2005, Decotto and Spradling, 2005, Goldstein et al., 2005, Haag and Doty, 2005, Horabin, 2005, Tarone et al., 2005, Xie et al., 2005, Buhler et al., 2004, Thompson et al., 2004, Banerjee et al., 2003, Lalli et al., 2003, Lei et al., 2003, Noor and Kliman, 2003, Zhimulev et al., 2003, Kim et al., 2000, Singh et al., 2000, Cline et al., 1999, Bhat and Schedl, 1997)
        Sxl-1 Sxl-2
        fs(1)K1274
        l(1)6Fa
        Name Synonyms
        Female lethal
        sex lethal
        Secondary FlyBase IDs
        • FBgn0003659
        • FBgn0000823
        • FBgn0029934
        • FBgn0053070
        • FBtr0089822
        • FBpp0088763
        • FBtr0089823
        • FBpp0088764
        • FBtr0089824
        • FBpp0088765
        • FBtr0089825
        • FBpp0088766
        • FBtr0089826
        • FBpp0088767
        • FBtr0089827
        • FBpp0088768
        • FBtr0089828
        • FBpp0088769
        • FBtr0089829
        • FBpp0088770
        • FBtr0089830
        • FBpp0088771
        • FBtr0089831
        • FBpp0088772
        • FBgn0029933
        Datasets (0)
        Study focus (0)
        Experimental Role
        Project
        Project Type
        Title
        References (811)