FB2025_01 , released February 20, 2025
Gene: Dmel\para
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General Information
Symbol
Dmel\para
Species
D. melanogaster
Name
paralytic
Annotation Symbol
CG9907
Feature Type
FlyBase ID
FBgn0285944
Gene Model Status
Stock Availability
Gene Summary
paralytic (para) is an essential gene required for locomotor activity. It encodes an α-subunit of voltage-gated sodium channels. It is required for generation of sodium-dependent action potentials. [Date last reviewed: 2019-03-14] (FlyBase Gene Snapshot)
Also Known As

bss, sbl, bang senseless, smellblind, olfD

Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
1-54
RefSeq locus
NC_004354 REGION:16455027..16533096
Sequence
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
Gene Ontology (GO) Annotations (18 terms)
Molecular Function (4 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
inferred from mutant phenotype
Terms Based on Predictions or Assertions (3 terms)
CV Term
Evidence
References
inferred from electronic annotation with InterPro:IPR002048
Biological Process (12 terms)
Terms Based on Experimental Evidence (7 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from mutant phenotype
inferred from direct assay
inferred from genetic interaction with FLYBASE:kcc; FB:FBgn0261794
inferred from mutant phenotype
inferred from mutant phenotype
Terms Based on Predictions or Assertions (5 terms)
CV Term
Evidence
References
inferred from electronic annotation with InterPro:IPR005821
inferred from biological aspect of ancestor with PANTHER:PTN000798901
inferred from electronic annotation with InterPro:IPR005821
Cellular Component (2 terms)
Terms Based on Experimental Evidence (1 term)
CV Term
Evidence
References
located_in plasma membrane
inferred from direct assay
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
located_in plasma membrane
inferred from electronic annotation with InterPro:IPR043203
Protein Family (UniProt)
Belongs to the sodium channel (TC 1.A.1.10) family. Para subfamily. (P35500)
Summaries
Gene Snapshot
paralytic (para) is an essential gene required for locomotor activity. It encodes an α-subunit of voltage-gated sodium channels. It is required for generation of sodium-dependent action potentials. [Date last reviewed: 2019-03-14]
Gene Group (FlyBase)
VOLTAGE-GATED SODIUM CHANNEL ALPHA SUBUNITS -
Voltage-gated sodium (NaV) channels allow the inward movement of Na+ ions in response to a change in membrane potential. The voltage-gated pore is formed by homotetramers of the α subunit. In D.mel there is only one α subunit gene, but splicing variants of para exhibit distinct gating properties and conductivities. (Adapted from FBrf0228338).
Protein Function (UniProtKB)
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
(UniProt, P35500)
Phenotypic Description (Red Book; Lindsley and Zimm 1992)
Shu: Shudderer (J.C. Hall)
Sudden leg jerks are frequent and enough to topple the fly; negative geotaxis is sluggish and seemingly not a consequence of shuddering bouts during climbing toward top of glass vials; neither of these behavioral abnormalities is pronounced in young adults, but they become maximal after about a week of adult life; lithium or ammonium ions placed in medium on which the mutant is grown reduce the severities of the eventual adult phenotypes. Homozygous females are not observed.
Summary (Interactive Fly)

α-subunit of voltage-gated sodium channel - neuromuscular junction - required for locomotor activity - generates sodium-dependent action potentials - regulated by RNA alternative splicing and translational repression

Gene Model and Products
Number of Transcripts
60
Number of Unique Polypeptides
57

Please see the JBrowse view of Dmel\para for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)
Isoform displayed:
Pfam protein domains
InterPro name
classification
start
end
Protein Domains (via SMART)
Isoform displayed:
SMART protein domains
InterPro name
classification
start
end
Structure
Protein 3D structure   (Predicted by AlphaFold)   (AlphaFold entry P35500)

If you don't see a structure in the viewer, refresh your browser.
Model Confidence:
  • Very high (pLDDT > 90)
  • Confident (90 > pLDDT > 70)
  • Low (70 > pLDDT > 50)
  • Very low (pLDDT < 50)

AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Some regions with low pLDDT may be unstructured in isolation.

Experimentally Determined Structures
Crossreferences
Comments on Gene Model

Multiphase exon postulated: exon reading frame differs in alternative transcripts (FBrf0209044); overlap >20aa.

Gene model reviewed during 5.55

Annotated transcripts do not represent all possible combinations of alternative exons and/or alternative promoters.

Gene model reviewed during 5.44

Stop-codon suppression (UGA) postulated; FBrf0216884.

Gene model reviewed during 5.51

Gene model reviewed during 5.56

Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0074298
6849
2131
FBtr0303677
6708
2084
FBtr0303678
6714
2086
FBtr0303679
11444
2084
FBtr0303680
6714
2086
FBtr0303681
6780
2108
FBtr0303682
6786
2110
FBtr0303683
6723
2089
FBtr0303684
6777
2107
FBtr0303685
6714
2086
FBtr0303686
6852
2132
FBtr0303687
12006
2097
FBtr0303688
6789
2111
FBtr0303689
6705
2083
FBtr0303690
6885
2143
FBtr0303691
6795
2113
FBtr0303692
6747
2097
FBtr0303693
6723
2089
FBtr0303694
6607
240
FBtr0303695
6657
2067
FBtr0303696
6624
2056
FBtr0303697
5965
1125
FBtr0303698
5941
1117
FBtr0303699
6642
2062
FBtr0303700
6753
2099
FBtr0303701
6852
2132
FBtr0303702
6789
2111
FBtr0111022
6849
2131
FBtr0303703
6852
2132
FBtr0303704
6654
2066
FBtr0303705
5712
872
FBtr0303706
6624
2056
FBtr0303707
6665
917
FBtr0331170
6849
2145
FBtr0342746
15578
2131
FBtr0344944
6621
2055
FBtr0111023
6849
2131
FBtr0290121
6798
2114
FBtr0303655
6780
2108
FBtr0303656
6780
2108
FBtr0303657
6717
2087
FBtr0303658
6747
2097
FBtr0303659
6693
2079
FBtr0303660
6756
2100
FBtr0303661
6684
2076
FBtr0303662
6717
2087
FBtr0303663
6756
2100
FBtr0303664
6756
2100
FBtr0303665
6732
2092
FBtr0303666
6819
2121
FBtr0303667
6684
2076
FBtr0303668
6693
2079
FBtr0303669
6756
2100
FBtr0303670
6786
2110
FBtr0303671
6810
2118
FBtr0303672
6747
2097
FBtr0303673
6762
2102
FBtr0303674
6831
2125
FBtr0303675
6870
2138
FBtr0303676
6723
2089
Additional Transcript Data and Comments
Reported size (kB)

3.0 (northern blot)

Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
FBpp0074073
239.4
2131
4.77
FBpp0292694
234.2
2084
4.70
FBpp0292695
234.2
2086
4.71
FBpp0292696
234.2
2084
4.70
FBpp0292697
234.2
2086
4.65
FBpp0292698
236.9
2108
4.73
FBpp0292699
237.0
2110
4.70
FBpp0292700
234.7
2089
4.65
FBpp0292701
236.4
2107
4.73
FBpp0292702
234.1
2086
4.68
FBpp0292703
239.3
2132
4.76
FBpp0292704
235.4
2097
4.71
FBpp0292705
237.0
2111
4.70
FBpp0292706
233.8
2083
4.68
FBpp0292707
240.7
2143
4.81
FBpp0292708
237.4
2113
4.75
FBpp0292709
235.6
2097
4.69
FBpp0292710
234.5
2089
4.72
FBpp0292712
232.1
2067
4.70
FBpp0292713
230.8
2056
4.66
FBpp0292714
126.9
1125
5.26
FBpp0292715
125.9
1117
5.26
FBpp0292716
231.5
2062
4.62
FBpp0292717
235.4
2099
4.73
FBpp0292718
239.4
2132
4.73
FBpp0292719
237.1
2111
4.68
FBpp0110321
239.5
2131
4.74
FBpp0292720
239.2
2132
4.75
FBpp0292721
231.9
2066
4.65
FBpp0292723
230.9
2056
4.63
FBpp0292724
102.8
917
4.80
FBpp0303597
241.0
2145
4.79
FBpp0309614
239.4
2131
4.77
FBpp0311217
230.8
2055
4.63
FBpp0110322
239.3
2131
4.76
FBpp0288560
237.4
2114
4.70
FBpp0292672
236.8
2108
4.76
FBpp0292673
236.7
2108
4.75
FBpp0292674
234.5
2087
4.70
FBpp0292675
235.4
2097
4.71
FBpp0292676
233.6
2079
4.70
FBpp0292677
235.8
2100
4.75
FBpp0292678
233.2
2076
4.69
FBpp0292679
234.5
2087
4.69
FBpp0292680
235.8
2100
4.76
FBpp0292681
236.1
2100
4.69
FBpp0292682
235.2
2092
4.69
FBpp0292683
238.4
2121
4.75
FBpp0292684
233.3
2076
4.70
FBpp0292685
233.5
2079
4.69
FBpp0292686
236.1
2100
4.68
FBpp0292687
236.8
2110
4.78
FBpp0292688
237.8
2118
4.78
FBpp0292689
235.5
2097
4.72
FBpp0292690
236.1
2102
4.72
FBpp0292691
238.7
2125
4.78
FBpp0292692
240.3
2138
4.77
FBpp0292693
234.8
2089
4.68
Polypeptides with Identical Sequences

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

2131 aa isoforms: para-PA, para-PBG
2097 aa isoforms: para-PAK, para-PH
2084 aa isoforms: para-PAA, para-PAC
Additional Polypeptide Data and Comments
Reported size (kDa)
Comments
External Data
Domain

The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.

(UniProt, P35500)
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\para using the Feature Mapper tool.

External Data
Crossreferences
Linkouts
Expression Data
Testis-specificity index

The testis specificity index was calculated from modENCODE tissue expression data by Vedelek et al., 2018 to indicate the degree of testis enrichment compared to other tissues. Scores range from -2.52 (underrepresented) to 5.2 (very high testis bias).

-0.63

Transcript Expression
No Assay Recorded
Stage
Tissue/Position (including subcellular localization)
Reference
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

para transcripts are detected in the eye, in thoracic ganglia, and in cortical regions of the brain.

Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Evidence
References
located_in plasma membrane
inferred from direct assay
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\para in JBrowse
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
Reference
See Gelbart and Emmert, 2013 for analysis details and data files for all genes.
Developmental Proteome: Life Cycle
Developmental Proteome: Embryogenesis
External Data and Images
Linkouts
DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
Images
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 127 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 13 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of para
Transgenic constructs containing regulatory region of para
Aberrations (Deficiencies and Duplications) ( 25 )
Inferred from experimentation ( 25 )
Inferred from location ( 22 )
Variants
Variant Molecular Consequences
Alleles Representing Disease-Implicated Variants
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
Sterility
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
Orthologs
Human Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Homo sapiens (Human) (38)
13 of 14
Yes
Yes
1  
12 of 14
No
Yes
12 of 14
No
Yes
1  
12 of 14
No
Yes
12 of 14
No
Yes
11 of 14
No
Yes
11 of 14
No
Yes
1  
11 of 14
No
Yes
8 of 14
No
Yes
8 of 14
No
Yes
2 of 14
No
No
5  
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
Yes
2 of 14
No
Yes
2 of 14
No
Yes
2 of 14
No
Yes
2 of 14
No
No
2 of 14
No
Yes
2 of 14
No
Yes
1 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1  
1 of 14
No
No
1  
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (30)
12 of 14
Yes
Yes
12 of 14
Yes
Yes
12 of 14
Yes
Yes
12 of 14
Yes
Yes
12 of 14
Yes
Yes
11 of 14
No
Yes
11 of 14
No
Yes
11 of 14
No
Yes
8 of 14
No
Yes
7 of 14
No
Yes
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
Yes
2 of 14
No
Yes
2 of 14
No
Yes
2 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
Yes
1 of 14
No
No
Mus musculus (laboratory mouse) (29)
12 of 14
Yes
Yes
12 of 14
Yes
Yes
12 of 14
Yes
Yes
12 of 14
Yes
Yes
12 of 14
Yes
Yes
11 of 14
No
Yes
11 of 14
No
Yes
11 of 14
No
Yes
8 of 14
No
Yes
8 of 14
No
Yes
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
Yes
2 of 14
No
Yes
2 of 14
No
Yes
2 of 14
No
Yes
2 of 14
No
No
2 of 14
No
Yes
2 of 14
No
Yes
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
Yes
Xenopus tropicalis (Western clawed frog) (27)
11 of 13
Yes
Yes
10 of 13
No
Yes
8 of 13
No
Yes
7 of 13
No
Yes
7 of 13
No
Yes
6 of 13
No
Yes
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
1 of 13
No
No
1 of 13
No
No
1 of 13
No
Yes
1 of 13
No
No
1 of 13
No
Yes
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
1 of 13
No
No
1 of 13
No
Yes
Danio rerio (Zebrafish) (30)
13 of 14
Yes
Yes
12 of 14
No
Yes
11 of 14
No
Yes
11 of 14
No
Yes
11 of 14
No
Yes
10 of 14
No
Yes
10 of 14
No
Yes
10 of 14
No
Yes
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
Yes
2 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
Yes
1 of 14
No
Yes
1 of 14
No
No
Caenorhabditis elegans (Nematode, roundworm) (8)
1 of 14
Yes
No
1 of 14
Yes
No
1 of 14
Yes
No
1 of 14
Yes
No
1 of 14
Yes
No
1 of 14
Yes
No
1 of 14
Yes
No
1 of 14
Yes
No
Anopheles gambiae (African malaria mosquito) (9)
11 of 12
Yes
Yes
Arabidopsis thaliana (thale-cress) (1)
3 of 13
Yes
Yes
Saccharomyces cerevisiae (Brewer's yeast) (1)
5 of 13
Yes
No
Schizosaccharomyces pombe (Fission yeast) (1)
4 of 12
Yes
No
Escherichia coli (enterobacterium) (0)
Other Organism Orthologs (via OrthoDB)
Data provided directly from OrthoDB:para. Refer to their site for version information.
Paralogs
Paralogs (via DIOPT v9.1)
Drosophila melanogaster (Fruit fly) (10)
8 of 13
6 of 13
5 of 13
4 of 13
3 of 13
1 of 13
1 of 13
1 of 13
1 of 13
1 of 13
Human Disease Associations
FlyBase Human Disease Model Reports
Disease Ontology (DO) Annotations
Models Based on Experimental Evidence ( 12 )
Allele
Disease
Evidence
References
Potential Models Based on Orthology ( 30 )
Human Ortholog
Disease
Evidence
References
Modifiers Based on Experimental Evidence ( 7 )
Allele
Disease
Interaction
References
ameliorates  epilepsy
model of  epilepsy
exacerbates  epilepsy
model of  epilepsy
is exacerbated by SLO2CRISPR
is ameliorated by GstS1M26
model of  epilepsy
is ameliorated by parats1
is ameliorated by paraGD3392
is ameliorated by parats115
is exacerbated by paraGEFS+
is ameliorated by parabss1
is ameliorated by GstS1GD16335
is ameliorated by GstS1M26
Disease Associations of Human Orthologs (via DIOPT v9.1 and OMIM)
Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.
Homo sapiens (Human)
Gene name
Score
OMIM
OMIM Phenotype
DO term
Complementation?
Transgene?
Functional Complementation Data
Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.
Interactions
Summary of Physical Interactions
esyN Network Diagram
Show neighbor-neighbor interactions:
Show/hide secondary interactors 
(data from AllianceMine provided by esyN)
Select Layout:
Legend:
Protein
RNA
Selected Interactor(s)
Other Interaction Browsers

Please see the Physical Interaction reports below for full details
RNA-protein
Physical Interaction
Assay
References
Summary of Genetic Interactions
esyN Network Diagram
Show/hide secondary interactors 
(data from AllianceMine provided by esyN)
esyN Network Key:
Suppression
Enhancement
Other Interaction Browsers

Please look at the allele data for full details of the genetic interactions
Starting gene(s)
Interaction type
Interacting gene(s)
Reference
Starting gene(s)
Interaction type
Interacting gene(s)
Reference
External Data
Linkouts
Pathways
Signaling Pathways (FlyBase)
Metabolic Pathways
FlyBase
External Links
External Data
Linkouts
Class of Gene
Genomic Location and Detailed Mapping Data
Chromosome (arm)
X
Recombination map
1-54
Cytogenetic map
Sequence location
FlyBase Computed Cytological Location
Cytogenetic map
Evidence for location
14C8-14E1
; Limits computationally determined from genome sequence between P{EP}EP1547EP1547 and P{EP}CG4928EP1341
Experimentally Determined Cytological Location
Cytogenetic map
Notes
References
14C-14C
(determined by in situ hybridisation)
14C-14D
(determined by in situ hybridisation)
14C6-14D1
(determined by in situ hybridisation)
14A-15A
(determined by in situ hybridisation)
Experimentally Determined Recombination Data
Notes

Mapped adjacent to eas. Mapped adjacent to nonA.

Mapping based on lethal phenotype.

Mapping based on 107 recombinants.

Stocks and Reagents
Stocks (66)
Genomic Clones (32)
cDNA Clones (10)
 

Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see JBrowse for alignment of the cDNAs and ESTs to the gene model.

cDNA clones, fully sequenced
BDGP DGC clones
    Other clones
      Drosophila Genomics Resource Center cDNA clones

      For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

        cDNA Clones, End Sequenced (ESTs)
        BDGP DGC clones
          Other clones
            RNAi and Array Information
            Linkouts
            Antibody Information
            Laboratory Generated Antibodies
            Commercially Available Antibodies
             
            Cell Line Information
            Publicly Available Cell Lines
             
              Other Stable Cell Lines
               
                Other Comments

                Sensitivity of para to DDT is not lowered by the 'super-kdr' mutation M918T, although this is reduced 10-fold by the 'kdr' mutation L1014F.

                The voltage dependent deactivation of para is made more negative by DDT.

                RNAi generated by PCR using primers directed to this gene causes a cell growth and viability phenotype when assayed in Kc167 and S2R+ cells.

                RNAi screen using dsRNA made from templates generated with primers directed against this gene causes a cell growth and viability phenotype when assayed in Kc167 and S2R+ cells.

                1-2μM AahIT significantly increases the Na+ current mediated by para as assayed in Xenopus oocytes. Domain 2 of para confers this AahIT sensitivity.

                para transcripts undergo adenosine-to-inosine RNA editing via a mechanism that apparently requires dsRNA secondary structure formation encompassing the edited exon and the downstream intron. The mlenap-ts1 mutation results in the occurrence of a "splicing catastrophe" of the para transcript in the region of the RNA editing site; more than 80% of para transcripts in this background are aberrant, owing to internal deletions that include the edited para exon.

                Rearing parats1 embryos, at restrictive temperatures, starting at different times during synaptogenesis, reveals neural activity at a certain period of development profoundly affects the distribution of GluRIIA receptors.

                Intragenic and extragenic suppressors of bss are isolated using an X ray screen of bss mutants for loss of paralytic behaviour.

                Heterologous expression of para sodium channels in Xenopus oocytes is poor. Coexpression of para with tipE results in robust sodium currents. The biophysical and biochemical properties of invertebrate and vertebrate neuronal sodium channels are distinct.

                The region that includes para contains a complex of neurally expressed genes, Cnx14D, Arp14D, Pp2B-14D and Cap. These five genes may represent a functionally related group sharing some coordinate regulatory mechanism.

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

                tipE encodes a novel integral membrane protein that dramatically stimulates functional para expression in Xenopus oocytes.

                The role of alternative splicing of the para gene in regulating sodium current expression has been investigated.

                The pattern of expression of para throughout development has been analysed.

                The "sbl" alleles represent a class of para alleles, and define a novel class of sodium channel mutation.

                The genomic organisation of the para locus has been analysed. A number of developmentally regulated alternative splice products have been identified.

                Distribution of para transcripts and protein studied in wild type and mlenap-ts1 mutants, where amount of para product is reduced.

                Ion channel mutants alter synaptic activity at the embryonic neuromuscular junction (NMJ). GluRIIA expression in the postsynaptic membrane is reduced by changes in presynaptic electrical activity. Synaptic transmission is blocked in para mutants in a temperature-dependent manner. Presynaptic electrical activity during embryonic synaptogenesis is constitutively required for GluRIIA expression at the NMJ and to induce receptor clustering at the NMJ. The size of the synaptic domain depends on the level of neural activity during embryonic synaptogenesis.

                para RNA expression in pupae and adults has been studied.

                Mutant analysis of para (unspecified) provides evidence for the participation of a G0-like protein in learning and memory. Sex-dependent enhancement in pertussis toxin catalysed ADP-ribosylation with respect to wild type: attributed in part to an increase in the α subunit of the G0-like protein.

                The olfactory phenotypes of para mutants has been studied with respect to courtship behaviour.

                Changes in the level of para+ expression can strongly influence neuronal excitability.

                Scaffold attachment regions in the region surrounding para have been mapped.

                Mutations of para cause abnormalities in the electroretinogram (ERG) and/or prolonged depolarization after potential (PDA).

                Viable alleles of para perform aberrantly in multiple olfactory paradigms as both larvae and adults.

                A cDNA that probably corresponds to the para locus has been cloned and sequenced.

                The para locus encodes an essential function. Genetic, electrophysiological, behavioral and pharmacological studies of mle and para mutants suggest that they effect sodium channels and the genes may encode different subunits.

                mlenap-ts1 is unconditionally lethal in a double mutant with parats1 (death occurring during 1st larval instar).

                Mutations of para have been recovered both as a consequence of their paralytic phenotype (as para) and as a consequence of their olfactory phenotype (as sbl). For the para alleles: exposure to 29-30oC causes rapid paralysis that is quickly reversed on shift to 22-25oC. Larvae are paralyzed, too, at somewhat higher temperatures. Flies of some para strains seem sluggish at lower temperatures. When these mutants are still paralyzed (i.e. at high temperatures), they appear to retain many of their 'vital functions,' their heart still beats (Grigliatti, Suzuki and Williamson, 1972) and they quickly regain normal behavior when shifted to 22oC after several hours at 29oC (Suzuki, Grigliatti and Williamson, 1971); in fact, after a less prolonged exposure (30 min) to high temperature, the still-heated mutant flies regain weak mobility and are even able to right themselves and walk (Suzuki, Grigliatti and Williamson, 1971). parats1/+ adults become paralyzed at 40oC within one min <up>10 min required to paralyze wild-type (Hall, 1973)</up>. parats1 larvae stop 'tracking' at high temperature (Wu, Ganetzky, Jan, Jan and Benzer, 1978). parats1 is nearly unconditionally lethal when uncovered by a deletion or other para-locus aberration, whereas other alleles lead to reduced viability (unconditional) when heterozygous with chromosomal aberrations at the locus (Ganetzky, 1984). Action potentials in larval nerves are reversibly temperature-sensitive (Wu and Ganetzky, 1980) and the same can be inferred for at least some adult neurons (indicated by brain stimulation and recording of responses in thoracic muscles (Siddiqi and Benzer, 1976; Benshalom and Dagan, 1981). Other 'excitable phenomena,' such as the electroretinogram responses and synaptic transmission, appear to be normal in parats1 adults at high temperature (Suzuki, Grigliatti and Williamson, 1971; Siddiqi and Benzer, 1976); also parats1 does not block action potentials in the cervical giant fiber at high temperature (Nelson and Baird, 1985) in contrast to results of recording from larval motor neurons (Wu and Ganetzky, 1980); other studies of the giant fiber pathway (involving adult mosaics bilaterally split, externally, for parats1 and para+) indicate that at least certain elements of the pathway (if not the giant fiber itself) fail to fire action potentials at elevated temperature (Benshalom and Dagan, 1981) and recordings from mosaics of this type also suggest 'functional coupling' between left and homologous right sides of this giant fiber pathway (Benshalom and Dagan, 1985). parats1 causes first larval instar death when in combination with mlenap-ts1 (Wu and Ganetzky, 1980; Ganetzky, 1984); similar lethality occurs when para+ dosage is decreased in a mlenap-ts1 background (Ganetzky, 1984). Other para alleles, in combination with mlenap-ts1, lead to reduced viability, with parats115 having the strongest effect, followed by paraST76 and paraST109 (Ganetzky, 1984). In combination with the tipE mutation, para mutations again cause decreased viability, but the allele-specific interactions are different from those of the series just noted <up>i.e. with respect to mlenap-ts1 (Ganetzky, 1986)</up>. Surviving para; tipE double mutants are weak and show accentuated heat-sensitivity (in regard to mobility and nerve conduction); para alleles are dominant for behavioral defects in a homozygous tipE background (Ganetzky, 1985). In adults doubly mutant for parats1 and mlenap-ts1, sensory cells (developing from imaginal discs in mosaics) appear to have no nerve conduction (Burg and Wu, 1984). In mosaics involving para mutations only one allele (paraST109) causes all legs to be either paralyzed or normal in different individual gynandromorphs (Siddiqi and Benzer, 1976), in contrast to independent paralysis of legs in mosaics constructed with respect to parats1 (Grigliatti, Suzuki and Williamson, 1972; Siddiqi and Benzer, 1978). These results (and others, e.g. Benshalom and Dagan, 1985), reveal poor correlation of the externally mutant genotype (in mosaics) and behavioral or physiological malfunctions <up>consistent with internal (no doubt neural) 'foci' for para's action</up>. In other studies, parats1 mosaics with mutant heads (scored externally) usually are immobile at high temperature, but maintain normal posture (Suzuki, Grigliatti and Williamson, 1971; Grigliatti, Suzuki and Williamson, 1972). Exposure of parats1 males to high temperature causes arrest of the oscillator underlying rhythmic component of courtship song (Kyriacou and Hall, 1985). At permissive tempe

                dominant cold-sensitive, reversible paralytic; heterozygous mutant females begin uncoordinated behavior (progressively: abnormal leg movements, leg stretching, wing fluttering) on shift from 25oC to 18-20oC; paralysis eventually occurs, and recovery is gradual on shift back to higher temperatures; critical temperature to include the debilitations is ca. 2oC lower from Ocd7 than for other alleles; also males hemizygous for Ocd7 have better viability than those expressing the other alleles, with Ocd4 being the most severely affected i.e., nearly lethal (Ocd4 also causes near lethality when heterozygous with any of the other alleles); at 25oC, mutant males walk in reeling manner and fall over frequently; none can fly and attempts to coax jumps (to initiate flight) cause the males merely to fall over when touched; these phenotypes also seen in homozygotes and heteroallelic combinations; certain of the homozygous mutant females (e.g. Ocd2 and Ocd3) hold their wings in drooped position; also seen in Ocd1 males; this phenotype also observed in Ocd2/+ and Ocd3/+ females, which also walk in unsteady manner; other alleles, when heterozygous, allow for seemingly normal behavior at 25oC, except that their legs shake under etherization (with Ocd4 causing the strongest aberrant shaking). Abrupt, anomalous changes in Arrhenius activation energy of the mitochondrial enzyme, succinate cytochrome c reductase, are seen at temperatures close to those which induce paralysis (Sondergaard et al. 1975). Two-dimension gels of mitochondria isolated from Ocd1 contain an additional polypeptide not seen in extracts of wild-type (Sondergaard, 1986).

                Separable by recombination from eas, which causes a similar phenotype and to which bss is closely linked.

                Mechanical shock or vortexing induces paralysis lasting for 2-3 minutes; heterozygous female are paralysed for 40-50 seconds. Homozygotes and hemizygotes have abnormally prolonged release of neurotransmitter at larval neuromuscular junctions, which is associated with multiple firing of action potentials in the nerves; behavioral and electrophysiological phenotypes suppressed by mlenap-ts1 at its permissive (low) temperature.

                Relationship to Other Genes
                Source for database merge of

                Source for merge of: para Ocd

                Source for merge of: para bss

                Source for merge of: para Shudderer

                Additional comments

                "bss" stated to correspond to "Dsp1".

                Nomenclature History
                Source for database identify of

                Source for identity of: Shudderer Shu

                Nomenclature comments

                The gene symbol "Shu" has been changed to "Shudderer" in order to reduce confusion with the "shu" ("shutdown") gene symbol, from which it differed only by case.

                Etymology
                Synonyms and Secondary IDs (39)
                Reported As
                Symbol Synonym
                Shu
                Shudderer
                l(1)14Da
                l(1)ESHS48
                para
                (Goodchild et al., 2024, Hunter and Leib, 2024, Hunter et al., 2024, Lansdon et al., 2024, Bossen et al., 2023, Corthals et al., 2023, Ffrench-Constant, 2023, Kasuya et al., 2023, Lopez-Ortiz et al., 2023, Luo et al., 2023, O'Farrell et al., 2023, Perlegos et al., 2023, Qie et al., 2023, Schenk and Gaudry, 2023, Scott et al., 2023, Voutyraki et al., 2023, Beaver et al., 2022, Corrales et al., 2022, Maksymchuk et al., 2022, Qie et al., 2022, Wenner and Pekala, 2022, Giachello et al., 2021, Iyengar and Wu, 2021, Lasko and Lüthy, 2021, Luong et al., 2021, McLaughlin et al., 2021, Mituzaite et al., 2021, Roemmich et al., 2021, Salim et al., 2021, Tapia et al., 2021, Wang et al., 2021, Xie et al., 2021, Dare et al., 2020, Demakova et al., 2020, Fendl et al., 2020, Jacobs and Sehgal, 2020, Kurmangaliyev et al., 2020, Pegoraro et al., 2020, Perry et al., 2020, Petruccelli et al., 2020, Ravenscroft et al., 2020, Samantsidis et al., 2020, Samuels et al., 2020, Sapiro et al., 2020, Singh et al., 2020, Takai et al., 2020, Yusuff et al., 2020, Deshpande et al., 2019, Kadas et al., 2019, Kasuya et al., 2019, Piggott et al., 2019, Radlicz et al., 2019, Rosch et al., 2019, Samantsidis et al., 2019, Zhang and Zhang, 2019, Al-Ramahi et al., 2018, Chen et al., 2018, Herman et al., 2018, Johan Arief et al., 2018, Li et al., 2018, Lin et al., 2018, Sekiya et al., 2018, Wang et al., 2018, Xing and Wu, 2018, Agrawal et al., 2017, Bussmann and Storkebaum, 2017, Fisher et al., 2017, Ghezzi et al., 2017, Giachello and Baines, 2017, Lin et al., 2017, Saras et al., 2017, Stessman et al., 2017, VanKirk et al., 2017, Xiao et al., 2017, Zajitschek et al., 2017, Ffrench-Constant et al., 2016, Iyer et al., 2016, Kaas et al., 2016, Saras and Tanouye, 2016, Saras and Tanouye, 2016, Schutte et al., 2016, Ugur et al., 2016, Wang et al., 2016, Chaston et al., 2015, Kern et al., 2015, Kroll et al., 2015, Loedige et al., 2015, Matthews et al., 2015, Pan et al., 2015, Petruccelli et al., 2015, Rieder et al., 2015, Ashwal-Fluss et al., 2014, Brown et al., 2014, Ghezzi et al., 2014, Schutte et al., 2014, Westholm et al., 2014, Buhl et al., 2013, Chow et al., 2013, Costa and Stanewsky, 2013, Ghezzi et al., 2013, Howlett and Tanouye, 2013, Howlett et al., 2013, Islam et al., 2013, Rieder et al., 2013, Yamamoto et al., 2013-, Garber et al., 2012, Rodriguez et al., 2012, Simon et al., 2012, Stewart et al., 2012, Sun et al., 2012, Tsai et al., 2012, Tsubouchi et al., 2012, Venables et al., 2012, Al-Hasan et al., 2011, Burton et al., 2011, Jungreis et al., 2011, Leiserson et al., 2011, Montell, 2011, Parker et al., 2011, Parker et al., 2011, Zhang et al., 2011, Zhou et al., 2011, Cook et al., 2010, Fergestad et al., 2010, Popodi et al., 2010-, Repnikova et al., 2010, Singh et al., 2010, Venken et al., 2010, Zhong et al., 2010, Zhu et al., 2010, Barber et al., 2009, Ruedi and Hughes, 2009, Venken et al., 2009, Lindsay et al., 2008, Muraro et al., 2008, Reenan and Rogina, 2008, Ruan and Wu, 2008, Sandstrom, 2008, Dietzl et al., 2007, Lagow et al., 2007, Rikhy et al., 2007, Song and Tanouye, 2007, Usherwood et al., 2007, Buscaino et al., 2006, Cardnell et al., 2006, Cohen et al., 2006, Hiesinger et al., 2006, Schulz et al., 2006, Stilwell et al., 2006, Glazov et al., 2005, Gleason, 2005, Sandstrom, 2005, Usherwood et al., 2005, Dallman et al., 2004, Franchini et al., 2004, Mee et al., 2004, Trotta et al., 2004, Wang et al., 2004, van Swinderen and Greenspan, 2003, Hodges et al., 2002, Park et al., 2002, Wang et al., 2002, Castella et al., 2001, Kuebler et al., 2001, Feng et al., 1995)
                Name Synonyms
                Out cold
                Shudderer
                bangsenseless
                voltage gated sodium ion channel
                voltage-sensitive sodium channel
                Secondary FlyBase IDs
                • FBgn0264255
                • FBgn0260993
                • FBgn0003036
                • FBgn0001727
                • FBgn0003320
                • FBgn0002980
                • FBgn0000231
                • FBgn0003402
                Datasets (0)
                Study focus (0)
                Experimental Role
                Project
                Project Type
                Title
                Study result (0)
                Result
                Result Type
                Title
                External Crossreferences and Linkouts ( 309 )
                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.
                RefSeq - A comprehensive, integrated, non-redundant, well-annotated set of reference sequences including genomic, transcript, and protein.
                UniProt/GCRP - The gene-centric reference proteome (GCRP) provides a 1:1 mapping between genes and UniProt accessions in which a single 'canonical' isoform represents the product(s) of each protein-coding gene.
                UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information
                Other crossreferences
                AlphaFold DB - AlphaFold provides open access to protein structure predictions for the human proteome and other key proteins of interest, to accelerate scientific research.
                DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
                EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
                FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
                KEGG Genes - Molecular building blocks of life in the genomic space.
                MARRVEL_MODEL - MARRVEL (model organism gene)
                Linkouts
                FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
                FlyCyc Genes - Genes from a BioCyc PGDB for Dmel
                iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
                Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
                References (560)