Q9VJY9 · LOQS_DROME
- ProteinProtein Loquacious
- Geneloqs
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids465 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Isoform PA
Double-stranded RNA-binding protein which can function in gene silencing by acting with Dcr-1 to enhance its ATP-independent processing of a specific subset of precursor micro-RNAs (pre-miRNAs) to mature miRNAs (PubMed:19635780, PubMed:26769856, PubMed:27184838).
Some reports found it was able to enhance the efficiency of pre-miRNA processing by Dcr-1, and can shift the cleavage site of Dcr-1 altering the length of the mature miRNAs produced by Dcr-1 alone (PubMed:17320391, PubMed:23063653, PubMed:29373753).
However, in contrast to isoform PB, it is not necessary or sufficient for enhancing miRNA biogenesis, and is not required for development or female germline stem cell (GSC) maintenance (PubMed:17320391, PubMed:23063653).
Another report also found that it decreases binding of Dcr-1 to the miRNA substrate let-7 (PubMed:17928574).
Some reports found it was able to enhance the efficiency of pre-miRNA processing by Dcr-1, and can shift the cleavage site of Dcr-1 altering the length of the mature miRNAs produced by Dcr-1 alone (PubMed:17320391, PubMed:23063653, PubMed:29373753).
However, in contrast to isoform PB, it is not necessary or sufficient for enhancing miRNA biogenesis, and is not required for development or female germline stem cell (GSC) maintenance (PubMed:17320391, PubMed:23063653).
Another report also found that it decreases binding of Dcr-1 to the miRNA substrate let-7 (PubMed:17928574).
Isoform PB
Double-stranded RNA-binding protein which functions in gene silencing by acting with Dcr-1 to enhance its ATP-independent processing of a specific subset of precursor micro-RNAs (pre-miRNAs) to mature miRNAs (PubMed:15918769, PubMed:15985611, PubMed:17666393, PubMed:17928574, PubMed:19635780, PubMed:26769856, PubMed:27184838, PubMed:36182693).
Function is essential for development and female germline stem cell (GSC) maintenance (PubMed:15985611, PubMed:17320391, PubMed:23063653).
Functions in miRNA-mediated gene silencing by enhancing the binding affinity and specific pre-miRNA processing activity of Dcr-1, and as part of the loqs-PB-Dcr-1 complex, is involved in substrate discrimination, correctly positioning the pre-miRNA in the Dcr-1 catalytic center for cleavage, and miRNA loading into the Argonaute 1 (Ago1)-containing RNA-induced silencing complex (miRISC) (PubMed:15918769, PubMed:17666393, PubMed:17928574, PubMed:23063653, PubMed:27184838, PubMed:36182693).
Increases the binding affinity of Dcr-1 to pre-miRNAs, thereby increasing dicing efficiency and broadening the range of substrates that can be processed by the dicer (PubMed:17928574, PubMed:23063653, PubMed:27184838, PubMed:36182693).
It may also confer the substrate specificity of Dcr-1 towards pre-miRNAs, as in its absence Dcr-1 displays siRNA-generating activity towards long dsRNA substrates (PubMed:15918769).
It can also shift the cleavage site of Dcr-1 for a small number of pre-miRNAs, changing the length of the mature miRNAs produced by Dcr-1 alone (PubMed:23063653, PubMed:29373753).
Increases the range of pre-miRNAs that can be processed by Dcr-1, by enhancing the dicing of suboptimal hairpin substrates including ones with mismatches at the dicing site (PubMed:27184838, PubMed:29373753).
This function may also promote the generation of novel miRNA genes as it appears to have an important role in processing evolutionarily young miRNA genes, suggesting that it may also enhance dicing of substrates that have not acquired hairpin features required for efficient miRNA processing (PubMed:27184838).
As newly emerged miRNAs can have deleterious or beneficial effects on fitness, this function is likely part of a regulatory system that prevents excessive emergence of active miRNA genes and thus keeps them within an optimal range (PubMed:27184838).
Also forms a RISC loading complex (miRLC) with Dcr-1 to mediate Ago1-loading of mature miRNAs into the RNA-induced silencing complex (miRISC) (PubMed:15918769, PubMed:36182693).
In female ovaries, required for Dcr-1 to generate the twenty-three nucleotide isomiR variant of miR-307a which is able to repress its targets Gk2 and tara (PubMed:23063653).
Function is essential for development and female germline stem cell (GSC) maintenance (PubMed:15985611, PubMed:17320391, PubMed:23063653).
Functions in miRNA-mediated gene silencing by enhancing the binding affinity and specific pre-miRNA processing activity of Dcr-1, and as part of the loqs-PB-Dcr-1 complex, is involved in substrate discrimination, correctly positioning the pre-miRNA in the Dcr-1 catalytic center for cleavage, and miRNA loading into the Argonaute 1 (Ago1)-containing RNA-induced silencing complex (miRISC) (PubMed:15918769, PubMed:17666393, PubMed:17928574, PubMed:23063653, PubMed:27184838, PubMed:36182693).
Increases the binding affinity of Dcr-1 to pre-miRNAs, thereby increasing dicing efficiency and broadening the range of substrates that can be processed by the dicer (PubMed:17928574, PubMed:23063653, PubMed:27184838, PubMed:36182693).
It may also confer the substrate specificity of Dcr-1 towards pre-miRNAs, as in its absence Dcr-1 displays siRNA-generating activity towards long dsRNA substrates (PubMed:15918769).
It can also shift the cleavage site of Dcr-1 for a small number of pre-miRNAs, changing the length of the mature miRNAs produced by Dcr-1 alone (PubMed:23063653, PubMed:29373753).
Increases the range of pre-miRNAs that can be processed by Dcr-1, by enhancing the dicing of suboptimal hairpin substrates including ones with mismatches at the dicing site (PubMed:27184838, PubMed:29373753).
This function may also promote the generation of novel miRNA genes as it appears to have an important role in processing evolutionarily young miRNA genes, suggesting that it may also enhance dicing of substrates that have not acquired hairpin features required for efficient miRNA processing (PubMed:27184838).
As newly emerged miRNAs can have deleterious or beneficial effects on fitness, this function is likely part of a regulatory system that prevents excessive emergence of active miRNA genes and thus keeps them within an optimal range (PubMed:27184838).
Also forms a RISC loading complex (miRLC) with Dcr-1 to mediate Ago1-loading of mature miRNAs into the RNA-induced silencing complex (miRISC) (PubMed:15918769, PubMed:36182693).
In female ovaries, required for Dcr-1 to generate the twenty-three nucleotide isomiR variant of miR-307a which is able to repress its targets Gk2 and tara (PubMed:23063653).
Isoform PD
Double-stranded RNA-binding protein which has an essential role in gene silencing (RNAi) by acting with Dcr-2 to enhance its ATP-dependent processing of a subset of endogenous (endo) and exogenous (exo) dsRNAs into short interfering RNAs (siRNAs) (PubMed:19635780, PubMed:19644447, PubMed:21245036, PubMed:23063653, PubMed:25891075, PubMed:27184838, PubMed:28874570, PubMed:29040648, PubMed:29550490, PubMed:34590626).
Functions in RNAi by increasing the initial binding affinity of Dcr-2 to certain dsRNA substrates, and in the absence of r2d2, may also function in siRNA loading into the Argonaute 2 (AGO2)-containing RNA-induced silencing complex (siRISC) and guide strand selection for target silencing by the siRISC (PubMed:19635780, PubMed:19644447, PubMed:21245036, PubMed:29550490).
Promotes Dcr-2 cleavage of a subset of dsRNAs, including endo-dsRNAs derived from convergent transcription, inverted repeats and transposons (PubMed:19635780, PubMed:19644447, PubMed:21245036, PubMed:23063653, PubMed:29550490).
Also enables Dcr-2 to produce hairpin-derived endo-siRNAs in the presence of cellular inhibitory inorganic phosphate, likely by increasing the binding affinity of the enzyme to the hairpin dsRNAs allowing the dsRNA to displace phosphate bound to Dcr-2 (PubMed:29550490).
According to many reports, the cleavage reaction mode of Dcr-2 changes according to the termini of the dsRNA substrate, with the enzyme displaying a preference for processing blunt termini (BLT), likely non-self dsRNAs, over dsRNAs with 2 nucleotides 3' overhanging (3'ovr) termini, which are typically the structure of endo-dsRNAs (PubMed:25891075, PubMed:29550490, PubMed:34590626).
According to many reports, interaction with Loqs-PD modifies the molecular recognition mechanisms of Dcr-2 towards sub-optimal 3'ovr dsRNA substrates and thus enables the dicer to cleave endo-dsRNA templates with diverse termini (PubMed:25891075, PubMed:29550490).
However, according to another report, the mode of cleavage reaction is not affected by the presence or absence of loqs-PD (PubMed:34590626).
In the absence of r2d2, may also form an alternative RISC loading complex (siRLC) with Dcr-2 to mediate AGO2-loading of endo- and exo-siRNAs into the RNA-induced silencing complex (siRISC) (PubMed:21245036, PubMed:29040648).
Many reports suggest that loqs-PD and r2d2 function independently with dcr-2 in distinct siRNA pathways, and may even compete for binding to the enzyme (PubMed:21245036, PubMed:29040648).
Loaded siRNAs serve as a guide to direct the siRISC to complementary RNAs to degrade them or prevent their translation (PubMed:29040648).
The siRLC plays an important role in the ATP-dependent asymmetry sensing of the duplex, and is therefore also responsible for the selection of the strand that ultimately acts as the guide siRNA for the siRISC (PubMed:29040648).
Thermodynamically asymmetric endo-siRNAs can be pre-oriented in the siRLC by the Loqs-PD and DCr-2 complex, which preferentially binds to the most thermodynamically stable strand prior to loading into the siRISC (PubMed:29040648).
Appears to be involved in promoting double-strand breaks (DSBs) following exposure to a low-dose/dose-rate (LDR) of ionizing radiation (PubMed:36057690).
Functions in RNAi by increasing the initial binding affinity of Dcr-2 to certain dsRNA substrates, and in the absence of r2d2, may also function in siRNA loading into the Argonaute 2 (AGO2)-containing RNA-induced silencing complex (siRISC) and guide strand selection for target silencing by the siRISC (PubMed:19635780, PubMed:19644447, PubMed:21245036, PubMed:29550490).
Promotes Dcr-2 cleavage of a subset of dsRNAs, including endo-dsRNAs derived from convergent transcription, inverted repeats and transposons (PubMed:19635780, PubMed:19644447, PubMed:21245036, PubMed:23063653, PubMed:29550490).
Also enables Dcr-2 to produce hairpin-derived endo-siRNAs in the presence of cellular inhibitory inorganic phosphate, likely by increasing the binding affinity of the enzyme to the hairpin dsRNAs allowing the dsRNA to displace phosphate bound to Dcr-2 (PubMed:29550490).
According to many reports, the cleavage reaction mode of Dcr-2 changes according to the termini of the dsRNA substrate, with the enzyme displaying a preference for processing blunt termini (BLT), likely non-self dsRNAs, over dsRNAs with 2 nucleotides 3' overhanging (3'ovr) termini, which are typically the structure of endo-dsRNAs (PubMed:25891075, PubMed:29550490, PubMed:34590626).
According to many reports, interaction with Loqs-PD modifies the molecular recognition mechanisms of Dcr-2 towards sub-optimal 3'ovr dsRNA substrates and thus enables the dicer to cleave endo-dsRNA templates with diverse termini (PubMed:25891075, PubMed:29550490).
However, according to another report, the mode of cleavage reaction is not affected by the presence or absence of loqs-PD (PubMed:34590626).
In the absence of r2d2, may also form an alternative RISC loading complex (siRLC) with Dcr-2 to mediate AGO2-loading of endo- and exo-siRNAs into the RNA-induced silencing complex (siRISC) (PubMed:21245036, PubMed:29040648).
Many reports suggest that loqs-PD and r2d2 function independently with dcr-2 in distinct siRNA pathways, and may even compete for binding to the enzyme (PubMed:21245036, PubMed:29040648).
Loaded siRNAs serve as a guide to direct the siRISC to complementary RNAs to degrade them or prevent their translation (PubMed:29040648).
The siRLC plays an important role in the ATP-dependent asymmetry sensing of the duplex, and is therefore also responsible for the selection of the strand that ultimately acts as the guide siRNA for the siRISC (PubMed:29040648).
Thermodynamically asymmetric endo-siRNAs can be pre-oriented in the siRLC by the Loqs-PD and DCr-2 complex, which preferentially binds to the most thermodynamically stable strand prior to loading into the siRISC (PubMed:29040648).
Appears to be involved in promoting double-strand breaks (DSBs) following exposure to a low-dose/dose-rate (LDR) of ionizing radiation (PubMed:36057690).
Miscellaneous
The name 'Loquacious' refers to the mutants being 'very talkative' as they display a loss of several types of gene silencing.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | nucleus | |
Cellular Component | RISC complex | |
Cellular Component | RISC-loading complex | |
Molecular Function | double-stranded RNA binding | |
Molecular Function | RISC complex binding | |
Molecular Function | siRNA binding | |
Biological Process | central nervous system development | |
Biological Process | dosage compensation by hyperactivation of X chromosome | |
Biological Process | female germ-line stem cell asymmetric division | |
Biological Process | germ-line stem cell population maintenance | |
Biological Process | miRNA metabolic process | |
Biological Process | pre-miRNA processing | |
Biological Process | regulation of regulatory ncRNA processing | |
Biological Process | RISC complex assembly | |
Biological Process | siRNA processing |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProtein Loquacious
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Metazoa > Ecdysozoa > Arthropoda > Hexapoda > Insecta > Pterygota > Neoptera > Endopterygota > Diptera > Brachycera > Muscomorpha > Ephydroidea > Drosophilidae > Drosophila > Sophophora
Accessions
- Primary accessionQ9VJY9
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Disruption phenotype
Larval lethal and displays miRNA processing defects (PubMed:17320391).
Embryos do not develop past the first instar larvae stage (PubMed:17320391).
Most females contain ovaries with empty germaria accompanied by one or two terminal stage egg chambers (PubMed:17320391).
Accumulates pre-miRNAs and displays a reduction in mature miRNAs (PubMed:17320391).
Embryos do not develop past the first instar larvae stage (PubMed:17320391).
Most females contain ovaries with empty germaria accompanied by one or two terminal stage egg chambers (PubMed:17320391).
Accumulates pre-miRNAs and displays a reduction in mature miRNAs (PubMed:17320391).
Isoform PA
No significant effect on female or male fertility.
Isoform PB
Female fertility is severely reduced whereas male fertility is relatively unaffected (PubMed:23063653).
Females lay very few eggs, and most of the eggs that are laid have abnormal appendages and do not hatch (PubMed:23063653).
Females lay very few eggs, and most of the eggs that are laid have abnormal appendages and do not hatch (PubMed:23063653).
Isoform PD
No significant effect on female or male fertility.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 308-309 | Abolishes interaction with pre-miRNA (pre let 7) in the presence of Dcr-1. | ||||
Sequence: AA → LL | ||||||
Mutagenesis | 347 | In isoform Q9VJY9-4; Reduced interaction with Dcr-2. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 356 | In isoform Q9VJY9-4; Reduced interaction with Dcr-2. | ||||
Sequence: F → D | ||||||
Mutagenesis | 359 | In isoform Q9VJY9-4; Reduced interaction with Dcr-2. | ||||
Sequence: I → D | ||||||
Mutagenesis | 379-382 | Strong reduction in Dcr-1 activity. | ||||
Sequence: LLKL → AAKA | ||||||
Mutagenesis | 419 | Strong reduction in Dcr-1 activity. | ||||
Sequence: F → A | ||||||
Mutagenesis | 426 | Decreased binding to Dcr-1. | ||||
Sequence: L → R | ||||||
Mutagenesis | 440-465 | Loss of activity, abolishes interaction with Dcr-1 and therefore does not enhance pre-miRNA processing by the dicer. | ||||
Sequence: Missing |
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000458898 | 1-465 | Protein Loquacious | |||
Sequence: MDQENFHGSSLPQQLQNLHIQPQQASPNPVQTGFAPRRHYNNLVGLGNGNAVSGSPVKGAPLGQRHVKLKKEKISAQVAQLSQPGQLQLSDVGDPALAGGSGLQGGVGLMGVILPSDEALKFVSETDANGLAMKTPVSILQELLSRRGITPGYELVQIEGAIHEPTFRFRVSFKDKDTPFTAMGAGRSKKEAKHAAARALIDKLIGAQLPESPSSSAGPSVTGLTVAGSGGDGNANATGGGDASDKTVGNPIGWLQEMCMQRRWPPPSYETETEVGLPHERLFTIACSILNYREMGKGKSKKIAKRLAAHRMWMRLQETPIDSGKISDSICGELEGEPRSSENYYGELKDISVPTLTTQHSNKVSQFHKTLKNATGKKLLKLQKTCLKNNKIDYIKLLGEIATENQFEVTYVDIEEKTFSGQFQCLVQLSTLPVGVCHGSGPTAADAQRHAAQNALEYLKIMTKK |
Proteomic databases
Expression
Tissue specificity
Isoform PA
Strong expression in males and females (PubMed:15918770).
Expression in ovaries is relatively weak (PubMed:15918770).
Expression in ovaries is relatively weak (PubMed:15918770).
Isoform PB
Strong expression in females and relatively weak expression in males (PubMed:15918770).
Strong expression in ovaries (PubMed:15918770).
Strong expression in ovaries (PubMed:15918770).
Induction
Isoform PD
Slightly down-regulated in response to a low-dose/dose-rate (LDR) of ionizing radiation.
Developmental stage
Isoform PA
Expressed both maternally and zygotically (at protein level). Detected in embryos, larvae and adults (at protein level).
Isoform PB
Expressed both maternally and zygotically (at protein level). Detected in embryos, larvae and adults (at protein level).
Gene expression databases
Interaction
Subunit
Homodimer.
Isoform PA
Interacts with dicer enzyme Dcr-1.
Isoform PB
Component of the miRNA-directed RNA-induced loading complex (miRLC), composed of at least Dcr-1, AGO1 and loqs isoform PB (loqs-PB), which processes pre-miRNAs and loads the resulting miRNAs into the Argonaute 1 (AGO1)-containing RNA-induced silencing complex (miRISC) to target the selective destruction of homologous RNAs (PubMed:15918769, PubMed:15985611, PubMed:19451544).
Interacts (via DRBM 3 domain) with dicer enzyme Dcr-1 (via helicase domain) (PubMed:15918769, PubMed:15918770, PubMed:15985611, PubMed:17666393, PubMed:19451544, PubMed:19635780, PubMed:19644447, PubMed:26769856, PubMed:36182693).
Different regions of the Dcr-1-loqs-PB heterodimer collaborate to recognize, bind and position the pre-miRNA for Dcr-1 mediated cleavage (PubMed:36182693).
In the absence of miRNA substrates, the heterodimer favors a closed, catalytically incompetent, conformation, whereas binding of authentic pre-miRNA substrates stabilizes the relatively rare open, catalytically competent, conformation of the heterodimer (PubMed:36182693).
During substrate recognition, the Dcr-1 PAZ domain and pre-miRNA interact with the DRBM 1 domain of loqs-PB, which likely contributes to substrate recognition and stabilization (PubMed:36182693).
At the miRNA binding stage, the Dcr-1 DRBM domain and the loqs-PB DRBM domains then bind the pre-miRNA in tandem to form a tight 'belt' around the pre-miRNA stem, the pre-miRNA loop is docked in the loop-binding region formed by DUF283, DRBM and part of the helicase domain of Dcr-1, and the loqs-PB DRBM 1 and the wing domain of Dcr-1 act together to bind the 5' and 3' pre-miRNA termini within the PAZ and platform domains of Dcr-1 (PubMed:36182693).
These interactions between the proteins and their pre-miRNA substrate stabilize a distorted form of the pre-miRNA and position the scissile phosphodiester bonds of the pre-miRNA at the RNase III catalytic cleavage sites of Dcr-1 (PubMed:36182693).
Following Dcr-1 mediated cleavage, the miRNA duplex remains bound to loqs-PB DRBM 1, which dissociates from the Dcr-1 RNase III 1 domain but remains in contact with the PAZ and wing domains suggesting that the heterodimer presents the mature miRNA to AGO2 for loading into the RNA-induced silencing complex (miRISC) (PubMed:36182693).
Interacts (via DRBM 3 domain) with dicer enzyme Dcr-1 (via helicase domain) (PubMed:15918769, PubMed:15918770, PubMed:15985611, PubMed:17666393, PubMed:19451544, PubMed:19635780, PubMed:19644447, PubMed:26769856, PubMed:36182693).
Different regions of the Dcr-1-loqs-PB heterodimer collaborate to recognize, bind and position the pre-miRNA for Dcr-1 mediated cleavage (PubMed:36182693).
In the absence of miRNA substrates, the heterodimer favors a closed, catalytically incompetent, conformation, whereas binding of authentic pre-miRNA substrates stabilizes the relatively rare open, catalytically competent, conformation of the heterodimer (PubMed:36182693).
During substrate recognition, the Dcr-1 PAZ domain and pre-miRNA interact with the DRBM 1 domain of loqs-PB, which likely contributes to substrate recognition and stabilization (PubMed:36182693).
At the miRNA binding stage, the Dcr-1 DRBM domain and the loqs-PB DRBM domains then bind the pre-miRNA in tandem to form a tight 'belt' around the pre-miRNA stem, the pre-miRNA loop is docked in the loop-binding region formed by DUF283, DRBM and part of the helicase domain of Dcr-1, and the loqs-PB DRBM 1 and the wing domain of Dcr-1 act together to bind the 5' and 3' pre-miRNA termini within the PAZ and platform domains of Dcr-1 (PubMed:36182693).
These interactions between the proteins and their pre-miRNA substrate stabilize a distorted form of the pre-miRNA and position the scissile phosphodiester bonds of the pre-miRNA at the RNase III catalytic cleavage sites of Dcr-1 (PubMed:36182693).
Following Dcr-1 mediated cleavage, the miRNA duplex remains bound to loqs-PB DRBM 1, which dissociates from the Dcr-1 RNase III 1 domain but remains in contact with the PAZ and wing domains suggesting that the heterodimer presents the mature miRNA to AGO2 for loading into the RNA-induced silencing complex (miRISC) (PubMed:36182693).
Isoform PC
Able to interact with dicer enzyme Dcr-1 (PubMed:17666393).
However, the relevance of such an interaction is unclear in vivo and another report found that it did not interact with Dcr-1 (PubMed:19635780).
However, the relevance of such an interaction is unclear in vivo and another report found that it did not interact with Dcr-1 (PubMed:19635780).
Isoform PD
Monomer (PubMed:28874570).
Interacts (via C-terminus) with dicer enzyme Dcr-2 (via N-terminus); interaction is required for RNAi activity in producing siRNAs from a subset of endo- and exo-dsRNAs, and in the alternative siRLC, the interaction enhances the binding preference of the protein for the thermodynamically more stable ends of endogenous siRNAs (PubMed:19635780, PubMed:19644447, PubMed:21245036, PubMed:28874570, PubMed:29040648, PubMed:35768513).
Interaction with Dcr-2 is RNA independent, however the isoform must bind both dsRNA and Dcr-2 to enhance Dcr-2 cleavage activity (PubMed:28874570).
Does not interact with Dcr-1 (PubMed:19644447).
Interacts (via C-terminus) with dicer enzyme Dcr-2 (via N-terminus); interaction is required for RNAi activity in producing siRNAs from a subset of endo- and exo-dsRNAs, and in the alternative siRLC, the interaction enhances the binding preference of the protein for the thermodynamically more stable ends of endogenous siRNAs (PubMed:19635780, PubMed:19644447, PubMed:21245036, PubMed:28874570, PubMed:29040648, PubMed:35768513).
Interaction with Dcr-2 is RNA independent, however the isoform must bind both dsRNA and Dcr-2 to enhance Dcr-2 cleavage activity (PubMed:28874570).
Does not interact with Dcr-1 (PubMed:19644447).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9VJY9 | Dcr-1 Q9VCU9 | 14 | EBI-162836, EBI-112170 |
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, domain, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-337 | Necessary for enhancing pre-miRNA processing by Dcr-1 | ||||
Sequence: MDQENFHGSSLPQQLQNLHIQPQQASPNPVQTGFAPRRHYNNLVGLGNGNAVSGSPVKGAPLGQRHVKLKKEKISAQVAQLSQPGQLQLSDVGDPALAGGSGLQGGVGLMGVILPSDEALKFVSETDANGLAMKTPVSILQELLSRRGITPGYELVQIEGAIHEPTFRFRVSFKDKDTPFTAMGAGRSKKEAKHAAARALIDKLIGAQLPESPSSSAGPSVTGLTVAGSGGDGNANATGGGDASDKTVGNPIGWLQEMCMQRRWPPPSYETETEVGLPHERLFTIACSILNYREMGKGKSKKIAKRLAAHRMWMRLQETPIDSGKISDSICGELEGE | ||||||
Region | 1-379 | Not required for interaction with Dcr-1 | ||||
Sequence: MDQENFHGSSLPQQLQNLHIQPQQASPNPVQTGFAPRRHYNNLVGLGNGNAVSGSPVKGAPLGQRHVKLKKEKISAQVAQLSQPGQLQLSDVGDPALAGGSGLQGGVGLMGVILPSDEALKFVSETDANGLAMKTPVSILQELLSRRGITPGYELVQIEGAIHEPTFRFRVSFKDKDTPFTAMGAGRSKKEAKHAAARALIDKLIGAQLPESPSSSAGPSVTGLTVAGSGGDGNANATGGGDASDKTVGNPIGWLQEMCMQRRWPPPSYETETEVGLPHERLFTIACSILNYREMGKGKSKKIAKRLAAHRMWMRLQETPIDSGKISDSICGELEGEPRSSENYYGELKDISVPTLTTQHSNKVSQFHKTLKNATGKKL | ||||||
Region | 1-392 | Important for homodimerization and interaction with Dcr-1 | ||||
Sequence: MDQENFHGSSLPQQLQNLHIQPQQASPNPVQTGFAPRRHYNNLVGLGNGNAVSGSPVKGAPLGQRHVKLKKEKISAQVAQLSQPGQLQLSDVGDPALAGGSGLQGGVGLMGVILPSDEALKFVSETDANGLAMKTPVSILQELLSRRGITPGYELVQIEGAIHEPTFRFRVSFKDKDTPFTAMGAGRSKKEAKHAAARALIDKLIGAQLPESPSSSAGPSVTGLTVAGSGGDGNANATGGGDASDKTVGNPIGWLQEMCMQRRWPPPSYETETEVGLPHERLFTIACSILNYREMGKGKSKKIAKRLAAHRMWMRLQETPIDSGKISDSICGELEGEPRSSENYYGELKDISVPTLTTQHSNKVSQFHKTLKNATGKKLLKLQKTCLKNNKI | ||||||
Region | 129-211 | Sufficient for binding RNA | ||||
Sequence: NGLAMKTPVSILQELLSRRGITPGYELVQIEGAIHEPTFRFRVSFKDKDTPFTAMGAGRSKKEAKHAAARALIDKLIGAQLPE | ||||||
Region | 129-322 | Necessary for promoting preferential binding of Dcr-2 to the less stably base paired ends of siRNAs | ||||
Sequence: NGLAMKTPVSILQELLSRRGITPGYELVQIEGAIHEPTFRFRVSFKDKDTPFTAMGAGRSKKEAKHAAARALIDKLIGAQLPESPSSSAGPSVTGLTVAGSGGDGNANATGGGDASDKTVGNPIGWLQEMCMQRRWPPPSYETETEVGLPHERLFTIACSILNYREMGKGKSKKIAKRLAAHRMWMRLQETPID | ||||||
Domain | 135-206 | DRBM 1 | ||||
Sequence: TPVSILQELLSRRGITPGYELVQIEGAIHEPTFRFRVSFKDKDTPFTAMGAGRSKKEAKHAAARALIDKLIG | ||||||
Region | 209-249 | Enables simultaneous binding of both DRBM 1 and 2 domains to dsRNA | ||||
Sequence: LPESPSSSAGPSVTGLTVAGSGGDGNANATGGGDASDKTVG | ||||||
Compositional bias | 210-232 | Polar residues | ||||
Sequence: PESPSSSAGPSVTGLTVAGSGGD | ||||||
Region | 210-246 | Disordered | ||||
Sequence: PESPSSSAGPSVTGLTVAGSGGDGNANATGGGDASDK | ||||||
Region | 220-465 | Necessary and sufficient for enhancing processing of pre-miRNAs by Dcr-1 | ||||
Sequence: SVTGLTVAGSGGDGNANATGGGDASDKTVGNPIGWLQEMCMQRRWPPPSYETETEVGLPHERLFTIACSILNYREMGKGKSKKIAKRLAAHRMWMRLQETPIDSGKISDSICGELEGEPRSSENYYGELKDISVPTLTTQHSNKVSQFHKTLKNATGKKLLKLQKTCLKNNKIDYIKLLGEIATENQFEVTYVDIEEKTFSGQFQCLVQLSTLPVGVCHGSGPTAADAQRHAAQNALEYLKIMTKK | ||||||
Region | 245-322 | Sufficient for binding RNA | ||||
Sequence: DKTVGNPIGWLQEMCMQRRWPPPSYETETEVGLPHERLFTIACSILNYREMGKGKSKKIAKRLAAHRMWMRLQETPID | ||||||
Domain | 250-318 | DRBM 2 | ||||
Sequence: NPIGWLQEMCMQRRWPPPSYETETEVGLPHERLFTIACSILNYREMGKGKSKKIAKRLAAHRMWMRLQE | ||||||
Region | 308-309 | Necessary for binding pre-miRNA | ||||
Sequence: AA | ||||||
Region | 338-359 | In isoform Q9VJY9-4; Required for binding to Dcr-2 and to fully enhance Dcr-2 mediated cleavage of 3' overhanging termini (3'ovr) and blunt termini (BLT) dsRNAs. However, this region is dispensable for binding the dsRNA substrates | ||||
Sequence: PRSSENYYGELKDISVPTLTTQ | ||||||
Region | 340-465 | Necessary for interaction with Dcr-1 | ||||
Sequence: SSENYYGELKDISVPTLTTQHSNKVSQFHKTLKNATGKKLLKLQKTCLKNNKIDYIKLLGEIATENQFEVTYVDIEEKTFSGQFQCLVQLSTLPVGVCHGSGPTAADAQRHAAQNALEYLKIMTKK | ||||||
Region | 392-463 | Sufficent for binding to Dcr-1 | ||||
Sequence: IDYIKLLGEIATENQFEVTYVDIEEKTFSGQFQCLVQLSTLPVGVCHGSGPTAADAQRHAAQNALEYLKIMT | ||||||
Domain | 393-461 | DRBM 3 | ||||
Sequence: DYIKLLGEIATENQFEVTYVDIEEKTFSGQFQCLVQLSTLPVGVCHGSGPTAADAQRHAAQNALEYLKI |
Domain
RNA-binding DRBM domains 1 and 2 bind dsRNA while DRBM 3 binds Dcr-1 (PubMed:29040648, PubMed:34590626, PubMed:36182693).
The RNA-binding DRBM 1 and 2 domains are able to bind dsRNA independently (PubMed:34590626).
The DRBM domains appears to bind to the RNA duplex and then slide along the siRNA helix to the ends of the siRNA (PubMed:29040648).
The DRBMs display a preference for binding to the more thermodynamically stable ends of the siRNA which is enhanced by interaction with Dcr-2 (PubMed:29040648).
This suggests that the domains may also function to pre-orientate the guide strand prior to loading into the (AGO2)-containing RNA-induced silencing complex (siRISC) (PubMed:29040648).
Both of the DRBM 1 and 2 domains are required for optimal Dcr-2 mediated cleavage of 3' overhanging termini (3'ovr) dsRNAs, whereas only the DRBM 3 domain appears to be necessary for Dcr-2 mediated cleavage of blunt termini (BLT) dsRNAs (PubMed:28874570).
The RNA-binding DRBM 1 and 2 domains are able to bind dsRNA independently (PubMed:34590626).
The DRBM domains appears to bind to the RNA duplex and then slide along the siRNA helix to the ends of the siRNA (PubMed:29040648).
The DRBMs display a preference for binding to the more thermodynamically stable ends of the siRNA which is enhanced by interaction with Dcr-2 (PubMed:29040648).
This suggests that the domains may also function to pre-orientate the guide strand prior to loading into the (AGO2)-containing RNA-induced silencing complex (siRISC) (PubMed:29040648).
Both of the DRBM 1 and 2 domains are required for optimal Dcr-2 mediated cleavage of 3' overhanging termini (3'ovr) dsRNAs, whereas only the DRBM 3 domain appears to be necessary for Dcr-2 mediated cleavage of blunt termini (BLT) dsRNAs (PubMed:28874570).
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 4 isoforms produced by Alternative splicing.
Q9VJY9-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- NamePB
- Synonymsloqs-PB, r3d1-L
- Length465
- Mass (Da)50,085
- Last updated2002-10-01 v2
- ChecksumB69684E6B912F929
Q9VJY9-2
- NamePA
- Synonymsloqs-PA, r3d1-S
- Differences from canonical
- 338-383: Missing
Q9VJY9-3
- NamePC
- Synonymsloqs-PC
Q9VJY9-4
- NamePD
- Synonymsloqs-PD
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Features
Showing features for compositional bias, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 210-232 | Polar residues | ||||
Sequence: PESPSSSAGPSVTGLTVAGSGGD | ||||||
Alternative sequence | VSP_062004 | 338-359 | in isoform PD | |||
Sequence: PRSSENYYGELKDISVPTLTTQ → VSIIQDIDRYEQVSKDFEFIKI | ||||||
Alternative sequence | VSP_062002 | 338-383 | in isoform PA | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_062003 | 338-383 | in isoform PC | |||
Sequence: PRSSENYYGELKDISVPTLTTQHSNKVSQFHKTLKNATGKKLLKLQ → NESVKHLFHTKVICFNSPLACVISNVCEMQWRKETKNFALLFTAPQ | ||||||
Alternative sequence | VSP_062005 | 360-465 | in isoform PD | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_062006 | 384-465 | in isoform PC | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AE014134 EMBL· GenBank· DDBJ | AAF53295.2 EMBL· GenBank· DDBJ | Genomic DNA | ||
AE014134 EMBL· GenBank· DDBJ | AAF53296.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AE014134 EMBL· GenBank· DDBJ | ABC65897.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AE014134 EMBL· GenBank· DDBJ | ADV37046.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ118034 EMBL· GenBank· DDBJ | AAZ40191.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ118035 EMBL· GenBank· DDBJ | AAZ40192.1 EMBL· GenBank· DDBJ | mRNA | ||
AY071070 EMBL· GenBank· DDBJ | AAL48692.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ026059 EMBL· GenBank· DDBJ | AAY40789.1 EMBL· GenBank· DDBJ | mRNA |