Q9VCU9 · DCR1_DROME
- ProteinEndoribonuclease Dcr-1
- GeneDcr-1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids2249 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Endoribonuclease which functions in microRNA- (miRNA) gene silencing and, independently of its ribonuclease III activity, also acts in the short interfering RNA- (siRNA) gene silencing pathway (PubMed:11201747, PubMed:11498593, PubMed:15066283, PubMed:15918769, PubMed:15985611, PubMed:17666393, PubMed:17928574, PubMed:19451544, PubMed:19635780, PubMed:21419681, PubMed:21926993, PubMed:24488111, PubMed:36182693).
Cleaves hairpin precursor miRNAs (pre-miRNA) to generate mature miRNAs (miRNAs) that are between twenty-one to twenty-four nucleotides in length and function in RNA silencing and post-transcriptional regulation of gene expression (PubMed:15066283, PubMed:15918769, PubMed:15985611, PubMed:17666393, PubMed:17928574, PubMed:19451544, PubMed:19635780, PubMed:21419681, PubMed:21926993, PubMed:23063653, PubMed:24488111, PubMed:36182693).
Also functions in miRNA loading and assembly of the Argonaute 1 (AGO1)-containing RNA-induced silencing complex (miRISC), with the miRNAs serving as a guide to direct the miRISC to complementary RNAs to degrade them or prevent their translation (PubMed:15066283, PubMed:17928574, PubMed:19451544).
Independently of its catalytic activity, functions in the siRNA silencing pathway by promoting assembly of the siRNA-directed Argonaute 2 (AGO2)-containing RISC (siRISC) (PubMed:15066283).
Required for the proper formation of a stable intermediate (R2) in siRISC assembly, which is formed from the R1 precursor complex (containing Dcr-2, R2D2 and the siRNA) and is used for assembly of the mature (R3) siRISC complex (PubMed:15066283).
It is not required for siRNA biogenesis (PubMed:15066283, PubMed:21419681).
During embryogenesis, involved in germline fate determination (PubMed:16949822).
Cleaves hairpin precursor miRNAs (pre-miRNA) to generate mature miRNAs (miRNAs) that are between twenty-one to twenty-four nucleotides in length and function in RNA silencing and post-transcriptional regulation of gene expression (PubMed:15066283, PubMed:15918769, PubMed:15985611, PubMed:17666393, PubMed:17928574, PubMed:19451544, PubMed:19635780, PubMed:21419681, PubMed:21926993, PubMed:23063653, PubMed:24488111, PubMed:36182693).
Also functions in miRNA loading and assembly of the Argonaute 1 (AGO1)-containing RNA-induced silencing complex (miRISC), with the miRNAs serving as a guide to direct the miRISC to complementary RNAs to degrade them or prevent their translation (PubMed:15066283, PubMed:17928574, PubMed:19451544).
Independently of its catalytic activity, functions in the siRNA silencing pathway by promoting assembly of the siRNA-directed Argonaute 2 (AGO2)-containing RISC (siRISC) (PubMed:15066283).
Required for the proper formation of a stable intermediate (R2) in siRISC assembly, which is formed from the R1 precursor complex (containing Dcr-2, R2D2 and the siRNA) and is used for assembly of the mature (R3) siRISC complex (PubMed:15066283).
It is not required for siRNA biogenesis (PubMed:15066283, PubMed:21419681).
During embryogenesis, involved in germline fate determination (PubMed:16949822).
Catalytic activity
Cofactor
Mn2+ (UniProtKB | Rhea| CHEBI:29035 )
Activity regulation
Activity towards pre-miRNAs is not inhibited by inorganic phosphate.
Features
Showing features for binding site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 37-44 | ATP (UniProtKB | ChEBI) | ||||
Sequence: LGHRSSKE | ||||||
Binding site | 1745 | Mg2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 1749 | Mg2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 1905 | Mg2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 1908 | Mg2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 1908 | Mg2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 2032 | Mg2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Site | 2132 | Important for activity | ||||
Sequence: K | ||||||
Binding site | 2136 | Mg2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 2139 | Mg2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameEndoribonuclease Dcr-1
- EC number
- Short namesProtein dicer-1
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Metazoa > Ecdysozoa > Arthropoda > Hexapoda > Insecta > Pterygota > Neoptera > Endopterygota > Diptera > Brachycera > Muscomorpha > Ephydroidea > Drosophilidae > Drosophila > Sophophora
Accessions
- Primary accessionQ9VCU9
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 1749 | Cleaves the 5' (top) strand but not the 3' (bottom) strand of pre-miRNA. | ||||
Sequence: D → A | ||||||
Mutagenesis | 1908 | Cleaves the 5' (top) strand but not the 3' (bottom) strand of pre-miRNA. Abolishes cleavage of pre-miRNA; when associated with A-2139. | ||||
Sequence: E → A | ||||||
Mutagenesis | 2036 | Cleaves the 3' (bottom) strand but not the 5' (top) strand of pre-miRNA. | ||||
Sequence: D → A | ||||||
Mutagenesis | 2139 | Cleaves the 3' (bottom) strand but not the 5' (top) strand of pre-miRNA. Abolishes cleavage of pre-miRNA; when associated with A-1908. | ||||
Sequence: E → A | ||||||
Mutagenesis | 2186-2249 | No effect on processing of the pre-miRNas, pre-let 7 and pre-bantam. | ||||
Sequence: Missing |
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000180474 | 1-2249 | Endoribonuclease Dcr-1 | |||
Sequence: MAFHWCDNNLHTTVFTPRDFQVELLATAYERNTIICLGHRSSKEFIALKLLQELSRRARRHGRVSVYLSCEVGTSTEPCSIYTMLTHLTDLRVWQEQPDMQIPFDHCWTDYHVSILRPEGFLYLLETRELLLSSVELIVLEDCHDSAVYQRIRPLFENHIMPAPPADRPRILGLAGPLHSAGCELQQLSAMLATLEQSVLCQIETASDIVTVLRYCSRPHEYIVQCAPFEMDELSLVLADVLNTHKSFLLDHRYDPYEIYGTDQFMDELKDIPDPKVDPLNVINSLLVVLHEMGPWCTQRAAHHFYQCNEKLKVKTPHERHYLLYCLVSTALIQLYSLCEHAFHRHLGSGSDSRQTIERYSSPKVRRLLQTLRCFKPEEVHTQADGLRRMRHQVDQADFNRLSHTLESKCRMVDQMDQPPTETRALVATLEQILHTTEDRQTNRSAARVTPTPTPAHAKPKPSSGANTAQPRTRRRVYTRRHHRDHNDGSDTLCALIYCNQNHTARVLFELLAEISRRDPDLKFLRCQYTTDRVADPTTEPKEAELEHRRQEEVLKRFRMHDCNVLIGTSVLEEGIDVPKCNLVVRWDPPTTYRSYVQCKGRARAAPAYHVILVAPSYKSPTVGSVQLTDRSHRYICATGDTTEADSDSDDSAMPNSSGSDPYTFGTARGTVKILNPEVFSKQPPTACDIKLQEIQDELPAAAQLDTSNSSDEAVSMSNTSPSESSTEQKSRRFQCELSSLTEPEDTSDTTAEIDTAHSLASTTKDLVHQMAQYREIEQMLLSKCANTEPPEQEQSEAERFSACLAAYRPKPHLLTGASVDLGSAIALVNKYCARLPSDTFTKLTALWRCTRNERAGVTLFQYTLRLPINSPLKHDIVGLPMPTQTLARRLAALQACVELHRIGELDDQLQPIGKEGFRALEPDWECFELEPEDEQIVQLSDEPRPGTTKRRQYYYKRIASEFCDCRPVAGAPCYLYFIQLTLQCPIPEEQNTRGRKIYPPEDAQQGFGILTTKRIPKLSAFSIFTRSGEVKVSLELAKERVILTSEQIVCINGFLNYTFTNVLRLQKFLMLFDPDSTENCVFIVPTVKAPAGGKHIDWQFLELIQANGNTMPRAVPDEERQAQPFDPQRFQDAVVMPWYRNQDQPQYFYVAEICPHLSPLSCFPGDNYRTFKHYYLVKYGLTIQNTSQPLLDVDHTSARLNFLTPRYVNRKGVALPTSSEETKRAKRENLEQKQILVPELCTVHPFPASLWRTAVCLPCILYRINGLLLADDIRKQVSADLGLGRQQIEDEDFEWPMLDFGWSLSEVLKKSRESKQKESLKDDTINGKDLADVEKKPTSEETQLDKDSKDDKVEKSAIELIIEGEEKLQEADDFIEIGTWSNDMADDIASFNQEDDDEDDAFHLPVLPANVKFCDQQTRYGSPTFWDVSNGESGFKGPKSSQNKQGGKGKAKGPAKPTFNYYDSDNSLGSSYDDDDNAGPLNYMHHNYSSDDDDVADDIDAGRIAFTSKNEAETIETAQEVEKRQKQLSIIQATNANERQYQQTKNLLIGFNFKHEDQKEPATIRYEESIAKLKTEIESGGMLVPHDQQLVLKRSDAAEAQVAKVSMMELLKQLLPYVNEDVLAKKLGDRRELLLSDLVELNADWVARHEQETYNVMGCGDSFDNYNDHHRLNLDEKQLKLQYERIEIEPPTSTKAITSAILPAGFSFDRQPDLVGHPGPSPSIILQALTMSNANDGINLERLETIGDSFLKYAITTYLYITYENVHEGKLSHLRSKQVANLNLYRLGRRKRLGEYMIATKFEPHDNWLPPCYYVPKELEKALIEAKIPTHHWKLADLLDIKNLSSVQICEMVREKADALGLEQNGGAQNGQLDDSNDSCNDFSCFIPYNLVSQHSIPDKSIADCVEALIGAYLIECGPRGALLFMAWLGVRVLPITRQLDGGNQEQRIPGSTKPNAENVVTVYGAWPTPRSPLLHFAPNATEELDQLLSGFEEFEESLGYKFRDRSYLLQAMTHASYTPNRLTDCYQRLEFLGDAVLDYLITRHLYEDPRQHSPGALTDLRSALVNNTIFASLAVRHGFHKFFRHLSPGLNDVIDRFVRIQQENGHCISEEYYLLSEEECDDAEDVEVPKALGDVFESIAGAIFLDSNMSLDVVWHVYSNMMSPEIEQFSNSVPKSPIRELLELEPETAKFGKPEKLADGRRVRVTVDVFCKGTFRGIGRNYRIAKCTAAKCALRQLKKQGLIAKKD | ||||||
Modified residue | 1423 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1877 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1880 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
Component of the miRNA-directed RISC loading complex (miRLC), composed of at least Dcr-1, AGO1 and loqs, which processes pre-miRNAs and loads the resulting miRNAs into the Argonaute 1 (AGO1)-containing RNA-induced silencing complex (miRISC) (PubMed:15918769, PubMed:19451544).
Interacts (via helicase domain) with dicing cofactor loqs isoform-PB (loqs-PB) (via DRBM 3 domain); this interaction enhances processing of pre-miRNAs by increasing substrate binding affinity of the dicer (PubMed:15985611, PubMed:17666393, PubMed:19635780, PubMed:36182693).
Also able to interact with loqs isoforms PA and PC, however the relevance of such interactions are unclear in vivo (PubMed:17666393, PubMed:19635780).
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 authentic 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 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 N terminus 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 with AGO2 and Fmr1 to form a RNA-induced silencing complex (siRISC), a ribonucleoprotein (RNP) complex involved in translation regulation; other components of the complex are RpL5, RpL11, AGO2 and Rm62 (PubMed:11498593, PubMed:12368261).
Interacts with piwi and vas; these interactions occur in the polar granules (PubMed:16949822).
Interacts (via helicase domain) with dicing cofactor loqs isoform-PB (loqs-PB) (via DRBM 3 domain); this interaction enhances processing of pre-miRNAs by increasing substrate binding affinity of the dicer (PubMed:15985611, PubMed:17666393, PubMed:19635780, PubMed:36182693).
Also able to interact with loqs isoforms PA and PC, however the relevance of such interactions are unclear in vivo (PubMed:17666393, PubMed:19635780).
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 authentic 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 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 N terminus 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 with AGO2 and Fmr1 to form a RNA-induced silencing complex (siRISC), a ribonucleoprotein (RNP) complex involved in translation regulation; other components of the complex are RpL5, RpL11, AGO2 and Rm62 (PubMed:11498593, PubMed:12368261).
Interacts with piwi and vas; these interactions occur in the polar granules (PubMed:16949822).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9VCU9 | loqs Q9VJY9 | 14 | EBI-112170, EBI-162836 |
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, domain, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-371 | Essential for miRNA substrate recognition | ||||
Sequence: MAFHWCDNNLHTTVFTPRDFQVELLATAYERNTIICLGHRSSKEFIALKLLQELSRRARRHGRVSVYLSCEVGTSTEPCSIYTMLTHLTDLRVWQEQPDMQIPFDHCWTDYHVSILRPEGFLYLLETRELLLSSVELIVLEDCHDSAVYQRIRPLFENHIMPAPPADRPRILGLAGPLHSAGCELQQLSAMLATLEQSVLCQIETASDIVTVLRYCSRPHEYIVQCAPFEMDELSLVLADVLNTHKSFLLDHRYDPYEIYGTDQFMDELKDIPDPKVDPLNVINSLLVVLHEMGPWCTQRAAHHFYQCNEKLKVKTPHERHYLLYCLVSTALIQLYSLCEHAFHRHLGSGSDSRQTIERYSSPKVRRLLQT | ||||||
Region | 1-690 | Important for interaction with loqs isoform PB (loqs-PB) | ||||
Sequence: MAFHWCDNNLHTTVFTPRDFQVELLATAYERNTIICLGHRSSKEFIALKLLQELSRRARRHGRVSVYLSCEVGTSTEPCSIYTMLTHLTDLRVWQEQPDMQIPFDHCWTDYHVSILRPEGFLYLLETRELLLSSVELIVLEDCHDSAVYQRIRPLFENHIMPAPPADRPRILGLAGPLHSAGCELQQLSAMLATLEQSVLCQIETASDIVTVLRYCSRPHEYIVQCAPFEMDELSLVLADVLNTHKSFLLDHRYDPYEIYGTDQFMDELKDIPDPKVDPLNVINSLLVVLHEMGPWCTQRAAHHFYQCNEKLKVKTPHERHYLLYCLVSTALIQLYSLCEHAFHRHLGSGSDSRQTIERYSSPKVRRLLQTLRCFKPEEVHTQADGLRRMRHQVDQADFNRLSHTLESKCRMVDQMDQPPTETRALVATLEQILHTTEDRQTNRSAARVTPTPTPAHAKPKPSSGANTAQPRTRRRVYTRRHHRDHNDGSDTLCALIYCNQNHTARVLFELLAEISRRDPDLKFLRCQYTTDRVADPTTEPKEAELEHRRQEEVLKRFRMHDCNVLIGTSVLEEGIDVPKCNLVVRWDPPTTYRSYVQCKGRARAAPAYHVILVAPSYKSPTVGSVQLTDRSHRYICATGDTTEADSDSDDSAMPNSSGSDPYTFGTARGTVKILNPEVFSKQPPTACDI | ||||||
Region | 1-761 | Helicase domain | ||||
Sequence: MAFHWCDNNLHTTVFTPRDFQVELLATAYERNTIICLGHRSSKEFIALKLLQELSRRARRHGRVSVYLSCEVGTSTEPCSIYTMLTHLTDLRVWQEQPDMQIPFDHCWTDYHVSILRPEGFLYLLETRELLLSSVELIVLEDCHDSAVYQRIRPLFENHIMPAPPADRPRILGLAGPLHSAGCELQQLSAMLATLEQSVLCQIETASDIVTVLRYCSRPHEYIVQCAPFEMDELSLVLADVLNTHKSFLLDHRYDPYEIYGTDQFMDELKDIPDPKVDPLNVINSLLVVLHEMGPWCTQRAAHHFYQCNEKLKVKTPHERHYLLYCLVSTALIQLYSLCEHAFHRHLGSGSDSRQTIERYSSPKVRRLLQTLRCFKPEEVHTQADGLRRMRHQVDQADFNRLSHTLESKCRMVDQMDQPPTETRALVATLEQILHTTEDRQTNRSAARVTPTPTPAHAKPKPSSGANTAQPRTRRRVYTRRHHRDHNDGSDTLCALIYCNQNHTARVLFELLAEISRRDPDLKFLRCQYTTDRVADPTTEPKEAELEHRRQEEVLKRFRMHDCNVLIGTSVLEEGIDVPKCNLVVRWDPPTTYRSYVQCKGRARAAPAYHVILVAPSYKSPTVGSVQLTDRSHRYICATGDTTEADSDSDDSAMPNSSGSDPYTFGTARGTVKILNPEVFSKQPPTACDIKLQEIQDELPAAAQLDTSNSSDEAVSMSNTSPSESSTEQKSRRFQCELSSLTEPEDTSDTTAEIDTAHSLA | ||||||
Region | 1-1042 | Necessary for processing certain pre-miRNas, such as pre-let 7 and pre-bantam | ||||
Sequence: MAFHWCDNNLHTTVFTPRDFQVELLATAYERNTIICLGHRSSKEFIALKLLQELSRRARRHGRVSVYLSCEVGTSTEPCSIYTMLTHLTDLRVWQEQPDMQIPFDHCWTDYHVSILRPEGFLYLLETRELLLSSVELIVLEDCHDSAVYQRIRPLFENHIMPAPPADRPRILGLAGPLHSAGCELQQLSAMLATLEQSVLCQIETASDIVTVLRYCSRPHEYIVQCAPFEMDELSLVLADVLNTHKSFLLDHRYDPYEIYGTDQFMDELKDIPDPKVDPLNVINSLLVVLHEMGPWCTQRAAHHFYQCNEKLKVKTPHERHYLLYCLVSTALIQLYSLCEHAFHRHLGSGSDSRQTIERYSSPKVRRLLQTLRCFKPEEVHTQADGLRRMRHQVDQADFNRLSHTLESKCRMVDQMDQPPTETRALVATLEQILHTTEDRQTNRSAARVTPTPTPAHAKPKPSSGANTAQPRTRRRVYTRRHHRDHNDGSDTLCALIYCNQNHTARVLFELLAEISRRDPDLKFLRCQYTTDRVADPTTEPKEAELEHRRQEEVLKRFRMHDCNVLIGTSVLEEGIDVPKCNLVVRWDPPTTYRSYVQCKGRARAAPAYHVILVAPSYKSPTVGSVQLTDRSHRYICATGDTTEADSDSDDSAMPNSSGSDPYTFGTARGTVKILNPEVFSKQPPTACDIKLQEIQDELPAAAQLDTSNSSDEAVSMSNTSPSESSTEQKSRRFQCELSSLTEPEDTSDTTAEIDTAHSLASTTKDLVHQMAQYREIEQMLLSKCANTEPPEQEQSEAERFSACLAAYRPKPHLLTGASVDLGSAIALVNKYCARLPSDTFTKLTALWRCTRNERAGVTLFQYTLRLPINSPLKHDIVGLPMPTQTLARRLAALQACVELHRIGELDDQLQPIGKEGFRALEPDWECFELEPEDEQIVQLSDEPRPGTTKRRQYYYKRIASEFCDCRPVAGAPCYLYFIQLTLQCPIPEEQNTRGRKIYPPEDAQQGFGILTTKRIPKLSAFSIFTRSGEVKVSLELAKERV | ||||||
Region | 371-491 | Dispensable for activity and substrate recognition | ||||
Sequence: TLRCFKPEEVHTQADGLRRMRHQVDQADFNRLSHTLESKCRMVDQMDQPPTETRALVATLEQILHTTEDRQTNRSAARVTPTPTPAHAKPKPSSGANTAQPRTRRRVYTRRHHRDHNDGSD | ||||||
Region | 436-486 | Disordered | ||||
Sequence: TTEDRQTNRSAARVTPTPTPAHAKPKPSSGANTAQPRTRRRVYTRRHHRDH | ||||||
Domain | 485-648 | Helicase C-terminal | ||||
Sequence: DHNDGSDTLCALIYCNQNHTARVLFELLAEISRRDPDLKFLRCQYTTDRVADPTTEPKEAELEHRRQEEVLKRFRMHDCNVLIGTSVLEEGIDVPKCNLVVRWDPPTTYRSYVQCKGRARAAPAYHVILVAPSYKSPTVGSVQLTDRSHRYICATGDTTEADSD | ||||||
Region | 496-606 | Essential for miRNA substrate recognition | ||||
Sequence: LIYCNQNHTARVLFELLAEISRRDPDLKFLRCQYTTDRVADPTTEPKEAELEHRRQEEVLKRFRMHDCNVLIGTSVLEEGIDVPKCNLVVRWDPPTTYRSYVQCKGRARAA | ||||||
Region | 617-761 | Dispensable for activity and substrate recognition | ||||
Sequence: SYKSPTVGSVQLTDRSHRYICATGDTTEADSDSDDSAMPNSSGSDPYTFGTARGTVKILNPEVFSKQPPTACDIKLQEIQDELPAAAQLDTSNSSDEAVSMSNTSPSESSTEQKSRRFQCELSSLTEPEDTSDTTAEIDTAHSLA | ||||||
Region | 640-665 | Disordered | ||||
Sequence: GDTTEADSDSDDSAMPNSSGSDPYTF | ||||||
Compositional bias | 649-665 | Polar residues | ||||
Sequence: SDDSAMPNSSGSDPYTF | ||||||
Region | 705-757 | Disordered | ||||
Sequence: LDTSNSSDEAVSMSNTSPSESSTEQKSRRFQCELSSLTEPEDTSDTTAEIDTA | ||||||
Domain | 825-920 | Dicer dsRNA-binding fold | ||||
Sequence: AIALVNKYCARLPSDTFTKLTALWRCTRNERAGVTLFQYTLRLPINSPLKHDIVGLPMPTQTLARRLAALQACVELHRIGELDDQLQPIGKEGFRA | ||||||
Region | 924-957 | Wing domain | ||||
Sequence: DWECFELEPEDEQIVQLSDEPRPGTTKRRQYYYK | ||||||
Region | 963-1108 | Platform domain | ||||
Sequence: FCDCRPVAGAPCYLYFIQLTLQCPIPEEQNTRGRKIYPPEDAQQGFGILTTKRIPKLSAFSIFTRSGEVKVSLELAKERVILTSEQIVCINGFLNYTFTNVLRLQKFLMLFDPDSTENCVFIVPTVKAPAGGKHIDWQFLELIQAN | ||||||
Domain | 1100-1246 | PAZ | ||||
Sequence: QFLELIQANGNTMPRAVPDEERQAQPFDPQRFQDAVVMPWYRNQDQPQYFYVAEICPHLSPLSCFPGDNYRTFKHYYLVKYGLTIQNTSQPLLDVDHTSARLNFLTPRYVNRKGVALPTSSEETKRAKRENLEQKQILVPELCTVHP | ||||||
Region | 1147-2249 | Essential for production of mature miRNAs from pre-miRNAs. Also important for proper formation of the siRISC complex but is dispensable for biogenesis of siRNAs | ||||
Sequence: QYFYVAEICPHLSPLSCFPGDNYRTFKHYYLVKYGLTIQNTSQPLLDVDHTSARLNFLTPRYVNRKGVALPTSSEETKRAKRENLEQKQILVPELCTVHPFPASLWRTAVCLPCILYRINGLLLADDIRKQVSADLGLGRQQIEDEDFEWPMLDFGWSLSEVLKKSRESKQKESLKDDTINGKDLADVEKKPTSEETQLDKDSKDDKVEKSAIELIIEGEEKLQEADDFIEIGTWSNDMADDIASFNQEDDDEDDAFHLPVLPANVKFCDQQTRYGSPTFWDVSNGESGFKGPKSSQNKQGGKGKAKGPAKPTFNYYDSDNSLGSSYDDDDNAGPLNYMHHNYSSDDDDVADDIDAGRIAFTSKNEAETIETAQEVEKRQKQLSIIQATNANERQYQQTKNLLIGFNFKHEDQKEPATIRYEESIAKLKTEIESGGMLVPHDQQLVLKRSDAAEAQVAKVSMMELLKQLLPYVNEDVLAKKLGDRRELLLSDLVELNADWVARHEQETYNVMGCGDSFDNYNDHHRLNLDEKQLKLQYERIEIEPPTSTKAITSAILPAGFSFDRQPDLVGHPGPSPSIILQALTMSNANDGINLERLETIGDSFLKYAITTYLYITYENVHEGKLSHLRSKQVANLNLYRLGRRKRLGEYMIATKFEPHDNWLPPCYYVPKELEKALIEAKIPTHHWKLADLLDIKNLSSVQICEMVREKADALGLEQNGGAQNGQLDDSNDSCNDFSCFIPYNLVSQHSIPDKSIADCVEALIGAYLIECGPRGALLFMAWLGVRVLPITRQLDGGNQEQRIPGSTKPNAENVVTVYGAWPTPRSPLLHFAPNATEELDQLLSGFEEFEESLGYKFRDRSYLLQAMTHASYTPNRLTDCYQRLEFLGDAVLDYLITRHLYEDPRQHSPGALTDLRSALVNNTIFASLAVRHGFHKFFRHLSPGLNDVIDRFVRIQQENGHCISEEYYLLSEEECDDAEDVEVPKALGDVFESIAGAIFLDSNMSLDVVWHVYSNMMSPEIEQFSNSVPKSPIRELLELEPETAKFGKPEKLADGRRVRVTVDVFCKGTFRGIGRNYRIAKCTAAKCALRQLKKQGLIAKKD | ||||||
Region | 1314-1351 | Disordered | ||||
Sequence: ESKQKESLKDDTINGKDLADVEKKPTSEETQLDKDSKD | ||||||
Compositional bias | 1426-1448 | Polar residues | ||||
Sequence: FWDVSNGESGFKGPKSSQNKQGG | ||||||
Region | 1426-1477 | Disordered | ||||
Sequence: FWDVSNGESGFKGPKSSQNKQGGKGKAKGPAKPTFNYYDSDNSLGSSYDDDD | ||||||
Domain | 1698-1919 | RNase III 1 | ||||
Sequence: ITSAILPAGFSFDRQPDLVGHPGPSPSIILQALTMSNANDGINLERLETIGDSFLKYAITTYLYITYENVHEGKLSHLRSKQVANLNLYRLGRRKRLGEYMIATKFEPHDNWLPPCYYVPKELEKALIEAKIPTHHWKLADLLDIKNLSSVQICEMVREKADALGLEQNGGAQNGQLDDSNDSCNDFSCFIPYNLVSQHSIPDKSIADCVEALIGAYLIECG | ||||||
Domain | 1993-2150 | RNase III 2 | ||||
Sequence: FEEFEESLGYKFRDRSYLLQAMTHASYTPNRLTDCYQRLEFLGDAVLDYLITRHLYEDPRQHSPGALTDLRSALVNNTIFASLAVRHGFHKFFRHLSPGLNDVIDRFVRIQQENGHCISEEYYLLSEEECDDAEDVEVPKALGDVFESIAGAIFLDSN | ||||||
Domain | 2175-2241 | DRBM | ||||
Sequence: VPKSPIRELLELEPETAKFGKPEKLADGRRVRVTVDVFCKGTFRGIGRNYRIAKCTAAKCALRQLKK |
Domain
The helicase domain is essential for substrate discrimination (PubMed:21926993).
Probably identifies authentic miRNA substrates, by binding to the miRNA characteristic single-stranded terminal loop, checking the loop size, and measuring the distance between the terminal loop and the 3' overhanging (3'ovr) termini which is bound by the PAZ domain (PubMed:21926993).
Probably identifies authentic miRNA substrates, by binding to the miRNA characteristic single-stranded terminal loop, checking the loop size, and measuring the distance between the terminal loop and the 3' overhanging (3'ovr) termini which is bound by the PAZ domain (PubMed:21926993).
The PAZ domain is important for substrate discrimination as it recognizes and binds the characteristic two-nucleotide, 3' overhanging (3'ovr) termini of pre-miRNA substrates prior to cleavage (PubMed:36182693).
The PAZ and platform domains form a binding pocket that binds the 5' terminal nucleotide of the pre-miRNA (PubMed:36182693).
The PAZ and platform domains form a binding pocket that binds the 5' terminal nucleotide of the pre-miRNA (PubMed:36182693).
RNase III 1 domain is necessary for cleaving the 3' (bottom) strand of pre-miRNA hairpins (pri-let-7) (PubMed:17666393, PubMed:36182693).
Together with the RNase III 2 domain forms a cleavage processing center with the RNase III 1 and RNase III 2 domains cutting the 3' (bottom) and 5' (top) strand respectively, excising the miRNA from the pre-miRNA pri-let-7 and creating the characteristic two-nucleotide 3' overhang terminus (PubMed:17666393, PubMed:36182693).
Together with the RNase III 2 domain forms a cleavage processing center with the RNase III 1 and RNase III 2 domains cutting the 3' (bottom) and 5' (top) strand respectively, excising the miRNA from the pre-miRNA pri-let-7 and creating the characteristic two-nucleotide 3' overhang terminus (PubMed:17666393, PubMed:36182693).
RNase III 2 domain is necessary for cleaving the 5' (top) strand of pre-miRNA hairpins (pri-let-7) (PubMed:17666393, PubMed:36182693).
Together with the RNase III 1 domain forms a cleavage processing center with the RNase III 1 and RNase III 2 domains cutting the 3' (bottom) and 5' (top) strand respectively, excising the miRNA from the pre-miRNA pri-let-7 and creating the characteristic two-nucleotide 3' overhang terminus (PubMed:17666393, PubMed:36182693).
Together with the RNase III 1 domain forms a cleavage processing center with the RNase III 1 and RNase III 2 domains cutting the 3' (bottom) and 5' (top) strand respectively, excising the miRNA from the pre-miRNA pri-let-7 and creating the characteristic two-nucleotide 3' overhang terminus (PubMed:17666393, PubMed:36182693).
Within the closed conformation of the Dcr-1-loqs-PB heterodimer, the DRBM domain blocks access of pre-miRNA substrates to the RNase III active sites.
Sequence similarities
Belongs to the helicase family. Dicer subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length2,249
- Mass (Da)255,330
- Last updated2000-05-01 v1
- ChecksumD693F0432AC8033D
Sequence caution
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 649-665 | Polar residues | ||||
Sequence: SDDSAMPNSSGSDPYTF | ||||||
Sequence conflict | 1338-1339 | in Ref. 3 | ||||
Sequence: PT → AI | ||||||
Sequence conflict | 1345 | in Ref. 3 | ||||
Sequence: L → I | ||||||
Compositional bias | 1426-1448 | Polar residues | ||||
Sequence: FWDVSNGESGFKGPKSSQNKQGG |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AE014297 EMBL· GenBank· DDBJ | AAF56056.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AY050230 EMBL· GenBank· DDBJ | AAK84929.1 EMBL· GenBank· DDBJ | mRNA | Different initiation |