The following text describes a protein:
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. 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. 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. Independently of its catalytic activity, functions in the siRNA silencing pathway by promoting assembly of the siRNA-directed Argonaute 2 (AGO2)-containing RISC (siRISC). 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. It is not required for siRNA biogenesis. During embryogenesis, involved in germline fate determination. Post-transcriptionally regulates mei-P26 expression through the microRNA pathway, which in turn post-translationally regulates myc protein levels; involved in regulating cell and tissue growth.
Subcellular Localization:
Cytoplasm. Cytoplasm, cytosol.
Domain:
The helicase domain is essential for substrate discrimination. 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; 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. The PAZ and platform domains form a binding pocket that binds the 5' terminal nucleotide of the pre-miRNA; RNase III 1 domain is necessary for cleaving the 3' (bottom) strand of pre-miRNA hairpins (pri-let-7). 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; RNase III 2 domain is necessary for cleaving the 5' (top) strand of pre-miRNA hairpins (pri-let-7). 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; 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:
MAFHWCDNNLHTTVFTPRDFQVELLATAYERNTIICLGHRSSKEFIALKLLQELSRRARRHGRVSVYLSCEVGTSTEPCSIYTMLTHLTDLRVWQEQPDMQIPFDHCWTDYHVSILRPEGFLYLLETRELLLSSVELIVLEDCHDSAVYQRIRPLFENHIMPAPPADRPRILGLAGPLHSAGCELQQLSAMLATLEQSVLCQIETASDIVTVLRYCSRPHEYIVQCAPFEMDELSLVLADVLNTHKSFLLDHRYDPYEIYGTDQFMDELKDIPDPKVDPLNVINSLLVVLHEMGPWCTQRAAHHFYQCNEKLKVKTPHERHYLLYCLVSTALIQLYSLCEHAFHRHLGSGSDSRQTIERYSSPKVRRLLQTLRCFKPEEVHTQADGLRRMRHQVDQADFNRLSHTLESKCRMVDQMDQPPTETRALVATLEQILHTTEDRQTNRSAARVTPTPTPAHAKPKPSSGANTAQPRTRRRVYTRRHHRDHNDGSDTLCALIYCNQNHTARVLFELLAEISRRDPDLKFLRCQYTTDRVADPTTEPKEAELEHRRQEEVLKRFRMHDCNVLIGTSVLEEGIDVPKCNLVVRWDPPTTYRSYVQCKGRARAAPAYHVILVAPSYKSPTVGSVQLTDRSHRYICATGDTTEADSDSDDSAMPNSSGSDPYTFGTARGTVKILNPEVFSKQPPTACDIKLQEIQDELPAAAQLDTSNSSDEAVSMSNTSPSESSTEQKSRRFQCELSSLTEPEDTSDTTAEIDTAHSLASTTKDLVHQMAQYREIEQMLLSKCANTEPPEQEQSEAERFSACLAAYRPKPHLLTGASVDLGSAIALVNKYCARLPSDTFTKLTALWRCTRNERAGVTLFQYTLRLPINSPLKHDIVGLPMPTQTLARRLAALQACVELHRIGELDDQLQPIGKEGFRALEPDWECFELEPEDEQIVQLSDEPRPGTTKRRQYYYKRIASEFCDCRPVAGAPCYLYFIQLTLQCPIPEEQNTRGRKIYPPEDAQQGFGILTTKRIPKLSAFSIFTRSGEVKVSLELAKERVILTSEQIVCINGFLNYTFTNVLRLQKFLMLFDPDSTENCVFIVPTVKAPAGGKHIDWQFLELIQANGNTMPRAVPDEERQAQPFDPQRFQDAVVMPWYRNQDQPQYFYVAEICPHLSPLSCFPGDNYRTFKHYYLVKYGLTIQNTSQPLLDVDHTSARLNFLTPRYVNRKGVALPTSSEETKRAKRENLEQKQILVPELCTVHPFPASLWRTAVCLPCILYRINGLLLADDIRKQVSADLGLGRQQIEDEDFEWPMLDFGWSLSEVLKKSRESKQKESLKDDTINGKDLADVEKKPTSEETQLDKDSKDDKVEKSAIELIIEGEEKLQEADDFIEIGTWSNDMADDIASFNQEDDDEDDAFHLPVLPANVKFCDQQTRYGSPTFWDVSNGESGFKGPKSSQNKQGGKGKAKGPAKPTFNYYDSDNSLGSSYDDDDNAGPLNYMHHNYSSDDDDVADDIDAGRIAFTSKNEAETIETAQEVEKRQKQLSIIQATNANERQYQQTKNLLIGFNFKHEDQKEPATIRYEESIAKLKTEIESGGMLVPHDQQLVLKRSDAAEAQVAKVSMMELLKQLLPYVNEDVLAKKLGDRRELLLSDLVELNADWVARHEQETYNVMGCGDSFDNYNDHHRLNLDEKQLKLQYERIEIEPPTSTKAITSAILPAGFSFDRQPDLVGHPGPSPSIILQALTMSNANDGINLERLETIGDSFLKYAITTYLYITYENVHEGKLSHLRSKQVANLNLYRLGRRKRLGEYMIATKFEPHDNWLPPCYYVPKELEKALIEAKIPTHHWKLADLLDIKNLSSVQICEMVREKADALGLEQNGGAQNGQLDDSNDSCNDFSCFIPYNLVSQHSIPDKSIADCVEALIGAYLIECGPRGALLFMAWLGVRVLPITRQLDGGNQEQRIPGSTKPNAENVVTVYGAWPTPRSPLLHFAPNATEELDQLLSGFEEFEESLGYKFRDRSYLLQAMTHASYTPNRLTDCYQRLEFLGDAVLDYLITRHLYEDPRQHSPGALTDLRSALVNNTIFASLAVRHGFHKFFRHLSPGLNDVIDRFVRIQQENGHCISEEYYLLSEEECDDAEDVEVPKALGDVFESIAGAIFLDSNMSLDVVWHVYSNMMSPEIEQFSNSVPKSPIRELLELEPETAKFGKPEKLADGRRVRVTVDVFCKGTFRGIGRNYRIAKCTAAKCALRQLKKQGLIAKKD