This domain is found in the protein Piwi and its relatives. The function of this domain is the dsRNA guided hydrolysis of ssRNA. Determination of the crystal structure of Argonaute reveals that PIWI is an RNase H domain, and identifies Argonaute as Slicer, the enzyme that cleaves mRNA in the RNAi RISC complex [[cite:PUB00020128]]. In addition, Mg+2 dependence and production of 3'-OH and 5' phosphate products are shared characteristics of RNaseH and RISC. The PIWI domain core has a tertiary structure belonging to the RNase H family of enzymes. RNase H fold proteins all have a five-stranded mixed beta-sheet surrounded by helices. By analogy to RNase H enzymes which cleave single-stranded RNA guided by the DNA strand in an RNA/DNA hybrid, the PIWI domain can be inferred to cleave single-stranded RNA, for example mRNA, guided by double stranded siRNA.
","llm":false,"checked":false,"updated":false}],"wikipedia":[{"title":"Argonaute","extract":"The Argonaute protein family, first discovered for its evolutionarily conserved stem cell function, plays a central role in RNA silencing processes as essential components of the RNA-induced silencing complex (RISC). RISC is responsible for the gene silencing phenomenon known as RNA interference (RNAi). Argonaute proteins bind different classes of small non-coding RNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs) and piwi-interacting RNAs (piRNAs). Small RNAs guide Argonaute proteins to their specific targets through sequence complementarity, which then leads to mRNA cleavage, translation inhibition, and/or the initiation of mRNA decay.
","thumbnail":null},{"title":"Piwi","extract":"Piwi genes were identified as regulatory proteins responsible for stem cell and germ cell differentiation. Piwi is an abbreviation of P-element Induced WImpy testis in Drosophila. Piwi proteins are highly conserved RNA-binding proteins and are present in both plants and animals. Piwi proteins belong to the Argonaute/Piwi family and have been classified as nuclear proteins. Studies on Drosophila have also indicated that Piwi proteins have no slicer activity conferred by the presence of the Piwi domain. In addition, Piwi associates with heterochromatin protein 1, an epigenetic modifier, and piRNA-complementary sequences. These are indications of the role Piwi plays in epigenetic regulation. Piwi proteins are also thought to control the biogenesis of piRNA as many Piwi-like proteins contain slicer activity which would allow Piwi proteins to process precursor piRNA into mature piRNA.
","thumbnail":null}],"literature":{"PUB00018283":{"PMID":11050429,"ISBN":null,"volume":"25","issue":"10","year":2000,"title":"Domains in gene silencing and cell differentiation proteins: the novel PAZ domain and redefinition of the Piwi domain.","URL":null,"raw_pages":"481-2","medline_journal":"Trends Biochem Sci","ISO_journal":"Trends Biochem. Sci.","authors":["Cerutti L","Mian N","Bateman A."],"DOI_URL":"http://dx.doi.org/10.1016/S0968-0004(00)01641-8"},"PUB00020128":{"PMID":15284453,"ISBN":null,"volume":"305","issue":"5689","year":2004,"title":"Crystal structure of Argonaute and its implications for RISC slicer activity.","URL":null,"raw_pages":"1434-7","medline_journal":"Science","ISO_journal":"Science","authors":["Song JJ","Smith SK","Hannon GJ","Joshua-Tor L."],"DOI_URL":"http://dx.doi.org/10.1126/science.1102514"}},"set_info":{"accession":"CL0219","name":"RNase_H"},"overlaps_with":null,"counters":{"subfamilies":0,"domain_architectures":757,"interactions":0,"matches":37384,"pathways":0,"proteins":36137,"proteomes":3610,"sets":1,"structural_models":{"alphafold":31839,"bfvd":0},"structures":148,"taxa":10874},"entry_annotations":{"hmm":0,"logo":0,"alignment:seed":15,"alignment:full":24154},"cross_references":{},"is_llm":false,"is_reviewed_llm":false,"is_updated_llm":false,"representative_structure":{"accession":"2w42","name":"THE STRUCTURE OF A PIWI PROTEIN FROM ARCHAEOGLOBUS FULGIDUS COMPLEXED WITH A 16NT DNA DUPLEX."}}}