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96  structures 415  species 4  interactions 2600  sequences 106  architectures

Family: Piwi (PF02171)

Summary: Piwi domain

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Piwi Edit Wikipedia article

Piwi domain
PDB 1z26 EBI.jpg
Structure of the Pyrococcus furiosus Argonaute protein.[1]
Symbol Piwi
Pfam PF02171
InterPro IPR003165
CDD cd02826
The piwi domain of an argonaute protein with bound siRNA, components of the RNA-induced silencing complex that mediates gene silencing by RNA interference.

The piwi (sometimes also PIWI; originally P-element induced wimpy testis in Drosophila[2]) class of genes was originally identified as encoding regulatory proteins responsible for maintaining incomplete differentiation in stem cells and maintaining the stability of cell division rates in germ line cells.[3] Piwi proteins are highly conserved across evolutionary lineages and are present in both plants and animals.[4] One of the major human homologues, whose upregulation is implicated in the formation of tumours such as seminomas, is called hiwi;[5] other variants on the theme include the miwi protein in mice.[6]

Role in RNA interference

The piwi domain[7] is a protein domain found in piwi proteins and a large number of related nucleic acid-binding proteins, especially those that bind and cleave RNA. The function of the domain is double stranded-RNA-guided hydrolysis of single stranded-RNA that has been determined in the argonaute family of related proteins.[1] Argonautes, the most well-studied family of nucleic-acid binding proteins, are RNase H-like enzymes that carry out the catalytic functions of the RNA-induced silencing complex (RISC). In the well-known cellular process of RNA interference, the argonaute protein in the RISC complex can bind both small interfering RNA (siRNA) generated from exogenous double-stranded RNA and microRNA (miRNA) generated from endogenous non-coding RNA, both produced by the ribonuclease Dicer, to form an RNA-RISC complex. This complex binds and cleaves complementary base pairing messenger RNA, destroying it and preventing its translation into protein. Crystallised piwi domains have a conserved basic binding site for the 5' end of bound RNA; in the case of argonaute proteins binding siRNA strands, the last unpaired nucleotide base of the siRNA is also stabilised by base stacking-interactions between the base and neighbouring tyrosine residues.[8]

Recent evidence suggests that the functional role of piwi proteins in germ-line determination is due to their capacity to interact with miRNAs. Components of the miRNA pathway appear to be present in pole plasm and to play a key role in early development and morphogenesis of Drosophila melanogaster embryos, in which germ-line maintenance has been extensively studied.[9]

piRNAs and transposon silencing

Recently, a novel class of longer-than-average miRNAs known as Piwi-interacting RNAs (piRNAs) has been defined in mammalian cells, about 26-31 nucleotides long as compared to the more typical miRNA or siRNA of about 21 nucleotides. These piRNAs are expressed specifically in spermatogenic cells in the testes of mammals.[10] piRNAs have been identified in the genomes of mice, rats, and humans, with an unusual "clustered" genomic organization[11] that may originate from repetitive regions of the genome such as retrotransposons or regions normally organized into heterochromatin, and which are normally derived exclusively from the antisense strand of double-stranded RNA.[12] piRNAs have thus been classified as repeat-associated small interfering RNAs (rasiRNAs).[2] Although their biogenesis is not yet well understood, piRNAs and Piwi proteins are thought to form an endogenous system for silencing the expression of selfish genetic elements such as retrotransposons and thus preventing the gene products of such sequences from interfering with germ cell formation.[12]


  1. ^ a b Rivas FV, Tolia NH, Song JJ; et al. (April 2005). "Purified Argonaute2 and an siRNA form recombinant human RISC". Nat. Struct. Mol. Biol. 12 (4): 340–9. doi:10.1038/nsmb918. PMID 15800637. 
  2. ^ a b Saito K, Nishida KM, Mori T, Kawamura Y, Miyoshi K, Nagami T, Siomi H, Siomi MC. (2006). Specific association of Piwi with rasiRNAs derived from retrotransposon and heterochromatic regions in the Drosophila genome. Genes Dev 20(16):2214-22. PMID 16882972
  3. ^ Cox DN, Chao A, Lin H. (2000). piwi encodes a nucleoplasmic factor whose activity modulates the number and division rate of germline stem cells. Development 127(3):503-14. PMID 10631171
  4. ^ Cox DN, Chao A, Baker J, Chang L, Qiao D, Lin H. (1998). A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal. Genes Dev 12(23):3715-27. doi:10.1101/gad.12.23.3715 PMID 9851978
  5. ^ Qiao D, Zeeman AM, Deng W, Looijenga LH, Lin H. (2002). Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas. Oncogene 21(25):3988-99. doi:10.1038/sj.onc.1205505 PMID 12037681
  6. ^ Deng W, Lin H. (2002). miwi, a murine homolog of piwi, encodes a cytoplasmic protein essential for spermatogenesis. Dev Cell 2(6):819-30. PMID 12062093
  7. ^ Cerutti L, Mian N, Bateman A (October 2000). "Domains in gene silencing and cell differentiation proteins: the novel PAZ domain and redefinition of the Piwi domain". Trends Biochem. Sci. 25 (10): 481–2. doi:10.1016/S0968-0004(00)01641-8. PMID 11050429. 
  8. ^ Ma J, Yuan Y, Meister G, Pei Y, Tuschl T, Patel D (2005). "Structural basis for 5'-end-specific recognition of guide RNA by the A. fulgidus Piwi protein". Nature 434 (7033): 666-70. doi:10.1038/nature03514 PMID 15800629
  9. ^ Megosh HB, Cox DN, Campbell C, Lin H. (2006). The role of PIWI and the miRNA machinery in Drosophila germline determination. Curr Biol 16(19):1884-94. PMID 16949822
  10. ^ Kim VN. (2006). Small RNAs just got bigger: Piwi-interacting RNAs (piRNAs) in mammalian testes. Genes Dev 20(15):1993-7. PMID 16882976
  11. ^ Girard A, Sachidanandam R, Hannon GJ, Carmell MA. (2006). A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 442(7099):199-202. PMID 16751776
  12. ^ a b Vagin VV, Sigova A, Li C, Seitz H, Gvozdev V, Zamore PD. (2006). A distinct small RNA pathway silences selfish genetic elements in the germline. Science 313(5785):320-4. PMID 16809489

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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Piwi domain Provide feedback

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 [2]. 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.

Literature references

  1. Cerutti L, Mian N, Bateman A; , Trends Biochem Sci 2000;25:481-482.: Domains in gene silencing and cell differentiation proteins: the novel PAZ domain and redefinition of the Piwi domain. PUBMED:11050429 EPMC:11050429

  2. Song JJ, Smith SK, Hannon GJ, Joshua-Tor L; , Science 2004;305:1434-1437.: Crystal structure of Argonaute and its implications for RISC slicer activity. PUBMED:15284453 EPMC:15284453

This tab holds annotation information from the InterPro database.

InterPro entry IPR003165

The piwi domain [PUBMED:11050429] is a protein domain found in piwi proteins and a large number of related nucleic acid-binding proteins, especially those that bind and cleave RNA. The function of the domain is double stranded-RNA-guided hydrolysis of single stranded-RNA, as has been determined in the argonaute family of related proteins [PUBMED:15284453].

Gene Ontology

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Seed source: Bateman A
Previous IDs: none
Type: Family
Author: Bateman A, Hammonds G
Number in seed: 17
Number in full: 2600
Average length of the domain: 264.70 aa
Average identity of full alignment: 33 %
Average coverage of the sequence by the domain: 34.58 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 11927849 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 19.9 19.9
Trusted cut-off 19.9 20.0
Noise cut-off 19.8 19.8
Model length: 302
Family (HMM) version: 14
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Archea Archea Eukaryota Eukaryota
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There are 4 interactions for this family. More...

PAZ Piwi ArgoL1 PAZ_siRNAbind


For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Piwi domain has been found. There are 96 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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