Protein: Piwi-like protein 2 (EC 3.1.26.-) (Q8CDG1)
Organism: Mus musculus (Mouse)
Function: Endoribonuclease that plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. Plays an essential role in meiotic differentiation of spermatocytes, germ cell differentiation and in self-renewal of spermatogonial stem cells. Its presence in oocytes suggests that it may participate in similar functions during oogenesis in females. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. During piRNA biosynthesis, plays a key role in the piRNA amplification loop, also named ping-pong amplification cycle, by acting as a 'slicer-competent' piRNA endoribonuclease that cleaves primary piRNAs, which are then loaded onto 'slicer-incompetent' PIWIL4. PIWIL2 slicing produces a pre-miRNA intermediate, which is then processed in mature piRNAs, and as well as a 16 nucleotide by-product that is degraded. Required for PIWIL4/MIWI2 nuclear localization and association with secondary piRNAs antisense. Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation. Indirectly modulates expression of genes such as PDGFRB, SLC2A1, ITGA6, GJA7, THY1, CD9 and STRA8. Represses circadian rhythms by promoting the stability and activity of core clock components BMAL1 and CLOCK by inhibiting GSK3B-mediated phosphorylation and ubiquitination-dependent degradation of these proteins.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:11578866, ECO:0000269|PubMed:18922463, ECO:0000269|PubMed:19114715, ECO:0000269|PubMed:19465913, ECO:0000269|PubMed:19584108, ECO:0000269|PubMed:20439430, ECO:0000269|PubMed:32381626}. Note=Present in chromatoid body. Probable component of the meiotic nuage, also named P granule, a germ-cell-specific organelle required to repress transposon activity during meiosis (PubMed:20439430). {ECO:0000269|PubMed:20439430}.
Interaction partners:
- Tudor domain-containing protein 1
- RNA helicase Mov10l1
- Putative ATP-dependent RNA helicase TDRD12
- ATP-dependent RNA helicase DDX4
- piRNA biogenesis protein EXD1
- Ankyrin repeat, SAM and basic leucine zipper domain-containing protein 1
- ATP-dependent RNA helicase TDRD9
- Pirin
- Tudor domain-containing protein 6
- RING finger protein 17
Sequence:
MDPVRPLFRGPTPVHPSQCVRMPGCWPQAPRPLEPAWGRAGPAGRGLVFRKPEDSSPPLQPVQKDSVGLVSMFRGMGLDTAFRPPSKREVPPLGRGVLGRGLSANMVRKDREEPRSSLPDPSVLAAGDSKLAEASVGWSRMLGRGSSEVSLLPLGRAASSIGRGMDKPPSAFGLTARDPPRLPQPPALSPTSLHSADPPPVLTMERKEKELLVKQGSKGTPQSLGLNLIKIQCHNEAVYQYHVTFSPSVECKSMRFGMLKDHQSVTGNVTAFDGSILYLPVKLQQVVELKSQRKTDDAEISIKIQLTKILEPCSDLCIPFYNVVFRRVMKLLDMKLVGRNFYDPTSAMVLQQHRLQIWPGYAASIRRTDGGLFLLADVSHKVIRNDSVLDVMHAIYQQNKEHFQDECSKLLVGSIVITRYNNRTYRIDDVDWNKTPKDSFVMSDGKEITFLEYYSKNYGITVKEDDQPLLIHRPSERQNNHGMLLKGEILLLPELSFMTGIPEKMKKDFRAMKDLTQQINLSPKQHHGALECLLQRISQNETASNELTRWGLSLHKDVHKIEGRLLPMERINLRNTSFVTSEDLNWVKEVTRDASILTIPMHFWALFYPKRAMDQARELVNMLEKIAGPIGMRISPPAWVELKDDRIETYIRTIQSLLGVEGKIQMVVCIIMGTRDDLYGAIKKLCCVQSPVPSQVINVRTIGQPTRLRSVAQKILLQMNCKLGGELWGVDIPLKQLMVIGMDVYHDPSRGMRSVVGFVASINLTLTKWYSRVVFQMPHQEIVDSLKLCLVGSLKKYYEVNHCLPEKIVVYRDGVSDGQLKTVANYEIPQLQKCFEAFDNYHPKMVVFVVQKKISTNLYLAAPDHFVTPSPGTVVDHTITSCEWVDFYLLAHHVRQGCGIPTHYICVLNTANLSPDHMQRLTFKLCHMYWNWPGTIRVPAPCKYAHKLAFLSGQILHHEPAIQLCGNLFFL