Molecular Target Synopsis
Domains and Structures
Drugs and Clinical Candidates
Ligand Efficiency Plot
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
Germline Genetics

PIWIL2 (Q8TC59) - Overview - Molecular Target Synopsis


PIWIL2, Piwi-like protein 2
Enzyme Classification 3.1.26.-
UniProt Q8TC59


Endoribonuclease that plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity (By similarity). Plays an essential role in meiotic differentiation of spermatocytes, germ cell differentiation and in self-renewal of spermatogonial stem cells (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). Required for PIWIL4/MIWI2 nuclear localization and association with secondary piRNAs antisense (By similarity). Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation (By similarity). Indirectly modulates expression of genes such as PDGFRB, SLC2A1, ITGA6, GJA7, THY1, CD9 and STRA8 (By similarity). When overexpressed, acts as an oncogene by inhibition of apoptosis and promotion of proliferation in tumors (PubMed:16377660). Represses circadian rhythms by promoting the stability and activity of core clock components ARNTL/BMAL1 and CLOCK by inhibiting GSK3B-mediated phosphorylation and ubiquitination-dependent degradation of these proteins (PubMed:28903391). Interacts with DDX4, MAEL, EIF3A, EIF4E, EIF4G, PRMT5 and WDR77 (By similarity). Associates with EIF4E- and EIF4G-containing m7G cap-binding complexes (By similarity). Interacts (when methylated on arginine residues) with TDRD1 and TDRKH/TDRD2 (By similarity). Interacts with TDRD12 (By similarity). Component of the PET complex, at least composed of EXD1, PIWIL2, TDRD12 and piRNAs (By similarity). Interacts with MOV10L1 (By similarity). Interacts with GPAT2 (By similarity). Interacts with TEX19 (By similarity). Interacts with GSK3B (By similarity). Interacts (via PIWI domain) with ARNTL/BMAL1 and CLOCK (PubMed:28903391).

Inspect Structure
See all 3D Structures for PIWIL2

Isoforms / Transcripts (Protein Coding)

Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
973ENSG00000197181ENST00000454009, ENST00000356766ENSP00000406956, ENSP00000349208Q8TC59-1

Sub-cellular localization

UniProt: PIWIL2 is active in the following subcellular-locations: cytoplasm.
GO terms: PIWIL2 is active in the following subcellular-locations: chromatoid body, cytoplasm, dense body, nucleus, P granule, perinucleolar chromocenter, PET complex, pi-body.

GO terms

Gene Copy Number Variation

In COSMIC - Cell Lines Project PIWIL2 has gain in 1 cell-lines, loss in 12 cell-lines and no signal in 992 cell-lines. (see details)

Gene Expression

In NCI60, the highest expressing cell lines are: KM12, MALME_3M, HOP_92

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: COLO-704, NTERA-2, KMM-1

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, NHLF, HSMM

(see details)

3D Structures

For PIWIL2 there are:
2 structures (8 chains) solved
0 are solved in complex with at least one small molecule ligand

(see details)
Molecular Target 3D Synopsis