Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

PIWIL4 (Q7Z3Z4) - Overview - Molecular Target Synopsis

Protein


PIWIL4, Piwi-like protein 4
UniProt Q7Z3Z4

Also Known as PIWL4_HUMAN, PIWIL4, HIWI2, PIWI

Plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity (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 governs the methylation and subsequent repression of transposons (By similarity). Directly binds piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements (By similarity). Associates with secondary piRNAs antisense and PIWIL2/MILI is required for such association (By similarity). The piRNA process acts upstream of known mediators of DNA methylation (By similarity). Does not show endonuclease activity (By similarity). Plays a key role in the piRNA amplification loop, also named ping-pong amplification cycle, by acting as a 'slicer-incompetent' component that loads cleaved piRNAs from the 'slicer-competent' component PIWIL2 and target them on genomic transposon loci in the nucleus (By similarity). May be involved in the chromatin-modifying pathway by inducing 'Lys-9' methylation of histone H3 at some loci (PubMed:17544373). In addition to its role in germline, PIWIL4 also plays a role in the regulation of somatic cells activities. Plays a role in pancreatic beta cell function and insulin secretion (By similarity). Involved in maintaining cell morphology and functional integrity of retinal epithelial through Akt/GSK3alpha/beta signaling pathway (PubMed:28025795). When overexpressed, acts as an oncogene by inhibition of apoptosis and promotion of cells proliferation in tumors (PubMed:22483988). Interacts with PRMT5 and WDR77. Interacts (when methylated on arginine residues) with TDRD1, TDRKH/TDRD2 and TDRD9. Interacts with MOV10L1.

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: PIWIL4 is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: PIWIL4 is active in the following subcellular-locations: cytoplasm, nucleus, P granule, piP-body.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PIWIL4 has gain in 3 cell-lines, loss in 1 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: HL_60, K_562, SW_620

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: MV-4-11, ML-2, THP-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: NHLF, HSMM, HMEC

(see details)

3D Structures


At greater than 50% identity similarity to PIWIL4 there are:
3 structures (3 chains) solved
0 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis