PIWIL4 belongs to the Argonaute family of proteins, which function in development and maintenance of germline stem cells (Sasaki et al., 2003 [PubMed 12906857]).[supplied by OMIM, Mar 2008] See more...

Aliases for PIWIL4 Gene

Aliases for PIWIL4 Gene

  • Piwi Like RNA-Mediated Gene Silencing 4 2 3 5
  • Piwi-Like Protein 4 3 4
  • HIWI2 3 4
  • Testis Tissue Sperm-Binding Protein Li 85P 3
  • Piwi-Like 4 (Drosophila) 2
  • Piwi-Like 4 3
  • MIWI2 3
  • PIWI 4

External Ids for PIWIL4 Gene

Previous GeneCards Identifiers for PIWIL4 Gene

  • GC00U991201
  • GC11P093989
  • GC11P093940
  • GC11P094300
  • GC11P090365
  • GC11P094278

Summaries for PIWIL4 Gene

Entrez Gene Summary for PIWIL4 Gene

  • PIWIL4 belongs to the Argonaute family of proteins, which function in development and maintenance of germline stem cells (Sasaki et al., 2003 [PubMed 12906857]).[supplied by OMIM, Mar 2008]

GeneCards Summary for PIWIL4 Gene

PIWIL4 (Piwi Like RNA-Mediated Gene Silencing 4) is a Protein Coding gene. Diseases associated with PIWIL4 include Cervical Cancer and Retinitis Pigmentosa 49. Among its related pathways are Gene Expression and Mitotic Prophase. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and piRNA binding. An important paralog of this gene is PIWIL1.

UniProtKB/Swiss-Prot Summary for PIWIL4 Gene

  • 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).

Additional gene information for PIWIL4 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PIWIL4 Gene

Genomics for PIWIL4 Gene

GeneHancer (GH) Regulatory Elements for PIWIL4 Gene

Promoters and enhancers for PIWIL4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PIWIL4 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PIWIL4

Top Transcription factor binding sites by QIAGEN in the PIWIL4 gene promoter:
  • AP-1
  • AREB6
  • Cdc5
  • E47
  • Pax-3
  • POU3F2
  • POU3F2 (N-Oct-5a)
  • POU3F2 (N-Oct-5b)
  • STAT5A
  • STAT5B

Genomic Locations for PIWIL4 Gene

Genomic Locations for PIWIL4 Gene
chr11:94,543,840-94,621,421
(GRCh38/hg38)
Size:
77,582 bases
Orientation:
Plus strand
chr11:94,277,006-94,354,587
(GRCh37/hg19)
Size:
77,582 bases
Orientation:
Plus strand

Genomic View for PIWIL4 Gene

Genes around PIWIL4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PIWIL4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PIWIL4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PIWIL4 Gene

Proteins for PIWIL4 Gene

  • Protein details for PIWIL4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q7Z3Z4-PIWL4_HUMAN
    Recommended name:
    Piwi-like protein 4
    Protein Accession:
    Q7Z3Z4
    Secondary Accessions:
    • B4DEG5
    • Q68CZ4
    • Q8N8G9
    • Q8N9V8
    • Q8NEH2

    Protein attributes for PIWIL4 Gene

    Size:
    852 amino acids
    Molecular mass:
    96589 Da
    Quaternary structure:
    • Interacts with PRMT5 and WDR77. Interacts (when methylated on arginine residues) with TDRD1, TDRKH/TDRD2 and TDRD9. Interacts with MOV10L1.
    SequenceCaution:
    • Sequence=BAC04873.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=CAH18436.1; Type=Frameshift; Evidence={ECO:0000305};

    Alternative splice isoforms for PIWIL4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PIWIL4 Gene

Post-translational modifications for PIWIL4 Gene

  • Arginine methylation by PRMT5 is required for the interaction with Tudor domain-containing protein (TDRD1, TDRKH/TDRD2 and TDRD9) and subsequent localization to the meiotic nuage, also named P granule.
  • Ubiquitination at Lys676 and Lys679
  • Modification sites at PhosphoSitePlus

Other Protein References for PIWIL4 Gene

No data available for DME Specific Peptides for PIWIL4 Gene

Domains & Families for PIWIL4 Gene

Gene Families for PIWIL4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for PIWIL4 Gene

Blocks:
  • Argonaute and Dicer protein, PAZ
  • Stem cell self-renewal protein Piwi
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for PIWIL4 Gene

GenScript: Design optimal peptide antigens:
  • Piwi-like protein 4 (PIWL4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q7Z3Z4

UniProtKB/Swiss-Prot:

PIWL4_HUMAN :
  • Belongs to the argonaute family. Piwi subfamily.
Family:
  • Belongs to the argonaute family. Piwi subfamily.
genes like me logo Genes that share domains with PIWIL4: view

Function for PIWIL4 Gene

Molecular function for PIWIL4 Gene

UniProtKB/Swiss-Prot Function:
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).
UniProtKB/Swiss-Prot Induction:
Up-regulated in vitreous aspirates of patients with proliferative diabetic retinopathies (at protein level). Up-regulated after exposure to oxidative stress and VEGF in adult retinal pigment epithelial cell line (ARPE19 cells) (PubMed:30145353). Up-regulated in cervical cancer tissues (PubMed:22483988).

Phenotypes From GWAS Catalog for PIWIL4 Gene

Gene Ontology (GO) - Molecular Function for PIWIL4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003723 RNA binding IEA --
GO:0004521 NOT endoribonuclease activity ISS --
GO:0005515 protein binding IEA --
GO:0034584 piRNA binding ISS --
genes like me logo Genes that share ontologies with PIWIL4: view
genes like me logo Genes that share phenotypes with PIWIL4: view

Animal Models for PIWIL4 Gene

MGI Knock Outs for PIWIL4:

Animal Model Products

miRNA for PIWIL4 Gene

miRTarBase miRNAs that target PIWIL4

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for PIWIL4 Gene

Localization for PIWIL4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PIWIL4 Gene

Nucleus. Cytoplasm. Note=Probable component of the meiotic nuage, also named P granule, a germ-cell-specific organelle required to repress transposon activity during meiosis. PIWIL2/MILI is required for nuclear localization (By similarity). {ECO:0000250 UniProtKB:Q8CGT6}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PIWIL4 gene
Compartment Confidence
nucleus 5
mitochondrion 3
plasma membrane 2
extracellular 2
cytoskeleton 2
cytosol 2
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Mitochondria (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for PIWIL4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus ISS --
GO:0005737 cytoplasm ISS --
GO:0043186 P granule ISS --
GO:0071547 piP-body ISS --
genes like me logo Genes that share ontologies with PIWIL4: view

Pathways & Interactions for PIWIL4 Gene

genes like me logo Genes that share pathways with PIWIL4: view

Pathways by source for PIWIL4 Gene

Gene Ontology (GO) - Biological Process for PIWIL4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006417 regulation of translation IEA --
GO:0007275 multicellular organism development IEA --
GO:0007283 spermatogenesis ISS --
GO:0010529 negative regulation of transposition ISS --
GO:0010669 epithelial structure maintenance IMP 28025795
genes like me logo Genes that share ontologies with PIWIL4: view

No data available for SIGNOR curated interactions for PIWIL4 Gene

Drugs & Compounds for PIWIL4 Gene

No Compound Related Data Available

Transcripts for PIWIL4 Gene

mRNA/cDNA for PIWIL4 Gene

1 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for PIWIL4 Gene

No ASD Table

Relevant External Links for PIWIL4 Gene

GeneLoc Exon Structure for
PIWIL4

Expression for PIWIL4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PIWIL4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for PIWIL4 Gene

This gene is overexpressed in Testis (31.8), Monocytes (23.7), and Ovary (13.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for PIWIL4 Gene



Protein tissue co-expression partners for PIWIL4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PIWIL4

SOURCE GeneReport for Unigene cluster for PIWIL4 Gene:

Hs.660188

mRNA Expression by UniProt/SwissProt for PIWIL4 Gene:

Q7Z3Z4-PIWL4_HUMAN
Tissue specificity: Ubiquitously expressed (PubMed:25038252, PubMed:17544373, PubMed:28025795, PubMed:28711973, PubMed:22483988). Detected in retina, retinal pigment epithelia cells (RPE) (at protein level) (PubMed:28025795).

Evidence on tissue expression from TISSUES for PIWIL4 Gene

  • Nervous system(4.7)
  • Heart(2.7)
genes like me logo Genes that share expression patterns with PIWIL4: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for PIWIL4 Gene

Orthologs for PIWIL4 Gene

This gene was present in the common ancestor of animals.

Orthologs for PIWIL4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PIWIL4 31 30
  • 99.53 (n)
OneToOne
dog
(Canis familiaris)
Mammalia PIWIL4 31 30
  • 85.41 (n)
OneToOne
cow
(Bos Taurus)
Mammalia PIWIL4 31 30
  • 84.75 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Piwil4 30
  • 78.94 (n)
mouse
(Mus musculus)
Mammalia Piwil4 17 31 30
  • 76.98 (n)
oppossum
(Monodelphis domestica)
Mammalia PIWIL4 31
  • 70 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia PIWIL4 31
  • 56 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia piwil4 30
  • 63.56 (n)
fruit fly
(Drosophila melanogaster)
Insecta AGO3 31
  • 34 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea ergo-1 31
  • 14 (a)
ManyToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 42 (a)
OneToMany
Species where no ortholog for PIWIL4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • zebrafish (Danio rerio)

Evolution for PIWIL4 Gene

ENSEMBL:
Gene Tree for PIWIL4 (if available)
TreeFam:
Gene Tree for PIWIL4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PIWIL4: view image

Paralogs for PIWIL4 Gene

Paralogs for PIWIL4 Gene

(3) SIMAP similar genes for PIWIL4 Gene using alignment to 3 proteins:

  • PIWL4_HUMAN
  • F5GX26_HUMAN
  • F5H116_HUMAN
genes like me logo Genes that share paralogs with PIWIL4: view

Variants for PIWIL4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PIWIL4 Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
728680 Likely Benign: not provided 94,587,139(+) G/A MISSENSE_VARIANT
730869 Benign: not provided 94,597,800(+) A/G INTRON_VARIANT
774699 Likely Benign: not provided 94,587,099(+) A/C MISSENSE_VARIANT
775296 Benign: not provided 94,593,554(+) A/G MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
779311 Benign: not provided 94,607,562(+) A/G MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for PIWIL4 Gene

Structural Variations from Database of Genomic Variants (DGV) for PIWIL4 Gene

Variant ID Type Subtype PubMed ID
esv2671948 CNV deletion 23128226

Variation tolerance for PIWIL4 Gene

Residual Variation Intolerance Score: 53.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.83; 83.54% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PIWIL4 Gene

Human Gene Mutation Database (HGMD)
PIWIL4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PIWIL4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PIWIL4 Gene

Disorders for PIWIL4 Gene

MalaCards: The human disease database

(3) MalaCards diseases for PIWIL4 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
cervical cancer
  • cervical cancer, somatic
retinitis pigmentosa 49
  • rp49
retinitis pigmentosa
  • retinitis pigmentosa 1
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for PIWIL4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with PIWIL4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PIWIL4 Gene

Publications for PIWIL4 Gene

  1. Identification of eight members of the Argonaute family in the human genome. (PMID: 12906857) Sasaki T … Shimizu N (Genomics 2003) 2 3 4 54
  2. Possible role of HIWI2 in modulating tight junction proteins in retinal pigment epithelial cells through Akt signaling pathway. (PMID: 28025795) Sivagurunathan S … Chidambaram S (Molecular and cellular biochemistry 2017) 3 4 54
  3. Association of PIWIL4 genetic variants with germ cell maturation arrest in infertile Spanish men. (PMID: 24969058) Muñoz X … Larriba S (Asian journal of andrology 2014) 3 4 54
  4. The human Piwi protein Hiwi2 associates with tRNA-derived piRNAs in somatic cells. (PMID: 25038252) Keam SP … Suter CM (Nucleic acids research 2014) 3 4 54
  5. PIWIL4 regulates cervical cancer cell line growth and is involved in down-regulating the expression of p14ARF and p53. (PMID: 22483988) Su C … Tang H (FEBS letters 2012) 3 4 54

Products for PIWIL4 Gene

Sources for PIWIL4 Gene