Details for: PWP2

Gene ID: 5822

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PWP2

Ensembl ID: ENSG00000241945

Description: PWP2 small subunit processome component

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • myeloid leukocyte CL0000766
    CSI 3.88
    rCSI 3.58%
    PRS 99.97

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PWP2](/details-gene/5822), or PWP2 small subunit processome component, is a protein-coding gene located on chromosome 21q22.3. It encodes a homolog of the yeast periodic tryptophan protein 2, which contains WD repeats [Link](https://doi.org/10.1006/geno.1996.0363), [Link](https://doi.org/10.1101/gr.6.12.1216). Functionally, [PWP2](/details-gene/5822) is an essential component of the small-subunit processome, a large ribonucleoprotein complex critical for the biogenesis of the ribosomal small subunit. Its primary roles involve the maturation and processing of ribosomal RNA (rRNA), a fundamental process for protein synthesis. Expression data suggests a particularly significant role within the hematopoietic system, specifically in the [myeloid leukocyte](/details-cell/CL0000766) lineage. The gene is associated with the clinical entry for progressive myoclonus epilepsy ([Link](https://doi.org/10.1159/000134402)) in OMIM ([153245](https://omim.org/entry/601475)). ## Cellular Roles and Expression Landscape The expression profile of [PWP2](/details-gene/5822) highlights its importance in hematopoietic cells. **Overall**, the most significant expression is observed in the [myeloid leukocyte](/details-cell/CL0000766) population (CSI: 3.88). Myeloid cells, which include monocytes, macrophages, and granulocytes, are characterized by high rates of protein synthesis to support their functions in innate immunity, such as phagocytosis and cytokine production. The high significance of [PWP2](/details-gene/5822) in this lineage is consistent with a critical demand for ribosome production to sustain these activities. The available data focuses on this cell type, suggesting that while ribosome biogenesis is a ubiquitous process, the activity of [PWP2](/details-gene/5822) may be particularly pronounced or rate-limiting in [myeloid leukocyte](/details-cell/CL0000766). ## Pathways and Molecular Function The functional annotations for [PWP2](/details-gene/5822) uniformly point to its central role in ribosome biogenesis. It is an integral component of the [small-subunit processome](/details-ontology/GO:0032040) and the [Pwp2p-containing subcomplex of the 90S preribosome](/details-ontology/GO:0034388), which are large molecular machines operating within the nucleoplasm ([GO:0005654](https://www.ebi.ac.uk/QuickGO/term/GO:0005654)). The primary biological processes involving [PWP2](/details-gene/5822) are the [maturation of SSU-rRNA](/details-ontology/GO:0000462) and the assembly and biogenesis of the [ribosomal small subunit](/details-ontology/GO:0000028), [GO:0042274](https://www.ebi.ac.uk/QuickGO/term/GO:0042274). This is further supported by its involvement in Reactome pathways such as [rRNA processing](/details-pathway/R-HSA-72312) and the [major pathway of rRNA processing in the nucleolus and cytosol](/details-pathway/R-HSA-6791226). At the molecular level, its function is mediated through its ability to bind both proteins ([GO:0005515](https://www.ebi.ac.uk/QuickGO/term/GO:0005515)) and RNA ([GO:0003723](https://www.ebi.ac.uk/QuickGO/term/GO:0003723)), which enables it to function as a scaffold within the preribosomal complex, guiding the modification and cleavage of precursor rRNA. ## Research Directions Given that [PWP2](/details-gene/5822) is a core component of ribosome biogenesis with heightened significance in myeloid cells, research should focus on its role in myeloid cell fate and function, particularly in pathological contexts. **Testable Hypotheses:** 1. **Hypothesis 1:** Dysregulation of [PWP2](/details-gene/5822) expression or function is a critical factor in myeloid differentiation and may contribute to myeloproliferative neoplasms (MPNs) or bone marrow failure syndromes by altering the translational capacity of hematopoietic progenitors. 2. **Hypothesis 2:** As [PWP2](/details-gene/5822) is located on chromosome 21, dosage alterations in Trisomy 21 (Down syndrome) contribute to the known hematological abnormalities seen in this condition, such as transient myeloproliferative disorder and an increased risk of acute myeloid leukemia, by driving excessive ribosome production. **Proposed Experimental Approach:** To test the first hypothesis, a robust experimental approach would involve modulating [PWP2](/details-gene/5822) levels in primary human hematopoietic stem and progenitor cells (HSPCs). Specifically, one could use a CRISPR-Cas9 or shRNA-based system to knock down [PWP2](/details-gene/5822) expression in CD34+ HSPCs. These modified cells would then be cultured in vitro under myeloid-promoting conditions (e.g., with GM-CSF, M-CSF, and G-CSF). The impact on myeloid differentiation would be assessed by flow cytometry for lineage markers (e.g., CD33, CD14, CD15), colony-forming unit (CFU) assays to quantify progenitor output, and functional assays on the resulting macrophages or neutrophils (e.g., phagocytosis, oxidative burst). Concurrently, RNA-sequencing and polysome profiling would reveal the downstream effects on the transcriptome and translatome, respectively. **Therapeutic Potential:** As [PWP2](/details-gene/5822) is an essential component of the cellular machinery required for proliferation in all cells, it presents a challenging therapeutic target for direct inhibition due to the high risk of on-target toxicity to healthy, dividing tissues. However, in cancers characterized by an addiction to high rates of protein synthesis, such as certain leukemias, targeting ribosome biogenesis is an emerging therapeutic strategy. While direct inhibition of [PWP2](/details-gene/5822) may be difficult, understanding its specific regulatory pathways in cancer cells could uncover more druggable upstream nodes. Therefore, [PWP2](/details-gene/5822) is more likely to serve as a biomarker of cellular proliferation and biosynthetic activity or as an indirect target rather than a direct candidate for small molecule inhibition.

Genular Protein ID: 1808849636

Symbol: PWP2_HUMAN

Name: Periodic tryptophan protein 2 homolog

UniProtKB Accession Codes:

Q15269 B2RAG8 Q96A77

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 2 BioGRID-ORCS 2 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 16 EMDB 3 Ensembl 1 ExpressionAtlas 1 GO 7 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PRINTS 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 2 RefSeq 3 SMART 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8661145

Title: Cloning the cDNA of human PWP2, which encodes a protein with WD repeats and maps to 21q22.3.

PubMed ID: 8661145

DOI: 10.1006/geno.1996.0363

PubMed ID: 8893822

Title: A periodic tryptophan protein 2 gene homologue (PWP2H) in the candidate region of progressive myoclonus epilepsy on 21q22.3.

PubMed ID: 8893822

DOI: 10.1159/000134402

PubMed ID: 8973917

Title: Isolation and genomic structure of a human homolog of the yeast periodic tryptophan protein 2 (PWP2) gene mapping to 21q22.3.

PubMed ID: 8973917

DOI: 10.1101/gr.6.12.1216

PubMed ID: 9205129

Title: Genomic organization and complete nucleotide sequence of the human PWP2 gene on chromosome 21.

PubMed ID: 9205129

DOI: 10.1006/geno.1997.4761

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 10830953

Title: The DNA sequence of human chromosome 21.

PubMed ID: 10830953

DOI: 10.1038/35012518

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 9196060

Title: Genomic organization and complete nucleotide sequence of the TMEM1 gene on human chromosome 21q22.3.

PubMed ID: 9196060

DOI: 10.1006/bbrc.1997.6758

PubMed ID: 12429849

Title: Functional proteomic analysis of human nucleolus.

PubMed ID: 12429849

DOI: 10.1091/mbc.e02-05-0271

PubMed ID: 34516797

Title: Nucleolar maturation of the human small subunit processome.

PubMed ID: 34516797

DOI: 10.1126/science.abj5338

Sequence Information:

  • Length: 919
  • Mass: 102452
  • Checksum: B2A94C5595DF4380
  • Sequence:
    • MKFAYRFSNL LGTVYRRGNL NFTCDGNSVI SPVGNRVTVF DLKNNKSDTL PLATRYNVKC 
VGLSPDGRLA IIVDEGGDAL LVSLVCRSVL HHFHFKGSVH SVSFSPDGRK FVVTKGNIAQ 
MYHAPGKKRE FNAFVLDKTY FGPYDETTCI DWTDDSRCFV VGSKDMSTWV FGAERWDNLI 
YYALGGHKDA IVACFFESNS LDLYSLSQDG VLCMWQCDTP PEGLRLKPPA GWKADLLQRE 
EEEEEEEDQE GDRETTIRGK ATPAEEEKTG KVKYSRLAKY FFNKEGDFNN LTAAAFHKKS 
HLLVTGFASG IFHLHELPEF NLIHSLSISD QSIASVAINS SGDWIAFGCS GLGQLLVWEW 
QSESYVLKQQ GHFNSMVALA YSPDGQYIVT GGDDGKVKVW NTLSGFCFVT FTEHSSGVTG 
VTFTATGYVV VTSSMDGTVR AFDLHRYRNF RTFTSPRPTQ FSCVAVDASG EIVSAGAQDS 
FEIFVWSMQT GRLLDVLSGH EGPISGLCFN PMKSVLASAS WDKTVRLWDM FDSWRTKETL 
ALTSDALAVT FRPDGAELAV ATLNSQITFW DPENAVQTGS IEGRHDLKTG RKELDKITAK 
HAAKGKAFTA LCYSADGHSI LAGGMSKFVC IYHVREQILM KRFEISCNLS LDAMEEFLNR 
RKMTEFGNLA LIDQDAGQED GVAIPLPGVR KGDMSSRHFK PEIRVTSLRF SPTGRCWAAT 
TTEGLLIYSL DTRVLFDPFE LDTSVTPGRV REALRQQDFT RAILMALRLN ESKLVQEALE 
AVPRGEIEVV TSSLPELYVE KVLEFLASSF EVSRHLEFYL LWTHKLLMLH GQKLKSRAGT 
LLPVIQFLQK SIQRHLDDLS KLCSWNHYNM QYALAVSKQR GTKRSLDPLG SEEEAEASED 
DSLHLLGGGG RDSEEEMLA