Details for: PUSL1

Gene ID: 126789

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: PUSL1

Ensembl ID: ENSG00000169972

Description: pseudouridine synthase like 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • common myeloid progenitor CL0000049
    CSI 3.86
    rCSI 3.12%
    PRS 99.43
  • neural crest cell CL0011012
    CSI 3.64
    rCSI 2.88%
    PRS 97.94
  • ciliated epithelial cell CL0000067
    CSI 2.93
    rCSI 2.57%
    PRS 95.92
  • keratinocyte CL0000312
    CSI 2.93
    rCSI 2.45%
    PRS 98.05
  • stem cell CL0000034
    CSI 2.83
    rCSI 2.73%
    PRS 98.42
  • lung ciliated cell CL1000271
    CSI 2.74
    rCSI 3.17%
    PRS 97.01
  • peripheral nervous system neuron CL2000032
    CSI 2.51
    rCSI 3.41%
    PRS 96.97
  • club cell CL0000158
    CSI 2.21
    rCSI 3.24%
    PRS 98.41
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.9
    rCSI 3.36%
    PRS 95.77

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

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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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 [PUSL1](/details-gene/126789) (pseudouridine synthase like 1) is a protein-coding gene located on chromosome 1p36.33. It encodes an enzyme with predicted pseudouridine synthase activity, which is crucial for the post-transcriptional modification of transfer RNA (tRNA). Functional annotations indicate its primary role is in tRNA pseudouridine synthesis ([GO:0031119](https://www.ebi.ac.uk/QuickGO/term/GO:0031119)), particularly within the [mitochondrion](/details-cell/GO:0005739). Expression data highlights its significance in a diverse range of cell types, including progenitor cells such as the [common myeloid progenitor](/details-cell/CL0000049), neural precursors like the [neural crest cell](/details-cell/CL0011012), and various specialized epithelial cells, suggesting a fundamental role in cellular maintenance, differentiation, and metabolism across multiple tissues. The gene was initially characterized as part of large-scale cDNA sequencing projects ([Link](https://doi.org/10.1038/ng1285), [Link](https://doi.org/10.1101/gr.2596504)). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [PUSL1](/details-gene/126789) suggests it is a functionally important gene in cells requiring high translational capacity or undergoing active differentiation. Its highest cell significance index (CSI) is observed in the [common myeloid progenitor](/details-cell/CL0000049) (CSI: 3.86) and [neural crest cell](/details-cell/CL0011012) (CSI: 3.64), pointing to a potential role in hematopoiesis and neural development. The gene also shows significant expression in several types of terminally differentiated or specialized cells, implying a role in cellular homeostasis and function. These include: * **Epithelial Cells:** High significance is noted in [ciliated epithelial cell](/details-cell/CL0000067) (CSI: 2.93), [keratinocyte](/details-cell/CL0000312) (CSI: 2.93), [lung ciliated cell](/details-cell/CL1000271) (CSI: 2.74), and [club cell](/details-cell/CL0000158) (CSI: 2.21). This pattern may reflect the high metabolic and protein synthesis demands of barrier and secretory tissues. * **Neural Cells:** Beyond precursor cells, [PUSL1](/details-gene/126789) is significant in mature [peripheral nervous system neuron](/details-cell/CL2000032) (CSI: 2.51) and [caudal ganglionic eminence derived cortical interneuron](/details-cell/CL4023064) (CSI: 1.90), suggesting its function is necessary for maintaining neuronal integrity and activity. * **Stem Cells:** A high CSI in the broad [stem cell](/details-cell/CL0000034) category (CSI: 2.83) reinforces its likely importance in pluripotency and self-renewal. This broad yet distinct expression pattern indicates that [PUSL1](/details-gene/126789) is not a simple housekeeping gene but rather a critical enzymatic component whose activity is particularly vital in progenitor populations and specialized, high-activity cell types. ## Pathways and Molecular Function The primary molecular function of [PUSL1](/details-gene/126789) is pseudouridine synthase activity ([GO:0009982](https://www.ebi.ac.uk/QuickGO/term/GO:0009982)), specifically targeting tRNA molecules ([GO:0106029](https://www.ebi.ac.uk/QuickGO/term/GO:0106029)). This enzymatic action results in the isomerization of uridine to pseudouridine within tRNA, a modification that helps stabilize tRNA structure and ensures accurate and efficient protein translation. The gene product is also annotated as having general RNA binding capabilities ([GO:0003723](https://www.ebi.ac.uk/QuickGO/term/GO:0003723)). Cellular component ontology places the [PUSL1](/details-gene/126789) protein within the [mitochondrion](/details-cell/GO:0005739) and other intracellular membrane-bounded organelles ([GO:0043231](https://www.ebi.ac.uk/QuickGO/term/GO:0043231)). Its mitochondrial localization is particularly significant, as it implies a specific role in modifying mitochondrial tRNAs. This is essential for the proper synthesis of the 13 protein components of the electron transport chain encoded by the mitochondrial genome, linking [PUSL1](/details-gene/126789) function directly to cellular respiration and energy production. ## Research Directions The widespread importance of [PUSL1](/details-gene/126789) in progenitor and metabolically active cells suggests several avenues for future investigation. Its role in tRNA modification, a process increasingly linked to the regulation of cell fate and stress responses, makes it a compelling subject for further study. **Proposed Hypotheses:** 1. Given its high significance in [common myeloid progenitor](/details-cell/CL0000049) and other [stem cell](/details-cell/CL0000034) populations, the activity of [PUSL1](/details-gene/126789) may be critical for regulating the translation of lineage-specific transcription factors, thereby controlling hematopoietic or neural differentiation. Dysregulation of [PUSL1](/details-gene/126789) could impair stem cell differentiation and contribute to developmental disorders or malignancies. 2. The mitochondrial localization of [PUSL1](/details-gene/126789) and its high expression in neurons and ciliated cells suggest that its function is essential for meeting the high energetic demands of these cell types. Loss-of-function mutations in [PUSL1](/details-gene/126789) may lead to mitochondrial dysfunction, resulting in cell-type-specific pathologies such as ciliopathies or neurodegenerative diseases. **Key Experimental Approach:** To test the first hypothesis regarding its role in hematopoiesis, a robust experimental plan would be to use a CRISPR-Cas9 system to knock out [PUSL1](/details-gene/126789) in primary human CD34+ hematopoietic stem and progenitor cells (HSPCs). These modified cells could then be cultured in vitro under conditions that promote differentiation towards myeloid lineages (e.g., using GM-CSF and M-CSF). The effect of [PUSL1](/details-gene/126789) loss could be quantified by colony-forming unit (CFU) assays and flow cytometric analysis of lineage markers (e.g., CD33, CD14, CD11b). To understand the molecular mechanism, ribosome profiling (Ribo-seq) combined with RNA-seq on knockout and control cells could reveal specific changes in the translational efficiency of key mRNAs involved in myeloid development. **Therapeutic Potential:** As a fundamental enzyme involved in mitochondrial protein synthesis, [PUSL1](/details-gene/126789) is likely essential for the viability of most cells. Direct inhibition would probably lead to significant systemic toxicity, making it a poor therapeutic target for inhibitory drugs. However, if specific cancers demonstrate a unique dependency on elevated [PUSL1](/details-gene/126789) activity for survival, it could represent a context-specific vulnerability. More plausibly, [PUSL1](/details-gene/126789) could serve as a biomarker for diseases characterized by mitochondrial dysfunction or translational stress.

Genular Protein ID: 1016896054

Symbol: PUSL1_HUMAN

Name: tRNA pseudouridine synthase-like 1

UniProtKB Accession Codes:

Q8N0Z8 B4DP76 Q5TA41

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 2 ChiTaRS 1 DMDM 1 DNASU 1 EC 1 EMBL 5 Ensembl 1 ExpressionAtlas 1 GO 6 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HAMAP 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIRSF 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 1 Rhea 3 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

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: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

Sequence Information:

  • Length: 303
  • Mass: 33233
  • Checksum: A1B41615F9F214DA
  • Sequence:
    • MSSAPASGSV RARYLVYFQY VGTDFNGVAA VRGTQRAVGV QNYLEEAAER LNSVEPVRFT 
ISSRTDAGVH ALSNAAHLDV QRRSGRPPFP PEVLAEALNT HLRHPAIRVL RAFRVPSDFH 
ARHAATSRTY LYRLATGCHR RDELPVFERN LCWTLPADCL DMVAMQEAAQ HLLGTHDFSA 
FQSAGSPVPS PVRTLRRVSV SPGQASPLVT PEESRKLRFW NLEFESQSFL YRQVRRMTAV 
LVAVGLGALA PAQVKTILES QDPLGKHQTR VAPAHGLFLK SVLYGNLGAA SCTLQGPQFG 
SHG