Details for: USP50

Gene ID: 373509

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: USP50

Ensembl ID: ENSG00000170236

Description: ubiquitin specific peptidase 50

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • neural progenitor cell CL0011020
    CSI 2.52
    rCSI 11.09%
    PRS 99.4

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 [USP50](/details-gene/373509) (ubiquitin specific peptidase 50) is a protein-coding gene that encodes a deubiquitinating enzyme (DUB) belonging to the ubiquitin-specific protease (USP) family. As a DUB, it functions to remove ubiquitin moieties from substrate proteins, thereby regulating their stability and function. **Overall**, expression data indicates that [USP50](/details-gene/373509) has a particularly significant expression profile in [neural progenitor cell](/details-cell/CL0011020)s, suggesting a specialized role in the context of neurogenesis or neural development. Functionally, it is implicated in several critical cellular processes, including the regulation of the G2/M cell cycle checkpoint and the positive regulation of NLRP3 inflammasome activation, highlighting its importance in both cell proliferation and innate immune signaling. ## Cellular Roles and Expression Landscape The expression profile of [USP50](/details-gene/373509), based on the available data, points towards a highly specialized cellular role. **Overall**, the gene's expression is most significant in [neural progenitor cell](/details-cell/CL0011020) (CSI: 2.52), suggesting it may function as a key regulator in this cell type. This is consistent with its annotated localization to cellular components relevant to neuronal function, such as the [dendritic spine](/details-cell/GO:0043197) and [postsynaptic density](/details-cell/GO:0014069). The prominent role in progenitor cells may be linked to its documented function in cell cycle regulation. The lack of broad expression across diverse cell lineages suggests a specific, rather than a housekeeping, function for [USP50](/details-gene/373509). A more comprehensive expression atlas would be required to fully delineate its cellular specificity. ## Pathways and Molecular Function [USP50](/details-gene/373509) primarily exerts its function through [cysteine-type deubiquitinase activity](/details-cell/GO:0004843), enabling it to cleave ubiquitin from target proteins. This core activity is leveraged across multiple biological processes. One of its most well-characterized roles is in the regulation of innate immunity. Research has shown that [USP50](/details-gene/373509) is a [positive regulation of nlrp3 inflammasome complex assembly](/details-cell/GO:1900227), which in turn promotes the production of pro-inflammatory cytokines such as [interleukin-1 beta](/details-cell/GO:0032731) and [interleukin-18](/details-cell/GO:0032741). This is achieved by targeting the ASC adaptor protein for deubiquitination, a key step in inflammasome activation ([Link](https://doi.org/10.1002/1873-3468.12558)). Additionally, [USP50](/details-gene/373509) plays a crucial role in cell division, specifically in the [regulation of cell cycle g2/m phase transition](/details-cell/GO:1902749). It has been identified as a regulator of HSP90-dependent stability of the Wee1 kinase, a critical inhibitor of the entry into mitosis ([Link](https://doi.org/10.4161/cc.9.18.13133)). This function is consistent with its localization to the [centrosome](/details-cell/GO:0005813) and [midbody](/details-cell/GO:0030496). Other annotated functions include involvement in [Ras protein signal transduction](/details-cell/GO:0007265) and [endosome organization](/details-cell/GO:0007032). ## Research Directions The specific expression of [USP50](/details-gene/373509) in [neural progenitor cell](/details-cell/CL0011020)s, combined with its known molecular functions in cell cycle control and inflammasome activation, opens up several avenues for future investigation. **Proposed Hypotheses:** 1. Given its role in regulating the G2/M checkpoint and its high significance in [neural progenitor cell](/details-cell/CL0011020)s, [USP50](/details-gene/373509) may be essential for maintaining the balance between self-renewal and differentiation in these cells by controlling the stability of key cell cycle regulators. 2. The pro-inflammatory function of [USP50](/details-gene/373509) via NLRP3 inflammasome activation may contribute to neuroinflammatory processes within the central nervous system, where dysregulation in progenitor or glial cells could exacerbate neurodegenerative or injury-induced pathologies. **Key Experimental Approach:** To test the first hypothesis regarding the role of [USP50](/details-gene/373509) in [neural progenitor cell](/details-cell/CL0011020) fate, a robust experimental approach would involve using a CRISPR-Cas9 system to create a knockout of [USP50](/details-gene/373509) in a human induced pluripotent stem cell (iPSC)-derived [neural progenitor cell](/details-cell/CL0011020) model. The impact on self-renewal versus differentiation could be quantified through neurosphere formation assays and immunofluorescence staining for progenitor (e.g., SOX2, PAX6) and mature neuronal (e.g., MAP2, Beta-III tubulin) markers. Cell cycle analysis via flow cytometry would determine if the knockout leads to cell cycle arrest or alterations. Furthermore, immunoprecipitation followed by mass spectrometry could identify the specific ubiquitinated substrates of [USP50](/details-gene/373509) in this cell type, confirming its mechanism of action. **Therapeutic Potential:** As an enzyme, [USP50](/details-gene/373509) is a potentially druggable target for small molecule inhibitors. Its established role as a positive regulator of the NLRP3 inflammasome makes it an attractive target for **inhibition** in the context of inflammatory diseases. Therapeutic blockade of [USP50](/details-gene/373509) could be beneficial in auto-inflammatory syndromes, metabolic disorders, or neuroinflammatory conditions where NLRP3 activity is pathogenic. However, given its significance in [neural progenitor cell](/details-cell/CL0011020)s and its role in the cell cycle, potential off-target effects on neurogenesis and tissue repair would need to be carefully evaluated during therapeutic development.

Genular Protein ID: 2283413515

Symbol: UBP50_HUMAN

Name: Ubiquitin carboxyl-terminal hydrolase 50

UniProtKB Accession Codes:

Q70EL3 E9PP86

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 3 Ensembl 1 ExpressionAtlas 1 GO 20 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 14715245

Title: Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases.

PubMed ID: 14715245

DOI: 10.1016/j.bbrc.2003.12.050

PubMed ID: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

PubMed ID: 15060002

Title: A genomic analysis of rat proteases and protease inhibitors.

PubMed ID: 15060002

DOI: 10.1101/gr.1946304

PubMed ID: 20930503

Title: A screen for deubiquitinating enzymes involved in the G(2)/M checkpoint identifies USP50 as a regulator of HSP90-dependent Wee1 stability.

PubMed ID: 20930503

DOI: 10.4161/cc.9.18.13133

PubMed ID: 28094437

Title: The deubiquitinating enzyme, ubiquitin-specific peptidase 50, regulates inflammasome activation by targeting the ASC adaptor protein.

PubMed ID: 28094437

DOI: 10.1002/1873-3468.12558

PubMed ID: 36876523

Title: Vitamin C promotes ACE2 degradation and protects against SARS-CoV-2 infection.

PubMed ID: 36876523

DOI: 10.15252/embr.202256374

Sequence Information:

  • Length: 339
  • Mass: 38955
  • Checksum: B41D707864CBB5AC
  • Sequence:
    • MTSQPSLPAD DFDIYHVLAE CTDYYDTLPV KEADGNQPHF QGVTGLWNLG NTCCVNAISQ 
CLCSILPLVE YFLTGKYITA LQKFLLPSDC SEVATAFAYL MTDMWLGDSD CVSPEIFWSA 
LGNLYPAFTK KMQQDAQEFL ICVLNELHEA LKKYHYSRRR SYEKGSTQRC CRKWITTETS 
IITQLFEEQL NYSIVCLKCE KCTYKNEVFT VFSLPIPSKY ECSLRDCLQC FFQQDALTWN 
NEIHCSFCET KQETAVRASI SKAPKIIIFH LKRFDIQGTT KRKLRTDIHY PLTNLDLTPY 
ICSIFRKYPK YNLCAVVNHF GDLDGGHYTA FCKNSVTQA