Details for: PRSS50

Gene ID: 29122

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: PRSS50

Ensembl ID: ENSG00000283706

Description: serine protease 50

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 6.23
    rCSI 7.55%
    PRS 99.23
  • melanocyte of skin CL1000458
    CSI 2.33
    rCSI 3.18%
    PRS 99.25

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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  • 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 [PRSS50](/details-gene/29122), also known as serine protease 50, is a protein-coding gene located on chromosome 3p21.31. Functionally, it is characterized as a serine- or threonine-type endopeptidase involved in proteolysis ([GO:0006508](https://www.ebi.ac.uk/QuickGO/term/GO:0006508)). **Overall**, expression data reveals a highly specific role for this gene, showing its most significant expression in immune cells, particularly [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203), with secondary significance observed in [melanocyte of skin](/details-cell/CL1000458). Originally isolated from a hypomethylated DNA fragment in human breast cancer, its function is implicated in both normal physiological processes and oncogenesis ([Link](https://pubmed.ncbi.nlm.nih.gov/10397268/)). ## Cellular Roles and Expression Landscape The expression profile of [PRSS50](/details-gene/29122) points to a specialized function within the adaptive immune system and pigment-producing cells. The gene's highest significance score (**Overall** CSI: 6.23) is found in [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203), suggesting it may be a key functional component in maintaining or executing the functions of this long-lived T cell subset. Its notable expression in [melanocyte of skin](/details-cell/CL1000458) further suggests a distinct role in this lineage. While originally described as a testis-specific protease ([Link](https://doi.org/10.1158/0008-5472.can-06-3688)), the available broad expression data highlights its primary significance in these non-gonadal cell types, indicating a complex, tissue-dependent regulatory landscape. The combination of high expression in memory T cells and its link to cancer biology suggests it may operate at the interface of immunosurveillance and tumor progression. ## Pathways and Molecular Function [PRSS50](/details-gene/29122) encodes a protease with catalytic activity classified as both serine-type endopeptidase activity ([GO:0004252](https://www.ebi.ac.uk/QuickGO/term/GO:0004252)) and threonine-type endopeptidase activity ([GO:0004298](https://www.ebi.ac.uk/QuickGO/term/GO:0004298)). This enzymatic function is central to its role in proteolysis ([GO:0006508](https://www.ebi.ac.uk/QuickGO/term/GO:0006508)), the targeted breakdown of proteins. Subcellular localization data places the protein within the cytoplasm ([GO:0005737](https://www.ebi.ac.uk/QuickGO/term/GO:0005737)) and the endoplasmic reticulum ([GO:0005783](https://www.ebi.ac.uk/QuickGO/term/GO:0005783)), suggesting its substrates may include cytosolic proteins or proteins being processed through the secretory pathway. In the context of [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203), this proteolytic activity could be involved in protein turnover critical for long-term cell survival, or in the rapid activation of signaling cascades upon antigen re-exposure. ## Research Directions The specific expression of [PRSS50](/details-gene/29122) in memory T cells, combined with its documented negative regulation by the tumor suppressor p53 ([Link](https://doi.org/10.1158/0008-5472.can-06-3688)), positions it as a gene of significant interest in both immunology and oncology. Its proteolytic function suggests it could be a key downstream effector in pathways controlling cell fate. Based on the available data, several testable hypotheses can be proposed: 1. The protease activity of [PRSS50](/details-gene/29122) is essential for the long-term survival and homeostatic maintenance of [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) by degrading specific pro-apoptotic factors or cell cycle inhibitors. 2. In p53-deficient cancers, aberrant overexpression of [PRSS50](/details-gene/29122) promotes cell proliferation and survival by cleaving and inactivating protein substrates that would normally restrain malignant growth. To directly test the first hypothesis, a key experiment could be designed. **To test the role of [PRSS50](/details-gene/29122) in memory T cell function, one could use CRISPR-Cas9 to knock out the gene in primary human [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203). The functional impact could be assessed by comparing the long-term viability, proliferation, and effector cytokine production (e.g., IFN-gamma, TNF-alpha) of knockout versus control cells following T-cell receptor (TCR) restimulation. Mass spectrometry-based proteomics could then be employed to identify the direct cleavage substrates of PRSS50 in this cellular context.** Given its enzymatic nature and association with cancer, [PRSS50](/details-gene/29122) presents a plausible therapeutic target. As a protease, it is potentially amenable to inhibition by small molecule drugs. The strategy would likely focus on **inhibition** to counteract its pro-tumorigenic effects in p53-mutant cancers. However, its high expression in memory T cells raises a critical concern for on-target toxicity, as inhibiting PRSS50 could impair long-term immune memory. Therefore, any therapeutic development would require careful consideration of the therapeutic window and potential immunological side effects.

Genular Protein ID: 3994439182

Symbol: TSP50_HUMAN

Name: Probable threonine protease PRSS50

UniProtKB Accession Codes:

Q9UI38

Database IDs:

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

Citations:

PubMed ID: 10397268

Title: Isolation of a novel gene, TSP50, by a hypomethylated DNA fragment in human breast cancer.

PubMed ID: 10397268

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: 17283160

Title: TSP50 encodes a testis-specific protease and is negatively regulated by p53.

PubMed ID: 17283160

DOI: 10.1158/0008-5472.can-06-3688

Sequence Information:

  • Length: 385
  • Mass: 43088
  • Checksum: F5B39D6E12798AE5
  • Sequence:
    • MGRWCQTVAR GQRPRTSAPS RAGALLLLLL LLRSAGCWGA GEAPGALSTA DPADQSVQCV 
PKATCPSSRP RLLWQTPTTQ TLPSTTMETQ FPVSEGKVDP YRSCGFSYEQ DPTLRDPEAV 
ARRWPWMVSV RANGTHICAG TIIASQWVLT VAHCLIWRDV IYSVRVGSPW IDQMTQTASD 
VPVLQVIMHS RYRAQRFWSW VGQANDIGLL KLKQELKYSN YVRPICLPGT DYVLKDHSRC 
TVTGWGLSKA DGMWPQFRTI QEKEVIILNN KECDNFYHNF TKIPTLVQII KSQMMCAEDT 
HREKFCYELT GEPLVCSMEG TWYLVGLVSW GAGCQKSEAP PIYLQVSSYQ HWIWDCLNGQ 
ALALPAPSRT LLLALPLPLS LLAAL