Details for: PRSS21

Gene ID: 10942

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: PRSS21

Ensembl ID: ENSG00000007038

Description: serine protease 21

Cell Significance Landscape

Associated with

Significant Cells

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

  • common myeloid progenitor CL0000049
    CSI 7.53
    rCSI 6.09%
    PRS 99.04
  • granulocyte monocyte progenitor cell CL0000557
    CSI 3.22
    rCSI 2.79%
    PRS 98.95
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.99
    rCSI 2.7%
    PRS 98.09
  • alternatively activated macrophage CL0000890
    CSI 2.79
    rCSI 3.5%
    PRS 99.62
  • epithelial cell CL0000066
    CSI 2.77
    rCSI 4.26%
    PRS 92.5
  • alveolar macrophage CL0000583
    CSI 2.4
    rCSI 3.96%
    PRS 98.48
  • fallopian tube secretory epithelial cell CL4030006
    CSI 2.33
    rCSI 2.25%
    PRS 97.6
  • promyelocyte CL0000836
    CSI 2.33
    rCSI 3.36%
    PRS 98.51
  • basophil mast progenitor cell CL0002028
    CSI 1.38
    rCSI 7.38%
    PRS 99.29
  • myeloid lineage restricted progenitor cell CL0000839
    CSI 1.06
    rCSI 5.46%
    PRS 99.53

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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  • 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 [PRSS21](/details-gene/10942), also known as Testisin, is a protein-coding gene located on chromosome 16p13.3 that encodes a serine-type endopeptidase. Functionally, it is involved in [proteolysis](/details-go/GO:0006508) and is annotated as a GPI-anchored, membrane-bound protein found in the [extracellular space](/details-go/GO:0005615). Expression data suggests a highly significant role for [PRSS21](/details-gene/10942) in the hematopoietic system, particularly as a defining marker for myeloid progenitor cells, including the [common myeloid progenitor](/details-cell/CL0000049) and the [granulocyte monocyte progenitor cell](/details-cell/CL0000557). It also maintains high significance in mature myeloid cells, such as [alternatively activated macrophages](/details-cell/CL0000890), and in specific non-hematopoietic cells like [fallopian tube secretory epithelial cells](/details-cell/CL4030006), indicating diverse physiological roles ranging from hematopoiesis to tissue-specific functions in reproduction and immunity. Early research identified its expression in testicular germ cells, suggesting a role in [spermatogenesis](/details-go/GO:0007283) ([Link](https://pubmed.ncbi.nlm.nih.gov/10397266)). ## Cellular Roles and Expression Landscape The expression profile of [PRSS21](/details-gene/10942) strongly implicates it as a key regulator within the myeloid lineage of the hematopoietic system. **Overall**, it exhibits its highest significance in early progenitor populations, including [common myeloid progenitor](/details-cell/CL0000049) (CSI: 7.53), [granulocyte monocyte progenitor cell](/details-cell/CL0000557) (CSI: 3.22), and [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 2.99). This pattern suggests that [PRSS21](/details-gene/10942) may be involved in the commitment and differentiation of these early myeloid precursors. The gene's significance extends to more differentiated myeloid cells, with notable expression in [alternatively activated macrophage](/details-cell/CL0000890) (CSI: 2.79) and [alveolar macrophage](/details-cell/CL0000583) (CSI: 2.40). This is consistent with its function as an extracellular protease, a class of enzymes crucial for tissue remodeling, phagocytosis, and immune modulation—key functions of macrophages. Beyond the hematopoietic system, [PRSS21](/details-gene/10942) shows a distinct role in specific epithelial tissues. It is a significant marker in [epithelial cells](/details-cell/CL0000066) generally and more specifically in [fallopian tube secretory epithelial cells](/details-cell/CL4030006) (CSI: 2.33). This, combined with its initial discovery in premeiotic testicular germ cells ([Link](https://pubmed.ncbi.nlm.nih.gov/10397266)), points towards a specialized function in the reproductive system, potentially related to tissue maintenance or gametogenesis. ## Pathways and Molecular Function [PRSS21](/details-gene/10942) functions primarily as a protease, with specific annotations for [serine-type endopeptidase activity](/details-go/GO:0004252) and involvement in the broad biological process of [proteolysis](/details-go/GO:0006508). As a secreted and membrane-anchored protein, its activity is directed towards the [extracellular region](/details-go/GO:0005576) and the [plasma membrane](/details-go/GO:0005886). This localization is critical for its function, allowing it to modify other cell-surface proteins or components of the extracellular matrix. Its involvement in the Reactome pathway for [post-translational modification: synthesis of gpi-anchored proteins](/details-reactome/R-HSA-163125) explains its association with the cell membrane. This GPI-anchor would tether the protease to the cell surface, focusing its proteolytic activity in the immediate pericellular environment. This mechanism is consistent with its proposed roles in modulating cell-cell interactions during myeloid differentiation or regulating the local microenvironment around macrophages and epithelial cells. ## Research Directions The specific expression patterns and enzymatic function of [PRSS21](/details-gene/10942) suggest several avenues for future research. The data points to specialized roles that could be pivotal in both normal physiology and disease. **Proposed Testable Hypotheses:** 1. **Hypothesis 1:** Given its high significance in multiple myeloid progenitor populations, [PRSS21](/details-gene/10942) is essential for the commitment or differentiation of hematopoietic stem cells into the myeloid lineage. Its proteolytic activity may be required to process cell surface receptors or signaling molecules that govern cell fate decisions. 2. **Hypothesis 2:** In [alternatively activated macrophages](/details-cell/CL0000890), [PRSS21](/details-gene/10942) activity contributes to M2 polarization or effector functions such as tissue repair and fibrosis. Its extracellular proteolytic activity could be responsible for remodeling the extracellular matrix or activating growth factors in the tissue microenvironment. 3. **Hypothesis 3:** Based on literature indicating its loss in testicular germ cell tumors ([Link](https://pubmed.ncbi.nlm.nih.gov/10397266)), [PRSS21](/details-gene/10942) may function as a tumor suppressor in reproductive tissues, including the fallopian tube epithelium where it is highly expressed. **Proposed Experimental Approach:** To test Hypothesis 1, one could utilize an in vitro model of human hematopoiesis. * CD34+ hematopoietic stem and progenitor cells (HSPCs) would be isolated from human cord blood. * Lentiviral vectors expressing shRNA or a CRISPR-Cas9 system targeting [PRSS21](/details-gene/10942) would be used to achieve stable knockdown or knockout. * These modified HSPCs, along with non-targeting controls, would be cultured in myeloid-promoting cytokine cocktails (e.g., SCF, FLT3L, IL-3, GM-CSF). * The differentiation outcome would be assessed over time using flow cytometry to quantify the emergence of progenitor populations (e.g., CMPs, GMPs) and mature myeloid cells (e.g., monocytes, granulocytes), and colony-forming unit (CFU) assays would be performed to quantify progenitor function. A significant reduction in myeloid output in the [PRSS21](/details-gene/10942)-deficient cells would validate the hypothesis. **Therapeutic Potential:** As an extracellular and membrane-anchored serine protease, [PRSS21](/details-gene/10942) is a potentially druggable target. If its activity is shown to promote pro-fibrotic or pro-inflammatory macrophage functions, developing specific small molecule inhibitors or therapeutic antibodies could be a viable strategy for diseases like idiopathic pulmonary fibrosis or certain cancers where M2-like macrophages are implicated. However, its potential role as a tumor suppressor in testicular cancer suggests that systemic inhibition would need to be approached with caution, and therapies would likely require tissue-specific targeting. Conversely, if its loss promotes tumorigenesis, strategies to restore its activity or a downstream signaling pathway could be explored in relevant cancers.

Genular Protein ID: 160979134

Symbol: TEST_HUMAN

Name: Testisin

UniProtKB Accession Codes:

Q9Y6M0 Q9NS34 Q9P2V6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 9 Ensembl 2 ExpressionAtlas 1 GO 10 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 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 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 Reactome 1 RefSeq 4 SIGNOR 1 SMART 1 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: 9826525

Title: Cloning and tissue distribution of a novel serine protease esp-1 from human eosinophils.

PubMed ID: 9826525

DOI: 10.1006/bbrc.1998.9645

PubMed ID: 10600542

Title: Structural analysis of esp-1 gene (PRSS 21).

PubMed ID: 10600542

DOI: 10.1006/bbrc.1999.1870

PubMed ID: 10397266

Title: Testisin, a new human serine proteinase expressed by premeiotic testicular germ cells and lost in testicular germ cell tumors.

PubMed ID: 10397266

PubMed ID: 11004480

Title: Localization, expression and genomic structure of the gene encoding the human serine protease testisin.

PubMed ID: 11004480

DOI: 10.1016/s0167-4781(00)00071-3

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

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

Sequence Information:

  • Length: 314
  • Mass: 34884
  • Checksum: E738CF73F6B56E98
  • Sequence:
    • MGARGALLLA LLLARAGLRK PESQEAAPLS GPCGRRVITS RIVGGEDAEL GRWPWQGSLR 
LWDSHVCGVS LLSHRWALTA AHCFETYSDL SDPSGWMVQF GQLTSMPSFW SLQAYYTRYF 
VSNIYLSPRY LGNSPYDIAL VKLSAPVTYT KHIQPICLQA STFEFENRTD CWVTGWGYIK 
EDEALPSPHT LQEVQVAIIN NSMCNHLFLK YSFRKDIFGD MVCAGNAQGG KDACFGDSGG 
PLACNKNGLW YQIGVVSWGV GCGRPNRPGV YTNISHHFEW IQKLMAQSGM SQPDPSWPLL 
FFPLLWALPL LGPV