Details for: PRSS57

Gene ID: 400668

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: PRSS57

Ensembl ID: ENSG00000185198

Description: serine protease 57

Cell Significance Landscape

Associated with

Significant Cells

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

  • hematopoietic stem cell CL0000037
    CSI 56.97
    rCSI 37.87%
    PRS 99.86
  • common myeloid progenitor CL0000049
    CSI 55.93
    rCSI 45.22%
    PRS 99.9
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 47.52
    rCSI 42.91%
    PRS 99.83
  • granulocyte monocyte progenitor cell CL0000557
    CSI 37.77
    rCSI 32.7%
    PRS 99.87
  • promyelocyte CL0000836
    CSI 32.37
    rCSI 46.69%
    PRS 99.75
  • early lymphoid progenitor CL0000936
    CSI 27.85
    rCSI 24.46%
    PRS 99.91
  • pro-B cell CL0000826
    CSI 27.74
    rCSI 22.97%
    PRS 99.87
  • hematopoietic precursor cell CL0008001
    CSI 22.53
    rCSI 23.18%
    PRS 99.91
  • mast cell CL0000097
    CSI 19.43
    rCSI 41.96%
    PRS 97.42
  • granulocyte CL0000094
    CSI 18.8
    rCSI 28.73%
    PRS 99.77
  • common lymphoid progenitor CL0000051
    CSI 18.71
    rCSI 25.01%
    PRS 99.94
  • common dendritic progenitor CL0001029
    CSI 18.44
    rCSI 23.14%
    PRS 99.98
  • precursor B cell CL0000817
    CSI 16.42
    rCSI 14.38%
    PRS 99.96
  • fraction A pre-pro B cell CL0002045
    CSI 13.24
    rCSI 15.16%
    PRS 99.9
  • myeloid lineage restricted progenitor cell CL0000839
    CSI 10.65
    rCSI 54.97%
    PRS 99.83
  • hematopoietic multipotent progenitor cell CL0000837
    CSI 10.58
    rCSI 25.46%
    PRS 99.94
  • activated type II NK T cell CL0000931
    CSI 8.37
    rCSI 9.42%
    PRS 99.97
  • neutrophil CL0000775
    CSI 8.18
    rCSI 45.77%
    PRS 98.09
  • eosinophil CL0000771
    CSI 7.58
    rCSI 49.76%
    PRS 99.86
  • erythroblast CL0000765
    CSI 7.48
    rCSI 19.84%
    PRS 99.74
  • megakaryocyte CL0000556
    CSI 7.33
    rCSI 31.81%
    PRS 99.35
  • erythrocyte CL0000232
    CSI 5.78
    rCSI 13.12%
    PRS 99.57
  • promonocyte CL0000559
    CSI 5.57
    rCSI 9.54%
    PRS 99.87
  • erythroid progenitor cell CL0000038
    CSI 4.29
    rCSI 24.6%
    PRS 99.84
  • basophil mast progenitor cell CL0002028
    CSI 3.12
    rCSI 16.63%
    PRS 99.82
  • lymphoid lineage restricted progenitor cell CL0000838
    CSI 2.06
    rCSI 8.01%
    PRS 99.97
  • pre-conventional dendritic cell CL0002010
    CSI 1.22
    rCSI 16.15%
    PRS 99.94

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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Comma-separated if multiple.
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 [PRSS57](/details-gene/400668), or Serine Protease 57, is a protein-coding gene located on chromosome 19p13.3. It encodes a serine-type endopeptidase primarily involved in [proteolysis](/details-go/GO:0006508) and [protein maturation](/details-go/GO:0051604). Expression data highlight its profound significance in the hematopoietic system, with its highest relevance observed in early progenitor populations, including [hematopoietic stem cell](/details-cell/CL0000037) and [common myeloid progenitor](/details-cell/CL0000049). Its function is further specified by its localization within the [azurophil granule lumen](/details-go/GO:0035578) of neutrophils, suggesting a dual role in both hematopoietic development and the effector functions of mature innate immune cells ([Link](https://doi.org/10.4049/jimmunol.1301293)). ## Cellular Roles and Expression Landscape The expression profile of [PRSS57](/details-gene/400668) firmly establishes it as a key enzyme within the hematopoietic compartment. **Overall**, its significance is most pronounced in the earliest stages of blood cell development. It is a top marker for [hematopoietic stem cell](/details-cell/CL0000037) (CSI: 56.97), as well as key lineage-committed progenitors such as the [common myeloid progenitor](/details-cell/CL0000049) (CSI: 55.93), [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 47.52), and [granulocyte monocyte progenitor cell](/details-cell/CL0000557) (CSI: 37.77). This suggests a fundamental role in regulating the differentiation and maturation of multiple hematopoietic lineages. While its significance is highest in primitive cells, [PRSS57](/details-gene/400668) also maintains relevance in more mature myeloid cells, including [promyelocyte](/details-cell/CL0000836) and [granulocyte](/details-cell/CL0000094). This expression pattern is consistent with research identifying it as Neutrophil Serine Protease 4 (NSP4), an enzyme stored within the azurophilic granules of neutrophils ([Link](https://doi.org/10.1073/pnas.1200470109), [Link](https://doi.org/10.4049/jimmunol.1301293)). The gene is also significantly expressed, albeit to a lesser degree, in early lymphoid progenitors, such as [early lymphoid progenitor](/details-cell/CL0000936) (CSI: 27.85) and [pro-B cell](/details-cell/CL0000826) (CSI: 27.74), indicating a broad but central role in hematopoiesis. ## Pathways and Molecular Function The functional annotations for [PRSS57](/details-gene/400668) align with its identity as a protease active in hematopoietic cells. Its molecular functions are characterized by [serine-type endopeptidase activity](/details-go/GO:0004252) and [heparin binding](/details-go/GO:0008201). These functions contribute to the broader biological processes of [proteolysis](/details-go/GO:0006508) and [protein maturation](/details-go/GO:0051604). The cellular component annotations are particularly revealing. [PRSS57](/details-gene/400668) is localized to the [azurophil granule lumen](/details-go/GO:0035578), a specialized lysosome-related organelle in neutrophils. Upon activation, neutrophils can release the contents of these granules, which is consistent with the gene product also being found in the [extracellular space](/details-go/GO:0005615). This dual localization suggests that [PRSS57](/details-gene/400668) may act on intracellular substrates during cell development (e.g., in [promyelocyte](/details-cell/CL0000836)) and on extracellular targets following its release from mature [granulocyte](/details-cell/CL0000094) at sites of inflammation or infection. ## Research Directions The specific expression pattern of [PRSS57](/details-gene/400668) in hematopoietic stem/progenitor cells and its function as a protease present unique research opportunities. ### Proposed Hypotheses: 1. **Hypothesis:** Given its high significance in [hematopoietic stem cell](/details-cell/CL0000037) and myeloid progenitors, [PRSS57](/details-gene/400668) may be a critical regulator of lineage commitment. It could proteolytically process key transcription factors or cell surface receptors (e.g., Notch, G-CSF receptor) that determine whether a progenitor cell commits to the myeloid versus lymphoid lineage. 2. **Hypothesis:** As an extracellular protease released by activated neutrophils, [PRSS57](/details-gene/400668) may function as a host-defense factor by directly degrading virulence factors from pathogens or by cleaving and activating other host proteins, such as chemokines or antimicrobial peptides, to amplify the local immune response. ### Experimental Approach: To test the first hypothesis regarding its role in lineage commitment, one could perform a CRISPR-Cas9-mediated knockout of [PRSS57](/details-gene/400668) in primary human CD34+ hematopoietic stem and progenitor cells. These modified cells would then be cultured *in vitro* under conditions that promote differentiation towards both myeloid (e.g., with G-CSF, M-CSF, IL-3) and lymphoid (e.g., with IL-7, Flt3L) fates. The resulting cell populations could be analyzed by multi-color flow cytometry and single-cell RNA sequencing to determine if the loss of [PRSS57](/details-gene/400668) skews differentiation, for instance, by impairing granulocyte development while leaving B-cell development intact. ### Therapeutic Potential: The high specificity of [PRSS57](/details-gene/400668) for hematopoietic progenitors and mature neutrophils suggests it could be a valuable therapeutic target. In hematological malignancies arising from myeloid progenitors, such as acute myeloid leukemia (AML), inhibition of [PRSS57](/details-gene/400668) with a specific small molecule inhibitor could potentially disrupt the survival or proliferation of the leukemic blasts. Conversely, in conditions characterized by excessive neutrophil-mediated tissue damage, such as acute respiratory distress syndrome (ARDS) or certain autoimmune diseases, targeting the extracellular activity of [PRSS57](/details-gene/400668) could be a strategy to mitigate inflammation. Therefore, inhibition of its proteolytic activity represents the most likely therapeutic approach.

Genular Protein ID: 3095655767

Symbol: PRS57_HUMAN

Name: Serine protease 57

UniProtKB Accession Codes:

Q6UWY2 B2RNW8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 6 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 5 KEGG 1 MEROPS 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 4 PDBsum 4 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SABIO-RK 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

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: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

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: 22474388

Title: NSP4, an elastase-related protease in human neutrophils with arginine specificity.

PubMed ID: 22474388

DOI: 10.1073/pnas.1200470109

PubMed ID: 23904161

Title: NSP4 is stored in azurophil granules and released by activated neutrophils as active endoprotease with restricted specificity.

PubMed ID: 23904161

DOI: 10.4049/jimmunol.1301293

PubMed ID: 25156428

Title: Structures of neutrophil serine protease 4 reveal an unusual mechanism of substrate recognition by a trypsin-fold protease.

PubMed ID: 25156428

DOI: 10.1016/j.str.2014.07.008

Sequence Information:

  • Length: 283
  • Mass: 30334
  • Checksum: 62A09B03C20CBDDA
  • Sequence:
    • MGLGLRGWGR PLLTVATALM LPVKPPAGSW GAQIIGGHEV TPHSRPYMAS VRFGGQHHCG 
GFLLRARWVV SAAHCFSHRD LRTGLVVLGA HVLSTAEPTQ QVFGIDALTT HPDYHPMTHA 
NDICLLRLNG SAVLGPAVGL LRPPGRRARP PTAGTRCRVA GWGFVSDFEE LPPGLMEAKV 
RVLDPDVCNS SWKGHLTLTM LCTRSGDSHR RGFCSADSGG PLVCRNRAHG LVSFSGLWCG 
DPKTPDVYTQ VSAFVAWIWD VVRRSSPQPG PLPGTTRPPG EAA

Genular Protein ID: 1769060201

Symbol: B7ZMF6_HUMAN

Name: N/A

UniProtKB Accession Codes:

B7ZMF6

Database IDs:

ARBA 1 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 2 Gene3D 1 InterPro 5 MEROPS 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 3 PeptideAtlas 1 Pfam 1 RefSeq 1 SAM 1 SMART 1 SUPFAM 1

Citations:

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: 282
  • Mass: 30323
  • Checksum: 91DC0BC9D09BDAA9
  • Sequence:
    • MGLGLRGWGR PLLTVATALM LPVKPPGSWG AQIIGGHEVT PHSRPYMASV RFGGQHHCGG 
FLLRARWVVS AAHCFSHRDL RTGLVVLGAH VLSTAEPTQQ VFGIDALTTH PDYHPMTHAN 
DICLLRLNGS AVLGPAVGLL RLPGRRARPP TAGTRCRVAG WGFVSDFEEL PPGLMEAKVR 
VLDPDVFNSS WKGHLTLTML CTRSGDSHRR GFCSADSGGP LVCRNRAHGL VSFSGLWCGD 
PKTPDVYTQV SAFVAWIWDV VRRSSPQPGP LPGTTRPPGE AA