Details for: ASPG

Gene ID: 374569

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: ASPG

Ensembl ID: ENSG00000166183

Description: asparaginase

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • colon epithelial cell CL0011108
    CSI 4.86
    rCSI 5.09%
    PRS 97.82
  • nasal mucosa goblet cell CL0002480
    CSI 3.81
    rCSI 4.42%
    PRS 97.7
  • hepatocyte CL0000182
    CSI 3.25
    rCSI 5.82%
    PRS 97.08
  • intestine goblet cell CL0019031
    CSI 3.15
    rCSI 2.79%
    PRS 97.69
  • centrilobular region hepatocyte CL0019029
    CSI 2.39
    rCSI 6.24%
    PRS 96.04
  • squamous epithelial cell CL0000076
    CSI 2.3
    rCSI 5.45%
    PRS 95.6
  • periportal region hepatocyte CL0019026
    CSI 2.28
    rCSI 8.88%
    PRS 96.34
  • cardiac muscle cell CL0000746
    CSI 2.21
    rCSI 3.18%
    PRS 95.1
  • corneal epithelial cell CL0000575
    CSI 1.92
    rCSI 5.5%
    PRS 98.25
  • regular atrial cardiac myocyte CL0002129
    CSI 1.6
    rCSI 5.16%
    PRS 96.41

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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  • 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 [ASPG](/details-gene/374569), or asparaginase, is a protein-coding gene located on chromosome 14q32.33 ([Link](https://doi.org/10.1038/nature01348)). It encodes a cytosolic enzyme with dual catalytic functions, exhibiting both [asparaginase activity](/details-go/GO:0004067) and [lysophospholipase activity](/details-go/GO:0004622). This suggests a role in integrating amino acid and lipid metabolism. **Overall**, expression data reveals that [ASPG](/details-gene/374569) is a significant marker for metabolically active and secretory cell types, with its highest significance observed in [colon epithelial cell](/details-cell/CL0011108)s, [nasal mucosa goblet cell](/details-cell/CL0002480)s, and [hepatocyte](/details-cell/CL0000182)s. Its function is primarily associated with the [aspartate family amino acid metabolic process](/details-go/GO:0009066) and [lipid catabolic process](/details-go/GO:0016042). ## Cellular Roles and Expression Landscape The expression profile of [ASPG](/details-gene/374569) points to a specialized role in tissues with high metabolic and secretory demands. Its highest significance index (**Overall** CSI: 4.86) is found in [colon epithelial cell](/details-cell/CL0011108)s, with similarly high significance in other secretory epithelial populations, including [nasal mucosa goblet cell](/details-cell/CL0002480)s and [intestine goblet cell](/details-cell/CL0019031)s. This strong association with mucus-producing cells suggests a potential role in maintaining the biochemical composition of mucosal barriers. Furthermore, [ASPG](/details-gene/374569) is highly significant in [hepatocyte](/details-cell/CL0000182)s and their subtypes ([centrilobular region hepatocyte](/details-cell/CL0019029), [periportal region hepatocyte](/details-cell/CL0019026)), which is consistent with the liver's central function in systemic amino acid and lipid metabolism. A notable expression is also observed in [cardiac muscle cell](/details-cell/CL0000746)s, where the metabolism of lipids is critical for energy production. The collective evidence indicates that [ASPG](/details-gene/374569) is a key functional component of epithelial, hepatic, and select muscle tissues. ## Pathways and Molecular Function Functionally, [ASPG](/details-gene/374569) is annotated as a dual-function enzyme operating in the [cytosol](/details-go/GO:0005829). Its [asparaginase activity](/details-go/GO:0004067) places it within the [Aspartate and asparagine metabolism](/details-reactome/R-HSA-8963693) pathway, where it catalyzes the hydrolysis of asparagine to aspartate and ammonia. This function is fundamental to controlling the cellular pool of these amino acids. Concurrently, its classification as a lysophospholipase, specifically demonstrating [1-alkyl-2-acetylglycerophosphocholine esterase activity](/details-go/GO:0003847), involves it in the [lipid catabolic process](/details-go/GO:0016042). This activity suggests a role in phospholipid remodeling, membrane turnover, or the regulation of lipid signaling molecules. The co-occurrence of these two distinct metabolic functions in a single protein suggests [ASPG](/details-gene/374569) may act as a node for cross-talk between amino acid and lipid metabolic networks, particularly in the highly active cell types where it is prominently expressed. This work is supported by foundational genomics research ([Link](https://doi.org/10.1101/gr.2596504)). ## Research Directions The dual enzymatic nature of [ASPG](/details-gene/374569) and its specific expression pattern present several intriguing avenues for future investigation. ### Proposed Hypotheses 1. In secretory epithelial cells of the gut and airway, such as [colon epithelial cell](/details-cell/CL0011108)s and [nasal mucosa goblet cell](/details-cell/CL0002480)s, [ASPG](/details-gene/374569) contributes to mucosal barrier integrity by modulating the lipid composition of secreted mucus via its lysophospholipase activity, while its asparaginase activity regulates local amino acid availability for pathogens or immune cells. 2. In [hepatocyte](/details-cell/CL0000182)s, [ASPG](/details-gene/374569) functions as a metabolic sensor that integrates cellular amino acid and lipid status. Its activity may be post-translationally regulated in response to nutritional cues, thereby helping to control the balance between lipid storage (e.g., in non-alcoholic fatty liver disease) and amino acid catabolism. ### Experimental Approach To test the first hypothesis regarding its role in mucosal barrier function, a compelling experiment would involve using 3D human colon organoids. [ASPG](/details-gene/374569) could be knocked down using shRNA or knocked out via CRISPR-Cas9. The impact on barrier function could be quantitatively assessed by measuring transepithelial electrical resistance (TEER) and permeability to fluorescently labeled dextran. Subsequently, multi-omic analyses, including lipidomics of the secreted mucus layer and metabolomics of the organoid lysate, would be performed to directly link the loss of [ASPG](/details-gene/374569)'s enzymatic activities to specific changes in lipid and asparagine profiles. ### Therapeutic Potential As an enzyme, [ASPG](/details-gene/374569) is a potentially druggable target. Given that bacterial asparaginases are effective chemotherapeutics for certain leukemias, exploring the role and inhibition of human [ASPG](/details-gene/374569) in cancers that may be dependent on asparagine or specific lipid pathways is a logical step. **Inhibition** would be the likely therapeutic strategy in such a context. However, the high expression of [ASPG](/details-gene/374569) in healthy epithelial tissues of the gut and liver suggests that systemic inhibition could lead to significant on-target toxicity. Therefore, any therapeutic development would likely require a targeted delivery system to selectively reach malignant cells while sparing healthy tissues.

Genular Protein ID: 2057100443

Symbol: LPP60_HUMAN

Name: 60 kDa lysophospholipase

UniProtKB Accession Codes:

Q86U10 B9EGQ2 Q8IV80

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 71 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EC 3 EMBL 7 Ensembl 1 ExpressionAtlas 1 GO 7 Gene3D 3 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 11 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIRSF 2 PRINTS 2 PRO 1 PROSITE 4 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 1 RefSeq 2 Rhea 32 SFLD 1 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

PubMed ID: 12508121

Title: The DNA sequence and analysis of human chromosome 14.

PubMed ID: 12508121

DOI: 10.1038/nature01348

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: 573
  • Mass: 60883
  • Checksum: 62DBC583FF9C3AD7
  • Sequence:
    • MARAVGPERR LLAVYTGGTI GMRSELGVLV PGTGLAAILR TLPMFHDEEH ARARGLSEDT 
LVLPPASRNQ RILYTVLECQ PLFDSSDMTI AEWVCLAQTI KRHYEQYHGF VVIHGTDTMA 
FAASMLSFML ENLQKTVILT GAQVPIHALW SDGRENLLGA LLMAGQYVIP EVCLFFQNQL 
FRGNRATKVD ARRFAAFCSP NLLPLATVGA DITINRELVR KVDGKAGLVV HSSMEQDVGL 
LRLYPGIPAA LVRAFLQPPL KGVVMETFGS GNGPTKPDLL QELRVATERG LVIVNCTHCL 
QGAVTTDYAA GMAMAGAGVI SGFDMTSEAA LAKLSYVLGQ PGLSLDVRKE LLTKDLRGEM 
TPPSVEERRP SLQGNTLGGG VSWLLSLSGS QEADALRNAL VPSLACAAAH AGDVEALQAL 
VELGSDLGLV DFNGQTPLHA AARGGHTEAV TMLLQRGVDV NTRDTDGFSP LLLAVRGRHP 
GVIGLLREAG ASLSTQELEE AGTELCRLAY RADLEGLQVW WQAGADLGQP GYDGHSALHV 
AEAAGNLAVV AFLQSLEGAV GAQAPCPEVL PGV