Details for: DPEP1

Gene ID: 1800

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: DPEP1

Ensembl ID: ENSG00000015413

Description: dipeptidase 1

Cell Significance Landscape

Associated with

Significant Cells

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

  • colonocyte CL1000347
    CSI 11.13
    rCSI 15.96%
    PRS 96.3
  • intestine goblet cell CL0019031
    CSI 8.31
    rCSI 7.38%
    PRS 96.12
  • cerebral cortex endothelial cell CL1001602
    CSI 5.44
    rCSI 9.41%
    PRS 95.27
  • myofibroblast cell CL0000186
    CSI 4.99
    rCSI 6.91%
    PRS 95.8
  • type L enteroendocrine cell CL0002279
    CSI 4.91
    rCSI 9.21%
    PRS 96.87
  • intestinal epithelial cell CL0002563
    CSI 4.37
    rCSI 4.57%
    PRS 96.13
  • pancreatic acinar cell CL0002064
    CSI 4.11
    rCSI 5.47%
    PRS 97.85
  • enteroendocrine cell CL0000164
    CSI 4.05
    rCSI 5.53%
    PRS 95.67
  • small intestine goblet cell CL1000495
    CSI 4.01
    rCSI 8.79%
    PRS 97.66
  • enterocyte CL0000584
    CSI 3.9
    rCSI 6.28%
    PRS 95.09
  • paneth cell of epithelium of small intestine CL1000343
    CSI 3.8
    rCSI 10.65%
    PRS 98
  • epithelial cell of proximal tubule CL0002306
    CSI 3.4
    rCSI 8.3%
    PRS 93.48
  • paneth cell CL0000510
    CSI 3.01
    rCSI 4.45%
    PRS 98.58
  • enteroendocrine cell of small intestine CL0009006
    CSI 2.91
    rCSI 6.41%
    PRS 97.29
  • goblet cell CL0000160
    CSI 2.9
    rCSI 2.74%
    PRS 96.14
  • IgG plasma cell CL0000985
    CSI 2.83
    rCSI 3.39%
    PRS 97.56
  • M cell of gut CL0000682
    CSI 2.76
    rCSI 2.93%
    PRS 97.58
  • BEST4+ enteroycte CL4030026
    CSI 2.73
    rCSI 3.39%
    PRS 96.68
  • colon epithelial cell CL0011108
    CSI 2.63
    rCSI 2.76%
    PRS 96.34
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 2.55
    rCSI 6.86%
    PRS 97.85
  • kidney epithelial cell CL0002518
    CSI 2.18
    rCSI 4.16%
    PRS 99.38
  • transit amplifying cell of small intestine CL0009012
    CSI 2.18
    rCSI 9.57%
    PRS 98.1
  • brush cell CL0002204
    CSI 2.1
    rCSI 4.15%
    PRS 97.28
  • transit amplifying cell CL0009010
    CSI 2.04
    rCSI 3.12%
    PRS 98.15
  • enterocyte of epithelium of small intestine CL1000334
    CSI 1.97
    rCSI 30.44%
    PRS 97.33
  • type EC enteroendocrine cell CL0000577
    CSI 1.11
    rCSI 3.94%
    PRS 96.87
  • P/D1 enteroendocrine cell CL0002268
    CSI 0.71
    rCSI 3.86%
    PRS 96.86
  • pancreatic stellate cell CL0002410
    CSI 0.59
    rCSI 3.46%
    PRS 97.49

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.

Comma-separated if multiple.
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)

Loading network (please wait)...

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 Dipeptidase 1 ([DPEP1](/details-gene/1800)) is a zinc-dependent metalloproteinase that is tethered to the cell surface via a glycosylphosphatidylinositol (GPI) anchor ([Link](https://doi.org/10.1042/bj2650429)). As a dipeptidase, its primary enzymatic function involves the hydrolysis of dipeptides, playing a key role in the final stages of protein digestion and in specific metabolic pathways, such as the breakdown of glutathione and the pro-inflammatory mediator leukotriene D4. Expression data from the **Overall** context show that [DPEP1](/details-gene/1800) is a highly significant marker for epithelial cells, particularly those in the gastrointestinal tract, such as [colonocytes](/details-cell/CL1000347) and [intestine goblet cells](/details-cell/CL0019031), as well as [epithelial cells of the proximal tubule](/details-cell/CL0002306) in the kidney. More recent evidence has expanded its functional repertoire, identifying it as a crucial adhesion receptor for neutrophil recruitment during inflammation ([Link](https://doi.org/10.1016/j.cell.2019.07.017)), positioning it at the intersection of metabolism and innate immunity. Its clinical relevance is noted in OMIM ([179780](https://omim.org/entry/179780)) and in the context of colorectal cancer ([Link](https://doi.org/10.3892/br.2017.870)). ## Cellular Roles and Expression Landscape The expression profile of [DPEP1](/details-gene/1800) highlights its specialized role in tissues with high metabolic and absorptive activity. **Overall**, it is most significantly expressed in the epithelial linings of the gut and kidneys. The highest significance is observed in [colonocytes](/details-cell/CL1000347) (CSI: 11.13), followed by various secretory and absorptive intestinal cells including [intestine goblet cells](/details-cell/CL0019031), [type L enteroendocrine cells](/details-cell/CL0002279), and [enterocytes](/details-cell/CL0000584). This pattern is consistent with its localization to the [apical plasma membrane](/https://www.ebi.ac.uk/QuickGO/term/GO:0016324) and [microvillus membrane](/https://www.ebi.ac.uk/QuickGO/term/GO:0031528), where it can act on luminal substrates. Beyond this well-established role in epithelial tissues, functional studies have revealed a critical, non-enzymatic function in the immune system. [DPEP1](/details-gene/1800) acts as an adhesion receptor on endothelial cells, mediating the recruitment of neutrophils to sites of inflammation in the lungs and liver ([Link](https://doi.org/10.1016/j.cell.2019.07.017)). This dual functionality suggests that [DPEP1](/details-gene/1800) serves not only as a metabolic gatekeeper at epithelial barriers but also as a regulator of immune cell trafficking in response to inflammatory cues. ## Pathways and Molecular Function The molecular functions of [DPEP1](/details-gene/1800) are centered on its [metallodipeptidase activity](/https://www.ebi.ac.uk/QuickGO/term/GO:0070573). It plays a significant role in the [glutathione metabolic process](/https://www.ebi.ac.uk/QuickGO/term/GO:0006749) by catabolizing the final dipeptide product. Critically, [DPEP1](/details-gene/1800) is involved in regulating the [inflammatory response](/https://www.ebi.ac.uk/QuickGO/term/GO:0006954) through its ability to process lipid mediators. It is responsible for the [leukotriene d4 catabolic process](/https://www.ebi.ac.uk/QuickGO/term/GO:1901749), converting the potent pro-inflammatory molecule LTD4 into the less active LTE4, which is a key step in the [synthesis of leukotrienes (lt) and eoxins (ex)](https://reactome.org/content/detail/R-HSA-2142691) pathway. This function directly links its enzymatic activity to the modulation of inflammation. Furthermore, [DPEP1](/details-gene/1800) exhibits [beta-lactamase activity](/https://www.ebi.ac.uk/QuickGO/term/GO:0008800), enabling it to hydrolyze beta-lactam antibiotics, a function first characterized in the kidney ([Link](https://doi.org/10.1016/s0021-9258(17)42642-1)). Its involvement is also noted in pathways related to parasitic diseases, such as [Leishmania infection](https://reactome.org/content/detail/R-HSA-9658195), suggesting a role in the host response to certain pathogens. Its function as an adhesion receptor further solidifies its connection to the [neutrophil chemotaxis](/https://www.ebi.ac.uk/QuickGO/term/GO:0030593) process, providing a physical mechanism for guiding immune cells. ## Research Directions The discovery of [DPEP1](/details-gene/1800)'s dual role as both a metabolic enzyme and an immune adhesion receptor opens several avenues for future investigation. Its high expression in epithelial tissues prone to inflammation and cancer, such as the colon, makes it a gene of significant interest. Based on the available data, the following hypotheses can be proposed: 1. The enzymatic and adhesive functions of [DPEP1](/details-gene/1800) are mechanistically coupled. Its role as a neutrophil adhesion receptor may depend on its dipeptidase activity to cleave a specific substrate on the endothelial or neutrophil surface, thereby creating a binding site and facilitating immune cell recruitment. 2. In colorectal cancer, dysregulation of [DPEP1](/details-gene/1800) expression ([Link](https://doi.org/10.3892/br.2017.870)) alters the tumor microenvironment by modulating leukotriene gradients and controlling the extent of neutrophil infiltration, thereby influencing tumor-associated inflammation and disease progression. A key experiment to test the first hypothesis would be to investigate the interplay between the catalytic and adhesive functions of [DPEP1](/details-gene/1800). This could be achieved by generating a catalytically inactive mutant of [DPEP1](/details-gene/1800) through site-directed mutagenesis of a critical active site residue, such as Glu-125 ([Link](https://doi.org/10.1016/0167-4838(93)90276-w)). Wild-type and catalytically dead versions of [DPEP1](/details-gene/1800) would then be expressed in an endothelial cell line. The ability of these cells to support neutrophil adhesion under physiological flow conditions would be quantified. A significant reduction in neutrophil binding to cells expressing the mutant protein would confirm that the enzymatic activity of [DPEP1](/details-gene/1800) is essential for its adhesive function. Given its cell-surface localization and role in mediating inflammation, [DPEP1](/details-gene/1800) presents a viable therapeutic target. **Inhibition** of [DPEP1](/details-gene/1800) could be a strategy to mitigate tissue damage caused by excessive neutrophil recruitment in acute inflammatory conditions like ARDS or sepsis. Its accessibility on the plasma membrane makes it a suitable target for both small molecule inhibitors and therapeutic antibodies designed to block its adhesive or enzymatic functions.

Genular Protein ID: 2344796580

Symbol: DPEP1_HUMAN

Name: Dipeptidase 1

UniProtKB Accession Codes:

P16444 D3DX80 Q96AK2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 25 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 6 DrugCentral 1 EC 2 EMBL 9 Ensembl 4 EvolutionaryTrace 1 ExpressionAtlas 1 GO 32 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PIR 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 3 RefSeq 5 Rhea 5 SABIO-RK 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8439558

Title: Cloning and structural analysis of genomic DNA for human renal dipeptidase.

PubMed ID: 8439558

DOI: 10.1016/0167-4781(93)90289-p

PubMed ID: 2303490

Title: Primary structure of human microsomal dipeptidase deduced from molecular cloning.

PubMed ID: 2303490

DOI: 10.1016/s0021-9258(19)39692-9

PubMed ID: 7764673

Title: Gene structural analysis and expression of human renal dipeptidase.

PubMed ID: 7764673

DOI: 10.1021/bp00026a002

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: 2137335

Title: Characterization of the glycosyl-phosphatidylinositol-anchored human renal dipeptidase reveals that it is more extensively glycosylated than the pig enzyme.

PubMed ID: 2137335

DOI: 10.1042/bj2650429

PubMed ID: 2768222

Title: Purification and characterization of human microsomal dipeptidase.

PubMed ID: 2768222

DOI: 10.1093/oxfordjournals.jbchem.a122787

PubMed ID: 15340161

Title: Signal peptide prediction based on analysis of experimentally verified cleavage sites.

PubMed ID: 15340161

DOI: 10.1110/ps.04682504

PubMed ID: 6334084

Title: Beta-lactamase activity of purified and partially characterized human renal dipeptidase.

PubMed ID: 6334084

DOI: 10.1016/s0021-9258(17)42642-1

PubMed ID: 2168407

Title: Identification of membrane anchoring site of human renal dipeptidase and construction and expression of a cDNA for its secretory form.

PubMed ID: 2168407

DOI: 10.1016/s0021-9258(18)77261-x

PubMed ID: 8097406

Title: Importance of Glu-125 in the catalytic activity of human renal dipeptidase.

PubMed ID: 8097406

DOI: 10.1016/0167-4838(93)90276-w

PubMed ID: 19159218

Title: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.

PubMed ID: 19159218

DOI: 10.1021/pr8008012

PubMed ID: 12144777

Title: Crystal structure of human renal dipeptidase involved in beta-lactam hydrolysis.

PubMed ID: 12144777

DOI: 10.1016/s0022-2836(02)00632-0

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

PubMed ID: 28413640

Title: Clinicopathological examination of dipeptidase 1 expression in colorectal cancer.

PubMed ID: 28413640

DOI: 10.3892/br.2017.870

PubMed ID: 31442408

Title: Dipeptidase-1 is an adhesion receptor for neutrophil recruitment in lungs and liver.

PubMed ID: 31442408

DOI: 10.1016/j.cell.2019.07.017

PubMed ID: 32325220

Title: Structure of human DPEP3 in complex with the SC-003 antibody Fab fragment reveals basis for lack of dipeptidase activity.

PubMed ID: 32325220

DOI: 10.1016/j.jsb.2020.107512

Sequence Information:

  • Length: 411
  • Mass: 45674
  • Checksum: C8C6474C3479D20D
  • Sequence:
    • MWSGWWLWPL VAVCTADFFR DEAERIMRDS PVIDGHNDLP WQLLDMFNNR LQDERANLTT 
LAGTHTNIPK LRAGFVGGQF WSVYTPCDTQ NKDAVRRTLE QMDVVHRMCR MYPETFLYVT 
SSAGIRQAFR EGKVASLIGV EGGHSIDSSL GVLRALYQLG MRYLTLTHSC NTPWADNWLV 
DTGDSEPQSQ GLSPFGQRVV KELNRLGVLI DLAHVSVATM KATLQLSRAP VIFSHSSAYS 
VCASRRNVPD DVLRLVKQTD SLVMVNFYNN YISCTNKANL SQVADHLDHI KEVAGARAVG 
FGGDFDGVPR VPEGLEDVSK YPDLIAELLR RNWTEAEVKG ALADNLLRVF EAVEQASNLT 
QAPEEEPIPL DQLGGSCRTH YGYSSGASSL HRHWGLLLAS LAPLVLCLSL L