Details for: MPEG1

Gene ID: 219972

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: MPEG1

Ensembl ID: ENSG00000197629

Description: macrophage expressed 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • plasmacytoid dendritic cell, human CL0001058
    CSI 71.26
    rCSI 49.75%
    PRS 88.15
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 69.26
    rCSI 53.36%
    PRS 88.04
  • myeloid leukocyte CL0000766
    CSI 28.46
    rCSI 26.26%
    PRS 86.09
  • immature B cell CL0000816
    CSI 25.88
    rCSI 19.22%
    PRS 93.01
  • plasmacytoid dendritic cell CL0000784
    CSI 24.44
    rCSI 24.75%
    PRS 93.56
  • intermediate monocyte CL0002393
    CSI 17.23
    rCSI 26%
    PRS 89.55
  • mononuclear phagocyte CL0000113
    CSI 17.16
    rCSI 37.78%
    PRS 87.81
  • conventional dendritic cell CL0000990
    CSI 15.38
    rCSI 12.84%
    PRS 82.15
  • colon macrophage CL0009038
    CSI 14.72
    rCSI 67.99%
    PRS 94.07
  • Hofbauer cell CL3000001
    CSI 14.1
    rCSI 26.62%
    PRS 91.14
  • dendritic cell CL0000451
    CSI 13.7
    rCSI 16.88%
    PRS 86.25
  • precursor B cell CL0000817
    CSI 12.89
    rCSI 11.29%
    PRS 90.41
  • CD14-positive monocyte CL0001054
    CSI 12.4
    rCSI 15.44%
    PRS 92.1
  • non-classical monocyte CL0000875
    CSI 11.86
    rCSI 19.02%
    PRS 92.02
  • promonocyte CL0000559
    CSI 11.31
    rCSI 19.38%
    PRS 89.1
  • Langerhans cell CL0000453
    CSI 10.31
    rCSI 15.75%
    PRS 93.35
  • alternatively activated macrophage CL0000890
    CSI 10.08
    rCSI 12.67%
    PRS 92.17
  • elicited macrophage CL0000861
    CSI 9.2
    rCSI 8.45%
    PRS 91.11
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 9.02
    rCSI 11.82%
    PRS 93.12
  • lung interstitial macrophage CL4033043
    CSI 8.92
    rCSI 20.03%
    PRS 93.78
  • Kupffer cell CL0000091
    CSI 8.88
    rCSI 20.31%
    PRS 85.7
  • CD14-positive, CD16-negative classical monocyte CL0002057
    CSI 8.43
    rCSI 51%
    PRS 93.03
  • monocyte CL0000576
    CSI 8.3
    rCSI 15%
    PRS 87.87
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 7.43
    rCSI 19.36%
    PRS 85.82
  • class switched memory B cell CL0000972
    CSI 6.08
    rCSI 4.54%
    PRS 93.97
  • dendritic cell, human CL0001056
    CSI 5.3
    rCSI 8.14%
    PRS 91.7
  • inflammatory macrophage CL0000863
    CSI 5.03
    rCSI 8.59%
    PRS 95.64
  • early lymphoid progenitor CL0000936
    CSI 4.24
    rCSI 3.72%
    PRS 89
  • lung macrophage CL1001603
    CSI 4.23
    rCSI 9.44%
    PRS 90.81
  • myeloid dendritic cell CL0000782
    CSI 3.37
    rCSI 4.88%
    PRS 94.7
  • mature B cell CL0000785
    CSI 3.36
    rCSI 2.92%
    PRS 92.35
  • common dendritic progenitor CL0001029
    CSI 2.8
    rCSI 3.52%
    PRS 91.57
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 2.55
    rCSI 3.09%
    PRS 91.2
  • transitional stage B cell CL0000818
    CSI 2.1
    rCSI 6.86%
    PRS 95.72
  • professional antigen presenting cell CL0000145
    CSI 1.82
    rCSI 6.25%
    PRS 92.13
  • promyelocyte CL0000836
    CSI 1.26
    rCSI 1.82%
    PRS 89.08
  • myeloid dendritic cell, human CL0001057
    CSI 1.03
    rCSI 5.8%
    PRS 94.64
  • pre-conventional dendritic cell CL0002010
    CSI 0.25
    rCSI 3.34%
    PRS 95.92

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):
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    • 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 [MPEG1](/details-gene/219972) (Macrophage Expressed 1), also known as Perforin-2, is a protein-coding gene located on chromosome 11q12.1. It functions as a key component of the innate immune system, exerting its effect by forming pores in the membranes of pathogenic bacteria. Its expression is highly enriched in myeloid lineage cells, particularly professional phagocytes and antigen-presenting cells. As a result, [MPEG1](/details-gene/219972) is a critical effector molecule for the intracellular defense against bacteria, and its deficiency has been linked to human immunodeficiency syndromes characterized by susceptibility to bacterial infections ([Link](https://doi.org/10.1172/jci.insight.89635)). ## Cellular Roles and Expression Landscape The expression profile of [MPEG1](/details-gene/219972) strongly indicates a specialized role in the myeloid compartment of the immune system. **Overall**, the gene shows the highest significance in [plasmacytoid dendritic cell, human](/details-cell/CL0001058) (CSI: 71.26) and [CD14-low, CD16-positive monocyte](/details-cell/CL0002396) (CSI: 69.26), highlighting its importance in both interferon-producing cells and patrolling monocyte subsets. The gene's broader expression pattern confirms its identity as a cornerstone of innate immunity. It is a significant marker across the myeloid lineage, including general [myeloid leukocyte](/details-cell/CL0000766) (CSI: 28.46), various subsets of [dendritic cell](/details-cell/CL0000451) and monocytes ([intermediate monocyte](/details-cell/CL0002393), [non-classical monocyte](/details-cell/CL0000875)), and tissue-resident macrophages like [colon macrophage](/details-cell/CL0009038) and [Hofbauer cell](/details-cell/CL3000001). This pattern is consistent with its primary function as a first-line defense mechanism against invading pathogens within phagocytic cells ([Link](https://doi.org/10.7554/elife.06508)). Interestingly, significant expression is also noted in developing B lymphocytes, such as [immature B cell](/details-cell/CL0000816) and [precursor B cell](/details-cell/CL0000817), which suggests a potential role in early B cell development or defense that is less well-characterized. ## Pathways and Molecular Function Functional annotations for [MPEG1](/details-gene/219972) are highly consistent with its observed cellular expression pattern. The gene product's molecular function is defined as [wide pore channel activity](/details-gene/GO:0022829), which is the mechanistic basis for its anti-bacterial action. Structurally, it is an acid-activatable pore-forming protein that oligomerizes to puncture microbial membranes ([Link](https://doi.org/10.1038/s41467-019-12279-2)). This molecular function is deployed in several key biological processes. [MPEG1](/details-gene/219972) is centrally involved in the [antibacterial innate immune response](/details-gene/GO:0140367), including specific defense responses to both [gram-positive](/details-gene/GO:0050830) and [gram-negative bacteria](/details-gene/GO:0050829). Its localization to the [phagocytic vesicle membrane](/details-gene/GO:0030670) and [phagolysosome membrane](/details-gene/GO:0061474) indicates that it acts on bacteria that have been engulfed by phagocytes. This intracellular killing mechanism is essential for clearing pathogens and also contributes to the [adaptive immune response](/details-gene/GO:0002250) by facilitating [antigen processing and presentation of exogenous peptide antigen](/details-gene/GO:0002478), a critical function of the dendritic cells and macrophages where it is highly expressed. ## Research Directions The established role of [MPEG1](/details-gene/219972) as a critical anti-bacterial effector in phagocytes provides a solid foundation for further research, particularly concerning its cell-type-specific functions and therapeutic potential. The link between [MPEG1](/details-gene/219972) mutations and susceptibility to nontuberculous mycobacterial and polymicrobial skin infections underscores its clinical relevance ([Link](https://doi.org/10.1172/jci.insight.89635), [Link](https://doi.org/10.3389/fimmu.2020.601584)). Based on the available data, several testable hypotheses can be proposed: 1. Given its high significance in [CD14-low, CD16-positive monocyte](/details-cell/CL0002396), [MPEG1](/details-gene/219972) may be a primary effector molecule used by these "patrolling" monocytes to eliminate bacteria directly from the bloodstream, thereby preventing systemic infection. 2. The high expression of [MPEG1](/details-gene/219972) in [plasmacytoid dendritic cell, human](/details-cell/CL0001058), a cell type specialized in antiviral responses, suggests that its pore-forming function may also be directed against enveloped viruses or is crucial for processing viral antigens following endocytosis. 3. The significant expression in [immature B cell](/details-cell/CL0000816) suggests a previously unappreciated role for [MPEG1](/details-gene/219972) in providing cell-autonomous protection against pathogens during critical stages of B cell development in the bone marrow. To test the first hypothesis regarding the role of [MPEG1](/details-gene/219972) in patrolling monocytes, a key experiment could involve isolating primary human CD16-positive monocytes and using CRISPR-Cas9 to knock out the gene. These engineered cells could then be co-cultured with fluorescently labeled bacteria (*e.g.*, *S. aureus*) in a microfluidic system that simulates vascular flow. Live-cell imaging and subsequent bactericidal assays would allow for a direct quantitative comparison of the ability of wild-type versus [MPEG1](/details-gene/219972)-deficient monocytes to capture and kill pathogens under physiological conditions. From a therapeutic perspective, [MPEG1](/details-gene/219972) is a candidate for activation or replacement strategies, not inhibition. For patients with haploinsufficiency or loss-of-function mutations, therapeutic approaches could include gene therapy to restore expression in hematopoietic stem cells. Furthermore, as its expression can be modulated by cytokines ([Link](https://doi.org/10.1016/j.cellimm.2017.07.001)), pharmacological agents that upregulate [MPEG1](/details-gene/219972) expression, such as interferon-gamma, could serve as an adjunctive therapy to boost innate immunity in susceptible individuals ([Link](https://doi.org/10.3389/fimmu.2020.601584)).

Genular Protein ID: 1273476546

Symbol: MPEG1_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q2M385 Q2M1T6 Q8TEF8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEMBL 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 EMDB 8 Ensembl 1 GO 14 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 5 PDBsum 5 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 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 7888681

Title: Isolation of a novel macrophage-specific gene by differential cDNA analysis.

PubMed ID: 7888681

PubMed ID: 23753625

Title: Perforin-2 restricts growth of Chlamydia trachomatis in macrophages.

PubMed ID: 23753625

DOI: 10.1128/iai.00497-13

PubMed ID: 26402460

Title: Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria.

PubMed ID: 26402460

DOI: 10.7554/elife.06508

PubMed ID: 28705375

Title: Regulation of expression and trafficking of perforin-2 by LPS and TNF-alpha.

PubMed ID: 28705375

DOI: 10.1016/j.cellimm.2017.07.001

PubMed ID: 28422754

Title: MPEG1/perforin-2 mutations in human pulmonary nontuberculous mycobacterial infections.

PubMed ID: 28422754

DOI: 10.1172/jci.insight.89635

PubMed ID: 30609079

Title: Single cell analyses reveal specific distribution of anti-bacterial molecule Perforin-2 in human skin and its modulation by wounding and Staphylococcus aureus infection.

PubMed ID: 30609079

DOI: 10.1111/exd.13870

PubMed ID: 31537793

Title: The cryo-EM structure of the acid activatable pore-forming immune effector Macrophage-expressed gene 1.

PubMed ID: 31537793

DOI: 10.1038/s41467-019-12279-2

PubMed ID: 33224153

Title: MPEG1/Perforin-2 Haploinsufficiency Associated Polymicrobial Skin Infections and Considerations for Interferon-gamma Therapy.

PubMed ID: 33224153

DOI: 10.3389/fimmu.2020.601584

Sequence Information:

  • Length: 716
  • Mass: 78587
  • Checksum: C863E3AF2029A0AA
  • Sequence:
    • MNNFRATILF WAAAAWAKSG KPSGEMDEVG VQKCKNALKL PVLEVLPGGG WDNLRNVDMG 
RVMELTYSNC RTTEDGQYII PDEIFTIPQK QSNLEMNSEI LESWANYQSS TSYSINTELS 
LFSKVNGKFS TEFQRMKTLQ VKDQAITTRV QVRNLVYTVK INPTLELSSG FRKELLDISD 
RLENNQTRMA TYLAELLVLN YGTHVTTSVD AGAALIQEDH LRASFLQDSQ SSRSAVTASA 
GLAFQNTVNF KFEENYTSQN VLTKSYLSNR TNSRVQSIGG VPFYPGITLQ AWQQGITNHL 
VAIDRSGLPL HFFINPNMLP DLPGPLVKKV SKTVETAVKR YYTFNTYPGC TDLNSPNFNF 
QANTDDGSCE GKMTNFSFGG VYQECTQLSG NRDVLLCQKL EQKNPLTGDF SCPSGYSPVH 
LLSQIHEEGY NHLECHRKCT LLVFCKTVCE DVFQVAKAEF RAFWCVASSQ VPENSGLLFG 
GLFSSKSINP MTNAQSCPAG YFPLRLFENL KVCVSQDYEL GSRFAVPFGG FFSCTVGNPL 
VDPAISRDLG APSLKKCPGG FSQHPALISD GCQVSYCVKS GLFTGGSLPP ARLPPFTRPP 
LMSQAATNTV IVTNSENARS WIKDSQTHQW RLGEPIELRR AMNVIHGDGG GLSGGAAAGV 
TVGVTTILAV VITLAIYGTR KFKKKAYQAI EERQSLVPGT AATGDTTYQE QGQSPA