Details for: MMP19

Gene ID: 4327

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: MMP19

Ensembl ID: ENSG00000123342

Description: matrix metallopeptidase 19

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • elicited macrophage CL0000861
    CSI 31.07
    rCSI 28.53%
    PRS 95.57
  • myeloid leukocyte CL0000766
    CSI 30.4
    rCSI 28.05%
    PRS 93.06
  • mononuclear phagocyte CL0000113
    CSI 6.93
    rCSI 15.25%
    PRS 94.1
  • intermediate monocyte CL0002393
    CSI 6.1
    rCSI 9.21%
    PRS 95.34
  • alternatively activated macrophage CL0000890
    CSI 5.16
    rCSI 6.49%
    PRS 96.28
  • Hofbauer cell CL3000001
    CSI 4.34
    rCSI 8.19%
    PRS 95.69
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 4.01
    rCSI 4.84%
    PRS 95.76
  • myofibroblast cell CL0000186
    CSI 3.6
    rCSI 4.98%
    PRS 88.97
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 3.56
    rCSI 4.67%
    PRS 96.83
  • colon macrophage CL0009038
    CSI 3.14
    rCSI 14.48%
    PRS 96.98
  • alveolar type 1 fibroblast cell CL4028004
    CSI 3.03
    rCSI 3.32%
    PRS 93.53
  • fibroblast of lung CL0002553
    CSI 2.96
    rCSI 2.75%
    PRS 93.23
  • lung interstitial macrophage CL4033043
    CSI 2.94
    rCSI 6.61%
    PRS 97.37
  • placental villous trophoblast CL2000060
    CSI 2.84
    rCSI 4.38%
    PRS 90.28
  • hepatic stellate cell CL0000632
    CSI 2.82
    rCSI 10.56%
    PRS 88.3
  • Kupffer cell CL0000091
    CSI 2.61
    rCSI 5.96%
    PRS 92.88
  • bronchus fibroblast of lung CL2000093
    CSI 2.47
    rCSI 2.01%
    PRS 91.29
  • alveolar macrophage CL0000583
    CSI 2.25
    rCSI 3.71%
    PRS 93.64
  • lung macrophage CL1001603
    CSI 2.04
    rCSI 4.56%
    PRS 95.67
  • fibroblast of breast CL4006000
    CSI 1.87
    rCSI 7.85%
    PRS 93.59
  • adventitial cell CL0002503
    CSI 1.86
    rCSI 4.44%
    PRS 93.9
  • monocyte CL0000576
    CSI 1.86
    rCSI 3.36%
    PRS 92.91
  • extravillous trophoblast CL0008036
    CSI 1.85
    rCSI 2.29%
    PRS 90.54
  • mesenchymal stem cell of adipose tissue CL0002570
    CSI 1.77
    rCSI 9.89%
    PRS 93.15
  • epicardial adipocyte CL1000309
    CSI 1.64
    rCSI 5.35%
    PRS 89.56
  • vascular associated smooth muscle cell CL0000359
    CSI 1.48
    rCSI 4.79%
    PRS 90.36
  • alveolar adventitial fibroblast CL4028006
    CSI 1.38
    rCSI 2.18%
    PRS 92.91
  • metallothionein-positive alveolar macrophage CL4033042
    CSI 1.22
    rCSI 13.31%
    PRS 96.23

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 [MMP19](/details-gene/4327) encodes Matrix Metallopeptidase 19, a zinc-dependent enzyme primarily involved in the degradation and remodeling of the extracellular matrix (ECM). Its principal molecular function is [metalloendopeptidase activity](/details-go/GO0004222), enabling it to break down key structural proteins, including collagen ([Link](https://doi.org/10.1016/s0014-5793(00)01819-6)). Expression data reveals that [MMP19](/details-gene/4327) is a prominent feature of myeloid lineage cells, showing particularly high significance in [elicited macrophages](/details-cell/CL0000861) and [myeloid leukocytes](/details-cell/CL0000766). This cellular profile, combined with its role in processes like [angiogenesis](/details-go/GO0001525) and [extracellular matrix disassembly](/details-go/GO0022617), suggests its importance in immune cell trafficking, tissue repair, and inflammatory responses. Dysregulation of [MMP19](/details-gene/4327) has been implicated in human diseases, including rheumatoid arthritis ([Link](https://doi.org/10.1016/s0171-2985(98)80049-1)) and certain developmental anomalies ([Link](https://doi.org/10.1002/humu.22754)). ## Cellular Roles and Expression Landscape The expression profile of [MMP19](/details-gene/4327) indicates a specialized role in cells central to tissue remodeling and innate immunity. **Overall**, the gene's significance is highest in phagocytic and stromal cell populations. Its most pronounced expression is observed in [elicited macrophage](/details-cell/CL0000861) (CSI: 31.07) and the broader [myeloid leukocyte](/details-cell/CL0000766) category (CSI: 30.40), establishing it as a key functional marker for these cells. This pattern extends across the mononuclear phagocyte system, with significant expression in [intermediate monocytes](/details-cell/CL0002393), [alternatively activated macrophages](/details-cell/CL0000890), and tissue-specific macrophages such as [Hofbauer cells](/details-cell/CL3000001) in the placenta and [lung interstitial macrophages](/details-cell/CL4033043). This widespread presence in macrophages suggests a fundamental role in their capacity to modify tissue environments during surveillance, inflammation, and repair. Beyond the myeloid compartment, [MMP19](/details-gene/4327) is also significantly expressed in several stromal cell types known for their active role in ECM dynamics. These include [myofibroblast cells](/details-cell/CL0000186), [fibroblasts of lung](/details-cell/CL0002553), and [hepatic stellate cells](/details-cell/CL0000632). This dual expression in both immune and structural cells highlights its central function at the interface of inflammation and tissue architecture. The gene's activity in [placental villous trophoblasts](/details-cell/CL2000060) further underscores its importance in physiological processes requiring extensive tissue remodeling. ## Pathways and Molecular Function [MMP19](/details-gene/4327) functions as a secreted enzyme that operates within the [extracellular space](/details-go/GO0005615) to mediate [proteolysis](/details-go/GO0006508). Its activity is dependent on [zinc ion binding](/details-go/GO0008270), characteristic of the matrix metallopeptidase family. The primary biological role of [MMP19](/details-gene/4327) is the catalytic breakdown of ECM components, as detailed in the Reactome pathways [Degradation of the extracellular matrix](/details-reactome/R-HSA-1474228) and [Collagen degradation](/details-reactome/R-HSA-1442490). Biochemical studies have confirmed its capacity as a potent basement membrane degrading enzyme ([Link](https://doi.org/10.1074/jbc.275.20.14809)) and have shown it can cleave substrates such as aggrecan and cartilage oligomeric matrix protein (COMP) ([Link](https://doi.org/10.1016/s0014-5793(00)01819-6)). These activities are crucial for physiological processes including [cell differentiation](/details-go/GO0030154) and [angiogenesis](/details-go/GO0001525), where controlled matrix breakdown is required for cell migration and new vessel formation. Clinically, mutations affecting the regulation of [MMP19](/details-gene/4327) are associated with cavitary optic disc anomaly ([OMIM: 601807](https://omim.org/entry/601807)), pointing to a critical role in ocular development ([Link](https://doi.org/10.1002/humu.22754)). Furthermore, its expression on activated immune cells and its identification as an autoantigen in rheumatoid arthritis suggest it is a key player in the pathology of inflammatory joint disease ([Link](https://doi.org/10.1016/s0171-2985(98)80049-1)). ## Research Directions The high expression of [MMP19](/details-gene/4327) in macrophages and fibroblasts, particularly in inflammatory contexts described in the literature, presents several avenues for future research. Based on the available data, the following hypotheses can be proposed: 1. Given its high expression in [macrophages](/details-cell/CL0000235) and its documented role as an autoantigen in rheumatoid arthritis ([Link](https://doi.org/10.1016/s0171-2985(98)80049-1)), overexpression of [MMP19](/details-gene/4327) by synovial macrophages is a primary driver of cartilage destruction in the arthritic joint. Its presence on the cell surface may also contribute to breaking immune tolerance and perpetuating the autoimmune response. 2. Considering its expression in [myofibroblast cells](/details-cell/CL0000186) and [hepatic stellate cells](/details-cell/CL0000632), [MMP19](/details-gene/4327) likely plays a key regulatory role in the development of tissue fibrosis. Dysregulation of its proteolytic activity could disrupt the balance between matrix deposition and degradation, contributing to the pathological accumulation of scar tissue in organs like the lung and liver. A key experiment to investigate the first hypothesis would involve leveraging a preclinical model of inflammatory arthritis. To test the role of [MMP19](/details-gene/4327) in rheumatoid arthritis, one could utilize MMP19-deficient mice in a collagen-induced arthritis (CIA) model. Comparing disease incidence, clinical severity scores, joint histology for evidence of synovitis and cartilage erosion, and local cytokine profiles between knockout and wild-type animals would directly assess its contribution to disease pathogenesis. As a therapeutic target, [MMP19](/details-gene/4327) holds potential, particularly for chronic inflammatory or fibrotic diseases. Because it is a secreted, catalytically active enzyme, **inhibition** is the most direct therapeutic strategy. Its specific upregulation in pathological contexts like rheumatoid arthritis suggests that a selective MMP19 inhibitor could reduce tissue damage with fewer side effects than broader-spectrum MMP inhibitors. Such a compound could limit the destructive capacity of activated [macrophages](/details-cell/CL0000235) and [fibroblasts](/details-cell/CL0000057) in affected tissues, representing a promising approach to slow disease progression.

Genular Protein ID: 521611972

Symbol: MMP19_HUMAN

Name: Matrix metalloproteinase-19

UniProtKB Accession Codes:

Q99542 B4E030 O15278 O95606 Q99580

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 2 CTD 1 ChEBI 6 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EC 1 EMBL 10 Ensembl 3 ExpressionAtlas 1 GO 12 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 10 KEGG 1 MANE-Select 1 MEROPS 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PIR 1 PIRSF 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 Reactome 2 RefSeq 2 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8920941

Title: Identification of MMP-18, a putative novel human matrix metalloproteinase.

PubMed ID: 8920941

DOI: 10.1006/bbrc.1996.1688

PubMed ID: 9020145

Title: Identification and characterization of a novel human matrix metalloproteinase with unique structural characteristics, chromosomal location and tissue distribution.

PubMed ID: 9020145

DOI: 10.1074/jbc.272.7.4281

PubMed ID: 9232430

Title: The matrix metalloproteinase RASI-1 is expressed in synovial blood vessels of a rheumatoid arthritis patient.

PubMed ID: 9232430

DOI: 10.1016/s0165-2478(97)00057-6

PubMed ID: 9562866

Title: Matrix metalloproteinase MMP-19 (RASI-1) is expressed on the surface of activated peripheral blood mononuclear cells and is detected as an autoantigen in rheumatoid arthritis.

PubMed ID: 9562866

DOI: 10.1016/s0171-2985(98)80049-1

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

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: 10809722

Title: Biochemical characterization of the catalytic domain of human matrix metalloproteinase 19. Evidence for a role as a potent basement membrane degrading enzyme.

PubMed ID: 10809722

DOI: 10.1074/jbc.275.20.14809

PubMed ID: 10922468

Title: Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protein (COMP).

PubMed ID: 10922468

DOI: 10.1016/s0014-5793(00)01819-6

PubMed ID: 25171405

Title: A secreted tyrosine kinase acts in the extracellular environment.

PubMed ID: 25171405

DOI: 10.1016/j.cell.2014.06.048

PubMed ID: 25581579

Title: Heterozygous triplication of upstream regulatory sequences leads to dysregulation of matrix metalloproteinase 19 in patients with cavitary optic disc anomaly.

PubMed ID: 25581579

DOI: 10.1002/humu.22754

Sequence Information:

  • Length: 508
  • Mass: 57357
  • Checksum: BA480549AA9A8972
  • Sequence:
    • MNCQQLWLGF LLPMTVSGRV LGLAEVAPVD YLSQYGYLQK PLEGSNNFKP EDITEALRAF 
QEASELPVSG QLDDATRARM RQPRCGLEDP FNQKTLKYLL LGRWRKKHLT FRILNLPSTL 
PPHTARAALR QAFQDWSNVA PLTFQEVQAG AADIRLSFHG RQSSYCSNTF DGPGRVLAHA 
DIPELGSVHF DEDEFWTEGT YRGVNLRIIA AHEVGHALGL GHSRYSQALM APVYEGYRPH 
FKLHPDDVAG IQALYGKKSP VIRDEEEEET ELPTVPPVPT EPSPMPDPCS SELDAMMLGP 
RGKTYAFKGD YVWTVSDSGP GPLFRVSALW EGLPGNLDAA VYSPRTQWIH FFKGDKVWRY 
INFKMSPGFP KKLNRVEPNL DAALYWPLNQ KVFLFKGSGY WQWDELARTD FSSYPKPIKG 
LFTGVPNQPS AAMSWQDGRV YFFKGKVYWR LNQQLRVEKG YPRNISHNWM HCRPRTIDTT 
PSGGNTTPSG TGITLDTTLS ATETTFEY