1. Gene Aliases

MMP12, Matrix Metallopeptidase 12, HME, Matrix Metalloproteinase 12 (Macrophage Elastase), Macrophage Metalloelastase, Macrophage Elastase, EC 3.4.24.65, MMP-12, MME, ME, Matrix Metallopeptidase 12 (Macrophage Elastase), Matrix Metalloproteinase-12, EC 3.4.24

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=MMP12&keywords=MMP-12]

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

Interactions with text mining support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

GO terms:

bronchiole development [The biological process whose specific outcome is the progression of a bronchiole from an initial condition to its mature state. This process begins with the formation of the bronchiole and ends with the mature structure. A bronchiole is the first airway branch that no longer contains cartilage; it is a branch of the bronchi. GO:0060435]

cellular response to virus [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a virus. GO:0098586]

collagen catabolic process [The proteolytic chemical reactions and pathways resulting in the breakdown of collagen in the extracellular matrix, usually carried out by proteases secreted by nearby cells. GO:0030574]

elastin catabolic process [The chemical reactions and pathways resulting in the breakdown of elastin. Elastin is a glycoprotein which is randomly coiled and crosslinked to form elastic fibers that are found in connective tissue. GO:0060309]

extracellular matrix organization [A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of an extracellular matrix. GO:0030198]

lung alveolus development [The process whose specific outcome is the progression of the alveolus over time, from its formation to the mature structure. The alveolus is a sac for holding air in the lungs; formed by the terminal dilation of air passageways. GO:0048286]

negative regulation of endothelial cell-matrix adhesion via fibronectin [Any process that stops, prevents or reduces the frequency, rate or extent of endothelial cell-matrix adhesion via fibronectin. GO:1904905]

negative regulation of transcription by RNA polymerase II [Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II. GO:0000122]

negative regulation of type I interferon-mediated signaling pathway [Any process that decreases the rate, frequency or extent of a type I interferon-mediated signaling pathway. GO:0060339]

positive regulation of epithelial cell proliferation [Any process that activates or increases the rate or extent of epithelial cell proliferation. GO:0050679]

positive regulation of epithelial cell proliferation involved in wound healing [Any process that activates or increases the rate or extent of epithelial cell proliferation, contributing to the restoration of integrity to a damaged tissue following an injury. GO:0060054]

positive regulation of gene expression [Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA). GO:0010628]

positive regulation of interferon-alpha production [Any process that activates or increases the frequency, rate, or extent of interferon-alpha production. GO:0032727]

positive regulation of transcription by RNA polymerase II [Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter. GO:0045944]

positive regulation of type I interferon-mediated signaling pathway [Any process that increases the rate, frequency or extent of a type I interferon-mediated signaling pathway. GO:0060340]

protein import into nucleus [The directed movement of a protein from the cytoplasm to the nucleus. GO:0006606]

proteolysis [The hydrolysis of proteins into smaller polypeptides and/or amino acids by cleavage of their peptide bonds. This term was intentionally placed under 'protein metabolic process ; GO:0019538' rather than 'protein catabolic process ; GO:0030163' to cover all processes centered on breaking peptide bonds, including those involved in protein processing. GO:0006508]

regulation of defense response to virus by host [Any host process that modulates the frequency, rate, or extent of the antiviral response of a host cell or organism. GO:0050691]

regulation of trophoblast cell migration [Any process that modulates the frequency, rate or extent of trophoblast cell migration. GO:1901163]

response to hypoxia [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level. Note that this term should not be confused with 'response to anoxia ; GO:0034059'. Note that in laboratory studies, hypoxia is typically studied at O2 concentrations ranging from 0.1 - 5%. GO:0001666]

response to organic cyclic compound [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an organic cyclic compound stimulus. GO:0014070]

response to xenobiotic stimulus [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a xenobiotic, a compound foreign to the organim exposed to it. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical. GO:0009410]

wound healing, spreading of epidermal cells [The migration of an epidermal cell along or through a wound gap that contributes to the reestablishment of a continuous epidermis. GO:0035313]

MSigDB Signatures:

REACTOME_COLLAGEN_DEGRADATION: Collagen degradation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_COLLAGEN_DEGRADATION.html]

WP_TGF_BETA_SIGNALING_PATHWAY: TGF beta signaling pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_TGF_BETA_SIGNALING_PATHWAY.html]

WP_MATRIX_METALLOPROTEINASES: Matrix metalloproteinases [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_MATRIX_METALLOPROTEINASES.html]

REACTOME_EXTRACELLULAR_MATRIX_ORGANIZATION: Extracellular matrix organization [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_EXTRACELLULAR_MATRIX_ORGANIZATION.html]

REACTOME_DEGRADATION_OF_THE_EXTRACELLULAR_MATRIX: Degradation of the extracellular matrix [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_DEGRADATION_OF_THE_EXTRACELLULAR_MATRIX.html]

NABA_MATRISOME_ASSOCIATED: Ensemble of genes encoding ECM-associated proteins including ECM-affiliated proteins, ECM regulators and secreted factors [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/NABA_MATRISOME_ASSOCIATED.html]

NABA_MATRISOME: Ensemble of genes encoding extracellular matrix and extracellular matrix-associated proteins [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/NABA_MATRISOME.html]

WP_SPINAL_CORD_INJURY: Spinal cord injury [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_SPINAL_CORD_INJURY.html]

7. Gene Descriptions

NCBI Gene Summary: This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature protease. This protease degrades soluble and insoluble elastin. This gene may play a role in aneurysm formation and mutations in this gene are associated with lung function and chronic obstructive pulmonary disease (COPD). This gene is part of a cluster of MMP genes on chromosome 11. [provided by RefSeq, Jan 2016]

GeneCards Summary: MMP12 (Matrix Metallopeptidase 12) is a Protein Coding gene. Diseases associated with MMP12 include Pulmonary Emphysema and Dermatitis Herpetiformis. Among its related pathways are Matrix metalloproteinases and Integrin Pathway. Gene Ontology (GO) annotations related to this gene include calcium ion binding and metallopeptidase activity. An important paralog of this gene is MMP3.

UniProtKB/Swiss-Prot Summary: May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3.

8. Cellular Location of Gene Product

Predicted location: Secreted [https://www.proteinatlas.org/ENSG00000262406/subcellular]

9. Mechanistic Information

Summary

MMP12, encoded by the Mmp12 gene, is a metalloproteinase involved in degrading extracellular matrix components, specifically elastin [CS: 10]. In the lung, its dysregulation often corresponds to harmful conditions such as chronic obstructive pulmonary disease (COPD) and asthma, mainly triggered by external factors like cigarette smoke, pollutants, and infections [CS: 9]. For instance, in response to cigarette smoke exposure, MMP12 expression is upregulated in alveolar macrophages, leading to an increase in elastolytic activity [CS: 8]. This upregulation is a direct response to the damage caused by smoke, as MMP12 breaks down the extracellular matrix, aiding in remodeling and repair of lung tissue [CS: 7]. However, this beneficial intent can lead to pathological conditions like emphysema when the balance of tissue breakdown and repair is disrupted [CS: 9].

Furthermore, MMP12 expression is increased in response to various lung infections and inflammatory conditions [CS: 8]. For example, in the case of asthma, MMP12 mRNA is upregulated in eosinophilic indicators, suggesting a response to inflammatory triggers [CS: 7]. MMP12's role here is to facilitate tissue remodeling and repair by breaking down damaged extracellular matrix [CS: 8]. However, this overactivity can contribute to lung tissue damage and disease progression [CS: 8].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: intestine, lymphoid tissue, urinary bladder (tissue enhanced) [https://www.proteinatlas.org/ENSG00000262406/tissue]

Cell type enchanced: extravillous trophoblasts, langerhans cells (group enriched) [https://www.proteinatlas.org/ENSG00000262406/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

Most relevant biomarkers with lower score or lower probability of association with disease or organ of interest: