MMP14 spans 11009 bp on chromosome 14 in the region of q11.2. It consists of 10 exons.

The human MMP-14 (MT1-MMP) transcript has been determined to be 3558 bp in length before splicing and 1749 bp after splicing. The start codon (ATG) of MMP-14 gene exists in the first exon and the stop codon (TGA) is present in the last and longest exon of the transcribed product of MMP-14. No TATA box, which controls the expression of 30% of all genes found in the human genome, is found in the proximal region in the MMP-14 promoter. In the promoter region, Egr-1 has been reported to be one of the most important transcription factors regulating the expression of MMP-14. MMP-14 expression is also regulated by other transcription factors, including AP-4, NF-kB, c-ETS1 and p53. However, some common transcription factors, such as AP-1, AP-2 and TGF-alpha, which play major roles in the regulation of other MMPs do not have binding sites within the promoter of MMP-14. Besides these common transcription factors, MMP-14 expression is also regulated by hypoxia inducible factor 2a (HIF-2alpha) under hypoxic conditions. Two HBSs (HIF binding site) have been identified in the proximal promoter region, the one around -125 bp relative to the transcription start site is shown to affect MMP-14 transcription. Some growth factors and cytokines, e.g IL1B, EGF, TNFalpha, bFGF, GM-CSF, SF/HGF, and TGF-beta have also been reported to induce the expression of MMP-14.
Two functional SNPs in the MMP-14 promoter have been found in focal-segmental glomerulosclerosis (FSGS) disease. -378 T/C and -364 G/T alterations cause a reduction in the expression of MMP-14 and correlate with significant risk reduction of FSGS. Epigenetic regulation is also involved in the regulation of MMP-14 expression. Hypermethylation of the CpG100 island, which spans a region from the proximal promoter to the 1st intron of MMP-14, and trimethylation of Histone H3 lysine-27 (known as a repressive marker) are determined as epigenetic controls causing the transcriptional silencing of MMP-14.

No pseudogenes have been identified.

Matrix metalloproteinases (MMPs) compose one of the metzincins super family also known as zinc endopeptidases. Highly conserved motif of this family contains three histidines that bind zinc ion in the catalytic site of the protein and conserved methionine. Besides the secreted MMPs of the MMP family, six membrane type-MMPs have been identified so far, all with similar domain compositions. The best characterized MT-MMP is MMP-14 or MT1-MMP, which contains seven domains from N-terminus to C-terminus: a signal peptide leading MMP-14 into the secretory pathway; a propeptide domain maintaining MMP in a latent form; a catalytic domain responsible for enzymatic activity; a hinge region maintaining proper conformation; a hemopexin domain required for substrate reorganization; a transmembrane domain anchoring MMP into the plasma membrane; and a cytoplasmic domain required for endocytosis. MT-1, MT2-, MT3- and MT5-MMPs all contain seven similar domains, whereas MT4- and MT6-MMPs lack the transmembrane and cytoplasmic domains. Both MT4- and MT6-MMPs are linked to the cell surface through GPI-anchorage. There is a furin consensus sequence (Arg¹⁰⁸-Arg¹⁰⁹-Lys¹¹⁰-Arg¹¹¹) between MMP-14 propeptide and catalytic domains. Furin has been reported to be responsible for MMP-14 activation. However, the activation mechanism of MMP-14 is still under debate. The hemopexin-like domain of MMP-14 is the largest domain, and it provides a suitable flat surface for the protein-protein interactions with the existence of four bladed beta-propeller structures.

MMP-14 is widely expressed in human tissues. Its expression has been proven in the adult human intestine, kidney, lung, ovary, placenta, prostate, and spleen. Increase in its expression level has also been observed in the wound healing area. A Mouse embryogenesis study provides evidence for the expression of MMP-14 mainly in the muscle cells, fibroblast, chondrocytes, and neural cells. MMP-14 is upregulated in most human cancers. Both cancer and stromal cells have been reported to be upregulated in tumor tissues.

Plasma Membrane (single-pass type I membrane protein). MMP-14 contains a 24 amino acid hydrophobic motif at the C-terminus which is responsible for plasma membrane localization of MMP-14.

MMP-14 plays an important role in remodelling of extracellular matrix (ECM) and enhancing cell migration. Besides the role of MMP-14 in these pathophysiological processes, it also plays an important physiological role during development. Studies performed with MMP-14 null mice have shown the importance of its function during embryogenesis as the lack of MMP-14 caused craniofacial dysmorphism, arthritis, osteopenia, dwarfism, fibrosis of soft tissues and premature death. In the adult life, MMP-14 is also required for the wound healing process. All of these functions are related to MMP-14s cleavage or activation of the protein within its substrate profile, which includes proteins in ECM, pro-MMPs, cell-adhesion molecules, cytokines, growth factors and receptors on the cell membrane. Recent studies have also demonstrated the activation of signal transduction pathways via the cytoplasmic tail of MMP-14 important for the invasion process. Functions of MMP-14 can be summarized under the categories of activation of proMMMPs; degradation of ECM; shedding of cell surface molecules; cleavage of cytokines and growth factors; and activation of ERK cascade.

I-) Activation of proMMPs and degradation of ECM
Pro-MMP2 was the first identified substrate of MMP-14 and the trimolecular complex consisting of MMP-14 and proMMP2-TIMP2 has been investigated very well for many years. TIMP2 (tissue inhibitor of metalloproteinases-2) is actually the inhibitor of the MMPs. However, low concentrations of TIMP-2 aids in the activation of proMMP-2 by MMP-14 within this complex by binding to the catalytic domain of MMP-14 and the C-terminal domain of pro-MMP2. Following the formation of the triplex, a second MMP-14, which is free of TIMP-2, forms a dimer with the pre-existing MMP-14 on the cell membrane and cleaves the latent pro-MMP2 to produce active MMP2. Active MMP-2 can then participate in other events such as the degradation of collagen type-IV, a major protein component of the basement membrane, which is not cleaved by MMP-14 itself. Another substrate of MMP-14 within the MMP family is the pro-MMP-13, which also functions as a collagenase in the surrounding tissue after its activation.
Besides activation of MMPs, especially pro-MMP-2, MMP-14 cleaves many proteins in the ECM and changes the composition of the matrix. Type I-Type II-Type III collagen, gelatin, fibronectin, laminin-1 and -5, fibrin and proteoglycans are the major direct targets of MMP-14 in the extracellular environment. Out of these substrates, collagen makes up a significant portion of the ECM and acts as a barrier for migratory cells. Within the collagenases, which includes MMP-1, MMP-2, MMP-8, MMP-13, only MMP-14 can stimulate invasion into collagen by epithelial cells, fibroblasts, and cancer cells. MMP-14 concentrates in the protrusions of the cells, called lamellipodia in normal cells and invadopodia in cancer cells, to induce a significant increase in cell migration and invasion by degrading components of the ECM and making a path in through the surrounding tissue. In this aspect, MMP-14 should be bound to the plasma membrane in vivo, as membrane-bound MMP-14 has been demonstrated to be more proteolytically active than the soluble recombinant MMP-14.

II-) Shedding of cell surface molecules
Studies underlying the mechanism of the constitutive shedding of CD44 from the human melanoma cell surface implicated the necessity of MMP-14 with the presence of ADAM-10 for this process. Especially in the hyaluronan based matrix, cleavage of CD44 at the stem region by MMP-14 sheds these molecules from the cell surface and concurrently promotes the migration of the cells from the leading edge. Another cell adhesion molecule, E-cadherin, is also cleaved by MMP-14 to disrupt contact between cells. In the ischemia-induced ARF (acute renal failure), MMP-14 expression is required for the disruption of the cadherin/catenin complex. Syndecan-1 is another cell surface molecule which is cleaved by MMP-14.

III-) Cleavage of cytokines and growth factors
MMP-14 indirectly plays a major role in cleavage of the cytokines and growth factors by activating pro-MMP-2 and pro-MMP13. It also makes direct contact with several chemokines and growth factors including; the neutrophil chemokine IL-8, secretory leukocyte protease inhibitor, pro-tumor necrosis factor, death receptor-6, and connective tissue growth factor.

IV-) Activation of ERK cascade by the cytoplasmic tail of MMP-14
In several studies, overexpression of MMP-14 has been reported to activate the ERK cascade. It is not yet clear how MMP-14 activates ERK signalling, but overexpression of the cytoplasmic-deleted form of MMP-14 has been shown to eradicate ERK activation. Within the cytoplasmic tail, the 573YCQR576 motif has been suggested to be involved in ERK activation. In addition to ERK activation, the role of MMP-14 in the p38 and JNK pathway has also been investigated.

V-) Inhibition of MMP-14 function
Function of MMP-14 can be abolished either by TIMPs (Tissue Inhibitor of MetalloProteinases) or proteolytic degradation. TIMP-2, -3 and -4 but not TIMP-1 specifically inactivates the functions of MMP-14. Besides TIMPs, RECK and N-Tes can also block the activity of MMP-14 in a similar manner. For the proteolytic cleavage of MMP-14, membrane bound MMP-14 should be internalized by the clathrin-dependent and caveolae-dependent pathways. There is an AP-2 binding site in the cytoplasmic domain of MMP-14, ⁵⁷¹LLY⁵⁷³ which is required for the incorporation of MMP-14 into clathrin-coated vesicles. The palmitoylation of the C574 right after the AP-2 binding site has also been demonstrated to be an essential modification for the internalization of MMP-14.

All MT-MMPs have shown a 40-50% identity according to their amino acid sequence. In the phylogenetic tree, MMP-14 shares the highest similarity rate with MT2-MMP (MMP-15).