This gene can be found at chromosome 11p15.4, and contains 6 exons spanning 4,24 kb.

MMP-26 has 998 mRNA nucleotides and no transcript variant. The transcription of this gene is regulated by three elements, estrogen-responsive element (ERE), T-cell factor-4 (TCF-4), and activator protein-1 (AP-1), due to the highly unusual poly (A) site located upstream of its promoter. Further regulation of TCF-4 is accomplished by the β-catenin/epithelial-cadherin (E-cadherin) pathway and suggests that MMP-26 is specifically expressed in cells of epithelial origin. The gene for MMP-26 has one transcriptional start site and a consensus TATA-box, located 35 and 60 nucleotides upstream of the translational start site respectively.

MMP-26 is the smallest member of the matrix metalloproteinase (MMP) family of zinc-dependent endopeptidases. Synthesized as a zymogen, the nascent form is composed of three domains: (1) "pre" domain, N-terminal signal sequence, which directs the protein into the endoplasmic reticulum; (2) an unconventional "pro" domain, which maintains enzyme-latency; and (3) a catalytic domain, which contains the conserved zinc-binding region for proteolysis. The MMP-26 pro-enzyme starts at residue 18, with the full length of the protein spanning 261 amino acids. The full-length enzyme has a theoretical molecular weight of 28 kDa that is truncated to 19 kDa upon activation (cleavage of the pro-domain). Among the MMPs, only MMP-26 has a "cysteine-switch" sequence that contains a histidine residue instead of the usual arginine residue (PH⁸¹CGVPDGSD) in the pro-peptide domain and has a zinc-binding motif (V²⁰⁵ATHEIGHSLGLQH) in the catalytic domain. Additionally, MMP-26 lacks the hinge region and hemopexin-like domain that is common to other family members. MMP-26 has two calcium binding sites: (1) a high-affinity site required for enzymatic activity, protein stability, and protection from denaturation; and (2) a low-affinity site primarily important for protein folding, tertiary structure, and native conformation. The protein also contains three possible N-linked glycosylation sites (N64, N133, N221).

MMP-26 has been found strictly expressed in normal tissues of the placenta and moderately expressed in the uterus. However, MMP-26 expression is also associated with human cancer cells, especially in estrogen receptor (ER)-α positive breast cancer cells and cancerous cells of the ovary and endometrium. The expression of MMP-26 in cancerous breast, colon, lung, brain, head and neck, prostate, and melanoma tissues was significantly elevated when compared with parallel normal tissues, while not significantly elevated in kidney cancer, ovarian cancer, and non-Hodgkins lymphoma.

Intracellular (endoplasmic reticulum-retained), secreted, pericellular, and extracellular.

MMP-26 cleaves many extracellular matrix and plasma proteins including: (1) amino terminus of estrogen receptor β; (2) α1-antitrypsin; (3) insulin-like growth factor-binding protein 1 (IGFBP-1); (4) fibronectin; (5) vitronectin; (6) fibrinogen; (7) gelatins of types I-IV; (8) gelatinase B (MMP-9); (9) α2-macroglobulin; and (10) type IV collagen. MMP-26 digests one peptide substrate of tumor necrosis factor-α converting enzyme (TACE/ADAM17) and four peptide substrates of MMPs. MMP-26 activates MMP-9 by cleavage of the pre-proenzyme (Ala93-Met94 site) and produces activated MMP-9 products that are more stable than those activated by MMP-7. MMP-26 also forms a complex with tissue inhibitors of metalloproteinases 4 (TIMP-4). MMP-26 is inhibited by GM6001 and TIMPs -2 (1,60 nM) and -4 (0,62 nM), exhibiting an inhibition profile most similar to those of MMPs with intermediate S1 pockets (His-233). MMP-26 can auto-digest itself during the folding process and is also capable of self-activation with its catalytic activity affected by detergents.

Belongs to matrix metalloproteinase (MMP) family and exhibits a similar domain structure to that of matrilysin (MMP-7) but is most homologous to metalloelastase (MMP-12) with ~52% identity.