MMP27

Matrix metallopeptidase 27 also known as MMP-27 is an is_associated_with::enzyme which in humans is encoded by the MMP27 is_associated_with::gene.

Structure
MMP-27 was discovered and cloned in 1998 by Yang and Kurkinen. Initially compared to the so-called Chicken MMP (CMMP), MMP-27 actually shows very little sequence homology with this protease. Sequence homology predicts that the human MMP-27 gene encodes the canonical domains shared by most MMPs (annotation based on Uniprot entry Q9H306): (i) a is_associated_with::signal peptide (residues 1-17), (ii) a is_associated_with::propeptide (18-98) containing the cysteine switch motif (89-96), (iii) a is_associated_with::catalytic domain (99-263) containing the typical HEXXHXXGXXH motif of the metzincins (M10 and M12 families of the MEROPS[2] database), (iv) a proline-rich hinge region (264-278) and (v) a hemopexin-like domain (279-465) folded as a four-bladed β-propeller through disulfide bond formation between the two flanking Cys residues (Cys279 and Cys465). MMP-27 could be classified in the stromelysin group of MMPs, since MMP-27 shows 51,6% homology with stromelysin-2 (MMP-10) and localizes in the cluster of MMPs located on chromosome 11.

Interestingly, like the six known MT-MMPs, human MMP-27 is prolonged by an additional C-terminal domain (466-513). The Spoctopus algorithm for topological prediction suggests that this C-terminal extension (CTE) includes a potential is_associated_with::transmembrane domain (490-510). However, this sequence is less hydrophobic than in transmembrane MT-MMPs (MMP-14, -15, -16 and -24) as it contains hydrophilic/charged residues, in particular His492, Lys493, His504 and Lys507.

Function
Proteins of the is_associated_with::matrix metalloproteinase (MMP) family are involved in the breakdown of is_associated_with::extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as is_associated_with::arthritis and is_associated_with::metastasis. Most MMPs are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases.

Cominelli A. and colleagues demonstrated that MMP-27 is an unusual protease which is not secreted and is efficiently retained in the is_associated_with::endoplasmic reticulum in three mammalian is_associated_with::cell lines. Deletion mutants and swapping with recombinant MMP-10 demonstrate that the unique MMP-27 C-terminal extension (CTE) is necessary and sufficient for endoplasmic reticulum retention but does not provide a stable membrane anchorage. Despite sequence homology with MT-MMPs, the CTE is not a transmembrane domain and does not interact permanently with membrane. This unique feature for an MMP raises important questions about potential functions of MMP-27, which remains to be investigated.

Clinical significance
Sparse information about MMP-27 expression was found in studies of gene expression profiling (micro-array) or in expression pattern analysis of MMP family members during developmental, physiological or pathological processes. MMP-27 transcript is detected in almost every tissue, except the brain, with the highest expression found in the liver during mouse development In the adult, MMP-27 mRNA is mostly abundant in anti-IgG/IgM stimulated B lymphocytes, bone and kidney but is present at lower levels in the heart.

A recent investigation of the transcriptome from distinct tissue compartments of the menstrual is_associated_with::endometrium disclosed specific MMP-27 overexpression in areas of stromal breakdown. In another transcriptomic study, MMP-27 was found to be increased in the human endometrium at the end of the secretory phase, before menstruation. Moreover, MMP-27 expression is down-regulated in macrophages when co-cultured with ovarian cancer cells but up-regulated in cartilages from patients with osteoarthritis or in abdominal aortic aneurysms. MMP-27 was also identified, at the protein level, in MDA-MB-231 breast cancer cell line and in primary human breast cancer. Recently, MMP-27 has been demonstrated to be expressed by CD163+/CD206+ macrophages in the human endometrium and in superficial endometriotic lesions.