MMP27

Last updated
MMP27
Identifiers
Aliases MMP27 , MMP-27, matrix metallopeptidase 27
External IDs OMIM: 618101; MGI: 3039232; HomoloGene: 23345; GeneCards: MMP27; OMA:MMP27 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

64066

234911

Ensembl

ENSG00000137675

ENSMUSG00000070323

UniProt

Q9H306

n/a

RefSeq (mRNA)

NM_022122

NM_001030289
NM_001310717

RefSeq (protein)

NP_071405

n/a

Location (UCSC) Chr 11: 102.69 – 102.71 Mb Chr 9: 7.57 – 7.58 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Matrix metallopeptidase 27 also known as MMP-27 is an enzyme which in humans is encoded by the MMP27 gene. [5]

Contents

Structure

MMP-27 was discovered and cloned in 1998 by Yang and Kurkinen. [6] 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 signal peptide (residues 1-17), (ii) a propeptide (18-98) containing the cysteine switch motif (89-96), (iii) a 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.

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 [7] suggests that this C-terminal extension (CTE) includes a potential 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 matrix metalloproteinase (MMP) 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. Most MMPs are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. [8]

Cominelli A. and colleagues demonstrated that MMP-27 is an unusual protease which is not secreted and is efficiently retained in the endoplasmic reticulum in three mammalian cell lines. [9] 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 [10] In the adult, MMP-27 mRNA is mostly abundant in anti-IgG/IgM stimulated B lymphocytes, [11] bone and kidney but is present at lower levels in the heart. [12]

A recent investigation of the transcriptome from distinct tissue compartments of the menstrual endometrium disclosed specific MMP-27 overexpression in areas of stromal breakdown. [13] In another transcriptomic study, MMP-27 was found to be increased in the human endometrium at the end of the secretory phase, before menstruation. [14] Moreover, MMP-27 expression is down-regulated in macrophages when co-cultured with ovarian cancer cells [15] but up-regulated in cartilages from patients with osteoarthritis [16] or in abdominal aortic aneurysms. [17] MMP-27 was also identified, at the protein level, in MDA-MB-231 breast cancer cell line [18] and in primary human breast cancer. [19] Recently, MMP-27 has been demonstrated to be expressed by CD163+/CD206+ macrophages in the human endometrium and in superficial endometriotic lesions. [20]

Related Research Articles

<span class="mw-page-title-main">MMP2</span> Protein-coding gene in the species Homo sapiens

72 kDa type IV collagenase also known as matrix metalloproteinase-2 (MMP-2) and gelatinase A is an enzyme that in humans is encoded by the MMP2 gene. The MMP2 gene is located on chromosome 16 at position 12.2.

Interstitial collagenase, also known as fibroblast collagenase and matrix metalloproteinase-1 (MMP-1), is an enzyme that in humans is encoded by the MMP1 gene. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. MMP-1 was the first vertebrate collagenase both purified to homogeneity as a protein, and cloned as a cDNA. MMP-1 has an estimated molecular mass of 54 kDa.

<span class="mw-page-title-main">TIMP2</span> Protein-coding gene in the species Homo sapiens

Tissue inhibitor of metalloproteinases 2 (TIMP2) is a gene and a corresponding protein. The gene is a member of the TIMP gene family. The protein is thought to be a metastasis suppressor.

<span class="mw-page-title-main">MMP7</span> Protein-coding gene in humans

Matrilysin also known as matrix metalloproteinase-7 (MMP-7), pump-1 protease (PUMP-1), or uterine metalloproteinase is an enzyme in humans that is encoded by the MMP7 gene. The enzyme has also been known as matrin, putative metalloproteinase-1, matrix metalloproteinase pump 1, PUMP-1 proteinase, PUMP, metalloproteinase pump-1, putative metalloproteinase, MMP). Human MMP-7 has a molecular weight around 30 kDa.

<span class="mw-page-title-main">TIMP1</span> Protein-coding gene in the species Homo sapiens

TIMP metallopeptidase inhibitor 1, also known as TIMP1, a tissue inhibitor of metalloproteinases, is a glycoprotein with a molecular weight of 28 kDa. TIMP1 is expressed from several tissues of organisms.

<span class="mw-page-title-main">Matrix metallopeptidase 13</span> Protein-coding gene in the species Homo sapiens

Collagenase 3 is an enzyme that in humans is encoded by the MMP13 gene. It is a member of the matrix metalloproteinase (MMP) family. Like most MMPs, it is secreted as an inactive pro-form. MMP-13 has a predicted molecular weight around 54 kDa. It is activated once the pro-domain is cleaved, leaving an active enzyme composed of the catalytic domain and the hemopexin-like domain PDB: 1PEX​. Although the actual mechanism has not been described, the hemopexin domain participates in collagen degradation, the catalytic domain alone being particularly inefficient in collagen degradation. During embryonic development, MMP-13 is expressed in the skeleton as required for restructuring the collagen matrix for bone mineralization. In pathological situations it is highly overexpressed; this occurs in human carcinomas, rheumatoid arthritis and osteoarthritis.

<span class="mw-page-title-main">Matrix metallopeptidase 12</span> Enzyme involved in breakdown of extracellular matrix, encoded for by the MMP12 gene in humans

Matrix metalloproteinase-12 (MMP-12) also known as macrophage metalloelastase (MME) or macrophage elastase (ME) is an enzyme that in humans is encoded by the MMP12 gene.

<span class="mw-page-title-main">MMP26</span> Protein-coding gene in the species Homo sapiens

Matrix metalloproteinase-26 also known as matrilysin-2 and endometase is an enzyme that in humans is encoded by the MMP26 gene.

<span class="mw-page-title-main">MMP19</span> Protein-coding gene in the species Homo sapiens

Matrix metalloproteinase-19 (MMP-19) also known as matrix metalloproteinase RASI is an enzyme that in humans is encoded by the MMP19 gene.

<span class="mw-page-title-main">MMP11</span> Protein-coding gene in the species Homo sapiens

Stromelysin-3 (SL-3) also known as matrix metalloproteinase-11 (MMP-11) is an enzyme that in humans is encoded by the MMP11 gene.

<span class="mw-page-title-main">MMP16</span> Protein-coding gene in the species Homo sapiens

Matrix metalloproteinase-16 is an enzyme that in humans is encoded by the MMP16 gene.

<span class="mw-page-title-main">TIMP4</span> Protein-coding gene in the species Homo sapiens

Metalloproteinase inhibitor 4 is an enzyme that in humans is encoded by the TIMP4 gene.

<span class="mw-page-title-main">Periostin</span> Protein-coding gene in the species Homo sapiens

Periostin is a protein that in humans is encoded by the POSTN gene. Periostin functions as a ligand for alpha-V/beta-3 and alpha-V/beta-5 integrins to support adhesion and migration of epithelial cells.

<span class="mw-page-title-main">MMP17</span> Protein-coding gene in the species Homo sapiens

Matrix metalloproteinase-17 (MMP-17) also known as membrane-type matrix metalloproteinase 4 is an enzyme that in humans is encoded by the MMP17 gene.

<span class="mw-page-title-main">MMP28</span> Protein-coding gene in the species Homo sapiens

Matrix metalloproteinase 28 also known as epilysin is an enzyme that in humans is encoded by the MMP28 gene.

<span class="mw-page-title-main">MMP24</span> Protein-coding gene in the species Homo sapiens

Matrix metalloproteinase-24 is an enzyme that in humans is encoded by the MMP24 gene.

<span class="mw-page-title-main">MMP20</span>

Matrix metalloproteinase-20 (MMP-20) also known as enamel metalloproteinase or enamelysin is an enzyme that in humans is encoded by the MMP20 gene.

<span class="mw-page-title-main">MMP8</span> Protein-coding gene in the species Homo sapiens

Neutrophil collagenase, also known as matrix metalloproteinase-8 (MMP-8) or PMNL collagenase (MNL-CL), is a collagen cleaving enzyme which is present in the connective tissue of most mammals. In humans, the MMP-8 protein is encoded by the MMP8 gene. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the enzyme encoded by this gene is stored in secondary granules within neutrophils and is activated by autolytic cleavage.

<span class="mw-page-title-main">MMP21</span> Protein-coding gene in the species Homo sapiens

Matrix metalloproteinase-21 (MMP-21) is an enzyme that in humans is encoded by the MMP21 gene.

<span class="mw-page-title-main">MMP15</span> Protein-coding gene in the species Homo sapiens

Matrix metalloproteinase 15 also known as MMP15 is an enzyme that in humans is encoded by the MMP15 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000137675 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000070323 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Nagase H, Woessner JF (July 1999). "Matrix metalloproteinases". J. Biol. Chem. 274 (31): 21491–4. doi: 10.1074/jbc.274.31.21491 . PMID   10419448.
  6. ↑ Yang M, Kurkinen M (1998). "Cloning and characterization of a novel matrix metalloproteinase (MMP), CMMP, from chicken embryo fibroblasts. CMMP, Xenopus XMMP, and human MMP19 have a conserved unique cysteine in the catalytic domain". J. Biol. Chem. 273 (28): 17893–900. doi: 10.1074/jbc.273.28.17893 . PMID   9651395.
  7. ↑ Viklund H, Bernsel A, Skwark M, Elofsson A (2008). "SPOCTOPUS: a combined predictor of signal peptides and membrane protein topology". Bioinformatics. 24 (24): 2928–9. doi: 10.1093/bioinformatics/btn550 . PMID   18945683.
  8. ↑ "Entrez Gene: MMP27".
  9. ↑ Cominelli A, Halbout M, N'Kuli F, Lemoine P, Courtoy PJ, Marbaix E, Tyteca D, Henriet P (2014). "A unique C-terminal domain allows retention of matrix metalloproteinase-27 in the endoplasmic reticulum". Traffic. 15 (4): 401–17. doi: 10.1111/tra.12149 . PMID   24548619. S2CID   38579214.
  10. ↑ Nuttall RK, Sampieri CL, Pennington CJ, Gill SE, Schultz GA, Edwards DR (2004). "Expression analysis of the entire MMP and TIMP gene families during mouse tissue development". FEBS Lett. 563 (1–3): 129–34. Bibcode:2004FEBSL.563..129N. doi: 10.1016/S0014-5793(04)00281-9 . PMID   15063736. S2CID   41113107.
  11. ↑ Bar-Or A, Nuttall RK, Duddy M, Alter A, Kim HJ, Ifergan I, Pennington CJ, Bourgoin P, Edwards DR, Yong VW (2003). "Analyses of all matrix metalloproteinase members in leukocytes emphasize monocytes as major inflammatory mediators in multiple sclerosis". Brain. 126 (Pt 12): 2738–49. doi: 10.1093/brain/awg285 . PMID   14506071.
  12. ↑ Bernal F, Hartung HP, Kieseier BC (2005). "Tissue mRNA expression in rat of newly described matrix metalloproteinases". Biol. Res. 38 (2–3): 267–71. doi: 10.4067/S0716-97602005000200016 . PMID   16238105.
  13. ↑ Gaide Chevronnay HP, Galant C, Lemoine P, Courtoy PJ, Marbaix E, Henriet P (2009). "Spatiotemporal coupling of focal extracellular matrix degradation and reconstruction in the menstrual human endometrium". Endocrinology. 150 (11): 5094–105. doi: 10.1210/en.2009-0750 . PMID   19819954.
  14. ↑ Talbi S, Hamilton AE, Vo KC, Tulac S, Overgaard MT, Dosiou C, Le Shay N, Nezhat CN, Kempson R, Lessey BA, Nayak NR, Giudice LC (2006). "Molecular phenotyping of human endometrium distinguishes menstrual cycle phases and underlying biological processes in normo-ovulatory women". Endocrinology. 147 (3): 1097–121. doi: 10.1210/en.2005-1076 . PMID   16306079.
  15. ↑ Hagemann T, Wilson J, Burke F, Kulbe H, Li NF, Plüddemann A, Charles K, Gordon S, Balkwill FR (2006). "Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype". J. Immunol. 176 (8): 5023–32. doi: 10.4049/jimmunol.176.8.5023 . PMID   16585599.
  16. ↑ Kevorkian L, Young DA, Darrah C, Donell ST, Shepstone L, Porter S, Brockbank SM, Edwards DR, Parker AE, Clark IM (2004). "Expression profiling of metalloproteinases and their inhibitors in cartilage". Arthritis Rheum. 50 (1): 131–41. doi: 10.1002/art.11433 . PMID   14730609.
  17. ↑ Lamblin N, Ratajczak P, Hot D, Dubois E, Chwastyniak M, Beseme O, Drobecq H, Lemoine Y, Koussa M, Amouyel P, Pinet F (2010). "Profile of macrophages in human abdominal aortic aneurysms: a transcriptomic, proteomic, and antibody protein array study". J. Proteome Res. 9 (7): 3720–9. doi:10.1021/pr100250s. PMID   20513153.
  18. ↑ Hegedüs L, Cho H, Xie X, Eliceiri GL (2008). "Additional MDA-MB-231 breast cancer cell matrix metalloproteinases promote invasiveness". J. Cell. Physiol. 216 (2): 480–5. doi:10.1002/jcp.21417. PMID   18286480. S2CID   10734191.
  19. ↑ Köhrmann A, Kammerer U, Kapp M, Dietl J, Anacker J (2009). "Expression of matrix metalloproteinases (MMPs) in primary human breast cancer and breast cancer cell lines: New findings and review of the literature". BMC Cancer. 9: 188. doi: 10.1186/1471-2407-9-188 . PMC   2706257 . PMID   19531263.
  20. ↑ Cominelli A, Gaide Chevronnay HP, Lemoine P, Courtoy PJ, Marbaix E, Henriet P (2014). "Matrix metalloproteinase-27 is expressed in CD163+/CD206+ M2 macrophages in the cycling human endometrium and in superficial endometriotic lesions". Mol. Hum. Reprod. 20 (8): 767–75. doi:10.1093/molehr/gau034. PMID   24810263.

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