MMP15 (matrix metallopeptidase 15 (membrane-inserted))

2012-10-01   Emiko Ito  , Ikuo Yana  , Nariaki Matsuura  

Department of Molecular Pathology, Graduate School of Medicine, Health Sciences, Osaka University, Suita, Osaka 565-0871, Japan

Identity

HGNC
LOCATION
16q21
LOCUSID
ALIAS
MMP-15,MT2-MMP,MT2MMP,MTMMP2,SMCP-2
FUSION GENES

DNA/RNA

Atlas Image

Description

This gene can be found on chromosome16 at location: 58028573-58163296.

Transcription

The DNA sequence contains 10 exons and the transcript length: 3530 bp translated to a 699 residues protein.

Proteins

Atlas Image

Description

MT2-MMP belongs to which consist a gene family over 25 different members in humans (refer to MT1-MMP).

Expression

Expression of MT2-MMP has been reported in many cancers, such as glioblastomas, ovarian, urothelial, and breast. In addition, MT2-MMP is involved in endothelial tubulogenesis, malignant conversion of keratinocytes, and is an antiapoptotic factor.
Both MT2-MMP and MT3-MMP were detected predominantly at the interface between the epithelium and substantia propia in mice intracornea infected with Pseudomonas aeruginosa. On the other hand, MT1-MMP was mainly expressed at epithelium in the same tissue (Dong et al., 2000). During pregnancy, MT2-MMP is expressed in the invaded cytotrophoblasts where both MT1-MMP and gelatinase A are extensively colocalized (Bjørn et al., 2000).
Over all, MT2-MMP may plays an important and distinct role from MT1-MMP in normal physiological processes.

Localisation

Plasma membrane.

Function

In a previous study with a cell line established from MT1-MMP gene knocked-out mice, MT2-MMP has been suggested to contribute alternatively to cell invasion through fibrin rich matrices (Hotary et al., 2002).
Like as MT1-MMP, MT2-MMP may also play some role in MMP-2 activation in microenvironment with TIMP-2 involvement (Morrison et al., 2001; Morrison and Overall, 2006).
In corporation with the enzymatic action of MT1-MMP, MT2-MMP can contribute to remodel basement membrane (Hotary et al., 2000; Hotary et al., 2006).

Development
1) Branching morphogenesis
MT2-MMP has been shown to be induced to the epithelia in migration, thereby speculated to be involved in branching morphogenesis of salivery gland (Harunaga et al., 2011), and submandibular gland (Rebustini et al., 2009).
2) Cardia valve development in endocardial cushion
Cardiac valve is constituted by tissue-specific fibroblasts originated from endocardial cushion through EMT. It has been demonstrated that MT2-MMP, which may play a key role in the valve formation, is likely expressed at the period of EMT by Snail1-related signal (Tao et al., 2011).
3) Placenta development (chorionic villus)
It has been demonstrated by separate research groups that MT2-MMP may play a important role in placental labyrinth formation at the period of embryogenesis or in menstrual cycle (Szabova et al., 2010; Plaisier et al., 2006). During the placenta development, MT2-MMP is induced at trophoblasts under TNF alpha-related signal.

Homology

MT2-MMP is supposed to be 72 kDa in molecular weight with overall similarity to MT1-MMP by 73,9%.

Implicated in

Entity name
Cancer progression
Note
Both MT1-MMP and MT2-MMP have potential to play important role in cancer either for proliferation or transmigration through extracellular matrix (ECM). Ota and his colleagues have suggested that membrane-localized proteolytic enzyme such as MT1/2-MMP can be induced and recruited towards the tumor cell surface during epithelial-mesenchymal transition (EMT) mediated by Snail1-related signal (Ota et al., 2009). Other group has indicated that cancer cells, such as PANC-1, induce MT2-MMP under hypoxia in a HIF-1 dependent manner (Zhu et al., 2011). These data suggest MT2-MMP may play some role in cancer progression against the physiological stress. It has not been clarified, however, that MT2-MMP can entirely substitute the function of MT1-MMP and vice versa.
Several IHS analyses with clinical samples suggested that MT2-MMP is expressed in several tumor types which include esophageal (Chen et al., 2010), bladder (Mohammad et al., 2010), colorectal (Lyall et al., 2006), and urothelial carcinoma (Kitagawa et al., 1998). In such reports for the colorectal and bladder cancer, the expression of MT2-MMP was shown to be associated with disease prognosis (Lyall et al., 2006; Mohammad et al., 2010).
Entity name
Idiopathic pulmonary fibrosis (IPF)
Note
IPF is a disease characterized by fibroblast expansion and ECM accumulation in lung. A previous report suggests MT1-MMP as well as MT2-MMP, was expressed in alveolar epithelial cells, and active MMP-2 was increased in bronchoalveolar lavage (BAL) fluids in IPF tissue. These MMPs possibly play roles in the pathogeny (García-Alvarez et al., 2006).

Article Bibliography

Pubmed IDLast YearTitleAuthors

Other Information

Locus ID:

NCBI: 4324
MIM: 602261
HGNC: 7161
Ensembl: ENSG00000102996

Variants:

dbSNP: 4324
ClinVar: 4324
TCGA: ENSG00000102996
COSMIC: MMP15

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000102996ENST00000219271P51511
ENSG00000102996ENST00000219271A0A024R6U8
ENSG00000102996ENST00000570065H3BT97

Expression (GTEx)

0
10
20
30
40
50
60
70
80
90
100

Pathways

PathwaySourceExternal ID
Extracellular matrix organizationREACTOMER-HSA-1474244
Degradation of the extracellular matrixREACTOMER-HSA-1474228
Activation of Matrix MetalloproteinasesREACTOMER-HSA-1592389
Collagen degradationREACTOMER-HSA-1442490

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
349889962022Bi-allelic null variant in matrix metalloproteinase-15, causes congenital cardiac defect, cholestasis jaundice, and failure to thrive.3
350419852022MT2-MMP is differentially expressed in multiple myeloma cells and mediates their growth and progression.3
350620572022Changes in the expression of membrane type-matrix metalloproteinases genes (MMP14, MMP15, MMP16, MMP24) during treatment and their potential impact on the survival of patients with non-small cell lung cancer (NSCLC).5
349889962022Bi-allelic null variant in matrix metalloproteinase-15, causes congenital cardiac defect, cholestasis jaundice, and failure to thrive.3
350419852022MT2-MMP is differentially expressed in multiple myeloma cells and mediates their growth and progression.3
350620572022Changes in the expression of membrane type-matrix metalloproteinases genes (MMP14, MMP15, MMP16, MMP24) during treatment and their potential impact on the survival of patients with non-small cell lung cancer (NSCLC).5
320498622020Dominative role of MMP-14 over MMP-15 in human urinary bladder carcinoma on the basis of its enhanced specific activity.7
325175712020Effect of indole-3-carbinol on transcriptional profiling of wound-healing genes in macrophages of systemic lupus erythematosus patients: an RNA sequencing assay.4
320498622020Dominative role of MMP-14 over MMP-15 in human urinary bladder carcinoma on the basis of its enhanced specific activity.7
325175712020Effect of indole-3-carbinol on transcriptional profiling of wound-healing genes in macrophages of systemic lupus erythematosus patients: an RNA sequencing assay.4
305990802019LncRNA MAFG-AS1 facilitates the migration and invasion of NSCLC cell via sponging miR-339-5p from MMP15.33
308098502019The prognostic value of matrix metalloproteinase-7 and matrix metalloproteinase-15 in acute myeloid leukemia.9
305990802019LncRNA MAFG-AS1 facilitates the migration and invasion of NSCLC cell via sponging miR-339-5p from MMP15.33
308098502019The prognostic value of matrix metalloproteinase-7 and matrix metalloproteinase-15 in acute myeloid leukemia.9
290618812017E-cadherin cleavage by MT2-MMP regulates apical junctional signaling and epithelial homeostasis in the intestine.11

Citation

Emiko Ito ; Ikuo Yana ; Nariaki Matsuura

MMP15 (matrix metallopeptidase 15 (membrane-inserted))

Atlas Genet Cytogenet Oncol Haematol. 2012-10-01

Online version: http://atlasgeneticsoncology.org/gene/41392/mmp15