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MMP15 (matrix metallopeptidase 15 (membrane-inserted))

Written2012-10Emiko Ito, Ikuo Yana, Nariaki Matsuura
Department of Molecular Pathology, Graduate School of Medicine, Health Sciences, Osaka University, Suita, Osaka 565-0871, Japan

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HGNC (Hugo) MMP15
HGNC Alias symbMT2-MMP
HGNC Previous namematrix metalloproteinase 15 (membrane-inserted)
 matrix metallopeptidase 15 (membrane-inserted)
LocusID (NCBI) 4324
Atlas_Id 41392
Location 16q21  [Link to chromosome band 16q21]
Location_base_pair Starts at 58025754 and ends at 58046900 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping MMP15.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
MMP15 (16q21)::CDH5 (16q21)


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.


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).

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 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 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).


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Membrane-type matrix metalloproteinases 1 and 2 exhibit broad-spectrum proteolytic capacities comparable to many matrix metalloproteinases.
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Eur J Biochem. 1997 Dec 15;250(3):751-7.
PMID 9461298


This paper should be referenced as such :
Ito, E ; Yana, I ; Matsuura, N
MMP15 (matrix metallopeptidase 15 (membrane-inserted))
Atlas Genet Cytogenet Oncol Haematol. 2013;17(3):193-198.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)MMP15   7161
Atlas Explorer : (Salamanque)MMP15
Entrez_Gene (NCBI)MMP15    matrix metallopeptidase 15
AliasesMMP-15; MT2-MMP; MT2MMP; MTMMP2; 
GeneCards (Weizmann)MMP15
Ensembl hg19 (Hinxton)ENSG00000102996 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000102996 [Gene_View]  ENSG00000102996 [Sequence]  chr16:58025754-58046900 [Contig_View]  MMP15 [Vega]
ICGC DataPortalENSG00000102996
TCGA cBioPortalMMP15
AceView (NCBI)MMP15
Genatlas (Paris)MMP15
SOURCE (Princeton)MMP15
Genetics Home Reference (NIH)MMP15
Genomic and cartography
GoldenPath hg38 (UCSC)MMP15  -     chr16:58025754-58046900 +  16q21   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)MMP15  -     16q21   [Description]    (hg19-Feb_2009)
GoldenPathMMP15 - 16q21 [CytoView hg19]  MMP15 - 16q21 [CytoView hg38]
Genome Data Viewer NCBIMMP15 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AW161057 BC006412 BC036495 BC055428 BF507560
RefSeq transcript (Entrez)NM_002428
Consensus coding sequences : CCDS (NCBI)MMP15
Gene ExpressionMMP15 [ NCBI-GEO ]   MMP15 [ EBI - ARRAY_EXPRESS ]   MMP15 [ SEEK ]   MMP15 [ MEM ]
Gene Expression Viewer (FireBrowse)MMP15 [ Firebrowse - Broad ]
GenevisibleExpression of MMP15 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4324
GTEX Portal (Tissue expression)MMP15
Human Protein AtlasENSG00000102996-MMP15 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP51511   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP51511  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP51511
Catalytic activity : Enzyme3.4.24.- [ Enzyme-Expasy ]   3.4.24.-3.4.24.- [ IntEnz-EBI ]   3.4.24.- [ BRENDA ]   3.4.24.- [ KEGG ]   [ MEROPS ]
Domaine pattern : Prosite (Expaxy)CYSTEINE_SWITCH (PS00546)    HEMOPEXIN (PS00024)    HEMOPEXIN_2 (PS51642)    ZINC_PROTEASE (PS00142)   
Domains : Interpro (EBI)Hemopexin-like_dom    Hemopexin-like_dom_sf    Hemopexin-like_repeat    Hemopexin_CS    M10A_MMP    MetalloPept_cat_dom_sf    MMP15    Pept_M10_metallopeptidase    Pept_M10A    Pept_M10A_metallopeptidase_C    Pept_M10A_Zn_BS    Peptidase_Metallo    Peptidoglycan-bd-like    PGBD-like_sf   
Domain families : Pfam (Sanger)DUF3377 (PF11857)    Hemopexin (PF00045)    Peptidase_M10 (PF00413)    PG_binding_1 (PF01471)   
Domain families : Pfam (NCBI)pfam11857    pfam00045    pfam00413    pfam01471   
Domain families : Smart (EMBL)HX (SM00120)  ZnMc (SM00235)  
Conserved Domain (NCBI)MMP15
AlphaFold pdb e-kbP51511   
Human Protein Atlas [tissue]ENSG00000102996-MMP15 [tissue]
Protein Interaction databases
IntAct (EBI)P51511
Ontologies - Pathways
Ontology : AmiGOmetalloendopeptidase activity  protein binding  plasma membrane  integral component of plasma membrane  cellular protein modification process  proteolysis  enzyme activator activity  zinc ion binding  extracellular matrix disassembly  extracellular matrix organization  collagen catabolic process  collagen catabolic process  extracellular matrix  response to estradiol  endodermal cell differentiation  metalloaminopeptidase activity  
Ontology : EGO-EBImetalloendopeptidase activity  protein binding  plasma membrane  integral component of plasma membrane  cellular protein modification process  proteolysis  enzyme activator activity  zinc ion binding  extracellular matrix disassembly  extracellular matrix organization  collagen catabolic process  collagen catabolic process  extracellular matrix  response to estradiol  endodermal cell differentiation  metalloaminopeptidase activity  
REACTOMEP51511 [protein]
REACTOME PathwaysR-HSA-1592389 [pathway]   
NDEx NetworkMMP15
Atlas of Cancer Signalling NetworkMMP15
Wikipedia pathwaysMMP15
Orthology - Evolution
GeneTree (enSembl)ENSG00000102996
Phylogenetic Trees/Animal Genes : TreeFamMMP15
Homologs : HomoloGeneMMP15
Homology/Alignments : Family Browser (UCSC)MMP15
Gene fusions - Rearrangements
Fusion : QuiverMMP15
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMMP15 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MMP15
Exome Variant ServerMMP15
GNOMAD BrowserENSG00000102996
Varsome BrowserMMP15
ACMGMMP15 variants
Genomic Variants (DGV)MMP15 [DGVbeta]
DECIPHERMMP15 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisMMP15 
ICGC Data PortalMMP15 
TCGA Data PortalMMP15 
Broad Tumor PortalMMP15
OASIS PortalMMP15 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICMMP15  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DMMP15
Mutations and Diseases : HGMDMMP15
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)MMP15
DoCM (Curated mutations)MMP15
CIViC (Clinical Interpretations of Variants in Cancer)MMP15
NCG (London)MMP15
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry MMP15
NextProtP51511 [Medical]
Target ValidationMMP15
Huge Navigator MMP15 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDMMP15
Pharm GKB GenePA30873
Clinical trialMMP15
DataMed IndexMMP15
PubMed46 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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