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MMP15 (matrix metallopeptidase 15 (membrane-inserted))

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

(Note : for Links provided by Atlas : click)

Identity

Alias_namesmatrix metalloproteinase 15 (membrane-inserted)
matrix metallopeptidase 15 (membrane-inserted)
Alias_symbol (synonym)MT2-MMP
MTMMP2
SMCP-2
Other alias
HGNC (Hugo) MMP15
LocusID (NCBI) 4324
Atlas_Id 41392
Location 16q21  [Link to chromosome band 16q21]
Location_base_pair Starts at 58025566 and ends at 58046900 bp from pter ( according to hg19-Feb_2009)  [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)

DNA/RNA

 
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.

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).

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

Note
  
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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Transcriptional upregulation of MT2-MMP in response to hypoxia is promoted by HIF-1? in cancer cells.
Zhu S, Zhou Y, Wang L, Zhang J, Wu H, Xiong J, Zhang J, Tian Y, Wang C, Wu H.
Mol Carcinog. 2011 Oct;50(10):770-80. doi: 10.1002/mc.20678. Epub 2011 Jul 12.
PMID 21751260
 
Membrane-type matrix metalloproteinases 1 and 2 exhibit broad-spectrum proteolytic capacities comparable to many matrix metalloproteinases.
d'Ortho MP, Will H, Atkinson S, Butler G, Messent A, Gavrilovic J, Smith B, Timpl R, Zardi L, Murphy G.
Eur J Biochem. 1997 Dec 15;250(3):751-7.
PMID 9461298
 

Citation

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 ]
On line version : http://AtlasGeneticsOncology.org/Genes/MMP15ID41392ch16q21.html


External links

Nomenclature
HGNC (Hugo)MMP15   7161
Cards
AtlasMMP15ID41392ch16q21
Entrez_Gene (NCBI)MMP15  4324  matrix metallopeptidase 15
AliasesMMP-15; MT2-MMP; MT2MMP; MTMMP2; 
SMCP-2
GeneCards (Weizmann)MMP15
Ensembl hg19 (Hinxton)ENSG00000102996 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000102996 [Gene_View]  chr16:58025566-58046900 [Contig_View]  MMP15 [Vega]
ICGC DataPortalENSG00000102996
TCGA cBioPortalMMP15
AceView (NCBI)MMP15
Genatlas (Paris)MMP15
WikiGenes4324
SOURCE (Princeton)MMP15
Genetics Home Reference (NIH)MMP15
Genomic and cartography
GoldenPath hg38 (UCSC)MMP15  -     chr16:58025566-58046900 +  16q21   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)MMP15  -     16q21   [Description]    (hg19-Feb_2009)
EnsemblMMP15 - 16q21 [CytoView hg19]  MMP15 - 16q21 [CytoView hg38]
Mapping of homologs : NCBIMMP15 [Mapview hg19]  MMP15 [Mapview hg38]
OMIM602261   
Gene and transcription
Genbank (Entrez)AW161057 BC006412 BC036495 BC055428 BF507560
RefSeq transcript (Entrez)NM_002428
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)MMP15
Cluster EST : UnigeneHs.80343 [ NCBI ]
CGAP (NCI)Hs.80343
Alternative Splicing GalleryENSG00000102996
Gene ExpressionMMP15 [ NCBI-GEO ]   MMP15 [ EBI - ARRAY_EXPRESS ]   MMP15 [ SEEK ]   MMP15 [ MEM ]
Gene Expression Viewer (FireBrowse)MMP15 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression 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
Splice isoforms : SwissVarP51511
Catalytic activity : Enzyme3.4.24.- [ Enzyme-Expasy ]   3.4.24.-3.4.24.- [ IntEnz-EBI ]   3.4.24.- [ BRENDA ]   3.4.24.- [ KEGG ]   
PhosPhoSitePlusP51511
Domaine pattern : Prosite (Expaxy)CYSTEINE_SWITCH (PS00546)    HEMOPEXIN (PS00024)    HEMOPEXIN_2 (PS51642)    ZINC_PROTEASE (PS00142)   
Domains : Interpro (EBI)Hemopexin-like_dom    Hemopexin-like_repeat    Hemopexin_CS    M10A_MMP    MetalloPept_cat_dom    MMP15    Pept_M10_metallopeptidase    Pept_M10A    Pept_M10A_metallopeptidase_C    Pept_M10A_stromelysin-type    Pept_M10A_Zn_BS    Peptidase_Metallo    Peptidoglycan-bd-like   
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
DMDM Disease mutations4324
Blocks (Seattle)MMP15
SuperfamilyP51511
Human Protein Atlas [tissue]ENSG00000102996-MMP15 [tissue]
Peptide AtlasP51511
HPRD03775
IPIIPI00019242   IPI00921047   
Protein Interaction databases
DIP (DOE-UCLA)P51511
IntAct (EBI)P51511
FunCoupENSG00000102996
BioGRIDMMP15
STRING (EMBL)MMP15
ZODIACMMP15
Ontologies - Pathways
QuickGOP51511
Ontology : AmiGOmetalloendopeptidase activity  calcium ion binding  protein binding  plasma membrane  integral component of plasma membrane  cellular protein modification process  proteolysis  enzyme activator activity  zinc ion binding  extracellular matrix disassembly  collagen catabolic process  extracellular matrix  response to estradiol  endodermal cell differentiation  positive regulation of catalytic activity  metalloaminopeptidase activity  
Ontology : EGO-EBImetalloendopeptidase activity  calcium ion binding  protein binding  plasma membrane  integral component of plasma membrane  cellular protein modification process  proteolysis  enzyme activator activity  zinc ion binding  extracellular matrix disassembly  collagen catabolic process  extracellular matrix  response to estradiol  endodermal cell differentiation  positive regulation of catalytic activity  metalloaminopeptidase activity  
REACTOMEP51511 [protein]
REACTOME PathwaysR-HSA-1592389 [pathway]   
NDEx NetworkMMP15
Atlas of Cancer Signalling NetworkMMP15
Wikipedia pathwaysMMP15
Orthology - Evolution
OrthoDB4324
GeneTree (enSembl)ENSG00000102996
Phylogenetic Trees/Animal Genes : TreeFamMMP15
HOVERGENP51511
HOGENOMP51511
Homologs : HomoloGeneMMP15
Homology/Alignments : Family Browser (UCSC)MMP15
Gene fusions - Rearrangements
Fusion: TCGAMMP15 16q21 CDH5 16q21 BLCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMMP15 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MMP15
dbVarMMP15
ClinVarMMP15
1000_GenomesMMP15 
Exome Variant ServerMMP15
ExAC (Exome Aggregation Consortium)ENSG00000102996
GNOMAD BrowserENSG00000102996
Genetic variants : HAPMAP4324
Genomic Variants (DGV)MMP15 [DGVbeta]
DECIPHERMMP15 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisMMP15 
Mutations
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]  
Mutations and Diseases : HGMDMMP15
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch MMP15
DgiDB (Drug Gene Interaction Database)MMP15
DoCM (Curated mutations)MMP15 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)MMP15 (select a term)
intoGenMMP15
NCG5 (London)MMP15
Cancer3DMMP15(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM602261   
Orphanet
MedgenMMP15
Genetic Testing Registry MMP15
NextProtP51511 [Medical]
TSGene4324
GENETestsMMP15
Target ValidationMMP15
Huge Navigator MMP15 [HugePedia]
snp3D : Map Gene to Disease4324
BioCentury BCIQMMP15
ClinGenMMP15
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD4324
Chemical/Pharm GKB GenePA30873
Clinical trialMMP15
Miscellaneous
canSAR (ICR)MMP15 (select the gene name)
Probes
Litterature
PubMed35 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineMMP15
EVEXMMP15
GoPubMedMMP15
iHOPMMP15
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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