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MMP19 (matrix metallopeptidase 19)

Written2013-10King Chi Chan, Maria Li Lung
Department of Clinical Oncology, Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong, P.R. China

(Note : for Links provided by Atlas : click)


Alias (NCBI)MMP18
HGNC (Hugo) MMP19
HGNC Alias symbRASI-1
HGNC Previous nameMMP18
HGNC Previous namematrix metalloproteinase 19
LocusID (NCBI) 4327
Atlas_Id 41395
Location 12q13.2  [Link to chromosome band 12q13]
Location_base_pair Starts at 55835436 and ends at 55842936 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping MMP19.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)


  Alternative splicing results in multiple transcript variants for this gene (provided by RefSeq, Jan 2013). With reference to UniProtKB database, variant 1 represents the longest transcript and encodes isoform 1 (508 aa, 57 kDa, also known as RASI-1). Variant 2 encoded protein isoform 2 (222 aa, 25 kDa, also known as RASI-9). Variant 3 encoded protein isoform 3 (63 aa, 6 kDa, also known as RASI-6). Isoform 1 has been described as the canonical sequence and all the information described here, unless stated, refers to isoform 1.
Description MMP-19 can be found at chromosome 12q13.2 at location 56229214-56236767. The DNA sequence contains nine exons and eight introns, spanning 7,55 kb.
Transcription The MMP-19 promoter contains a TATA-box at position -29 and AP-1 binding site at position -73. Potential binding sites for other transcription factors such as NFκB, AP-2, and SP-1 also exist (Mueller et al., 2000).


  MMP-19 shares a typical MMP structural domain, containing the signal peptide, propeptide, catalytic domain, hinge region, and four hemopexin repeats (Pendás et al., 1997).
Description MMP-19 is a secreted protein. It contains a signal peptide for targeting to secretory vesicles. Like most secreted MMPs, MMP-19 is translated and secreted as catalytic inactive proproteins (zymogens), which needed to be activated by proteolytic cleavage of the propeptide region by other extracellular matrix (EMC) proteinases (Ra and Parks, 2007).
MMP-19 is a zinc-dependent endopeptidase. The catalytic domain contains the active site for zinc ion binding and functions in catalytic activity such as substrate degradation. The hemopexin domain is responsible for substrate recognition (Ra and Parks, 2007).
The catalytic activities of MMPs were reported to be regulated by tissue inhibitor of metalloproteinases (TIMPs). MMP-19 is reported to be strongly inhibited by TIMP-2, TIMP-3, and TIMP-4, and less efficiently by TIMP-1 (Clark et al., 2008).
Expression MMP-19 was found to be expressed in a wide range of normal tissue types, such as nasopharyngeal epithelial cells, lung, breast, skin, intestine, pancreas, spleen, and ovary. MMP-19 was down-regulated or lost during neoplastic progression in nasopharyngeal carcinoma (NPC), mammary gland tumor, skin neoplasm, intestine, and colon cancers (Pendás et al., 1997; Djonov et al., 2001; Impola et al., 2003; Bister et al., 2004; Chan et al., 2011).
Localisation MMP-19 is located in the cytoplasm and secreted into the extracellular matrix.
Function MMP-19 is a member of the MMP family of zinc-dependent endopeptidases. The catalytic domain responsible for degradation of various components of the ECM include collagen type IV, nidogen-1, fibronectin, tenascin-C isoform, aggrecan, and laminin-5-gamma-2-chain (Stracke et al., 2000; Shiomi et al., 2010). MMP-19 is involved in many physiological activities such as cell proliferation, migration, and anti-angiogenesis.

Implicated in

Entity Various cancers
Note Due to the ability of MMPs to degrade a variety of substrates, which may be involved in both cancer progression and repression, the role of MMP-19 in cancer development is as controversial as for all other MMPs.
MMP-19 is reported to cleave insulin-like growth factor binding protein-3 (IGFBP-3), thereby causing the release of IGF-1 and enhanced human keratinocyte cell proliferation, migration, and adhesion on type I collagen (Sadowski et al., 2003). Also, MMP-19 was reported to process the laminin-5-gamma-2-chain in keratinocyte cells, which leads to the integrin switch favoring epithelial cell migration (Sadowski et al., 2005).
On the other hand, a MMP-19 deficiency mouse model increased the onset of skin tumor invasion and vascularization, implicating the role of MMP-19 in inhibition of tumor invasion and anti-angiogenesis (Jost et al., 2006).
The anti-angiogenic role of MMP-19 was demonstrated in the tube formation assay in human microvascular endothelial cells (HMEC-1). MMP-19 inhibited tube formation by degradation of nidogen-1, which is a scaffolding protein required for stabilizing new capillary formation (Titz et al., 2004). Further studies of MMP-19 on endothelial cells suggested other mechanisms of MMP-19 in inhibition of angiogenesis. MMP-19 digests plasminogen to generate angiostatin-like fragments, which are antagonists of angiogenesis and inhibit migration and proliferation of endothelial cells (Brauer et al., 2011).
Functional studies of MMP-19 demonstrated its tumor suppressive and anti-angiogenesis functions in nasopharyngeal carcinoma (NPC). MMP-19 reduces colony-forming ability of NPC cells and suppresses tumor formation in nude mice. Also, MMP-19 reduces tube-forming ability in human umbilical vein endothelial cells (HuVEC) and human microvascular endothelial cells (HMEC-1). The anti-angiogenic activity of MMP-19 in NPC is associated with reduction of secreted vascular endothelial growth factor (VEGF) in the conditioned media (Chan et al., 2011). Recent study in NPC cells demonstrated MMP-19 increased cisplatin sensitivity through production of γ-H2AX and attenuation of NER activity to repair cisplatin-induced DNA damage, therefore increasing the cisplatin-induced apoptosis in NPC (Liu et al., 2013).
Entity Rheumatoid arthritis (RA)
Note MMP-19 was first isolated as an autoantigen from the synovium of a rheumatoid arthritis patient suggesting its role in RA-associated joint tissue destruction (Sedlacek et al., 1998).


Differential expression of three matrix metalloproteinases, MMP-19, MMP-26, and MMP-28, in normal and inflamed intestine and colon cancer.
Bister VO, Salmela MT, Karjalainen-Lindsberg ML, Uria J, Lohi J, Puolakkainen P, Lopez-Otin C, Saarialho-Kere U.
Dig Dis Sci. 2004 Apr;49(4):653-61.
PMID 15185874
Matrix metalloproteinase-19 inhibits growth of endothelial cells by generating angiostatin-like fragments from plasminogen.
Brauer R, Beck IM, Roderfeld M, Roeb E, Sedlacek R.
BMC Biochem. 2011 Jul 25;12:38. doi: 10.1186/1471-2091-12-38.
PMID 21787393
Catalytic activity of Matrix metalloproteinase-19 is essential for tumor suppressor and anti-angiogenic activities in nasopharyngeal carcinoma.
Chan KC, Ko JM, Lung HL, Sedlacek R, Zhang ZF, Luo DZ, Feng ZB, Chen S, Chen H, Chan KW, Tsao SW, Chua DT, Zabarovsky ER, Stanbridge EJ, Lung ML.
Int J Cancer. 2011 Oct 15;129(8):1826-37. doi: 10.1002/ijc.25855. Epub 2011 Apr 1.
PMID 21165953
The regulation of matrix metalloproteinases and their inhibitors.
Clark IM, Swingler TE, Sampieri CL, Edwards DR.
Int J Biochem Cell Biol. 2008;40(6-7):1362-78. doi: 10.1016/j.biocel.2007.12.006. Epub 2007 Dec 24. (REVIEW)
PMID 18258475
MMP-19: cellular localization of a novel metalloproteinase within normal breast tissue and mammary gland tumours.
Djonov V, Hogger K, Sedlacek R, Laissue J, Draeger A.
J Pathol. 2001 Sep;195(2):147-55.
PMID 11592092
Matrix metalloproteinase-19 is expressed by proliferating epithelium but disappears with neoplastic dedifferentiation.
Impola U, Toriseva M, Suomela S, Jeskanen L, Hieta N, Jahkola T, Grenman R, Kahari VM, Saarialho-Kere U.
Int J Cancer. 2003 Mar 1;103(6):709-16.
PMID 12516088
Earlier onset of tumoral angiogenesis in matrix metalloproteinase-19-deficient mice.
Jost M, Folgueras AR, Frerart F, Pendas AM, Blacher S, Houard X, Berndt S, Munaut C, Cataldo D, Alvarez J, Melen-Lamalle L, Foidart JM, Lopez-Otin C, Noel A.
Cancer Res. 2006 May 15;66(10):5234-41.
PMID 16707448
Overexpression of asparagine synthetase and matrix metalloproteinase 19 confers cisplatin sensitivity in nasopharyngeal carcinoma cells.
Liu RY, Dong Z, Liu J, Zhou L, Huang W, Khoo SK, Zhang Z, Petillo D, Teh BT, Qian CN, Zhang JT.
Mol Cancer Ther. 2013 Oct;12(10):2157-66. doi: 10.1158/1535-7163.MCT-12-1190. Epub 2013 Aug 16.
PMID 23956056
Structure of the human MMP-19 gene.
Mueller MS, Mauch S, Sedlacek R.
Gene. 2000 Jul 11;252(1-2):27-37.
PMID 10903435
Identification and characterization of a novel human matrix metalloproteinase with unique structural characteristics, chromosomal location, and tissue distribution.
Pendas AM, Knauper V, Puente XS, Llano E, Mattei MG, Apte S, Murphy G, Lopez-Otin C.
J Biol Chem. 1997 Feb 14;272(7):4281-6.
PMID 9020145
Control of matrix metalloproteinase catalytic activity.
Ra HJ, Parks WC.
Matrix Biol. 2007 Oct;26(8):587-96. Epub 2007 Jul 7. (REVIEW)
PMID 17669641
Matrix metalloproteinase 19 processes the laminin 5 gamma 2 chain and induces epithelial cell migration.
Sadowski T, Dietrich S, Koschinsky F, Ludwig A, Proksch E, Titz B, Sedlacek R.
Cell Mol Life Sci. 2005 Apr;62(7-8):870-80.
PMID 15868410
Matrix metalloproteinase MMP-19 (RASI-1) is expressed on the surface of activated peripheral blood mononuclear cells and is detected as an autoantigen in rheumatoid arthritis.
Sedlacek R, Mauch S, Kolb B, Schatzlein C, Eibel H, Peter HH, Schmitt J, Krawinkel U.
Immunobiology. 1998 Feb;198(4):408-23.
PMID 9562866
Matrix metalloproteinases, a disintegrin and metalloproteinases, and a disintegrin and metalloproteinases with thrombospondin motifs in non-neoplastic diseases.
Shiomi T, Lemaitre V, D'Armiento J, Okada Y.
Pathol Int. 2010 Jul;60(7):477-96. doi: 10.1111/j.1440-1827.2010.02547.x. (REVIEW)
PMID 20594269
Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protein (COMP).
Stracke JO, Fosang AJ, Last K, Mercuri FA, Pendas AM, Llano E, Perris R, Di Cesare PE, Murphy G, Knauper V.
FEBS Lett. 2000 Jul 28;478(1-2):52-6.
PMID 10922468
Activity of MMP-19 inhibits capillary-like formation due to processing of nidogen-1.
Titz B, Dietrich S, Sadowski T, Beck C, Petersen A, Sedlacek R.
Cell Mol Life Sci. 2004 Jul;61(14):1826-33.
PMID 15241558


This paper should be referenced as such :
Chan, KC ; Lung, ML
MMP19 (matrix metallopeptidase 19)
Atlas Genet Cytogenet Oncol Haematol. 2014;18(5):327-329.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)MMP19   7165
Atlas Explorer : (Salamanque)MMP19
Entrez_Gene (NCBI)MMP19    matrix metallopeptidase 19
AliasesCODA; MMP18; RASI-1
GeneCards (Weizmann)MMP19
Ensembl hg19 (Hinxton)ENSG00000123342 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000123342 [Gene_View]  ENSG00000123342 [Sequence]  chr12:55835436-55842936 [Contig_View]  MMP19 [Vega]
ICGC DataPortalENSG00000123342
TCGA cBioPortalMMP19
AceView (NCBI)MMP19
Genatlas (Paris)MMP19
SOURCE (Princeton)MMP19
Genetics Home Reference (NIH)MMP19
Genomic and cartography
GoldenPath hg38 (UCSC)MMP19  -     chr12:55835436-55842936 -  12q13.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)MMP19  -     12q13.2   [Description]    (hg19-Feb_2009)
GoldenPathMMP19 - 12q13.2 [CytoView hg19]  MMP19 - 12q13.2 [CytoView hg38]
Genome Data Viewer NCBIMMP19 [Mapview hg19]  
OMIM601807   611543   
Gene and transcription
Genbank (Entrez)AK225939 AK297999 AK303202 AL545199 BC030206
RefSeq transcript (Entrez)NM_001032360 NM_001272101 NM_002429 NM_022790 NM_022792
Consensus coding sequences : CCDS (NCBI)MMP19
Gene ExpressionMMP19 [ NCBI-GEO ]   MMP19 [ EBI - ARRAY_EXPRESS ]   MMP19 [ SEEK ]   MMP19 [ MEM ]
Gene Expression Viewer (FireBrowse)MMP19 [ Firebrowse - Broad ]
GenevisibleExpression of MMP19 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4327
GTEX Portal (Tissue expression)MMP19
Human Protein AtlasENSG00000123342-MMP19 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ99542   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ99542  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ99542
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)HEMOPEXIN_2 (PS51642)    ZINC_PROTEASE (PS00142)   
Domains : Interpro (EBI)Hemopexin-like_dom    Hemopexin-like_dom_sf    Hemopexin-like_repeat    M10A_MMP    MetalloPept_cat_dom_sf    MMP19    Pept_M10_metallopeptidase    Pept_M10A    Peptidase_Metallo    Peptidoglycan-bd-like    PGBD-like_sf   
Domain families : Pfam (Sanger)Hemopexin (PF00045)    Peptidase_M10 (PF00413)    PG_binding_1 (PF01471)   
Domain families : Pfam (NCBI)pfam00045    pfam00413    pfam01471   
Domain families : Smart (EMBL)HX (SM00120)  ZnMc (SM00235)  
Conserved Domain (NCBI)MMP19
AlphaFold pdb e-kbQ99542   
Human Protein Atlas [tissue]ENSG00000123342-MMP19 [tissue]
Protein Interaction databases
IntAct (EBI)Q99542
Ontologies - Pathways
Ontology : AmiGOangiogenesis  ovarian follicle development  ovulation from ovarian follicle  luteolysis  metalloendopeptidase activity  metalloendopeptidase activity  metalloendopeptidase activity  serine-type endopeptidase activity  extracellular region  extracellular space  proteolysis  zinc ion binding  response to hormone  extracellular matrix disassembly  cell differentiation  extracellular matrix organization  collagen catabolic process  extracellular matrix  response to cAMP  
Ontology : EGO-EBIangiogenesis  ovarian follicle development  ovulation from ovarian follicle  luteolysis  metalloendopeptidase activity  metalloendopeptidase activity  metalloendopeptidase activity  serine-type endopeptidase activity  extracellular region  extracellular space  proteolysis  zinc ion binding  response to hormone  extracellular matrix disassembly  cell differentiation  extracellular matrix organization  collagen catabolic process  extracellular matrix  response to cAMP  
REACTOMEQ99542 [protein]
REACTOME PathwaysR-HSA-1474228 [pathway]   
NDEx NetworkMMP19
Atlas of Cancer Signalling NetworkMMP19
Wikipedia pathwaysMMP19
Orthology - Evolution
GeneTree (enSembl)ENSG00000123342
Phylogenetic Trees/Animal Genes : TreeFamMMP19
Homologs : HomoloGeneMMP19
Homology/Alignments : Family Browser (UCSC)MMP19
Gene fusions - Rearrangements
Fusion : FusionHubC1ORF63--MMP19    FRS2--MMP19    MMP19--AP2M1    MMP19--FAM114A1    MMP19--HNRNPH1    MMP19--METAZOA_SRP    MMP19--P4HB    MMP19--ZDHHC7    SARNP--MMP19   
Fusion : QuiverMMP19
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMMP19 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MMP19
Exome Variant ServerMMP19
GNOMAD BrowserENSG00000123342
Varsome BrowserMMP19
ACMGMMP19 variants
Genomic Variants (DGV)MMP19 [DGVbeta]
DECIPHERMMP19 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisMMP19 
ICGC Data PortalMMP19 
TCGA Data PortalMMP19 
Broad Tumor PortalMMP19
OASIS PortalMMP19 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICMMP19  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DMMP19
Mutations and Diseases : HGMDMMP19
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)MMP19
DoCM (Curated mutations)MMP19
CIViC (Clinical Interpretations of Variants in Cancer)MMP19
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM601807    611543   
Genetic Testing Registry MMP19
NextProtQ99542 [Medical]
Target ValidationMMP19
Huge Navigator MMP19 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDMMP19
Pharm GKB GenePA30876
Clinical trialMMP19
DataMed IndexMMP19
PubMed69 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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