MMP2 (matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase).

2005-10-01   Gopal Chandra Kundu , Pralhad Deepak Patil 

CSIR-JRF,c\\\/o Dr. G. C. Kundu, National Center for Cell Science, NCCS Complex, Ganeshkhind, Pune(Maharastra)-411007, India




Atlas Image


This gene can be found on chromosome 16 at location: 54,070,604-54,097,652


The DNA sequence contains 13 exons and the transcript length: 3,069 bps translated to a 660 residues protein.


Atlas Image
Domain structure of the MMP2.
  • Pre: signal sequence;
  • Pro: propeptide with a free zinc-ligating thiol (SH) group;
  • Zn: zinc-binding site;
  • II: collagen-binding fibronectin type II inserts;
  • H: hinge region;
  • The hemopexin/vitronectin-like domain contains four repeats with the first and last linked by a disulfide bond.


    MMP2 is a Zn+2 dependent endopeptidase, synthesized and secreted in zymogen form. The nascent form of the protein shows an N-terminal signal sequence ("pre" domain) that directs the protein to the endoplasmic reticulum. The pre domain is followed by a propeptide-"pro" domain that maintains enzyme-latency until cleaved or disrupted, and a catalytic domain that contains the conserved zinc-binding region. A hemopexin/vitronectin-like domain is also seen, that is connected to the catalytic domain by a hinge or linker region. The hemopexin domain is involved in TIMP (Tissue Inhibitors of Metallo-Proteinases) binding, the binding of certain substrates, membrane activation, and some proteolytic activities. It also shows a series of three head-to-tail cysteine-rich repeats within its catalytic domain. These inserts resemble the collagen-binding type II repeats of fibronectin and are required to bind and cleave collagen and elastin.

    The regulation of MMP-2 activity occurs at many levels, of which regulation through TIMP-2 and its cell surface receptor, MT1-MMP (MMP14) is critically decisive. At higher levels of TIMP-2, MT1-MMP forms a ternary complex with MMP-2 through, leaving no free MT1-MMP receptors, thereby inhibiting the activation of pro-MMP-2 by MT1-MMP. But at lower levels of TIMP-2, due to availability of free MT1-MMP, MT1-MMP mediated activation of MMP-2 is observed. Further data also indicates that expression of TIMP-2, MMP-2 and MT1-MMP (MMP-14) is co-regulated transcriptionally, demonstrating an intricate network of regulation. Pro-MMP-2 activation is also seen by complex signaling induced by ECM proteins like osteopontin, various cytokines for example IL-8 in endothelial cells and other factors.


    MMP2 is tightly regulated at the transcriptional and post-transcriptional levels.




    Primary function is degradation of proteins in the extracellular matrix. It proteolytically digests gelatin (denatured collagen), and types IV, V, VII, IX and X collagen. Physiologically, MMP-2 in coordination with other MMPs, play a role in normal tissue remodeling events such as embryonic development, angiogenesis, ovulation, mammary gland involution and wound healing. MMP2 is also involved in osteoblastic bone formation and/or inhibits osteoclastic bone resorption.


    Homology in amino acid sequence is seen with the other members of Metalloproteinase family especially with MMP-9.



    A G-to-A transition in codon 101 of exon 2 of MMP2 gene was detected in a Saudi family with idiopathic multicentric osteolysis. This mutation showed a replacement of an arginine by histidine (R101H) in the prodomain, a region highly conserved across species and other members of the MMP gene family that is involved in autoproteolytic activation of MMP2.
    In a case of Winchester Syndrome, a homozygous 1210G-A transition in exon 8 of the MMP2 gene, leads to glu-to-lys (E404K) substitution in the catalytic domain of the protein. The glutamic acid at codon 404 is believed to be essential for the peptidase activity of all metalloproteinases, as its carboxyl group catalyzes 2 proton transfers, helps stabilize the transition state, and triggers the release of the products.

    Implicated in

    Entity name
    Elevated expression of MMP-2, along with MMP-9 is usually seen in invasive and highly tumorigenic cancers such as colorectal tumors, gastric carcinoma, pancreatic carcinoma, breast cancer, oral cancer, melanoma, malignant gliomas, Chondrosarcoma, gastrointestinal adenocarcinoma. Levels are also increased in malignant astrocytomas, carcinomatous meningitis, and brain metastases.
    MMPs promote tumor progression and metastasis in invasive cancers by degradation of the ECM (ExtraCellular Matrix), which consists of two main components: Basement membranes and interstitial connective tissue. Though ECM comprises of many proteins (laminin-5, proteoglycans, entactin, osteonectin) collagen IV is the major element. MMP-2 & MMP-9 efficiently degrade collagen IV and laminin-5 thereby, assisting the metastatic cancerous cells to pass through the basement membrane. The degradation of ECM not only assists migration of metastatic cancerous cells, but also allows enhanced tumor growth by providing necessary space. Further, it is noteworthy that the ratio of active to latent form of MMP-2 increased with tumor progression in invasive cancers. MMP-2, with its family members also promotes angiogenesis (a critical process required for tumor cell survival) by degrading the vascular basement membrane and the interstitium.
    Arthritis, Autosomal recessive osteolysis disorder, Coronary Artery disease, pulmonary-emphysema and diabetic retinopathy.


    Pubmed IDLast YearTitleAuthors
    121675812002Matrix metalloproteinases and their role in pancreatic cancer: a review of preclinical studies and clinical trials.Bloomston M et al
    84947111993Activity of type IV collagenases in benign and malignant breast disease.Davies B et al
    110626052000Active synovial matrix metalloproteinase-2 is associated with radiographic erosions in patients with early synovitis.Goldbach-Mansky R et al
    65253361984An interactive computer graphics study of thermolysin-catalyzed peptide cleavage and inhibition by N-carboxymethyl dipeptides.Hangauer DG et al
    113492152001The role of matrix metalloproteinases in tumor angiogenesis and tumor metastasis.John A et al
    161326192005Autocrine role of interleukin-8 in induction of endothelial cell proliferation, survival, migration and MMP-2 production and angiogenesis.Li A et al
    114316972001Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome.Martignetti JA et al
    129528362003Matrix metalloproteinases as novel disease markers in Takayasu arteritis.Matsuyama A et al
    103563961999Structure of human pro-matrix metalloproteinase-2: activation mechanism revealed.Morgunova E et al
    121101222002Matrix metalloproteinases in arthritic disease.Murphy G et al
    127146572003Production and activation of matrix metalloproteinase-2 in proliferative diabetic retinopathy.Noda K et al
    157507842004Matrix metalloproteinase-2: mechanism and regulation of NF-kappaB-mediated activation and its role in cell motility and ECM-invasion.Philip S et al
    124736702003Osteopontin induces nuclear factor kappa B-mediated promatrix metalloproteinase-2 activation through I kappa B alpha /IKK signaling pathways, and curcumin (diferulolylmethane) down-regulates these pathways.Philip S et al
    102259661999Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention.Stetler-Stevenson WG et al
    114316822001Don't mess with the matrix.Vu TH et al
    156913652005Winchester syndrome caused by a homozygous mutation affecting the active site of matrix metalloproteinase 2.Zankl A et al
    103341901999Loss of basement membrane type IV collagen is associated with increased expression of metalloproteinases 2 and 9 (MMP-2 and MMP-9) during human colorectal tumorigenesis.Zeng ZS et al

    Other Information

    Locus ID:

    NCBI: 4313
    MIM: 120360
    HGNC: 7166
    Ensembl: ENSG00000087245


    dbSNP: 4313
    ClinVar: 4313
    TCGA: ENSG00000087245


    Gene IDTranscript IDUniprot

    Expression (GTEx)



    PathwaySourceExternal ID
    Leukocyte transendothelial migrationKEGGko04670
    GnRH signaling pathwayKEGGko04912
    Bladder cancerKEGGko05219
    Leukocyte transendothelial migrationKEGGhsa04670
    GnRH signaling pathwayKEGGhsa04912
    Pathways in cancerKEGGhsa05200
    Bladder cancerKEGGhsa05219
    Proteoglycans in cancerKEGGhsa05205
    Proteoglycans in cancerKEGGko05205
    Estrogen signaling pathwayKEGGhsa04915
    Estrogen signaling pathwayKEGGko04915
    Metabolism of proteinsREACTOMER-HSA-392499
    Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)REACTOMER-HSA-381426
    Immune SystemREACTOMER-HSA-168256
    Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
    Signaling by InterleukinsREACTOMER-HSA-449147
    Extracellular matrix organizationREACTOMER-HSA-1474244
    Degradation of the extracellular matrixREACTOMER-HSA-1474228
    Activation of Matrix MetalloproteinasesREACTOMER-HSA-1592389
    Collagen degradationREACTOMER-HSA-1442490
    Developmental BiologyREACTOMER-HSA-1266738
    Axon guidanceREACTOMER-HSA-422475
    EPH-Ephrin signalingREACTOMER-HSA-2682334
    EPH-ephrin mediated repulsion of cellsREACTOMER-HSA-3928665
    AGE-RAGE signaling pathway in diabetic complicationsKEGGko04933
    AGE-RAGE signaling pathway in diabetic complicationsKEGGhsa04933
    Endocrine resistanceKEGGko01522
    Endocrine resistanceKEGGhsa01522
    Interleukin-4 and 13 signalingREACTOMER-HSA-6785807
    Fluid shear stress and atherosclerosisKEGGko05418
    Fluid shear stress and atherosclerosisKEGGhsa05418

    Protein levels (Protein atlas)

    Not detected


    Pubmed IDYearTitleCitations
    174293932007Mediators of vascular remodelling co-opted for sequential steps in lung metastasis.248
    118395882002Shedding of the matrix metalloproteinases MMP-2, MMP-9, and MT1-MMP as membrane vesicle-associated components by endothelial cells.140
    183403782008The initial steps of ovarian cancer cell metastasis are mediated by MMP-2 cleavage of vitronectin and fibronectin.125
    170654362006Matrix metalloproteinases expressed by astrocytes mediate extracellular amyloid-beta peptide catabolism.102
    180939862008Visfatin induces human endothelial VEGF and MMP-2/9 production via MAPK and PI3K/Akt signalling pathways: novel insights into visfatin-induced angiogenesis.102
    245700262015Neutrophil extracellular traps induce endothelial dysfunction in systemic lupus erythematosus through the activation of matrix metalloproteinase-2.99
    145003492003Matrix metalloproteinases (MMP9 and MMP2) induce the release of vascular endothelial growth factor (VEGF) by ovarian carcinoma cells: implications for ascites formation.94
    186448622008The AIB1 oncogene promotes breast cancer metastasis by activation of PEA3-mediated matrix metalloproteinase 2 (MMP2) and MMP9 expression.88
    155699942004Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer with a special reference to activator protein-2, HER2, and prognosis.85
    199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85


    Gopal Chandra Kundu ; Pralhad Deepak Patil

    MMP2 (matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase).

    Atlas Genet Cytogenet Oncol Haematol. 2005-10-01

    Online version: