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Matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase)
Protein MMP2 PDB 1ck7.png
PDB rendering based on 1ck7.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols MMP2 ; CLG4; CLG4A; MMP-II; MONA; TBE-1
External IDs OMIM120360 MGI97009 HomoloGene3329 IUPHAR: 1629 ChEMBL: 333 GeneCards: MMP2 Gene
EC number
RNA expression pattern
PBB GE MMP2 201069 at tn.png
More reference expression data
Species Human Mouse
Entrez 4313 17390
Ensembl ENSG00000087245 ENSMUSG00000031740
UniProt P08253 P33434
RefSeq (mRNA) NM_001127891 NM_008610
RefSeq (protein) NP_001121363 NP_032636
Location (UCSC) Chr 16:
55.42 – 55.54 Mb
Chr 8:
92.83 – 92.85 Mb
PubMed search [1] [2]

72 kDa type IV collagenase also known as matrix metalloproteinase-2 (MMP-2) and gelatinase A is an enzyme that in humans is encoded by the MMP2 gene.[1]


Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. This gene encodes an enzyme which degrades type IV collagen, the major structural component of basement membranes. The enzyme plays a role in endometrial menstrual breakdown, regulation of vascularization and the inflammatory response.[2]


Activation of MMP-2 requires proteolytic processing. A complex of membrane type 1 MMP (MT1-MMP/MMP14) and tissue inhibitor of metalloproteinase 2 recruits pro-MMP 2 from the extracellular milieu to the cell surface. Activation then requires an active molecule of MT1-MMP and auto catalytic cleavage. Clustering of integrin chains promotes activation of MMP-2. Another factor that will support the activation of MMP-2 is cell-cell clustering. A wild-type activated leukocyte cell adhesion molecule (ALCAM) is also required to activate MMP-2.

Clinical significance[edit]

Mutations in the MMP2 gene are associated with Torg-Winchester syndrome, multicentric osteolysis, arthritis syndrome,[3] and possibly keloids.


MMP2 has been shown to interact with:


  1. ^ Devarajan P, Johnston JJ, Ginsberg SS, Van Wart HE, Berliner N (December 1992). "Structure and expression of neutrophil gelatinase cDNA. Identity with type IV collagenase from HT1080 cells". J. Biol. Chem. 267 (35): 25228–32. PMID 1460022. 
  2. ^ "Entrez Gene: MMP2 matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase)". 
  3. ^ Martignetti JA, Aqeel AA, Sewairi WA, Boumah CE, Kambouris M, Mayouf SA et al. (July 2001). "Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome". Nat. Genet. 28 (3): 261–5. doi:10.1038/90100. PMID 11431697. 
  4. ^ McQuibban GA, Gong JH, Tam EM, McCulloch CA, Clark-Lewis I, Overall CM (August 2000). "Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3". Science 289 (5482): 1202–6. doi:10.1126/science.289.5482.1202. PMID 10947989. 
  5. ^ a b Bein K, Simons M (October 2000). "Thrombospondin type 1 repeats interact with matrix metalloproteinase 2. Regulation of metalloproteinase activity". J. Biol. Chem. 275 (41): 32167–73. doi:10.1074/jbc.M003834200. PMID 10900205. 
  6. ^ Morgunova E, Tuuttila A, Bergmann U, Tryggvason K (May 2002). "Structural insight into the complex formation of latent matrix metalloproteinase 2 with tissue inhibitor of metalloproteinase 2". Proc. Natl. Acad. Sci. U.S.A. 99 (11): 7414–9. doi:10.1073/pnas.102185399. PMC 124245. PMID 12032297. 
  7. ^ Overall CM, Tam E, McQuibban GA, Morrison C, Wallon UM, Bigg HF et al. (December 2000). "Domain interactions in the gelatinase A.TIMP-2.MT1-MMP activation complex. The ectodomain of the 44-kDa form of membrane type-1 matrix metalloproteinase does not modulate gelatinase A activation". J. Biol. Chem. 275 (50): 39497–506. doi:10.1074/jbc.M005932200. PMID 10991943. 
  8. ^ a b Bigg HF, Shi YE, Liu YE, Steffensen B, Overall CM (June 1997). "Specific, high affinity binding of tissue inhibitor of metalloproteinases-4 (TIMP-4) to the COOH-terminal hemopexin-like domain of human gelatinase A. TIMP-4 binds progelatinase A and the COOH-terminal domain in a similar manner to TIMP-2". J. Biol. Chem. 272 (24): 15496–500. doi:10.1074/jbc.272.24.15496. PMID 9182583. 
  9. ^ a b Kai HS, Butler GS, Morrison CJ, King AE, Pelman GR, Overall CM (December 2002). "Utilization of a novel recombinant myoglobin fusion protein expression system to characterize the tissue inhibitor of metalloproteinase (TIMP)-4 and TIMP-2 C-terminal domain and tails by mutagenesis. The importance of acidic residues in binding the MMP-2 hemopexin C-domain". J. Biol. Chem. 277 (50): 48696–707. doi:10.1074/jbc.M209177200. PMID 12374789. 

Further reading[edit]

  • Massova I, Kotra LP, Fridman R, Mobashery S (1998). "Matrix metalloproteinases: structures, evolution, and diversification". FASEB J. 12 (12): 1075–95. doi:10.1142/S0217984998001256. PMID 9737711. 
  • Nagase H, Woessner JF (1999). "Matrix metalloproteinases". J. Biol. Chem. 274 (31): 21491–4. doi:10.1074/jbc.274.31.21491. PMID 10419448. 
  • Goffin F, Frankenne F, Béliard A, Perrier D'Hauterive S, Pignon MR, Geenen V et al. (2002). "Human endometrial epithelial cells modulate the activation of gelatinase a by stromal cells". Gynecol. Obstet. Invest. 53 (2): 105–11. doi:10.1159/000053003. PMID 11961384. 
  • Hrabec E, Naduk J, Strek M, Hrabec Z (2007). "[Type IV collagenases (MMP-2 and MMP-9) and their substrates--intracellular proteins, hormones, cytokines, chemokines and their receptors]". Postepy Biochem. 53 (1): 37–45. PMID 17718386. 

External links[edit]

  • The MEROPS online database for peptidases and their inhibitors: M10.003