MMP2

Gene Information
 
Gene Symbol
MMP2
 
Aliases
CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1
 
Entrez Gene ID
 
Gene Name
Matrix metallopeptidase 2
 
Chromosomal Location
16q12.2
 
HGNC ID
 
Summary
This gene is a member of the matrix metalloproteinase (MMP) gene family, that are zinc-dependent enzymes capable of cleaving components of the extracellular matrix and molecules involved in signal transduction. The protein encoded by this gene is a gelatinase A, type IV collagenase, that contains three fibronectin type II repeats in its catalytic site that allow binding of denatured type IV and V collagen and elastin. Unlike most MMP family members, activation of this protein can occur on the cell membrane. This enzyme can be activated extracellularly by proteases, or, intracellulary by its S-glutathiolation with no requirement for proteolytical removal of the pro-domain. This protein is thought to be involved in multiple pathways including roles in the nervous system, endometrial menstrual breakdown, regulation of vascularization, and metastasis. Mutations in this gene have been associated with Winchester syndrome and Nodulosis-Arthropathy-Osteolysis (NAO) syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]
 
RefSeq DNA
 
RefSeq mRNA
  e!Ensembl
Gene
Transcript  
Protein

Gene Ontology (GO)

GO ID Ontology Function Evidence Reference
GO:0001666 Biological process Response to hypoxia IBA 21873635
GO:0006508 Biological process Proteolysis IDA 15863497
GO:0022617 Biological process Extracellular matrix disassembly TAS 24970228
GO:0030198 Biological process Extracellular matrix organization IBA 21873635
GO:0030574 Biological process Collagen catabolic process IBA 21873635
Protein Information
 
Protein Name
72 kDa type IV collagenase, collagenase type IV-A, matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase), matrix metalloproteinase-2, matrix metalloproteinase-II, neutrophil gelatinase
 
Function
Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of the fibrovascular tissues in association with MMP14.; PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels.; [Isoform 2]: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways
 
Refseq Proteins
 
UniProt
 
PDB
 
Pfam
Pfam Accession Pfam ID
PF00040 fn2
PF00045 Hemopexin
PF00413 Peptidase_M10
PF01471 PG_binding_1
Pathways
 
KEGG
 
Reactome
 

Endocrine resistance
Leukocyte transendothelial migration
GnRH signaling pathway
Estrogen signaling pathway
Relaxin signaling pathway
AGE-RAGE signaling pathway in diabetic complications
Pathways in cancer
Proteoglycans in cancer
Bladder cancer
Fluid shear stress and atherosclerosis

 

Collagen degradation
Degradation of the extracellular matrix
Activation of Matrix Metalloproteinases
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
EPH-ephrin mediated repulsion of cells
Interleukin-4 and Interleukin-13 signaling
Extra-nuclear estrogen signaling

Interactions
 
STRING MINT IntAct
ENSP00000230588 Q16819 Q16819
    View interactions
     

Associated Diseases

Disease groupDisease NameReferences
Cardiovascular Diseases
Aortic Rupture
Myocardial Infarction
Aortic Aneurysm
Hypertensive disease
Aortic Diseases
References
 
 
PubMed ID Associated gene/s Associated condition Genetic Mutation Diagnostic Criteria Association with PCOS Ethnicity Conclusion
MMP-9 and TIMP-1 
Follicular atresia, formation of multiple ovarian cysts 
 
 
Related 
 
Thus the MMP-TIMP balance is shifted toward greater MMP activity in luteinized granulosa cells from women with PCOS 
MMP-9, TIMP-1 
Cardiovascular risk,menstrual irregularities 
 
Rotterdam criteria 
Related 
 
Obese women with PCOS have elevated serum concentrations of MMP-2 and -9. 
MMP-9, TIMP-1, TIMP-2 
 
 
 
Related 
 
Significantly higher levels of MMP-2 and MMP-9 were found in the PCOS group compared to controls. 
MMP-8, MMP-9, TIMP-1, TIMP-2 
 
 
 
Related 
 
We found higher MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in PCOS patients than in healthy controls 
AP-1,EGR-1,TF 
Chronic low-grade inflammation,atherothrombosis,hyperandrogenism 
 
Rotterdam criteria 
Related 
 
Lean women with PCOS exhibited greater AP-1 activation and MMP2 protein content after glucose ingestion and higher plasma MMP9 and CRP levels than lean controls 

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