72 kDa type IV collagenase

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.

Classification

Family (Pfam)

PF00040 fn2, PF00045 Hemopexin, PF00413 Peptidase_M10

InterPro

FN_type2_dom, FN_type2_sf, Hemopexin-like_dom, Hemopexin-like_dom_sf, Hemopexin-like_repeat, Hemopexin_CS, Kringle-like, M10A_MMP, MetalloPept_cat_dom_sf, Pept_M10_metallopeptidase, Pept_M10A, Pept_M10A_Zn_BS, Peptidase_Metallo, PGBD-like_sf

Functional cluster

Venom Serine Proteases & Phospholipase A2

Experimental structures · PDB · 14

• 1CK7 X-ray 2.80A
• 1CXW NMR
• 1EAK X-ray 2.66A
• 1GEN X-ray 2.15A
• 1GXD X-ray 3.10A
• 1HOV NMR
• 1J7M NMR
• 1KS0 NMR
• 1QIB X-ray 2.80A
• 1RTG X-ray 2.60A
• 3AYU X-ray 2.00A
• 7XGJ X-ray 2.80A
• … and 2 more

A predicted model is available from AlphaFold.

Gene Ontology · 52

• GO:0031012 extracellular matrix
• GO:0005576 extracellular region
• GO:0005615 extracellular space
• GO:0005739 mitochondrion
• GO:0005634 nucleus
• GO:0005886 plasma membrane
• GO:0030017 sarcomere
• GO:0004175 endopeptidase activity
• GO:0001968 fibronectin binding
• GO:0004222 metalloendopeptidase activity
• GO:0008237 metallopeptidase activity
• GO:0004252 serine-type endopeptidase activity
• GO:0008270 zinc ion binding
• GO:0001525 angiogenesis
• GO:0016477 cell migration
• GO:0071392 cellular response to estradiol stimulus
• GO:0071498 cellular response to fluid shear stress
• GO:0071347 cellular response to interleukin-1
• GO:0071492 cellular response to UV-A
• GO:0030574 collagen catabolic process
• GO:0035987 endodermal cell differentiation
• GO:0048013 ephrin receptor signaling pathway
• GO:0022617 extracellular matrix disassembly
• GO:0030198 extracellular matrix organization
• GO:0007507 heart development
• GO:0001553 luteinization
• GO:0048246 macrophage chemotaxis
• GO:0007162 negative regulation of cell adhesion
• GO:0045906 negative regulation of vasoconstriction
• GO:0001541 ovarian follicle development
• GO:0001542 ovulation from ovarian follicle
• GO:0007567 parturition
• GO:0014012 peripheral nervous system axon regeneration
• GO:0030335 positive regulation of cell migration
• GO:1903378 positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
• GO:1904707 positive regulation of vascular associated smooth muscle cell proliferation
• GO:0060740 prostate gland epithelium morphogenesis
• GO:0030163 protein catabolic process
• GO:0006508 proteolysis
• GO:0014823 response to activity
• GO:1904645 response to amyloid-beta
• GO:0051602 response to electrical stimulus
• GO:0043627 response to estrogen
• GO:0042542 response to hydrogen peroxide
• GO:0055093 response to hyperoxia
• GO:0001666 response to hypoxia
• GO:0009612 response to mechanical stimulus
• GO:0035094 response to nicotine
• GO:0032526 response to retinoic acid
• GO:0009410 response to xenobiotic stimulus
• GO:0048771 tissue remodeling
• GO:0061450 trophoblast cell migration

Disease associations

• multicentric osteolysis, nodulosis, and arthropathy MONDO:0009809

Drugs targeting this protein · 3

• MARIMASTAT inhibitor
• CTS-1027 inhibitor
• REBIMASTAT inhibitor

Related proteins · sequence + function similarity

• 72 kDa type IV collagenase 0.99
• 72 kDa type IV collagenase 0.99
• 72 kDa type IV collagenase 0.99
• 72 kDa type IV collagenase 0.99
• 72 kDa type IV collagenase 0.97
• Matrix metalloproteinase-9 0.90
• Matrix metalloproteinase-9 0.89
• Matrix metalloproteinase-9 0.87
• Matrix metalloproteinase-9 0.87
• Stromelysin-2 0.86
• Matrix metalloproteinase-9 0.85
• Stromelysin-1 0.85

Co-cited proteins · studied together in the literature

• Metalloproteinase inhibitor 2 4 shared papers
• 72 kDa type IV collagenase 1 shared papers
• Gingipain R2 1 shared papers
• Matrix metalloproteinase-14 1 shared papers
• Matrix metalloproteinase-9 2 shared papers
• Metastasis-suppressor KiSS-1 1 shared papers
• Glycogen synthase kinase-3 beta 1 shared papers
• Histatin-3 1 shared papers

Literature · 38 cited papers

• Resveratrol-induced changes of the human adipocyte secretion profile. J. Proteome Res. · 2012
• A novel intracellular isoform of matrix metalloproteinase-2 induced by oxidative stress activates innate immunity. PLoS ONE · 2012
• Structural basis for matrix metalloproteinase-2 (MMP-2)-selective inhibitory action of beta-amyloid precursor protein-derived inhibitor. J. Biol. Chem. · 2011
• Glycogen synthase kinase-3beta is activated by matrix metalloproteinase-2 mediated proteolysis in cardiomyoblasts. Cardiovasc. Res. · 2009
• Aspirin inhibits MMP-2 and MMP-9 expressions and activities through upregulation of PPARalpha/gamma and TIMP gene expressions in ox-LDL-stimulated macrophages derived from human monocytes. Pharmacology · 2009
• Regulation of matrix metalloproteinase-2 (MMP-2) activity by phosphorylation. FASEB J. · 2007
• The consensus coding sequences of human breast and colorectal cancers. Science · 2006
• A novel homozygous MMP2 mutation in a family with Winchester syndrome. Clin. Genet. · 2006
• Winchester syndrome caused by a homozygous mutation affecting the active site of matrix metalloproteinase 2. Clin. Genet. · 2005
• The sequence and analysis of duplication-rich human chromosome 16. Nature · 2004
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Matrix metalloproteinase-2 (MMP-2) is present in the nucleus of cardiac myocytes and is capable of cleaving poly (ADP-ribose) polymerase (PARP) in vitro. FASEB J. · 2004
• … and 26 more in the literature graph