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Degradation of the extracellular matrix
Stable Identifier
R-HSA-1474228
DOI
10.3180/REACT_118572.5
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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Extracellular matrix organization (Homo sapiens)
Degradation of the extracellular matrix (Homo sapiens)
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Matrix metalloproteinases (MMPs), previously referred to as matrixins because of their role in degradation of the extracellular matrix (ECM), are zinc and calcium dependent proteases belonging to the metzincin family. They contain a characteristic zinc-binding motif HEXXHXXGXXH (Stocker & Bode 1995) and a conserved Methionine which forms a Met-turn. Humans have 24 MMP genes giving rise to 23 MMP proteins, as MMP23 is encoded by two identical genes. All MMPs contain an N-terminal secretory signal peptide and a prodomain with a conserved PRCGXPD motif that in the inactive enzyme is localized with the catalytic site, the cysteine acting as a fourth unpaired ligand for the catalytic zinc atom. Activation involves delocalization of the domain containing this cysteine by a conformational change or proteolytic cleavage, a mechanism referred to as the cysteine-switch (Van Wart & Birkedal-Hansen 1990). Most MMPs are secreted but the membrane type MT-MMPs are membrane anchored and some MMPs may act on intracellular proteins. Various domains determine substrate specificity, cell localization and activation (Hadler-Olsen et al. 2011). MMPs are regulated by transcription, cellular location (most are not activated until secreted), activating proteinases that can be other MMPs, and by metalloproteinase inhibitors such as the tissue inhibitors of metalloproteinases (TIMPs). MMPs are best known for their role in the degradation and removal of ECM molecules. In addition, cleavage of the ECM and other cell surface molecules can release ECM-bound growth factors, and a number of non-ECM proteins are substrates of MMPs (Nagase et al. 2006). MMPs can be divided into subgroups based on domain structure and substrate specificity but it is clear that these are somewhat artificial, many MMPs belong to more than one functional group (Vise & Nagase 2003, Somerville et al. 2003).
Literature References
PubMed ID
Title
Journal
Year
21917992
Extracellular matrix degradation and remodeling in development and disease
Weaver, VM
,
Takai, K
,
Werb, Z
,
Lu, P
Cold Spring Harb Perspect Biol
2011
Participants
Events
Activation of Matrix Metalloproteinases
(Homo sapiens)
Collagen degradation
(Homo sapiens)
Elastin degradation by elastin-degrading extracellular proteinases
(Homo sapiens)
Elastin degradation by MMP14
(Homo sapiens)
Fibrillin 1, 2,(3) degradation by MMP2, 9, 12 and 13
(Homo sapiens)
Fibrillin-1 degradation by MMP3, CTSK, CTSL2
(Homo sapiens)
Fibrillin-1 degradation by MMP14
(Homo sapiens)
Fibrillin-1 degradation by ELANE
(Homo sapiens)
Fibronectin degradation by MMP1, 3, 7, 12, 13, 19, CTSS
(Homo sapiens)
Fibronectin degradation by MMP10
(Homo sapiens)
Fibronectin degradation by MMP14
(Homo sapiens)
Fibronectin degradation by CTSG
(Homo sapiens)
Fibronectin degradation by ADAM8
(Homo sapiens)
Laminin-332 degradation by laminin-322 degrading extracellular proteinases
(Homo sapiens)
Laminin-322 degradation by MMP14
(Homo sapiens)
Laminin-511 degradation by MMP14
(Homo sapiens)
NID1 degradation by MMP1, 9, 12, ELANE
(Homo sapiens)
NID1 degradation by MMP3, 7
(Homo sapiens)
NID1 degradation by MMP14, MMP15
(Homo sapiens)
NID1 degradation by MMP19
(Homo sapiens)
Aggrecan degradation by ADAMTSs
(Homo sapiens)
Aggrecan degradation by MMP1,2,3,7,9,12,13
(Homo sapiens)
HTRA1 hydrolyzes ACAN (Aggrecan)
(Homo sapiens)
Brevican degradation by ADAMTS4, ADAMTS5
(Homo sapiens)
Brevican degradation by MMP1, 2, 3, 7,8,10,13,19
(Homo sapiens)
HSPG2 (perlecan) degradation by MMP3, plasmin, (MMP12)
(Homo sapiens)
HSPG2 (perlecan) degradation by MMP13, CTSS
(Homo sapiens)
HSPG2 (perlecan) degradation by MMP14, MMP15
(Homo sapiens)
HSPG2 (perlecan) is cleaved by BMP1, TLL1, TLL2, Cathepsin L1
(Homo sapiens)
DCN (decorin) degradation by MMP2, MMP3, MMP7
(Homo sapiens)
DCN (decorin) degradation by MMP14
(Homo sapiens)
E-cadherin degradation by MMP3, MMP7 and plasmin.
(Homo sapiens)
E-cadherin degradation by MMP9, KLK7
(Homo sapiens)
E-cadherin degradation by ADAM10, ADAM15
(Homo sapiens)
E-cadherin degradation by PS1:NCSTN (Gamma-secretase)
(Homo sapiens)
E-cadherin degradation by caspase-3 and calpain-1
(Homo sapiens)
MMP1,3,13 (2, 7-12, 19) binding by Alpha-2 macroglubulin
(Homo sapiens)
MMP2, MMP7, MMP9 bind CD44
(Homo sapiens)
Basigin binds Matrix metalloproteinase-1
(Homo sapiens)
OPN (osteopontin) degradation by MMP3, MMP7
(Homo sapiens)
CAPN:4xCa2+:CAPNS cleave cytoskeletal proteins
(Homo sapiens)
MMP2 cleaves OPTC
(Homo sapiens)
MMP7 cleaves OPTC
(Homo sapiens)
MMP13 cleaves OPTC
(Homo sapiens)
MMP2, MMP9 cleave SCUBE3
(Homo sapiens)
SCUBE1, SCUBE3 oligomerize
(Homo sapiens)
Participates
as an event of
Extracellular matrix organization (Homo sapiens)
Event Information
Go Biological Process
extracellular matrix disassembly (0022617)
Orthologous Events
Degradation of the extracellular matrix (Bos taurus)
Degradation of the extracellular matrix (Caenorhabditis elegans)
Degradation of the extracellular matrix (Canis familiaris)
Degradation of the extracellular matrix (Danio rerio)
Degradation of the extracellular matrix (Dictyostelium discoideum)
Degradation of the extracellular matrix (Drosophila melanogaster)
Degradation of the extracellular matrix (Gallus gallus)
Degradation of the extracellular matrix (Mus musculus)
Degradation of the extracellular matrix (Plasmodium falciparum)
Degradation of the extracellular matrix (Rattus norvegicus)
Degradation of the extracellular matrix (Sus scrofa)
Degradation of the extracellular matrix (Xenopus tropicalis)
Authored
Jupe, S (2011-09-09)
Reviewed
D'Eustachio, P (2012-02-28)
Created
Jupe, S (2011-08-05)
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