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. Author manuscript; available in PMC: 2022 Jul 1.
Published in final edited form as: Cell Signal. 2021 Mar 27;83:109993. doi: 10.1016/j.cellsig.2021.109993

Table 1:

Similarities and differences between RECK and TIMPs 1–4, focused on their structure, substrates and functions, as well as their knockout phenotype

Enzyme RECK TIMP1 TIMP2 TIMP3 TIMP4
Substrates MMP-(2,7,9,14,17), ADAMTS, ADAM10/17, EGFR, IL-6R, uPA MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 and MMP16
Low affinity for membrane type MMPs
pro-MMP2, MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-13, MMP-14, MMP-15, MMP-16 and MMP-19. MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, MMP-14 and MMP-15.
Broadest inhibition spectrum, inhibits several members of the ADAM and ADAMTS families
MMP-1, MMP-2, MMP-3, MMP-7 and MMP-9.
KO phenotype • Embryonic lethality due to improper blood vessel maturation • Increased ventricular remodeling
• Altered ventricularstructure and function
• Accelerated hepatocyte cell cycle
• Increased resistance to corneal and pulmonary infection
• Decreased adiposetissue weight on HFD
• Impaired learning and memory
• Motor defects and deficiency in prepulse inhibitor of the startle reflex • Enlargement of airspace in lungs
• Enhanced apoptosis during mammary gland involution
• Excessive cardiac fibrosis
• Increased TGFβ1and TNFα.
• Increased risk of endotoxin shock
• Unaltered tumorigenesis and angiogenesis
• Reduced adipose tissue hypertrophy and fibrosis on a high fat diet.
• Lower metabolic rate and energy expenditure.
Role in Angiogene sis • Negatively Regulates • Negatively Regulates • Negatively Regulates
• Enhances expression of RECK by interacting with α3β1 integrin switching signaling from Rac 1 to Rap 1
• NegativelyRegulates
• Binds VEGFR2 to block VEGF signaling on endothelial cells.
• Binds AT2R
• Negatively Regulates
Role in Cell Migration • Inhibitsendothelial cell migration
• SuppressesSMC proliferation and migration
• Increases lungcancer cell migration
• Increases hepatoma cell migration
• Increases cancer associated fibroblasts migration
• Decreases microvascular endothelial cell migration
• Inhibits cancercell migration
• Inhibitsmacrophage migration to atherosclerotic plaques
• Suppresses SMC proliferation and migration • Inhibits SMCs migration
Role in Proliferation • Anti-proliferative • Promotes growth ofkeratinocytes and fibroblasts
• Increases Ras-GTP
• Inhibits caspase mediated apoptosis
• Potentiates erythroid activity and cell growth in metanephric mesenchyme cells
• Increases amount of Ras-GTP
• Reduces apoptosis
• Promotes apoptosis in a number of cancer cell lines and rat vascular smooth muscle cells • Induces aortic SMC apoptosis
Structure • Rich incysteine residues
• 971 residues
• 110kDa
• 6 disulfidebonds (Kazal motif)
• 5 asparagine glycosylation sites
• Conserved cysteineresidues
• 207 residues
• 25kDa
• 6 disulfide bonds (NTR module)
• 2 asparagine glycosylation sites
• Conserved cysteine residues
• 220 residues
• 25kDa
• 6 disulfide bonds (NTR module)
• Conserved cysteineresidues
• 211 residues
• 25kDa
• 6 disulfide bonds (NTR module)
• Conserved cysteine residues
• 224 residues
• 25kDa
• 6 disulfidebonds (NTR module)