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Table 1 Properties of human TIMPs, summarizing their activities in inhibiting metzincin metalloproteinases and in modulating phenotypic cell behavior [6]

From: Tissue inhibitors of metalloproteinases

Property TIMP1 TIMP2 TIMP3 TIMP4
Amino acid residues 184 194 188 194
pI 8.5 6.5 9.1 7.2
Protein kDa 28 22 24 or 27 22
N-glycosylation sites 2 0 1 0
Synapsin gene SYN1 n/a SYN3 SYN2
Protein localization Soluble/cell surface Soluble/cell surface Extracellular matrix/cell surface Soluble/cell surface
Pro-MMP binding proMMP9 proMMP2 proMMP2, 9 proMMP2
MMPs poorly inhibited MT1-MMP, MT3-MMP, MT5-MMP, MMP19 None None None
ADAM inhibition ADAM10 ADAM12 ADAM10, ADAM12, ADAM17, ADAM19, ADAM33, ADAMTS1, ADAMTS4, ADAMTS5, ADAMTS2 (weak) ADAM17, ADAM28
Binding partners CD63, LRP1/MMP9 α3β1integrin, LRP1 EFEMP1, AngIIR, VEGFR  
Cell proliferation ↑Erythroid precursors ↑Erythroid precursors ↑Smooth muscle cells and cancer cells ↑Mammary tumor cells
  ↑Tumor cells ↑Tumor cells   ↓Wilm's tumor cells
   ↑Fibroblasts   
   ↑Smooth muscle cells   
   ↓Endothelial cells   
Apoptosis ↓Burkitt's lymphoma cells ↑Colorectal cancer cells
↓Melanoma
↑Smooth muscle
↑Tumor cells
↑Retinal pigment epithelial cells
 
Tumor angiogenesis ↑Mammary
↓Liver
↓Melanoma
↓Mammary
↓Melanoma  
Angiogenesis in 3D collagen or fibrin gels No effect Inhibits Inhibits Inhibits
Tumorigenesis effects Inhibits Inhibits Inhibits Inhibits
Metastasis effects Stimulates    Stimulates
Genetic defects   Idiopathic scoliosis Sorsby's fundus dystrophy Kawasaki disease
  1. AngIIR, angiotensin II receptor; EFEMP1, EGF-containing fibulin-like extracellular matrix protein 1; VEGFR, vascular endothelial growth factor receptor