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Sep. 10, 2014:
A total of 174 experimentally verified S-nitrosylation sites on 94 S-nitrosylated proteins from individualized human colorectal cancer tissues using a label-free quantitation strategy.

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Protein Name: Metalloproteinase inhibitor 3

UniprotKB/SwissProt ID: P35625 (P35625)

Gene Name: TIMP3

Organism: Homo sapiens (Human)

Function: Mediates a variety of processes including matrix regulation and turnover, inflammation, and angiogenesis, through reversible inhibition of zinc protease superfamily enzymes, primarily matrix metalloproteinases (MMPs). Regulates extracellular matrix (ECM) remodeling through inhibition of matrix metalloproteinases (MMP) including MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, MMP-14 and MMP-15. Additionally, modulates the processing of amyloid precursor protein (APP) and apolipoprotein E receptor ApoER2 by inhibiting two alpha-secretases ADAM10 and ADAM17 (PubMed:17913923). Functions as a tumor suppressor and a potent inhibitor of angiogenesis. Exerts its anti-angiogenic effect by directly interacting with vascular endothelial growth factor (VEGF) receptor-2/KDR, preventing its binding to the VEGFA ligand (PubMed:12652295). Selectively induces apoptosis in angiogenic endothelial cells through a caspase-independent cell death pathway (PubMed:25558000). Mechanistically, inhibits matrix-induced focal adhesion kinase PTK2 tyrosine phosphorylation and association with paxillin/PXN and disrupts the incorporation of ITGB3, PTK2 and PXN into focal adhesion contacts on the matrix (PubMed:25558000)

Other Modifications: View all modification sites in dbPTM

Protein Subcellular Localization: Secreted, extracellular space, extracellular matrix

Graphical Visualization of S-nitrosylation Sites:
InterPro ID Domain Name
IPR001134 Netrin_domain
IPR001820 TIMP
IPR008993 TIMP-like_OB-fold
IPR027465 TIMP_C
IPR030490 TIMP_CS