Metalloproteinase inhibitor 3 (Protein MIG-5) (Tissue inhibitor of metalloproteinases 3) (TIMP-3)
1_MTPWL 6_ GLIVL 11_ LGSWS 16_ LGDWG 21_ AEACT 26_ CSPSH 31_ PQDAF 36_ CNSDI 41_ VIRAK 46_ VVGKK 51_ LVKEG 56_ PFGTL 61_ VYTIK 66_ QMKMY 71_ RGFTK 76_ MPHVQ 81_ YIHTE 86_ ASESL 91_ CGLKL 96_ EVNKY 101_ QYLLT 106_ GRVYD 111_ GKMYT 116_ GLCNF 121_ VERWD 126_ QLTLS 131_ QRKGL 136_ NYRYH 141_ LGCNC 146_ KIKSC 151_ YYLPC 156_ FVTSK 161_ NECLW 166_ TDMLS 171_ NFGYP 176_ GYQSK 181_ HYACI 186_ RQKGG 191_ YCSWY 196_ RGWAP 201_ PDKSI 206_INATD
1: 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)