motifs/domains
| a catalytic domain |
|
three zinc-binding histidines |
|
a catalytic glutamic acid in the conserved HEXXHXXGXXH motif |
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a prodomain/catalytic domain cationic molecular switch, regulated by exogenous heparan sulfate and heparin but also endogenous cell surface proteoglycans and the polyanion, calcium pentosan polysulfate  |
|
a Zn-binding site metalloproteinase |
|
a disintegrin-like domain |
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a cysteine rich domains |
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an EGF-like repeat |
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a transmembrane domain |
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a cytoplasmic tail, proteolytic activity (after cleavage of the prodomain at a site for a furin-like endopeptidase) |
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a c-Src interaction site in the cytoplasmic domain required for the induction of invadopodia clusters |
SUBCELLULAR LOCALIZATION
| plasma membrane
|
| intracellular
|
|
| intracellular,cytoplasm,organelle,mitochondria
|
|
| intracellular,cytoplasm,organelle,membrane
|
|
| intracellular,cytoplasm,organelle,endoplasmic reticulum
|
|
| intracellular,nucleus,nucleoplasm
|
| basic FUNCTION
| involved in tumor cell adhesion |
|
contribution to protease activity in pregnancy serum |
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required for myotube formation and in osteoblast differentiation |
|
involved in the development of white adipose tissue, and in obesity induced by high- fat diet |
|
membrane-anchored metalloprotease, which has been implicated in activation-inactivation of growth factors that play an important role in wound healing |
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increased expression of ADAM12 in chronic wounds impairs wound healing through the inhibition of keratinocyte migration |
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would be functional in a highly chondroitin sulfate-rich environment |
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multifunctional zinc-dependent enzyme, regulating |
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the availability of bioreactive molecules, such as cell-surface receptors, growth factors and cytokines |
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in normal tissue, may inhibit cell migration by mediating cell adhesion via integrin interactions, whereas, in tumor cells, higher levels of ADAM12-S proteolytic function stimulate cell migration and invasion |
|
constitutively internalized primarily via the clathrin-dependent pathway and is subsequently detected in both early and recycling endosomes |
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ADAM12 internalization involves the clathrin-dependent pathway and GRB2 |
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can activate membrane-anchored proteins, such as SHH, DLL1 and certain epidermal growth factor receptor ligands, through a process called ectodomain shedding |
|
role for ADAM12 in ectodomain shedding of several membrane-anchored endothelial proteins and likely this process may have importance in tumour neovascularization or/and tumour cell extravasation |
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function for ADAM12 in trophoblast biology, where ADAM12 may play a central role regulating the behavior of invasive trophoblast subsets in early pregnancy |
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BSG and ADAM12 play a major role in cancer invasion and metastasis owing to the fact that they are directly related to the cell microenvironment and extracellular matrix (ECM) degradation |
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function for ADAM12 in regulating trophoblast fusion |
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novel role for ADAM12 in placental development, specifically important role in controlling the differentiation of villous cytotrophoblasts into multinucleated cellular structures |
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ADAM12 and ADAM17 are essential molecules for hypoxia-induced impairment of neural vascular barrier function |
