Genomes and Genes
Summary: A family of membrane-anchored glycoproteins that contain a disintegrin and metalloprotease domain. They are responsible for the proteolytic cleavage of many transmembrane proteins and the release of their extracellular domain.
- Zheng X. Structure-function and regulation of ADAMTS-13 protease. J Thromb Haemost. 2013;11 Suppl 1:11-23 pubmed publisher..Together, these findings provide novel insight into the mechanism of VWF proteolysis and tools for the therapy of acquired TTP and perhaps other arterial thrombotic disorders. ..
- Ashlin T, Kwan A, Ramji D. Regulation of ADAMTS-1, -4 and -5 expression in human macrophages: differential regulation by key cytokines implicated in atherosclerosis and novel synergism between TL1A and IL-17. Cytokine. 2013;64:234-42 pubmed publisher..These studies provide new insight into the regulation of key ADAMTS family members in human macrophages by major cytokines in relation to atherosclerosis. ..
- Shah N, Rutherford C, Matevosyan K, Shen Y, Sarode R. Role of ADAMTS13 in the management of thrombotic microangiopathies including thrombotic thrombocytopenic purpura (TTP). Br J Haematol. 2013;163:514-9 pubmed publisher..In conclusion, ADAMTS13 can be used to diagnose TTP and guide appropriate PLEX therapy. ..
- Lin J, Lemke C, Redies C, Yan X, Mix E, Rolfs A, et al. ADAM17 overexpression promotes angiogenesis by increasing blood vessel sprouting and pericyte number during brain microvessel development. Int J Dev Biol. 2011;55:961-8 pubmed publisher..Our data suggest that overexpression of ADAM17 in the developing tectum promotes angiogenesis by increasing the number of pericytes and capillary sprouting in the radial vessels...
- De Meyer S, Savchenko A, HAAS M, Schatzberg D, Carroll M, Schiviz A, et al. Protective anti-inflammatory effect of ADAMTS13 on myocardial ischemia/reperfusion injury in mice. Blood. 2012;120:5217-23 pubmed publisher..Our data show that ADAMTS13 reduces myocardial ischemia/reperfusion injury in mice and indicate that rhADAMTS13 could be of therapeutic value to limit myocardial ischemia/reperfusion injury. ..
- Turner N, Nolasco L, Moake J. Generation and breakdown of soluble ultralarge von Willebrand factor multimers. Semin Thromb Hemost. 2012;38:38-46 pubmed publisher..New inhibitors of platelet adhesion to EC-anchored ULVWF multimeric strings and soluble ULVWF include an aptamer, a nanobody, and N-acetylcysteine. ..
- Adrain C, Zettl M, Christova Y, Taylor N, Freeman M. Tumor necrosis factor signaling requires iRhom2 to promote trafficking and activation of TACE. Science. 2012;335:225-8 pubmed publisher..Given the role of TNF in autoimmune and inflammatory diseases, iRhom2 may represent an attractive therapeutic target. ..
- Xiao L, Lin P, Lin F, Liu X, Qin W, Zou H, et al. ADAM17 targets MMP-2 and MMP-9 via EGFR-MEK-ERK pathway activation to promote prostate cancer cell invasion. Int J Oncol. 2012;40:1714-24 pubmed publisher..This study suggests that the ADAM17 expression level may be a new predictive biomarker of invasion and metastasis of prostate cancer, and ADAM17 could provide a target for treating metastatic PCa. ..
- De Meyer S, Stoll G, Wagner D, Kleinschnitz C. von Willebrand factor: an emerging target in stroke therapy. Stroke. 2012;43:599-606 pubmed publisher..Preclinical and clinical evidence illustrates an important role of VWF in ischemic stroke, suggesting that VWF could become a promising target in stroke therapy. ..
- Yang Y, Jalal F, Thompson J, Walker E, Candelario Jalil E, Li L, et al. Tissue inhibitor of metalloproteinases-3 mediates the death of immature oligodendrocytes via TNF-?/TACE in focal cerebral ischemia in mice. J Neuroinflammation. 2011;8:108 pubmed publisher..Future studies will be needed to delineate the role of MMP-3 and MMP-9 that were increased in the Timp-3 wild type. ..
- Murthy A, Shao Y, Narala S, Molyneux S, Zuniga Pflucker J, Khokha R. Notch activation by the metalloproteinase ADAM17 regulates myeloproliferation and atopic barrier immunity by suppressing epithelial cytokine synthesis. Immunity. 2012;36:105-19 pubmed publisher..Our findings uncover an essential role of ADAM17 in the adult epidermis, demonstrating a gatekeeper function of the ADAM17-Notch-c-Fos triad in barrier immunity...
- Capasso R, Sambri I, Cimmino A, Salemme S, Lombardi C, Acanfora F, et al. Homocysteinylated albumin promotes increased monocyte-endothelial cell adhesion and up-regulation of MCP1, Hsp60 and ADAM17. PLoS ONE. 2012;7:e31388 pubmed publisher..Treatment with homocysteinylated albumin specifically increases monocyte adhesion to endothelial cells through up-regulation of effectors involved in vascular remodeling. ..
- Cochet M, Donneger R, Cassier E, Gaven F, Lichtenthaler S, Marin P, et al. 5-HT4 receptors constitutively promote the non-amyloidogenic pathway of APP cleavage and interact with ADAM10. ACS Chem Neurosci. 2013;4:130-40 pubmed publisher..These findings describe a new mechanism whereby a GPCR constitutively stimulates the cleavage of APP by ?-secretase and promotes the nonamyloidogenic pathway of APP processing. ..
- Tripathi P, Awasthi S, Prasad R, Husain N, Ganesh S. Association of ADAM33 gene polymorphisms with adult-onset asthma and its severity in an Indian adult population. J Genet. 2011;90:265-73 pubmed..013-<0.0001, OR = 0.34-0.10). Our data suggest that ADAM33 gene polymorphisms serve as genetic risk factors for asthma in Indian adult population. ..
- Lin P, Sun X, Feng T, Zou H, Jiang Y, Liu Z, et al. ADAM17 regulates prostate cancer cell proliferation through mediating cell cycle progression by EGFR/PI3K/AKT pathway. Mol Cell Biochem. 2012;359:235-43 pubmed publisher..Collectively, this study demonstrates that over-expression of ADAM17 might target cyclin E, CDK2, p21, and p27 to promote prostate cancer cell proliferation through activation of the EGFR/PI3K/AKT pathway. ..
- Trad A, Hedemann N, Shomali M, Pawlak V, Grötzinger J, Lorenzen I. Development of sandwich ELISA for detection and quantification of human and murine a disintegrin and metalloproteinase17. J Immunol Methods. 2011;371:91-6 pubmed publisher..A panel of monoclonal antibodies was generated for first time to measure mouse ADAM17 with a sensitivty of 2 ng/ml. Such systems provide a useful tool to quantify protein levels of ADAM17 and are valuable tools for diagnostic purposes. ..
- Bekris L, Lutz F, Li G, Galasko D, Farlow M, Quinn J, et al. ADAM10 expression and promoter haplotype in Alzheimer's disease. Neurobiol Aging. 2012;33:2229.e1-2229.e9 pubmed publisher..Taken together, these findings suggest that ADAM10 expression is modulated according to a promoter haplotype that is influenced in a brain region- and cell type-specific manner. ..
- Basu R, Lee J, Wang Z, Patel V, Fan D, Das S, et al. Loss of TIMP3 selectively exacerbates diabetic nephropathy. Am J Physiol Renal Physiol. 2012;303:F1341-52 pubmed publisher..Our data provide definitive evidence for a critical and selective role of TIMP3 in diabetic renal injury consistent with gene expression findings from human diabetic kidneys. ..
- Stautz D, Leyme A, Grandal M, Albrechtsen R, van Deurs B, Wewer U, et al. Cell-surface metalloprotease ADAM12 is internalized by a clathrin- and Grb2-dependent mechanism. Traffic. 2012;13:1532-46 pubmed publisher..These studies establish that internalization is indeed a mechanism that regulates ADAM cell surface levels and show that ADAM12 internalization involves the clathrin-dependent pathway and Grb2. ..
- Didangelos A, Mayr U, Monaco C, Mayr M. Novel role of ADAMTS-5 protein in proteoglycan turnover and lipoprotein retention in atherosclerosis. J Biol Chem. 2012;287:19341-5 pubmed publisher..This study provides the first evidence implicating ADAMTS-5 in the regulation of proteoglycan turnover and lipoprotein retention in atherosclerosis. ..
- Ren P, Zhang L, Xu G, Palmero L, Albini P, Coselli J, et al. ADAMTS-1 and ADAMTS-4 levels are elevated in thoracic aortic aneurysms and dissections. Ann Thorac Surg. 2013;95:570-7 pubmed publisher..Increased expression of ADAMTS proteins may promote thoracic aortic aneurysm progression by degrading versican and facilitating macrophage invasion. ..
- Westwood J, Webster H, McGuckin S, McDonald V, Machin S, Scully M. Rituximab for thrombotic thrombocytopenic purpura: benefit of early administration during acute episodes and use of prophylaxis to prevent relapse. J Thromb Haemost. 2013;11:481-90 pubmed publisher..Although limited by being retrospective and non-randomized, this study demonstrates the potential benefit of early administration of rituximab in acute TTP, and prophylactic use to prevent acute relapse. ..
- Wang J, Markova D, Anderson D, Zheng Z, Shapiro I, Risbud M. TNF-? and IL-1? promote a disintegrin-like and metalloprotease with thrombospondin type I motif-5-mediated aggrecan degradation through syndecan-4 in intervertebral disc. J Biol Chem. 2011;286:39738-49 pubmed publisher..We conclude that in nucleus pulposus, TNF-? and IL-1? regulate SDC4 expression, which plays a key role in pathogenesis of degenerative disc disease by promoting aggrecan degradation by ADAMTS-5...
- Troeberg L, Mulloy B, Ghosh P, Lee M, Murphy G, Nagase H. Pentosan polysulfate increases affinity between ADAMTS-5 and TIMP-3 through formation of an electrostatically driven trimolecular complex. Biochem J. 2012;443:307-15 pubmed publisher..4 M NaCl. These results suggest that PPS enhances the affinity between ADAMTS-5 and TIMP-3 by forming electrostatically driven trimolecular complexes under physiological conditions. ..
- Mimata Y, Kamataki A, Oikawa S, Murakami K, Uzuki M, Shimamura T, et al. Interleukin-6 upregulates expression of ADAMTS-4 in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Int J Rheum Dis. 2012;15:36-44 pubmed publisher..These results suggest IL-6 may participate in cartilage destruction in RA as an inducer of ADAMTS-4 expression from FLS. ..
- Tokuhiro K, Ikawa M, Benham A, Okabe M. Protein disulfide isomerase homolog PDILT is required for quality control of sperm membrane protein ADAM3 and male fertility [corrected]. Proc Natl Acad Sci U S A. 2012;109:3850-5 pubmed publisher..Moreover, the importance of primary sperm ZP binding, which has been thought to be a critical step in mammalian fertilization, should be reconsidered. ..
- Fu X, Chen J, Gallagher R, Zheng Y, Chung D, Lopez J. Shear stress-induced unfolding of VWF accelerates oxidation of key methionine residues in the A1A2A3 region. Blood. 2011;118:5283-91 pubmed publisher..These findings suggest that neutrophil oxidants will both render newly secreted VWF uncleavable and alter the largest plasma VWF forms such that they become hyperfunctional and resistant to proteolysis by ADAMTS13. ..
- Chen L, Yang L, Zha Y, Cui L. Association of serum a disintegrin and metalloproteinase with thrombospodin motif 4 levels with the presence and severity of coronary artery disease. Coron Artery Dis. 2011;22:570-6 pubmed publisher..94) ng/ml, P<0.05]. In conclusion, serum ADAMTS4 levels are associated with the presence and the severity of CAD, ADAMTS4 might serve as an independent factor for predicting CAD. Statin therapy reduces the serum levels of ADAMTS4. ..
- Warren K, Reeves T, Phillips L. MT5-MMP, ADAM-10, and N-cadherin act in concert to facilitate synapse reorganization after traumatic brain injury. J Neurotrauma. 2012;29:1922-40 pubmed publisher..Persistent ADAM-10 expression was correlated with attenuated N-cadherin level and reduced functional recovery. MMP inhibition shifted ADAM-10 and N-cadherin toward adaptive expression and improved synaptic function. ..
- Haining E, Yang J, Bailey R, Khan K, Collier R, Tsai S, et al. The TspanC8 subgroup of tetraspanins interacts with A disintegrin and metalloprotease 10 (ADAM10) and regulates its maturation and cell surface expression. J Biol Chem. 2012;287:39753-65 pubmed publisher..This finding has therapeutic implications because focusing on specific TspanC8-ADAM10 complexes may allow cell type- and/or substrate-specific ADAM10 targeting...
- Krstic D, Rodríguez M, Knuesel I. Regulated proteolytic processing of Reelin through interplay of tissue plasminogen activator (tPA), ADAMTS-4, ADAMTS-5, and their modulators. PLoS ONE. 2012;7:e47793 pubmed publisher..While this pattern remained stable during normal aging, changes in their protein levels coincided with accelerated Reelin aggregation in a mouse model of AD. ..
- Pelisek J, Pongratz J, Deutsch L, Reeps C, Stadlbauer T, Eckstein H. Expression and cellular localization of metalloproteases ADAMs in high graded carotid artery lesions. Scand J Clin Lab Invest. 2012;72:648-56 pubmed publisher..In conclusion, the ADAM family of proteases seems to play an important role in the maintenance of proper vessel physiology and some ADAMs such as ADAM10 and ADAM12 might also contribute to the progression of atherosclerosis. ..
- Scheller J, Chalaris A, Garbers C, Rose John S. ADAM17: a molecular switch to control inflammation and tissue regeneration. Trends Immunol. 2011;32:380-7 pubmed publisher..Tissue-specific deletion, or hypomorphic knock-in, of Adam17 demonstrates an in vivo role for ADAM17 in controlling inflammation and tissue regeneration. The potential of ADAM17 as therapeutic target is also discussed. ..
- Aldahmesh M, Khan A, Mohamed J, Alkuraya H, Ahmed H, Bobis S, et al. Identification of ADAMTS18 as a gene mutated in Knobloch syndrome. J Med Genet. 2011;48:597-601 pubmed publisher..The power of combining exome and autozygome analysis in the study of genetics of autosomal recessive disorders, even in simplex cases, has been demonstrated. ..
- Khan A, Aldahmesh M, Mohamed J, Al Mesfer S, Alkuraya F. The distinct ophthalmic phenotype of Knobloch syndrome in children. Br J Ophthalmol. 2012;96:890-5 pubmed publisher..Although it is a defining feature of the syndrome, clinically discernible occipital defect is not a sine qua non for the diagnosis. Ophthalmologists are uniquely able to diagnose Knobloch syndrome. ..
- Cho C. Testicular and epididymal ADAMs: expression and function during fertilization. Nat Rev Urol. 2012;9:550-60 pubmed publisher..It has been suggested that ADAM2 and ADAM3 have roles in sperm-egg interactions. Mouse knockout studies have revealed that the ADAM2-ADAM3 complex is critical for in vivo sperm migratory function in the female reproductive tract...
- Kuo P, Huang M, Cheng D, Hung J, Yang C, Chou S. Lung cancer-derived galectin-1 enhances tumorigenic potentiation of tumor-associated dendritic cells by expressing heparin-binding EGF-like growth factor. J Biol Chem. 2012;287:9753-64 pubmed publisher..Antagonists of the effect of lung cancer-derived galectin-1 on DCs and anti-HB-EGF blocking antibodies could, therefore, have therapeutic potential as antitumor agents. ..
- Hamada S, Satoh K, Fujibuchi W, Hirota M, Kanno A, Unno J, et al. MiR-126 acts as a tumor suppressor in pancreatic cancer cells via the regulation of ADAM9. Mol Cancer Res. 2012;10:3-10 pubmed publisher..We showed for the first time that the miR-126/ADAM9 axis plays essential role in the inhibition of invasive growth of pancreatic cancer cells. ..
- Rao V, Kandel A, Lynch D, Pena Z, Marwaha N, Deng C, et al. A positive feedback loop between HER2 and ADAM12 in human head and neck cancer cells increases migration and invasion. Oncogene. 2012;31:2888-98 pubmed publisher..Collectively, these results reveal a novel positive activation loop between ADAM12 and HER2 that may contribute to HNSCC progression. ..
- Linford A, Yoshimura S, Nunes Bastos R, Langemeyer L, Gerondopoulos A, Rigden D, et al. Rab14 and its exchange factor FAM116 link endocytic recycling and adherens junction stability in migrating cells. Dev Cell. 2012;22:952-66 pubmed publisher..FAM116 and Rab14 therefore define an endocytic recycling pathway needed for ADAM protease trafficking and regulation of cell-cell junctions. ..
- Kumar S, Sharghi Namini S, Rao N, Ge R. ADAMTS5 functions as an anti-angiogenic and anti-tumorigenic protein independent of its proteoglycanase activity. Am J Pathol. 2012;181:1056-68 pubmed publisher..This is the first report that ADAMTS5 is an anti-angiogenic and anti-tumorigenic protein independent of its proteoglycanase activity. ..
- Sahraravand M, Järvelä I, Laitinen P, Tekay A, Ryynanen M. The secretion of PAPP-A, ADAM12, and PP13 correlates with the size of the placenta for the first month of pregnancy. Placenta. 2011;32:999-1003 pubmed publisher..After 8 weeks of pregnancy, which is the time for luteoplacental shift, the correlation disappears, possibly reflecting the morphologic transformation in the placenta. ..
- Na H, Shin W, Ludwig A, Lee S. The cytosolic domain of protein-tyrosine kinase 7 (PTK7), generated from sequential cleavage by a disintegrin and metalloprotease 17 (ADAM17) and ?-secretase, enhances cell proliferation and migration in colon cancer cells. J Biol Chem. 2012;287:25001-9 pubmed publisher..Our findings demonstrate a novel role for PTK7 in the tumorigenesis via generation of PTK7-CTF2 by sequential cleavage of ADAM17 and ?-secretase. ..
- Long J, Li M, Ren Q, Zhang C, Fan J, Duan Y, et al. Phylogenetic and molecular evolution of the ADAM (A Disintegrin And Metalloprotease) gene family from Xenopus tropicalis, to Mus musculus, Rattus norvegicus, and Homo sapiens. Gene. 2012;507:36-43 pubmed publisher..These results not only provide valuable information of the evolution of ADAM genes, but may also help in understanding the role of ADAM genes in the pathobiology of relevant diseases. ..