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Gene Review

ADAMTS1  -  ADAM metallopeptidase with thrombospondin...

Homo sapiens

Synonyms: A disintegrin and metalloproteinase with thrombospondin motifs 1, ADAM-TS 1, ADAM-TS1, ADAMTS-1, C3-C5, ...
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Disease relevance of ADAMTS1


Psychiatry related information on ADAMTS1


High impact information on ADAMTS1

  • Treatment of methylcholanthrene-induced (Meth A) ascites tumors with IL-2 and > or =3 mg per kg body weight M40403 induced 50% complete remissions lasting for more than 200 d, which was longer than those of untreated mice (15-d median survival) or mice treated with IL-2 alone (22-d median) [12].
  • A predicted gene in the identified interval corresponds to a segment of a much larger transcript, identifying a new member of the ADAMTS family of zinc metalloproteinase genes (ADAMTS13) [13].
  • Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura [13].
  • Targeted disruption of the mouse ADAMTS-1 gene resulted in growth retardation with adipose tissue malformation [14].
  • Furthermore, ADAMTS-1(-/-) mice demonstrated enlarged renal calices with fibrotic changes from the ureteropelvic junction through the ureter, and abnormal adrenal medullary architecture without capillary formation [14].

Chemical compound and disease context of ADAMTS1

  • Catechin gallate esters therefore provide selective inhibition of certain members of the ADAMTS group of enzymes and could constitute an important nutritional aid in the prevention of arthritis as well as being part of an effective therapy in the treatment of joint disease and other pathologies involving the action of these enzymes [15].
  • Chemical modification of recombinant interleukin 2 by polyethylene glycol increases its potency in the murine Meth A sarcoma model [16].
  • The transplantable murine fibrosarcoma, Meth A, a TNF-sensitive line in vivo, was less sensitive to rhTNF and host toxicity was reduced when the hosts were pretreated with uric acid, a major reactive oxygen scavenger in humans and certain other primates [17].
  • The antitumor effects of recombinant human tumor necrosis factor-alpha (rTNF-alpha) and 5-fluorouracil (5-FU) in combination treatment were examined on Meth A fibrosarcoma implanted intradermally in mice [18].
  • Homologous series of L-methionine alkyl ester hydrochlorides and tosylates were synthesized and evaluated for in vitro growth inhibitory activity in Meth A sarcoma [19].

Biological context of ADAMTS1


Anatomical context of ADAMTS1


Associations of ADAMTS1 with chemical compounds

  • The interaction required the heparin-binding domain of the growth factor, because VEGF121 failed to bind to ADAMTS1 [20].
  • The effect of ADAMTS1 on endothelial cell proliferation was evaluated using siRNA knockdown and [3H] thymidine incorporation [1].
  • VEGF upregulation of ADAMTS1 expression was completely abolished by the inhibition of protein kinase C by calphostin C and largely blocked by the specific inhibition of PKCbeta [1].
  • VWFCP consists of 1427 amino acid residues and has a signal peptide, a short propeptide terminating in the sequence RQRR, a reprolysin-like metalloprotease domain, a disintegrin-like domain, a thrombospondin-1 repeat, a Cys-rich domain, an ADAMTS spacer, seven additional thrombospondin-1 repeats, and two CUB domains [26].
  • High-density lipoprotein subfraction 3 decreases ADAMTS-1 expression induced by lipopolysaccharide and tumor necrosis factor-alpha in human endothelial cells [27].

Physical interactions of ADAMTS1

  • The ability of ADAMTS1 to bind VEGF and functionally inactivate VEGFR2 is reversible as dissociation of the complex results in active growth factor [28].

Enzymatic interactions of ADAMTS1

  • We conclude that versican V1 proteolysis in vivo can be catalyzed by one or more members of the ADAMTS family of metalloproteinases [29].

Regulatory relationships of ADAMTS1

  • CONCLUSIONS: These results indicate that VEGF significantly induces ADAMTS1 expression in endothelial cells in a PKC-dependent fashion [1].
  • In vivo, the application of wortmannin promoted the formation of TNF-induced hemorrhages and intratumoral necroses in murine meth A tumors [30].
  • This study aims to identify other metalloproteinase genes of the ADAM (A Disintegin And Metalloproteinase) and ADAMTS families that are regulated by PPAR gamma or RXR agonists, which are potentially important in type 2 diabetes and/or related atherosclerosis [31].
  • A species at 115 kDa and some other protein bands began with F(236)VSSHRYV(243), indicating that METH-1 proenzyme might be activated by a proprotein convertase such as furin by cleaving the R(235)-F(236) peptide bond [32].
  • Moreover, the concentration needed for total inhibition of these members of the ADAMTS group is approximately two orders of magnitude lower than that which is needed to partially inhibit collagenase or ADAM-10 activity [15].

Other interactions of ADAMTS1

  • CONCLUSION: This is the first comprehensive expression profile of all known MMP, ADAMTS, and TIMP genes in cartilage [33].
  • CONCLUSIONS: OSM+TNFalpha up regulates membrane associated aggrecanase activity and several ADAMTS aggrecanase mRNAs in chondrocytes [23].
  • A sub-group of the ADAMTS lineage of metalloproteases possess versican-degrading properties and are potential regulators of proteoglycan accumulation associated with BPH [24].
  • Oncostatin M in combination with tumour necrosis factor {alpha} induces a chondrocyte membrane associated aggrecanase that is distinct from ADAMTS aggrecanase-1 or -2 [23].
  • The adamalysin-thrombospondin (ADAMTS) proteinases are a relatively newly described branch of the metzincin family that contain metalloproteinase, disintegrin, and thrombospondin motifs [2].

Analytical, diagnostic and therapeutic context of ADAMTS1


  1. Vascular endothelial growth factor upregulates expression of ADAMTS1 in endothelial cells through protein kinase C signaling. Xu, Z., Yu, Y., Duh, E.J. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  2. Dysregulated expression of adamalysin-thrombospondin genes in human breast carcinoma. Porter, S., Scott, S.D., Sassoon, E.M., Williams, M.R., Jones, J.L., Girling, A.C., Ball, R.Y., Edwards, D.R. Clin. Cancer Res. (2004) [Pubmed]
  3. Triptolide suppresses proinflammatory cytokine-induced matrix metalloproteinase and aggrecanase-1 gene expression in chondrocytes. Liacini, A., Sylvester, J., Zafarullah, M. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  4. Expression of ADAMTS metalloproteinases in the retinal pigment epithelium derived cell line ARPE-19: transcriptional regulation by TNFalpha. Bevitt, D.J., Mohamed, J., Catterall, J.B., Li, Z., Arris, C.E., Hiscott, P., Sheridan, C., Langton, K.P., Barker, M.D., Clarke, M.P., McKie, N. Biochim. Biophys. Acta (2003) [Pubmed]
  5. The quantification of ADAMTS expression in an animal model of cerebral ischemia using real-time PCR. Tian, Y.F., Zhang, P.B., Xiao, X.L., Zhang, J.S., Zhao, J.J., Kang, Q.Y., Chen, X.L., Qiu, F., Liu, Y. Acta anaesthesiologica Scandinavica (2007) [Pubmed]
  6. ADAMTS1 is a unique hypoxic early response gene expressed by endothelial cells. Hatipoglu, O.F., Hirohata, S., Cilek, M.Z., Ogawa, H., Miyoshi, T., Obika, M., Demircan, K., Shinohata, R., Kusachi, S., Ninomiya, Y. J. Biol. Chem. (2009) [Pubmed]
  7. Metalloproteinase ADAMTS-1 but not ADAMTS-5 is manifold overexpressed in neurodegenerative disorders as Down syndrome, Alzheimer's and Pick's disease. Miguel, R.F., Pollak, A., Lubec, G. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  8. Calcineurin/NFAT-induced up-regulation of the Fas ligand/Fas death pathway is involved in methamphetamine-induced neuronal apoptosis. Jayanthi, S., Deng, X., Ladenheim, B., McCoy, M.T., Cluster, A., Cai, N.S., Cadet, J.L. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  9. Methamphetamine Use, Impulsivity, and Sexual Risk Behavior Among HIV-Positive Men Who Have Sex with Men. Semple, S.J., Zians, J., Grant, I., Patterson, T.L. Journal of addictive diseases : the official journal of the ASAM, American Society of Addiction Medicine (2006) [Pubmed]
  10. Safety and efficiency of an anti-(+)-methamphetamine monoclonal antibody in the protection against cardiovascular and central nervous system effects of (+)-methamphetamine in rats. Gentry, W.B., Laurenzana, E.M., Williams, D.K., West, J.R., Berg, R.J., Terlea, T., Owens, S.M. Int. Immunopharmacol. (2006) [Pubmed]
  11. MDMA, methamphetamine and their combination: possible lessons for party drug users from recent preclinical research. Clemens, K.J., McGregor, I.S., Hunt, G.E., Cornish, J.L. Drug and alcohol review (2007) [Pubmed]
  12. A nonpeptidyl mimic of superoxide dismutase, M40403, inhibits dose-limiting hypotension associated with interleukin-2 and increases its antitumor effects. Samlowski, W.E., Petersen, R., Cuzzocrea, S., Macarthur, H., Burton, D., McGregor, J.R., Salvemini, D. Nat. Med. (2003) [Pubmed]
  13. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Levy, G.G., Nichols, W.C., Lian, E.C., Foroud, T., McClintick, J.N., McGee, B.M., Yang, A.Y., Siemieniak, D.R., Stark, K.R., Gruppo, R., Sarode, R., Shurin, S.B., Chandrasekaran, V., Stabler, S.P., Sabio, H., Bouhassira, E.E., Upshaw, J.D., Ginsburg, D., Tsai, H.M. Nature (2001) [Pubmed]
  14. ADAMTS-1: a metalloproteinase-disintegrin essential for normal growth, fertility, and organ morphology and function. Shindo, T., Kurihara, H., Kuno, K., Yokoyama, H., Wada, T., Kurihara, Y., Imai, T., Wang, Y., Ogata, M., Nishimatsu, H., Moriyama, N., Oh-hashi, Y., Morita, H., Ishikawa, T., Nagai, R., Yazaki, Y., Matsushima, K. J. Clin. Invest. (2000) [Pubmed]
  15. Selective inhibition of ADAMTS-1, -4 and -5 by catechin gallate esters. Vankemmelbeke, M.N., Jones, G.C., Fowles, C., Ilic, M.Z., Handley, C.J., Day, A.J., Knight, C.G., Mort, J.S., Buttle, D.J. Eur. J. Biochem. (2003) [Pubmed]
  16. Chemical modification of recombinant interleukin 2 by polyethylene glycol increases its potency in the murine Meth A sarcoma model. Katre, N.V., Knauf, M.J., Laird, W.J. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  17. The role of oxidant injury in tumor cell sensitivity to recombinant human tumor necrosis factor in vivo. Implications for mechanisms of action. Zimmerman, R.J., Marafino, B.J., Chan, A., Landre, P., Winkelhake, J.L. J. Immunol. (1989) [Pubmed]
  18. The efficacy of combined treatment with recombinant human tumor necrosis factor-alpha and 5-fluorouracil is dependent on the development of capillaries in tumor. Manda, T., Nishigaki, F., Mukumoto, S., Masuda, K., Nakamura, T., Shimomura, K. Eur. J. Cancer (1990) [Pubmed]
  19. Cytotoxic effects of methionine alkyl esters and amides in normal and neoplastic cell lines. Clement, M.A., Chapman, J.M., Roberts, J. Journal of pharmaceutical sciences. (1989) [Pubmed]
  20. ADAMTS1/METH1 inhibits endothelial cell proliferation by direct binding and sequestration of VEGF165. Luque, A., Carpizo, D.R., Iruela-Arispe, M.L. J. Biol. Chem. (2003) [Pubmed]
  21. ADAMTS8 and ADAMTS15 expression predicts survival in human breast carcinoma. Porter, S., Span, P.N., Sweep, F.C., Tjan-Heijnen, V.C., Pennington, C.J., Pedersen, T.X., Johnsen, M., Lund, L.R., Rømer, J., Edwards, D.R. Int. J. Cancer (2006) [Pubmed]
  22. ADAMTS1 cleaves aggrecan at multiple sites and is differentially inhibited by metalloproteinase inhibitors. Rodríguez-Manzaneque, J.C., Westling, J., Thai, S.N., Luque, A., Knauper, V., Murphy, G., Sandy, J.D., Iruela-Arispe, M.L. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  23. Oncostatin M in combination with tumour necrosis factor {alpha} induces a chondrocyte membrane associated aggrecanase that is distinct from ADAMTS aggrecanase-1 or -2. Hui, W., Barksby, H.E., Young, D.A., Cawston, T.E., McKie, N., Rowan, A.D. Ann. Rheum. Dis. (2005) [Pubmed]
  24. The expression and regulation of ADAMTS-1, -4, -5, -9, and -15, and TIMP-3 by TGFbeta1 in prostate cells: relevance to the accumulation of versican. Cross, N.A., Chandrasekharan, S., Jokonya, N., Fowles, A., Hamdy, F.C., Buttle, D.J., Eaton, C.L. Prostate (2005) [Pubmed]
  25. Differential expression of genes coding for EGF-like factors and ADAMTS1 following gonadotropin stimulation in normal and transformed human granulosa cells. Freimann, S., Ben-Ami, I., Dantes, A., Armon, L., Ben Ya'cov-Klein, A., Ron-El, R., Amsterdam, A. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  26. Structure of von Willebrand factor-cleaving protease (ADAMTS13), a metalloprotease involved in thrombotic thrombocytopenic purpura. Zheng, X., Chung, D., Takayama, T.K., Majerus, E.M., Sadler, J.E., Fujikawa, K. J. Biol. Chem. (2001) [Pubmed]
  27. High-density lipoprotein subfraction 3 decreases ADAMTS-1 expression induced by lipopolysaccharide and tumor necrosis factor-alpha in human endothelial cells. Norata, G.D., Björk, H., Hamsten, A., Catapano, A.L., Eriksson, P. Matrix Biol. (2004) [Pubmed]
  28. ADAMTS1: a matrix metalloprotease with angioinhibitory properties. Iruela-Arispe, M.L., Carpizo, D., Luque, A. Ann. N. Y. Acad. Sci. (2003) [Pubmed]
  29. Versican V1 proteolysis in human aorta in vivo occurs at the Glu441-Ala442 bond, a site that is cleaved by recombinant ADAMTS-1 and ADAMTS-4. Sandy, J.D., Westling, J., Kenagy, R.D., Iruela-Arispe, M.L., Verscharen, C., Rodriguez-Mazaneque, J.C., Zimmermann, D.R., Lemire, J.M., Fischer, J.W., Wight, T.N., Clowes, A.W. J. Biol. Chem. (2001) [Pubmed]
  30. Negative regulatory role of PI3-kinase in TNF-induced tumor necrosis. Matschurat, S., Blum, S., Mitnacht-Kraus, R., Dijkman, H.B., Kanal, L., De Waal, R.M., Clauss, M. Int. J. Cancer (2003) [Pubmed]
  31. Metalloproteinase expression in PMA-stimulated THP-1 cells. Effects of peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonists and 9-cis-retinoic acid. Worley, J.R., Baugh, M.D., Hughes, D.A., Edwards, D.R., Hogan, A., Sampson, M.J., Gavrilovic, J. J. Biol. Chem. (2003) [Pubmed]
  32. Protein engineering and properties of human metalloproteinase and thrombospondin 1. Wei, P., Zhao, Y.G., Zhuang, L., Hurst, D.R., Ruben, S., Sang, Q.X. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  33. Expression profiling of metalloproteinases and their inhibitors in cartilage. Kevorkian, L., Young, D.A., Darrah, C., Donell, S.T., Shepstone, L., Porter, S., Brockbank, S.M., Edwards, D.R., Parker, A.E., Clark, I.M. Arthritis Rheum. (2004) [Pubmed]
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