Crystal structures of VAP1 reveal ADAMs' MDC domain architecture and its unique C‐shaped scaffold
Open accessAbstract
ADAMs (a disintegrin and metalloproteinase) are sheddases possessing extracellular metalloproteinase/disintegrin/cysteine-rich (MDC) domains. ADAMs uniquely display both proteolytic and adhesive activities on the cell surface, however, most of their physiological targets and adhesion mechanisms remain unclear. Here for the first time, we reveal the ADAMs' MDC architecture and a potential target-binding site by solving crystal structures of VAP1, a snake venom homolog of mammalian ADAMs. The D-domain protrudes from the M-domain opposing the catalytic site and constituting a C-shaped arm with cores of Ca2+ ions. The disintegrin-loop, supposed to interact with integrins, is packed by the C-domain and inaccessible for protein binding. Instead, the hyper-variable region (HVR) in the C-domain, which has a novel fold stabilized by the strictly conserved disulfide bridges, constitutes a potential protein-protein adhesive interface. The HVR is located at the distal end of the arm and faces toward the catalytic site. The C-shaped structure implies interplay between the ADAMs' proteolytic and adhesive domains and suggests a molecular mechanism for ADAMs' target recognition for shedding.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Based on the model, known disease-causing mutations in TANGO2 could act by hindering catalysis (R26K, R32Q, and L50P, near active site) or produce steric clashes (G154R) in the hydrophobic core.
“Based on the model, known mutations that cause disease (magenta spheres in Fig. 3A) could act by hindering catalysis (R26K, R32Q, and L50P, near active site) or produce steric clashes (G154R) (19) in the hydrophobic core.”
From Accurate prediction of protein structures and interactions using a 3-track network (2021) · cites this paper as [19]
The Structural analysis section describes a crystal model of VAP1, not a model of TANGO2. Searches for TANGO2, G154R, R26K, R32Q, and L50P found no passage addressing those mutations or the proposed effects on catalysis and the hydrophobic core. (LLM, conf=0.77)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The CCP4 suite: programs for protein crystallography
Number Collaborative Computational Project (1994) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444994003112 · Cited by 17,299 · see citing works
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination
Brünger, A. T., Adams, P. D., Clore, G. M., DeLano, W. L., Gros, P., Grosse‐Kunstleve, R. W., Jiang, J., Kuszewski, J. J., Nilges, M., Pannu, N., et al. (1998) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444998003254 · Cited by 15,720 · see citing works
A metalloproteinase disintegrin that releases tumour-necrosis factor-α from cells
Black, R. A., Rauch, C. T., Kozlosky, C. J., Peschon, J. J., Slack, J. L., Wolfson, M. F., Castner, B. J., Stocking, K. L., Reddy, P., Srinivasan, S., et al. (1997) · Nature · doi:10.1038/385729a0 · Cited by 3,149 · see citing works
Automated protein model building combined with iterative structure refinement.
Perrakis, A., Morris, R. J., & Lamzin, V. S. (1999) · Nature Structural Biology · doi:10.1038/8263 · Cited by 2,423 · see citing works
Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-α
Moss, M. L., Jin, S.-L. C., Milla, M. E., Burkhart, W., Carter, H. L., Chen, W., Clay, W. C., Didsbury, J. R., Hassler, D. F., Hoffman, C. R., et al. (1997) · Nature · doi:10.1038/385733a0 · Cited by 1,611 · see citing works
ADAMs: key components in EGFR signalling and development
Blobel, C. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1548 · Cited by 1,091 · see citing works
Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness
Eerdewegh, P. V., Little, R. D., Dupuis, J., Mastro, R. G. D., Falls, K., Simon, J. S., Torrey, D., Pandit, S., McKenny, J., Braunschweiger, K. I., et al. (2002) · Nature · doi:10.1038/nature00878 · Cited by 1,082 · see citing works
The ADAMs family of metalloproteases: multidomain proteins with multiple functionsPreprint
Seals, D. F., & Courtneidge, S. A. (2003) · Genes & Development · doi:10.1101/gad.1039703 · Cited by 1,058 · see citing works
Bode, W., Gomis‐Rüth, F. X., & Stöckler, W. (1993) · FEBS Letters · doi:10.1016/0014-5793(93)80312-i · Cited by 762 · see citing works
A potential fusion peptide and an integrin ligand domain in a protein active in sperm–egg fusion
Blobel, C., Wolfsberg, T. G., Turck, C. W., Myles, D. G., Primakoff, P., & White, J. M. (1992) · Nature · doi:10.1038/356248a0 · Cited by 672 · see citing works
Fox, J. W., & Serrano, S. M. T. (2005) · Toxicon · doi:10.1016/j.toxicon.2005.02.012 · Cited by 587 · see citing works
Pan, D., & Rubin, G. M. (1997) · Cell · doi:10.1016/s0092-8674(00)80335-9 · Cited by 519 · see citing works
Functional Analysis of the Domain Structure of Tumor Necrosis Factor-α Converting Enzyme
Reddy, P., Slack, J. L., Davis, R., Cerretti, D. P., Kozlosky, C. J., Blanton, R. A., Shows, D. M., Peschon, J. J., & Black, R. A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.19.14608 · Cited by 501 · see citing works
A metalloprotease-disintegrin participating in myoblast fusion
Yagami-Hiromasa, T., Sato, T., Kurisaki, T., Kamijo, K., Nabeshima, Y.-I., & Fujisawa‐Sehara, A. (1995) · Nature · doi:10.1038/377652a0 · Cited by 480 · see citing works
Mouse egg integrin α6β1functions as a sperm receptor
Almeida, E. A. C., Huovila, A.-P. J., Sutherland, A. E., Stephens, L., Calarco, P. G., Shaw§, L. M., Mercurio, A. M., Sonnenberg, A., Primakoff, P., Myles, D. G., et al. (1995) · Cell · doi:10.1016/s0092-8674(05)80014-5 · Cited by 470 · see citing works
Janes, P. W., Saha, N., Barton, W. A., Kolev, M. V., Wimmer-Kleikamp, S. H., Nievergall, E., Blobel, C., Himanen, J., Lackmann, M., & Nikolov, D. B. (2005) · Cell · doi:10.1016/j.cell.2005.08.014 · Cited by 443 · see citing works
ADAMs: modulators of cell–cell and cell–matrix interactions
White, J. M. (2003) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2003.08.001 · Cited by 416 · see citing works
Processing of the Notch Ligand Delta by the Metalloprotease Kuzbanian
Qi, H., Rand, M. D., Wu, X., Šestan, N., Wang, W., RAKIC, P. T., Xu, T., & Artavanis‐Tsakonas, S. (1999) · Science · doi:10.1126/science.283.5398.91 · Cited by 415 · see citing works
Crystal structure of the catalytic domain of human tumor necrosis factor-α-converting enzyme
Maskos, K., Fernandez-Catalan, C., Huber, R., Bourenkov, G. P., Bartunik, H. D., Ellestad, G. A., Reddy, P., Wolfson, M. F., Rauch, C. T., Castner, B. J., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.7.3408 · Cited by 387 · see citing works
Primakoff, P., Hyatt, H., & Tredick-Kline, J. (1987) · The Journal of Cell Biology · doi:10.1083/jcb.104.1.141 · Cited by 371 · see citing works
KUZ, a Conserved Metalloprotease-Disintegrin Protein with Two Roles in Drosophila Neurogenesis
Rooke, J. E., Pan, D., Xu, T., & Rubin, G. M. (1996) · Science · doi:10.1126/science.273.5279.1227 · Cited by 328 · see citing works
Huang, T., Holt, J., ŁUKASIEWICZ, H., & Niewiarowski, S. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47710-1 · Cited by 324 · see citing works
Snake venom disintegrins: evolution of structure and function
Calvete, J. J., Marcinkiewicz, C., Monleón, D., Esteve, V., Celda, B., Juárez, P., & Sanz, L. (2005) · Toxicon · doi:10.1016/j.toxicon.2005.02.024 · Cited by 310 · see citing works
Iba, K., Albrechtsen, R., Gilpin, B., Fröhlich, C., Loechel, F., Żółkiewska, A., Ishiguro, K., Kojima, T., Liu, W., Langford, J. K., et al. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.149.5.1143 · Cited by 247 · see citing works
Myles, D. G., Kimmel, L. H., Blobel, C., White, J. M., & Primakoff, P. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.10.4195 · Cited by 235 · see citing works
Blobel, C., Myles, D. G., Primakoff, P., & White, J. M. (1990) · The Journal of Cell Biology · doi:10.1083/jcb.111.1.69 · Cited by 215 · see citing works
Snake venom metalloproteinases: Structure, function and relationship to the ADAMs family of proteins
Jia, L.-G., Shimokawa, K., Bjarnason, J. B., & Fox, J. W. (1996) · Toxicon · doi:10.1016/s0041-0101(96)00108-0 · Cited by 186 · see citing works
Functional Classification of ADAMs Based on a Conserved Motif for Binding to Integrin α9β1
Eto, K., Huet, C., Tarui, T., Kupriyanov, S., Liu, H.-Z., Puzon-McLaughlin, W., Zhang, X.-P., Sheppard, D., Engvall, E., & Takada, Y. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200086200 · Cited by 164 · see citing works
Fertilin β and other ADAMs as integrin ligands: insights into cell adhesion and fertilization
Evans, J. P. (2001) · BioEssays · doi:10.1002/bies.1088 · Cited by 147 · see citing works
Therapeutic Benefits from Targeting of ADAM Family Members
Moss, M. L., & Bartsch, J. W. (2004) · Biochemistry · doi:10.1021/bi049677f · Cited by 125 · see citing works
The cysteine-rich domain regulates ADAM protease function in vivo
Smith, K., Gaultier, A., Cousin, H., Alfandari, D., White, J. M., & DeSimone, D. W. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200206023 · Cited by 115 · see citing works
Becherer, J. D., & Blobel, C. (2003) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(03)54006-6 · Cited by 94 · see citing works
Gaultier, A., Cousin, H., Darribère, T., & Alfandari, D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201792200 · Cited by 90 · see citing works
Crystal Structure of the Catalytic Domain of Human ADAM33
Orth, P., Reichert, P., Wang, W., Prosise, W. W., Yarosh-Tomaine, T., Hammond, G., Ingram, R. N., Xiao, L., Mirza, U. A., Zou, J., et al. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2003.10.037 · Cited by 90 · see citing works
Crystal Structure of Trimestatin, a Disintegrin Containing a Cell Adhesion Recognition Motif RGD
Fujii, Y., Okuda, D., Fujimoto, Z., Horii, K., Morita, T., & Mizuno, H. (2003) · Journal of Molecular Biology · doi:10.1016/s0022-2836(03)00991-4 · Cited by 88 · see citing works
Kamiguti, A. S., Gallagher, P., Marcinkiewicz, C., Theakston, R. D. G., Zuzel, M., & Fox, J. W. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00799-3 · Cited by 86 · see citing works
Masuda, S., Hayashi, H., & Araki, S. (1998) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1998.2530036.x · Cited by 85 · see citing works
Self-citationJia, L.-G., Wang, X., Shannon, J. D., Bjarnason, J. B., & Fox, J. W. (2000) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1999.1517 · Cited by 75 · see citing works
The ADAMs family of proteins: from basic studies to potential clinical applications
Lynn, D. J., Lloyd, A. T., O'Shea, C., & Duffy, M. J. (2003) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1613568 · Cited by 75 · see citing works
Serrano, S. M. T., Jia, L.-G., Wang, D., Shannon, J. D., & Fox, J. W. (2005) · Biochemical Journal · doi:10.1042/bj20050483 · Cited by 71 · see citing works
cDNA Cloning and Characterization of Vascular Apoptosis-Inducing Protein 1
Masuda, S., Ohta, T., Kaji, K., Fox, J. W., Hayashi, H., & Araki, S. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3770 · Cited by 62 · see citing works
Self-citationDisintegrin-like/Cysteine-Rich Region of ADAM 12 Is an Active Cell Adhesion Domain
Żółkiewska, A. (1999) · Experimental Cell Research · doi:10.1006/excr.1999.4632 · Cited by 60 · see citing works
Nakamura, T., Abe, H., Hirata, A., & Shimoda, C. (2004) · Eukaryotic Cell · doi:10.1128/ec.3.1.27-39.2004 · Cited by 40 · see citing works
Zhu, X., Teng, M., & Niu, L. (1999) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444999010306 · Cited by 38 · see citing works
Bridges, L. C., Hanson, K. R., Tani, P. H., Mather, T., & Bowditch, R. D. (2003) · Biochemistry · doi:10.1021/bi026871y · Cited by 34 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Accurate prediction of protein structures and interactions using a 3-track network
Baek, M., DiMaio, F., Anishchenko, I., Dauparas, J., Ovchinnikov, S., Lee, G. R., Wang, J., Cong, Q., Kinch, L. N., Schaeffer, R. D., et al. (2021) · doi:10.1101/2021.06.14.448402 · Cited by 5,542 · see citing works
“The ADAMs contain prodomain and metalloprotease domains; the fold of the metalloprotease is known (18, 19), but not that of the prodomain, which has no homologs of known structure.”
Edwards, D. R., Handsley, M. M., & Pennington, C. (2008) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2008.08.001 · Cited by 1,165 · see citing works
“(2006) .”
BackgroundInfluentialThe ADAMs: signalling scissors in the tumour microenvironment
Murphy, G. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2459 · Cited by 528 · see citing works
Wilke, G. A., & Wardenburg, J. B. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1001815107 · Cited by 461 · see citing works
“Crystallographic studies of a portion of native ADAM10 and the related vascular apoptosis-inducing protein-1 reveal a highly conserved, multidomain C-shaped structure containing 17 disulfide bonds and several calcium-binding sites (25, 26).”
BackgroundFox, J. W., & Serrano, S. M. T. (2008) · FEBS Journal · doi:10.1111/j.1742-4658.2008.06466.x · Cited by 454 · see citing works
Snake venom metalloproteinases
Markland, F. S., & Swenson, S. D. (2012) · Toxicon · doi:10.1016/j.toxicon.2012.09.004 · Cited by 345 · see citing works
Enzymatic toxins from snake venom: structural characterization and mechanism of catalysis
Kang, T. S., Georgieva, D. N., Genov, N. C., Murakami, M. T., Sinha, M., Kumar, R. P., Kaur, P., Kumar, S., Dey, S., Sharma, S., et al. (2011) · FEBS Journal · doi:10.1111/j.1742-4658.2011.08115.x · Cited by 316 · see citing works
Self-citationShiomi, T., Lemaître, V., D'Armiento, J. M., & Okada, Y. (2010) · Pathology International · doi:10.1111/j.1440-1827.2010.02547.x · Cited by 275 · see citing works
Emerging roles of ADAM and ADAMTS metalloproteinases in cancer
Rocks, N., Paulissen, G., Hour, M. E., Quesada, F., Crahay, C., Gueders, M. M., Foidart, J. M., Noël, A., & Cataldo, D. D. (2007) · Biochimie · doi:10.1016/j.biochi.2007.08.008 · Cited by 266 · see citing works
“In a recent study by Takeda et al, the disintegrin domain has been shown not to be available for protein binding due to protein folding [17].”
Ectodomain shedding and ADAMs in development
Weber, S., & Säftig, P. (2012) · Development · doi:10.1242/dev.076398 · Cited by 259 · see citing works
“This region seems to be important for determining substrate specificity or for regulating protease activity (Takeda et al., 2006).”
BackgroundKey events in microvascular damage induced by snake venom hemorrhagic metalloproteinases
Escalante, T., Rucavado, A., Fox, J. W., & Gutiérrez, J. M. (2011) · Journal of Proteomics · doi:10.1016/j.jprot.2011.03.026 · Cited by 245 · see citing works
Cell–cell signaling via Eph receptors and ephrins
Himanen, J., Saha, N., & Nikolov, D. B. (2007) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2007.08.004 · Cited by 241 · see citing works
Takeda, S., Takeya, H., & Iwanaga, S. (2011) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2011.04.009 · Cited by 230 · see citing works
“5) has been designated as the hyper-variable-region (HVR) [50].”
BackgroundInfluentialSelf-citationSuh, J., Choi, S. H., Romano, D. M., Gannon, M. A., Lesinski, A. N., Kim, D. Y., & Tanzi, R. E. (2013) · Neuron · doi:10.1016/j.neuron.2013.08.035 · Cited by 217 · see citing works
Kini, R. M., & Koh, C. Y. (2016) · Toxins · doi:10.3390/toxins8100284 · Cited by 192 · see citing works
“Within the Ch subdomain, a hyper-variable region (HVR) can be identified and may function in specific protein–protein interactions [18].”
BackgroundA Disintegrin and Metalloprotease (ADAM): Historical Overview of Their Functions
Giebeler, N., & Zigrino, P. (2016) · Toxins · doi:10.3390/toxins8040122 · Cited by 184 · see citing works
“In addition to mediating interactions with cell surface receptors for adhesive and fusogenic purposes, the disintegrin and cysteine domains were suggested to regulate the proteolytic function of ADAMs as shown for the shedding of interleukin-1 receptor-II by ADAM-17 [19].”
BackgroundInfluentialCellular roles of ADAM12 in health and disease
Kveiborg, M., Albrechtsen, R., Couchman, J., & Wewer, U. M. (2008) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2008.01.025 · Cited by 181 · see citing works
Calvete, J. J., Fasoli, E., Sanz, L., Boschetti, E., & Righetti, P. G. (2009) · Journal of Proteome Research · doi:10.1021/pr900249q · Cited by 180 · see citing works
Timeline of key events in snake venom metalloproteinase research
Fox, J. W., & Serrano, S. M. T. (2009) · Journal of Proteomics · doi:10.1016/j.jprot.2009.01.015 · Cited by 173 · see citing works
Snake Venom Metalloproteinases (SVMPs): A structure-function update
Olaoba, O. T., dos Santos, P. K., Selistre-de-Araújo, H. S., & de Souza, D. H. F. (2020) · Toxicon X · doi:10.1016/j.toxcx.2020.100052 · Cited by 167 · see citing works
ADAM and ADAMTS Family Proteins and Snake Venom Metalloproteinases: A Structural Overview
Takeda, S. (2016) · Toxins · doi:10.3390/toxins8050155 · Cited by 164 · see citing works
“In ADAMs and P-III SVMPs, the RGD sequence is usually replaced by an (D/S)XCD sequence (residues 466–469 in the catrocollastatin/VAP2B sequence).”
BackgroundInfluentialSelf-citationAkiyama, M., Takeda, S., Kokame, K., Takagi, J., & Miyata, T. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909755106 · Cited by 163 · see citing works
“The D domain has an additional disulfide bond (Cys-322-Cys-347) that is strictly conserved among the ADAM counterparts (22, 24).”
BackgroundSelf-citationEvolution of Snake Venom Disintegrins by Positive Darwinian Selection
Juarez, P., Comas, I., Gónzález‐Candelas, F., & Calvete, J. J. (2008) · Molecular Biology and Evolution · doi:10.1093/molbev/msn179 · Cited by 161 · see citing works
“From the crystal structure of PIII-SVMP vascular apoptosis protein-1 (VAP1) from Crotalus atrox (Takeda et al. 2006) it was clearly observed that the ECD sequence motif (numbering as in Fig.”
BackgroundAccurate prediction of protein structures and interactions using a three-track neural network
Baek, M., DiMaio, F., Anishchenko, I. V., Dauparas, J., Ovchinnikov, S., Lee, G. R., Wang, J., Cong, Q., Kinch, L. N., Schaeffer, R. D., et al. (2022) · Yearbook of pediatric endocrinology · doi:10.1530/ey.19.15.15 · Cited by 199 · see citing works
Regulation of Mature ADAM17 by Redox Agents for L-Selectin Shedding
Wang, Y., Herrera, A. H., Li, Y., Belani, K., & Walcheck, B. K. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0802770 · Cited by 136 · see citing works
“An alignment of 39 ADAM sequences, including 23 human ADAMs, reveals that the CXXC sequence preceding the hypervariable region occurs only in ADAM10 and ADAM17 (43), two sheddases that have several substrates in common (17).”
BackgroundInfluentialADAM8 as a drug target in pancreatic cancer
Schlomann, U., Koller, G., Conrad, C., Ferdous, T., Golfi, P., Garcia, A. M., Höfling, S., Parsons, M., Costa, P., Soper, R., et al. (2015) · Nature Communications · doi:10.1038/ncomms7175 · Cited by 121 · see citing works
Zhong, S., & Khalil, R. A. (2019) · Biochemical Pharmacology · doi:10.1016/j.bcp.2019.03.033 · Cited by 119 · see citing works
“The discovery of the C-shape scaffold, was a landmark study in deciphering the crystal structure of ADAMs and how they function [9].”
BackgroundInfluentialCross-domain inhibition of TACE ectodomain
Tape, C. J., Willems, S. H., Dombernowsky, S. L., Stanley, P. L. D., Fogarasi, M., Ouwehand, W. H., McCafferty, J., & Murphy, G. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1017067108 · Cited by 118 · see citing works
“Specifically, the crystal structures of ADAM homologs VAP1 (13), VAP2B (16), RVVX (17), and the nonproteolytic ectodomain of human ADAM22 (18) support the notion that ADAM proteins are “C-shaped” (Fig.”
BackgroundEscalante, T., Shannon, J. D., Moura-da-Silva, A. M., Gutiérrez, J. M., & Fox, J. W. (2006) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2006.09.018 · Cited by 111 · see citing works
Igarashi, T., Araki, S., Mori, H., & Takeda, S. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.04.057 · Cited by 107 · see citing works
“We designated this region as the hyper-variable-region (HVR), and have proposed that it represents a potential exosite for target recognition [19].”
BackgroundInfluentialSelf-citationWisniewska, M., Goettig, P., Maskos, K., Belouski, E., Winters, D., Hecht, R. I., Black, R. A., & Bode, W. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.06.088 · Cited by 105 · see citing works
Regulation of the proteolytic disintegrin metalloproteinases, the ‘Sheddases’
Murphy, G. (2008) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2008.09.004 · Cited by 103 · see citing works
“[85] Takeda S, Igarashi T, Mori H, Araki S.”
ADAM proteases: ligand processing and modulation of the Notch pathway
Żółkiewska, A. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-7586-4 · Cited by 100 · see citing works
Gerhardt, S., Hassall, G., Hawtin, P., McCall, E. J., Flavell, L., Minshull, C. A., Hargreaves, D., Ting, A. K. T., Pauptit, R. A., Parker, A. E., et al. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.07.047 · Cited by 99 · see citing works
Andrews, R. K., Karunakaran, D., Gardiner, E. E., & Berndt, M. C. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.141390 · Cited by 98 · see citing works
An Overview of ADAM9: Structure, Activation, and Regulation in Human Diseases
Chou, C., Huang, Y., Kuo, T.-T., Liu, J.-P., & Sher, Y. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207790 · Cited by 96 · see citing works
“ADAMs are biosynthesized as zymogens with the pro-domains preserving their inactive state.”
BackgroundInfluentialCrystal structure of RVV‐X: An example of evolutionary gain of specificity by ADAM proteinases
Takeda, S., Igarashi, T., & Mori, H. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.11.062 · Cited by 94 · see citing works
“Previously, we suggested that the HVR may constitute an exosite that captures the target or associated proteins, and that is processed by the catalytic site [11].”
BackgroundInfluentialSelf-citationAngiotensin Converting Enzyme (ACE) and ACE2 Bind Integrins and ACE2 Regulates Integrin Signalling
Clarke, N. E., Fisher, M. J., Porter, K. E., Lambert, D., & Turner, A. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034747 · Cited by 91 · see citing works
“ADAM 9, for example, binds through a hypervariable loop stabilised by disulphide bridges, which protrudes from the surface of the protein structure [43,44].”
Essential role of the disintegrin-like domain in ADAMTS13 function
de Groot, R., Bardhan, A., Ramroop, N., Lane, D. A., & Crawley, J. T. B. (2009) · Blood · doi:10.1182/blood-2008-11-187914 · Cited by 90 · see citing works
Düsterhöft, S., Jung, S., Hung, C., Tholey, A., Sönnichsen, F. D., Grötzinger, J., & Lorenzen, I. (2013) · Journal of the American Chemical Society · doi:10.1021/ja400340u · Cited by 89 · see citing works
Serrano, S. M. T., Kim, J., Wang, D., Dragulev, B. P., Shannon, J. D., Mann, H. H., Veit, G., Wagener, R., Koch, M., & Fox, J. W. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604855200 · Cited by 88 · see citing works
Quinn, J. A., Graeber, C. T., Frackelton, A. R., Kim, M., Schwarzbauer, J. E., & Filardo, E. J. (2009) · Molecular Endocrinology · doi:10.1210/me.2008-0262 · Cited by 84 · see citing works
“In support of this concept, integrin v 3 has been reported to associate directly with MMP-2 (53), and ADAMs (a Disintegrin and a Metalloproteinase) family members have integrin interaction domains (54, 55).”
BackgroundSnake Venom Disintegrins and Cell Migration
Selistre-de-Araújo, H. S., Pontes, C. L. S., Montenegro, C. F., & Martin, A. C. B. M. (2010) · Toxins · doi:10.3390/toxins2112606 · Cited by 83 · see citing works
“Depending on the disulfide pairing, the D domain may assume at least two types of conformation, a C-shaped or an I-shaped scaffold; the former was suggested to play a key role in substrate recognition by the catalytic domain [27].”
BackgroundToxins in thrombosis and haemostasis: potential beyond imagination
Kini, R. M. (2011) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2011.04279.x · Cited by 82 · see citing works
Sánchez, E. F., Flores-Ortiz, R., de Alvarenga, V. G., & Eble, J. A. (2017) · Toxins · doi:10.3390/toxins9120392 · Cited by 81 · see citing works
“Furthermore, SVMPs, ADAMs and ADAMTSs, the latter of which contain an additional thrombospondin (TS) motifs, share a topological similarity to matrix metalloproteinases of tissues (MMPs) within the structural organization of their catalytic center [19].”
BackgroundInfluentialThree-dimensional domain architecture of the ADAM family proteinases
Takeda, S. (2008) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2008.07.009 · Cited by 81 · see citing works
Self-citationMolecular insights into the multilayered regulation of ADAM17: The role of the extracellular region
Grötzinger, J., Lorenzen, I., & Düsterhöft, S. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2017.05.024 · Cited by 79 · see citing works
ADAM proteases: Emerging role and targeting of the non-catalytic domains
Saha, N., Tzvetkova‐Robev, D., Himanen, J. P., & Nikolov, D. B. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.10.003 · Cited by 78 · see citing works
Collagen binding is a key factor for the hemorrhagic activity of snake venom metalloproteinases
Moura-da-Silva, A. M., Ramos, O. H. P., Baldo, C., Niland, S., Hansen, U. J., Ventura, J. S., Furlan, S., Butera, D., Della-Casa, M. S., Tanjoni, I., et al. (2007) · Biochimie · doi:10.1016/j.biochi.2007.11.009 · Cited by 78 · see citing works
Düsterhöft, S., Hoebel, K., Oldefest, M., Lokau, J., Waetzig, G. H., Chalaris, A., Garbers, C., Scheller, J., Rose‐John, S., Lorenzen, I., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.557322 · Cited by 75 · see citing works
“In this structural model, the extracellular part adopts a C-shaped structure, placing the MPD in close proximity to the catalytic domain (18, 27).”
BackgroundAn activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth
Atapattu, L., Saha, N., Chheang, C., Eissmann, M. F., Xu, K. Y., Vail, M. E., Hii, L. L., Llerena, C., Liu, Z., Horvay, K., et al. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20151095 · Cited by 76 · see citing works
“Processing has been suggested to produce the active form of ADAMs by releasing the Pro domain, which can interact with and inhibit the mature MP, although for ADAM10 and 17 this does not occur via the cysteine switch mechanism of other MPs (Moss et al., 2007).”
BackgroundInfluentialMuniz, J. R. C., Ambrosio, A. L. B., Selistre-de-Araújo, H. S., Cominetti, M. R., Moura-da-Silva, A. M., Oliva, G., Garratt, R. C., & de Souza, D. H. F. (2008) · Toxicon · doi:10.1016/j.toxicon.2008.08.021 · Cited by 73 · see citing works
“It has been proposed that the HVR is involved with the recognition of the target for proteolytically attack of the M domain (Takeda et al., 2006) but this hypothesis, although very reasonable, needs experimental confirmation.”
BackgroundMethodResultInfluentialLorenzen, I., Lokau, J., Düsterhöft, S., Trad, A., Garbers, C., Scheller, J., Rose‐John, S., & Grötzinger, J. (2012) · FEBS Letters · doi:10.1016/j.febslet.2012.03.012 · Cited by 72 · see citing works
“The extracellular part of mature ADAM17 most likely adopts a C-shaped conformation [11,13], thereby localizing the membrane-proximal domain close to the active site.”
BackgroundNyren‐Erickson, E. K., Jones, J. M., Srivastava, D. K., & Mallik, S. (2013) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2013.05.011 · Cited by 70 · see citing works
“, have explored the hypervariable loop region of the cysteine region of ADAMs, and have suggested this as an attractive targeting site for inhibition [96,97].”
BackgroundCatalytic Properties of ADAM12 and Its Domain Deletion Mutants
Jacobsen, J., Visse, R., Sørensen, H. P., Enghild, J. J., Brew, K., Wewer, U. M., & Nagase, H. (2007) · Biochemistry · doi:10.1021/bi701629c · Cited by 69 · see citing works
Who decides when to cleave an ectodomain?
Hartmann, M., Herrlich, A., & Herrlich, P. A. (2013) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2012.12.002 · Cited by 68 · see citing works
Liu, H., Shim, A. H.-R., & He, X. L. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.014258 · Cited by 68 · see citing works
ADAMTS13 and von Willebrand factor interactions
Zander, C. B., Cao, W., & Zheng, X. L. (2015) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000169 · Cited by 67 · see citing works
Role of ADAM-9 Disintegrin-Cysteine-rich Domains in Human Keratinocyte Migration
Zigrino, P., Steiger, J., Fox, J. W., Löffek, S., Schild, A., Nischt, R., & Mauch, C. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m701658200 · Cited by 66 · see citing works
Mackessy, S. P., & Mackessy, S. P. (2016) · CRC Press eBooks · doi:10.1201/9781420008661-11 · Cited by 65 · see citing works
Doley, R., Mackessy, S. P., & Kini, R. M. (2009) · BMC Evolutionary Biology · doi:10.1186/1471-2148-9-146 · Cited by 64 · see citing works
“This hypervariable region has been predicted to be a potential exosite for target recognition [83].”
BackgroundADAMs family and relatives in cardiovascular physiology and pathology
Zhang, P., Shen, M., Fernández-Patrón, C., & Kassiri, Z. (2015) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2015.10.031 · Cited by 63 · see citing works
“Modified from [15].”
BackgroundInfluentialLee, H., Koo, B.-S., Kim, Y. H., Jeon, O., & Kim, D. (2012) · The FASEB Journal · doi:10.1096/fj.11-201681 · Cited by 63 · see citing works
“binding on the same plasma membrane (37).”
Zigrino, P., Nischt, R., & Mauch, C. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.168617 · Cited by 62 · see citing works
Jararhagin, a hemorrhagic snake venom metalloproteinase from Bothrops jararaca
Moura-da-Silva, A. M., & Baldo, C. (2012) · Toxicon · doi:10.1016/j.toxicon.2012.03.026 · Cited by 60 · see citing works
“The crystal structure of bothropasin complexed with the inhibitor POL647 showed the major features already described for VAP-I (Igarashi et al., 2007; Takeda et al., 2006): The catalytic domain is consisted of two sub-domains including the zinc and calcium-binding sites.”
BackgroundStatus update on iRhom and ADAM17: It's still complicated
Düsterhöft, S., Babendreyer, A., Giese, A. A., Flasshove, C., & Ludwig, A. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2019.06.017 · Cited by 60 · see citing works
Guan, H., Goh, K.-S., Davamani, F. A., Wu, P.-L., Huang, Y.-W., Jeyakanthan, J., Wu, W., & Chen, C. (2009) · Journal of Structural Biology · doi:10.1016/j.jsb.2009.11.009 · Cited by 59 · see citing works
“4A and B, atragin maintains a C-shaped architecture as its structure adopts a similar D-shoulder (Ds) domain (a.a. 410–442) with three disulfide bonds (pairs of 3, 4, and 5) and a D-arm (Da) domain (a.a. 443–493) with another three disulfide bonds (pairs of 7, 8, and 9) constituting the C-shaped arm as in VAP1 and VAP…”
BackgroundInfluentialProcessing of Snake Venom Metalloproteinases: Generation of Toxin Diversity and Enzyme Inactivation
Moura-da-Silva, A. M., de Almeida, M. T., Portes-Junior, J. A., Nicolau, C. A., Gomes‐Neto, F., & Valente, R. H. (2016) · Toxins · doi:10.3390/toxins8060183 · Cited by 62 · see citing works
“Class P-III SVMPs VAP1 and VAP2 from Crotalus atrox have been crystallized in their dimeric form [74,75] exerting potent pro-apoptotic activity in endothelial cell cultures [76].”
BackgroundTanjoni, I., Evangelista, K. S., Della-Casa, M. S., Butera, D., Magalhães, G. S., Baldo, C., Clissa, P. B., Fernandes, I., Eble, J. A., & Moura-da-Silva, A. M. (2010) · Toxicon · doi:10.1016/j.toxicon.2009.12.010 · Cited by 57 · see citing works
The role of proteases in regulating Eph/ephrin signaling
Atapattu, L., Lackmann, M., & Janes, P. W. (2014) · Cell Adhesion & Migration · doi:10.4161/19336918.2014.970026 · Cited by 55 · see citing works
“For example the VAP1 structure shares a curved DCC domain structure with ADAM10, which confers an overall C-shape structure with the MP domain in proximity to the substrate binding region of the C domain, consistent with the idea binding to the C domain controls specificity by positioning the substrate for cleavage.(3…”
BackgroundJoo, C.-K., Kim, H. S., Park, J.-Y., Seomun, Y., Son, M.-J., & Kim, J.-T. (2007) · Oncogene · doi:10.1038/sj.onc.1210649 · Cited by 55 · see citing works
Ectodomain shedding and remnant peptide signalling of EGFRs and their ligands
Higashiyama, S., Nanba, D., Nakayama, H., Inoue, H., & Fukuda, S. (2011) · The Journal of Biochemistry · doi:10.1093/jb/mvr068 · Cited by 52 · see citing works
Chen, H.-S., Tsai, H.-Y., Wang, Y., & Tsai, I. (2008) · Biochimie · doi:10.1016/j.biochi.2008.05.012 · Cited by 51 · see citing works
Targeting ADAM17 Sheddase Activity in Cancer
Rossello, A., Nuti, E., Ferrini, S., & Fabbi, M. (2016) · Current Drug Targets · doi:10.2174/1389450117666160727143618 · Cited by 50 · see citing works
Kawasaki, K., Freimuth, J., Meyer, D. S., Lee, M. M., Tochimoto-Okamoto, A., Benzinou, M., Clermont, F. F., Wu, G., Roy, R., Letteboer, T. G. W., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1318761111 · Cited by 47 · see citing works
“Ileu613Val variant is located within the cysteine-rich substrate recognition domain (43); thus, variation in Adam17 p.”
BackgroundADAM Proteins- Therapeutic Potential in Cancer
Lu, X., Lu, D., Scully, M. F., & Kakkar, V. V. (2008) · Current Cancer Drug Targets · doi:10.2174/156800908786733478 · Cited by 46 · see citing works
Programmed autologous cleavage of platelet receptors
Berndt, M. C., Karunakaran, D., Gardiner, E. E., & Andrews, R. K. (2007) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2007.02484.x · Cited by 46 · see citing works
Menezes, M. C., Leme, A. F. P., Melo, R. L. D., Alberto-Silva, C., Della-Casa, M. S., Bruni, F. M., Lima, C., Lopes‐Ferreira, M., de Camargo, A. C. M., Fox, J. W., et al. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.10.034 · Cited by 45 · see citing works
“In VAP1 and catrocollastatin/VAP2B, the HVR is located at the distal end of the arm constituted by disintegrin-like domain and faces toward the catalytic site [14,15].”
BackgroundInfluentialHiguchi, D. A., Almeida, M. C., Barros, C. C., Sánchez, E. F., Pesquero, P. R., Lang, E. A. S., Samaan, M., Araújo, R. C., Pesquero, J. B., & Pesquero, J. L. (2011) · Toxicon · doi:10.1016/j.toxicon.2011.05.013 · Cited by 43 · see citing works
Connective tissue growth factor is a substrate of ADAM28
Mochizuki, S., Tanaka, R., Shimoda, M., Onuma, J., Fujii, Y., Jinno, H., & Okada, Y. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.10.077 · Cited by 43 · see citing works
“5 and 1 mg/ml) of (465)CRPAKDECDLPEMC(478) corresponding to the disintegrin loop of the Dis domain [20], (567)QGGSDNLPWKGRIVT(581) and (582)FLTAKTFDPEDTSQEI(597) corresponding to the hyper-variable region of the CR domain [21] or an RGDS peptide (a negative control) prior to the binding assay.”
BackgroundMethodPinto, A. F. M., Terra, R. M. S., Guimarães, J. A., & Fox, J. W. (2006) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2006.10.010 · Cited by 41 · see citing works
Limam, I., Bazaa, A., Srairi‐Abid, N., Taboubi, S., Jebali, J., Zouari-Kessentini, R., Kallech-Ziri, O., Mejdoub, H., Hammami, A., Ayeb, M. E., et al. (2009) · Matrix Biology · doi:10.1016/j.matbio.2009.09.009 · Cited by 41 · see citing works
Wakatsuki, S., Yumoto, N., Komatsu, K., Araki, T., & Sehara‐Fujisawa, A. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803191200 · Cited by 41 · see citing works
Shimoda, M., Hashimoto, G., Mochizuki, S., Ikeda, E., Nagai, N., Ishida, S., & Okada, Y. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702414200 · Cited by 41 · see citing works
The EGFR-ADAM17 Axis in Chronic Obstructive Pulmonary Disease and Cystic Fibrosis Lung Pathology
Stolarczyk, M., & Scholte, B. J. (2018) · Mediators of Inflammation · doi:10.1155/2018/1067134 · Cited by 39 · see citing works
Chen, H., Chen, J., Lin, C., Khoo, K., & Tsai, I. (2008) · FEBS Journal · doi:10.1111/j.1742-4658.2008.06540.x · Cited by 39 · see citing works
Snake Venom Metalloproteinases
Fox, J. W., & Gutiérrez, J. M. (2017) · MDPI eBooks · doi:10.3390/books978-3-03842-427-7 · Cited by 40 · see citing works
Gordon, K., Balyasnikova, I. V., Nesterovitch, A. B., Schwartz, D. E., Sturrock, E. D., & Danilov, S. M. (2009) · Tissue Antigens · doi:10.1111/j.1399-0039.2009.01416.x · Cited by 36 · see citing works
Domain integration of ADAM family proteins: Emerging themes from structural studies
Seegar, T. C. M., & Blacklow, S. C. (2019) · Experimental Biology and Medicine · doi:10.1177/1535370219865901 · Cited by 35 · see citing works
“The ADAM cysteine-rich domain also contains a segment dubbed the “hypervariable region” (HVR), named for the significant divergence in length and amino acid composition among the different ADAMs in this region.(47) Within the ADAM family, the HVR ranges in length from 37 residues in ADAM17 to 87 residues in ADAM19.”
BackgroundCell surface annexins regulate ADAM-mediated ectodomain shedding of proamphiregulin
Nakayama, H., Fukuda, S., Inoue, H., Nishida‐Fukuda, H., Shirakata, Y., Hashimoto, K., & Higashiyama, S. (2012) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-08-0683 · Cited by 32 · see citing works
“Previous reports have shown that the hypervariable region (HVR) of ADAMs may have a significant effect on substrate recognition and may adjust the spatial alignment of the catalytic and adhesion sites (Takeda et al., 2006; Igarashi et al., 2007).”
BackgroundMarques-Porto, R., Lebrun, I., & Pimenta, D. C. (2008) · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology · doi:10.1016/j.cbpc.2008.01.011 · Cited by 30 · see citing works
Menezes, M. C., Oliveira, A. K., Melo, R. L. D., Lopes‐Ferreira, M., Rioli, V., Balan, A., Leme, A. F. P., & Serrano, S. M. T. (2010) · Biochimie · doi:10.1016/j.biochi.2010.10.007 · Cited by 29 · see citing works
Modulation of integrin α4β1 by ADAM28 promotes lymphocyte adhesion and transendothelial migration
McGinn, O. J., English, W., Roberts, S., Ager, A., Newham, P., & Murphy, G. (2011) · Cell Biology International · doi:10.1042/cbi20100885 · Cited by 28 · see citing works
“for binding to integrins since the disintegrin loop is buried within a MDC (metalloproteinase, disintegrin and cysteine-rich) fold (Takeda et al., 2006).”
BackgroundSajevic, T., Leonardi, A., Kovačič, L., Balija, M. L., Kurtović, T., Pungerčar, J., Halassy, B., Trampuš-Bakija, A., & Križaj, I. (2013) · Biochimie · doi:10.1016/j.biochi.2013.01.003 · Cited by 28 · see citing works
“Non-catalytic Dis and CR domains contain several substrate-binding sites located in the so-called disintegrin loop and in the hyper-variable region [5,6].”
BackgroundInfluentialThe proteinase-rich proteome of Bothrops jararaca venom
Serrano, S. M. T., Oliveira, A. K., Menezes, M. C., & Zelanis, A. (2014) · Toxin Reviews · doi:10.3109/15569543.2014.922581 · Cited by 27 · see citing works
“Interestingly, the determination of crystal structures of P-III class SVMPs also showed that the folding of the metalloproteinase domain is similar between these enzymes and those of the P-I class (Igarashi et al., 2007; Muniz et al., 2008; Takeda et al., 2006, 2007).”
BackgroundInfluentialCamacho, E. T., Villalobos, E., Sanz, L., Pérez, A., Escalante, T., Lomonte, B., Calvete, J. J., Gutiérrez, J. M., & Rucavado, A. (2014) · Biochimie · doi:10.1016/j.biochi.2014.01.008 · Cited by 26 · see citing works
Teklemariam, T., Seoane, A. I., Ramos, C. J., Sanchez, E. E., Lucena, S. E., Pérez, J. C., Mandal, S. A., & Soto, J. G. (2011) · Toxicon · doi:10.1016/j.toxicon.2011.01.007 · Cited by 26 · see citing works
“Crystallography studies of two PIII-SVMPs (VAP1 and catrocollastatin/VAP2B) indicate that their disintegrin-like loop is not accessible for integrin binding (Takeda et al., 2006; Igarashi et al., 2007).”
Brief History and Molecular Determinants of Snake Venom Disintegrin Evolution
Calvete, J. J. (2010) · Springer eBooks · doi:10.1007/978-90-481-9295-3_18 · Cited by 25 · see citing works
Interaction of Bothrops jararaca venom metalloproteinases with protein inhibitors
Asega, A. F., Oliveira, A. K., Menezes, M. C., Neves‐Ferreira, A. G. C., & Serrano, S. M. T. (2014) · Toxicon · doi:10.1016/j.toxicon.2014.01.001 · Cited by 25 · see citing works
Sant′Ana, E. M. C., Gouvêa, C. M. C. P., Nakaie, C. R., & Selistre-de-Araújo, H. S. (2008) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2008.07.030 · Cited by 24 · see citing works
- Authors
- Takeda, S., Igarashi, T., Mori, H., & Araki, S.
- Affiliations
- SPring-8 (JP)
- National Cerebral and Cardiovascular Center (JP)
- Nagoya University (JP)
- Corresponding author
- Takeda, Soichi
- ORCID
- Takeda, Soichi
- Venue
- The EMBO Journal
- Published
- 2006-05-11
- Volume
- 25
- Issue
- 11
- Pages
- 2388-2396
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1478178
- OpenAlex
- W2000001290
- Cited by
- 202
- References
- 45
- Citations by year
- 2025: 10 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 9 · 2020: 4 · 2019: 5 · 2018: 2 · 2017: 11 · 2016: 12 · 2015: 7 · 2014: 14 · 2013: 9 · 2012: 17
- FWCI
- 8.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Takeda Science Foundation
- Senri Life Science Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- ADAMS, snake venom proteins, disintegrins, metalloproteinases, hypervariable region, disulfide bonds, calcium ions, extracellular matrix, crystal structure
- MeSH terms
- Amino Acid Sequence, Animals, Crotalid Venoms, Humans, Metalloendopeptidases, Models, Molecular, Molecular Sequence Data, Sequence Alignment, Protein Structure, Tertiary, Crystallography, X-Ray, Apoptosis Regulatory Proteins, ADAM Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
