Active Metalloproteases of the A Disintegrin And Metalloprotease (ADAM) Family: Biological Function and Structure
Abstract
The "a disintegrin and metalloproteases" (ADAMs) are membrane-anchored metzincins of the adamalysin subfamily. This review gives an overview over the biological function and structure of ADAMs focusing on members of the family that display proteolytic activity. ADAMs are involved in a range of human diseases such as cancer metastasis, inflammatory disorders, neurological disease or asthma. It is, however, often difficult to assign a definitive role to a specific member of the ADAM family in a given disease mechanism due to overlapping activities and redundancy in function, as shown in various knock-out studies. The review discusses the structural domains that are not directly linked to protease activity followed by a more detailed overview over the role of the metalloprotease domain. Different family members are critically reviewed with respect to their role in biological processes with particular emphasis on disease-relevant functions.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Deficiencies in TANGO2 lead to metabolic disorders, and the protein plays an unknown role in Golgi membrane redistribution into the ER.
“Deficiencies in TANGO2 (transport and Golgi organization protein 2) lead to metabolic disorders, and the protein plays an unknown role in Golgi membrane redistribution into the ER (16, 17).”
From Accurate prediction of protein structures and interactions using a 3-track network (2021) · cites this paper as [16]
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 ADAM (A Disintegrin And Metalloprotease) and ADAMTS families of metalloproteases are encoded by over 40 human genes, mediate cell-cell and cell-matrix interactions (15, 16) and are involved in a range of human diseases, including cancer metastasis, inflammatory disorders, neurological diseases and asthma (16, 17).”
Vandooren, J., den Steen, P. E. V., & Opdenakker, G. (2013) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2013.770819 · Cited by 767 · see citing works
“…e.g. serine proteinases and thiol proteases (Barrett et al., 2012), other subfamilies, including, A disintegrin and metalloproteinases (ADAMs) (Klein & Bischoff, 2011; Murphy, 2008) and a disintegrin and MMP with thrombospondin motifs (ADAMTSs) (Apte, 2009) and unique members such as t-PA.”
BackgroundMetalloproteinases and their natural inhibitors in inflammation and immunity
Khokha, R., Murthy, A., & Weiss, A. (2013) · Nature reviews. Immunology · doi:10.1038/nri3499 · Cited by 552 · see citing works
Matrix metalloproteinases and epidermal wound repair
Martins, V., Caley, M. P., & O’Toole, E. A. (2012) · Cell and Tissue Research · doi:10.1007/s00441-012-1410-z · Cited by 251 · see citing works
“ADAMs are widely characterised for their role in fertilisation but have been linked to roles in cell adhesion, migration, proteolysis and signalling (Edwards et al. 2008; Klein and Bischoff 2011).”
BackgroundSbardella, D., Fasciglione, G., Gioia, M., Ciaccio, C., Tundo, G., Marini, S., & Coletta, M. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2011.10.015 · Cited by 247 · see citing works
“Human members of M12 family are classified in two subfamilies, A and B, which include astacins, ADAM and ADAMTS proteases, respectively (see for review Edwards et al., 2008; Klein and Bischoff, 2011; Mochizuki and Okada, 2007; Murphy, 2008; Tousseyn et al., 2006; Van Goor et al., 2009).”
BackgroundKlein, T., Eckhard, U., Dufour, A., Solis, N., & Overall, C. M. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00120 · Cited by 229 · see citing works
Self-citationArchitecture and function of metallopeptidase catalytic domains
Cerdà‐Costa, N., & Gomis‐Rüth, F. X. (2013) · Protein Science · doi:10.1002/pro.2400 · Cited by 205 · see citing works
Cell-Surface Receptors Transactivation Mediated by G Protein-Coupled Receptors
Cattaneo, F., Guerra, G., Parisi, M., Marinis, M. D., Tafuri, D., Cinelli, M., & Ammendola, R. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms151119700 · Cited by 191 · see citing works
“Ectodomain cleavage is made specific by a number of intracellular signals, such as calcium influx, activation of GPCRs (Figure 1), and the release of diacylglycerol [38,39].”
BackgroundInhibition of MMPs and ADAM/ADAMTS
Malemud, C. J. (2019) · Biochemical Pharmacology · doi:10.1016/j.bcp.2019.02.033 · Cited by 184 · see citing works
Hatzirodos, N., Irving‐Rodgers, H. F., Hummitzsch, K., et al. (2014) · BMC Genomics · doi:10.1186/1471-2164-15-24 · Cited by 170 · see citing works
“These three proteases together are capable of degrading fibronectin and collagen IV, and shed Fas and kit ligand from epithelial cells in vitro [59] and thus may regulate the breakdown of matrix and differentiation of granulosa cells prior to ovulation.”
Endothelial endoglin is involved in inflammation: role in leukocyte adhesion and transmigration
Rossi, E., Sanz-Rodrı́guez, F., Eleno, N., Düwel, A., Blanco, F. J., Langa, C., Botella, L. M., Cabañas, C., López-Novoa, J. M., & Bernabéu, C. (2012) · Blood · doi:10.1182/blood-2012-06-435347 · Cited by 161 · see citing works
Accurate 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
Multipotent stromal cells: One name, multiple identities
Soliman, H., Theret, M., Scott, W., Hill, L., Underhill, T. M., Hinz, B., & Rossi, F. M. V. (2021) · Cell Stem Cell · doi:10.1016/j.stem.2021.09.001 · Cited by 147 · see citing works
Huang, X., Zhang, G., Tang, T., & Liang, T. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01310-0 · Cited by 151 · see citing works
“For example, ADAM9 is involved in tumor cell metastasis, proliferation, angiogenesis and immune evasion [30, 31] and high levels of ADAM-9 in pancreatic cancer is associated with short OS and higher tumor grade and progression [32, 33].”
BackgroundWang, Y., He, G., Guo, Y., Tang, H., Shi, Y., Bian, X., Zhu, M., Kang, X., Zhou, M., Lyu, J., et al. (2019) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14430 · Cited by 144 · see citing works
Functions of ‘A disintegrin and metalloproteases (ADAMs)’ in the mammalian nervous system
Hsia, H., Tüshaus, J., Brummer, T., Zheng, Y., Scilabra, S. D., & Lichtenthaler, S. F. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03173-7 · Cited by 133 · see citing works
Secretome Signature of Invasive Glioblastoma Multiforme
Formolo, C. A., Williams, R., Gordish‐Dressman, H., MacDonald, T. J., Lee, N. H., & Hathout, Y. (2011) · Journal of Proteome Research · doi:10.1021/pr200210w · Cited by 131 · see citing works
Matthews, A. L., Noy, P. J., Reyat, J. S., & Tomlinson, M. G. (2016) · Platelets · doi:10.1080/09537104.2016.1184751 · Cited by 122 · see citing works
“The ADAM family consists of 22 members, as identified in the human genome, of which only 12 (ADAM8, 9, 10, 12, 15, 17, 19, 20, 21, 28, 30, and 33) encode active enzymes [2].”
BackgroundThe epidermal growth factor receptor pathway in chronic kidney diseases
Harskamp, L. R., Gansevoort, R. T., van Goor, H., & Meijer, E. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.91 · 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
“There are 22 ADAMs in human [62], 14 of these ADAMs including ADAM-1, 2, 3, 6, 7, 18, 20, 21, 22, 28, 29, 30, 32 and 33 are restricted to embryo development, and are mainly expressed and conduct their function in the reproductive system such as testis, epididymis and uterus.”
BackgroundNew and Paradoxical Roles of Matrix Metalloproteinases in the Tumor Microenvironment
Noël, A., Gutiérrez‐Fernández, A., Sounni, N. E., Behrendt, N., Maquoi, E., Lund, I. K., Cal, S., Høyer‐Hansen, G., & López-Otı́n, C. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00140 · Cited by 110 · see citing works
“…the catalytic domain with the MMPs but which include two main differences: (1) the absence of a hemopexin-like domain and (2) the insertion of three additional domains [cysteine-rich domain, epidermal growth factor (EGF)-like domain and the disintegrin domain; Figure 1; Klein and Bischoff, 2011].”
BackgroundMatrix metalloproteinases as therapeutic targets in protozoan parasitic infections
Geurts, N., Opdenakker, G., & den Steen, P. E. V. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.11.008 · Cited by 104 · see citing works
Metalloproteinases in melanoma
Moro, N., Mauch, C., & Zigrino, P. (2014) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2014.01.002 · Cited by 103 · see citing works
Testicular and epididymal ADAMs: expression and function during fertilization
Cho, C. (2012) · Nature Reviews Urology · doi:10.1038/nrurol.2012.167 · Cited by 101 · see citing works
Matrix metalloproteinases: Expression, regulation and role in the immunopathology of tuberculosis
Sabir, N., Hussain, T. A., Mangi, M. H., Zhao, D., & Zhou, X. (2019) · Cell Proliferation · doi:10.1111/cpr.12649 · Cited by 100 · see citing works
Rapoport, B., & McLachlan, S. M. (2015) · Endocrine Reviews · doi:10.1210/er.2015-1098 · Cited by 87 · see citing works
RetractedMetalloproteinases and their roles in human cancer
Roy, R., Morad, G., Jedinak, A., & Moses, M. A. (2019) · The Anatomical Record · doi:10.1002/ar.24188 · Cited by 84 · see citing works
“ADAMs and MMPs regulate the bioavailability of growth factors as well as the function of cell surface receptors.”
BackgroundInfluentialRegulated ADAM17-dependent EGF family ligand release by substrate-selecting signaling pathways
Dang, M., Armbruster, N. S., Miller, M. A., Cermeño, E. A., Hartmann, M., Bell, G. W., Root, D. E., Lauffenburger, D. A., Lodish, H. F., & Herrlich, A. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1307478110 · Cited by 83 · see citing works
“Of the 12 functional ADAMs encoded in the human genome (3) only two—ADAM10 and ADAM17—handle most of the numerous ADAM substrates, in particular, the EGF ligands.”
BackgroundAbdel‐Hamid, N. M., & Abass, S. A. (2021) · Molecular Biology Reports · doi:10.1007/s11033-021-06635-z · Cited by 83 · see citing works
Proteolytic processing of the prion protein in health and disease.
Altmeppen, H. C., Puig, B., Dohler, F., Thurm, D., Falker‐Gieske, C., Krasemann, S., & Glatzel, M. (2012) · Europe PMC (PubMed Central) · Cited by 93 · see citing works
Han, K., Dugas‐Ford, J., Seiki, M., et al. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-14417 · Cited by 81 · 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
Proteases decode the extracellular matrix cryptome
Ricard‐Blum, S., & Vallet, S. D. (2015) · Biochimie · doi:10.1016/j.biochi.2015.09.016 · Cited by 76 · see citing works
A Role for Soluble IL-6 Receptor in Osteoarthritis
Akeson, G., & Malemud, C. (2017) · Journal of Functional Morphology and Kinesiology · doi:10.3390/jfmk2030027 · Cited by 72 · see citing works
“However, proteolytic cleavage of the mIL-6R protein is mediated by a class of enzymes termed metzincin proteases [69] which yields a soluble form of the IL-6R (sIL-6R).”
BackgroundMiR-126 regulated breast cancer cell invasion by targeting ADAM9.
Wang, C., Yuan, P., & Li, Y. (2015) · PubMed · Cited by 73 · see citing works
Scissor sisters: regulation of ADAM10 by the TspanC8 tetraspanins
Matthews, A. L., Szyroka, J., Collier, R., Noy, P. J., & Tomlinson, M. G. (2017) · Biochemical Society Transactions · doi:10.1042/bst20160290 · Cited by 71 · see citing works
Protease Regulation: The Yin and Yang of Neural Development and Disease
Bai, G., & Pfaff, S. L. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.012 · Cited by 70 · see citing works
“…activity, interactions with enzyme modulators, and control of the spatiotemporal distribution of the enzymes and their substrates (Antalis et al., 2010; De Strooper and Annaert, 2010; Hadler-Olsen et al., 2011; Hunt and Turner, 2009; Klein and Bischoff, 2011; Kuranaga, 2011; Otlewski et al., 2005).”
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
Recent Advances and Emerging Trends in Cancer Biomarker Detection Technologies
Kumar, R. K. R., Kumar, A., Chuang, C.-H., & Shaikh, M. O. (2023) · Industrial & Engineering Chemistry Research · doi:10.1021/acs.iecr.2c04097 · Cited by 62 · see citing works
ADAM10 Is the Major Sheddase Responsible for the Release of Membrane-associated Meprin A
Herzog, C., Haun, R. S., Ludwig, A., Shah, S. V., & Kaushal, G. P. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.559088 · Cited by 60 · see citing works
Sexual differences in the sialomes of the zebra tick, Rhipicephalus pulchellus
Tan, A. W. L., Francischetti, I. M. B., Slovák, M., Kini, R. M., & Ribeiro, J. M. C. (2015) · Journal of Proteomics · doi:10.1016/j.jprot.2014.12.014 · Cited by 59 · see citing works
“The zinc metalloproteases, ubiquitous enzymes found in metazoans, are associatedwith embryonic development, inflammation, angiogenesis and connective tissue remodeling, among other functions (see [47,48]).”
Role of ADAM and ADAMTS proteases in pathological tissue remodeling
Wang, Z.-N., Li, W., Chen, S., & Tang, X. X. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01744-z · Cited by 61 · 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
“ADAMs ADAMs (A Disintegrin And Metalloproteases) are transmembrane metalloproteases that process and shed the ectodomains of membrane-anchored growth factors, cytokines and receptors.(10) They belong to the metazincin superfamily(11) which also includes the ADAM-TS, class III snake venoms and matrix metalloproteases (…”
BackgroundAdam10 Mediates the Choice between Principal Cells and Intercalated Cells in the Kidney
Guo, Q., Wang, Y., Tripathi, P., et al. (2014) · Journal of the American Society of Nephrology · doi:10.1681/asn.2013070764 · Cited by 54 · 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
Regulation of ADAM10 by the TspanC8 Family of Tetraspanins and Their Therapeutic Potential
Harrison, N. J., Koo, C. Z., & Tomlinson, M. G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136707 · Cited by 49 · see citing works
“Of the 22 ADAM genes currently identified in humans, 12 are catalytically active but 10 are catalytically inactive and remain poorly characterized [3].”
BackgroundZhang, Y., Lin, Z., Foolen, J., Schoen, I., Santoro, A., Zenobi‐Wong, M., & Viola Vogel, B. (2014) · Matrix Biology · doi:10.1016/j.matbio.2014.09.001 · Cited by 45 · see citing works
“Several human MMPs were reported to interact with Fn, namely MMP-2 and 3, MMP-7, MMP-9-12, MMP-14, MMP-16, MMP-24-26 (Overall, 2002; Klein and Bischoff, 2011) and their activities can be inhibited by four different TIMPs (Visse and Nagase, 2003).”
BackgroundKarhemo, P., Ravela, S., Laakso, M., Ritamo, I., Tatti, O., Mäkinen, S., Steve Goodison, B., Stenman, U., Hölttä, E., Hautaniemi, S., et al. (2012) · Journal of Proteomics · doi:10.1016/j.jprot.2012.07.009 · Cited by 46 · see citing works
“High expression of ADAM10 [54] and various integrins [55], which in our analysis were overexpressed in the metastatic cell line, has been shown to promote metastatic growth.”
BackgroundHartmann, M., Parra, L. M., Ruschel, A., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.610204 · Cited by 45 · see citing works
“Regulation of ectodomain cleavage is highly important for homeostasis of the organism, most apparent in the release of active growth factors from their transmembrane precursors, which needs to be tightly regulated in respect to both its overall abundance and time course (1, 2).”
BackgroundRenal ADAM10 and 17: Their Physiological and Medical Meanings
Kato, T., Hagiyama, M., & Ito, A. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00153 · Cited by 45 · see citing works
Kathamuthu, G. R., Kumar, N. P., Moideen, K., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00419 · Cited by 45 · see citing works
Effects of ADAM 10 upregulation on progression, migration, and prognosis of nasopharyngeal carcinoma
You, B., Shan, Y., Shi, S., Li, X., & You, Y. (2015) · Cancer Science · doi:10.1111/cas.12800 · Cited by 42 · see citing works
Proliferative signaling by ERBB proteins and RAF/MEK/ERK effectors in polycystic kidney disease
Parker, M. I., Nikonova, A. S., Sun, D., & Golemis, E. A. (2019) · Cellular Signalling · doi:10.1016/j.cellsig.2019.109497 · Cited by 40 · see citing works
“However, many ligands circulate in the plasma, and HB-EGF, AREG, BTC, EPGN, EREG, and TGF-α have been reported as acting in the kidney [34-39].”
BackgroundThe Versatile Role of Matrix Metalloproteinase for the Diverse Results of Fibrosis Treatment
Chuang, H.-M., Chen, Y.-S., & Harn, H. (2019) · Molecules · doi:10.3390/molecules24224188 · Cited by 40 · see citing works
“There are other membrane-anchored metalloproteinases with a disintegrin domain, which belong to two new families, referred to as the ADAMs (A Disintegrin And Metalloproteinases) and ADAMTs (A Disintegrin And Metalloproteinases with Thrombospondin Motifs) [9].”
BackgroundLi, W., Wang, D., Sun, X., et al. (2018) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2018.4028 · Cited by 38 · see citing works
“Because angiogenesis is essential for tumor growth and metastasis (32,33), and ADAM17 is a central regulator of angiogenesis (34), ADAM17 may also influence tumor angiogenesis and invasion (35).”
BackgroundZinc enzymes in medicinal chemistry
Hou, R., He, Y., Yan, G., Hou, S., Xie, Z., & Liao, C. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113877 · Cited by 38 · see citing works
Silencing ADAM10 inhibits the in vitro and in vivo growth of hepatocellular carcinoma cancer cells
Liu, S., Zhang, W., Liu, K., Ji, B., & Wang, G. (2014) · Molecular Medicine Reports · doi:10.3892/mmr.2014.2652 · Cited by 34 · see citing works
Xie, Q. R., Guo, H., He, P., et al. (2021) · Molecular Oncology · doi:10.1002/1878-0261.12980 · Cited by 34 · see citing works
“ADAM10 is a member of the superfamily of Zn2+-dependent transmembrane disintegrin and metalloproteases that are responsible for a significant proportion of transmembrane protein shedding [41].”
BackgroundUnraveling the Processing and Activation of Snake Venom Metalloproteinases
Portes-Junior, J. A., Yamanouye, N., Carneiro, S. M., Knittel, P. S., Sant’Anna, S. S., Nogueira, F. C. S., Junqueira, M., Magalhães, G. S., Domont, G. B., & Moura-da-Silva, A. M. (2014) · Journal of Proteome Research · doi:10.1021/pr500185a · Cited by 33 · see citing works
Enzymatic reaction-based nanopore detection of zinc ions
Roozbahani, G. M., Zhang, Y., Chen, X., et al. (2019) · The Analyst · doi:10.1039/c9an01784d · Cited by 32 · see citing works
Nwogu, N., Boyne, J. R., Dobson, S. J., et al. (2018) · PLoS Pathogens · doi:10.1371/journal.ppat.1007276 · Cited by 31 · see citing works
Recent developments and strategies for the discovery of TACE inhibitors
Murumkar, P. R., Ghuge, R. B., Chauhan, M., Barot, R. R., Sorathiya, S., Choudhary, K. M., Joshi, K. D., & Yadav, M. R. (2020) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2020.1744559 · Cited by 32 · see citing works
“As shown in Figure 1(b), TACE consists of an N-terminal signal sequence (1–17 amino acids) and multidomains like prodomain (18–214 amino acids), metalloprotease/catalytic (215–473 amino acids), disintegrin (474–572 amino acids), cysteine-rich (573–671 amino acids), transmembrane region (672–694 amino acids), and cytop…”
BackgroundGrigoletto, L., Santana, M. H. D. A., Bressan, F. F., et al. (2020) · Animals · doi:10.3390/ani10071185 · Cited by 31 · see citing works
“The three proteases (ADAM9, ADAM10, and ADAM12) together seem to regulate the breakdown of matrix and differentiation of granulosa cells prior to ovulation [62].”
BackgroundSela-Passwell, N., Trahtenherts, A., Krüger, A., & Sagi, I. (2011) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2011.560936 · Cited by 31 · see citing works
“This feature is present in most metzincins, including MMPs and ADAMs [108].”
BackgroundADAMDEC1 Is a Metzincin Metalloprotease with Dampened Proteolytic Activity
Lund, J., Olsen, O. H., Sørensen, E. S., Stennicke, H. R., Petersen, H. H., & Overgaard, M. T. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.474536 · Cited by 31 · see citing works
“of 5 mM (1,10)-phenanthroline, visualized by anti-HPC4 Western blot analysis.”
BackgroundMethodInfluentialProteolysis in Helicobacter pylori-Induced Gastric Cancer
Posselt, G., Crabtree, J. E., & Weßler, S. (2017) · Toxins · doi:10.3390/toxins9040134 · Cited by 31 · see citing works
“However they also have a well-established role in chronic inflammation and tumorigenesis, especially migration and proliferation in metastatic tumors [31,33].”
BackgroundFaber, M., Shaw, S., Yoon, S., Alves, E. D. P., Wang, B., Qi, Z., Okamura, B., Hartikainen, H., Secombes, C. J., & Holland, J. W. (2021) · Scientific Reports · doi:10.1038/s41598-020-77881-7 · Cited by 30 · see citing works
ADAM9 silencing inhibits breast tumor cell invasion in vitro
Micocci, K. C., Martin, A. C. B. M., Montenegro, C. D. F., et al. (2013) · Biochimie · doi:10.1016/j.biochi.2013.03.001 · Cited by 29 · see citing works
“, ADAM9 silencing diseases such as inflammatory disorders, neurological diseases, asthma and cancer metastasis [6,7].”
BackgroundYang, C., Jiang, F.-Q., Xu, F., et al. (2012) · Tumor Biology · doi:10.1007/s13277-012-0405-4 · Cited by 28 · see citing works
“ADAMs exhibit diverse expression profiles and cellular functions and are involved in a range of human diseases such as cancer metastasis, inflammatory diseases, and asthma [6, 7].”
BackgroundMalik, V. A., & Benedetto, B. D. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00127 · Cited by 31 · see citing works
“In the adulthood, it mostly regulates synaptic remodeling, epithelial differentiation, bone remodeling, immune function, insulin secretion and stem cell self-renewal (Kullander and Klein, 2002; Yamaguchi and Pasquale, 2004; Pasquale, 2005, 2008).”
BackgroundDranse, H. J., Muruganandan, S., Fawcett, J. P., & Sinal, C. J. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.07.017 · Cited by 26 · see citing works
“MMP3 is secreted in an inactive form and is activated by removal of the prodomain by extracellular enzymes such as serine proteases (Klein and Bischoff, 2011).”
Morgan, R. L., Behbahani‐Nejad, N., Endres, J., Amin, M. A., Lepore, N. J., Du, Y., Urquhart, A. G., Chung, K. C., & Fox, D. A. (2016) · PLoS ONE · doi:10.1371/journal.pone.0162008 · Cited by 25 · see citing works
The evolution of ADAM gene family in eukaryotes
de Souza, J. S. M., Lisboa, A. B. P., Santos, T. M., de Andrade, M. V. S., Neves, V. B. S., Teles-Souza, J., de Jesus, H. N. R., Bezerra, T. G., Falcão, V. G. O., Oliveira, R. C., et al. (2020) · Genomics · doi:10.1016/j.ygeno.2020.05.010 · Cited by 24 · see citing works
Lopes, P. H., van den Berg, C. W., & Tambourgi, D. V. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00636 · Cited by 23 · see citing works
“These PCs, which are serine proteases (Seidah, 2006; Klein and Bischoff, 2011), are activated themselves during transport through the Golgi.”
BackgroundInfluentialSalt-Mediated Nanopore Detection of ADAM-17
Chen, X., Zhang, Y., Roozbahani, G. M., et al. (2018) · ACS Applied Bio Materials · doi:10.1021/acsabm.8b00689 · Cited by 23 · see citing works
CD9 regulates keratinocyte migration by negatively modulating the sheddase activity of ADAM17
Liu, J., Zhu, G., Jia, N., Wang, W., Wang, Y., Yin, M., Jiang, X., Huang, Y., & Zhang, J. (2019) · International Journal of Biological Sciences · doi:10.7150/ijbs.29404 · Cited by 23 · see citing works
“The ADAM family consists of 22 known members; however, only ADAM17 is thought to be a key regulator in repair of skin [14].”
BackgroundA Novel Mechanism of Latency in Matrix Metalloproteinases
López‐Pelegrín, M., Książęk, M., Karim, A., Guevara, T., Arolas, J. L., Potempa, J., & Gomis‐Rüth, F. X. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.605956 · Cited by 22 · see citing works
Zhang, W., Liu, S., Liu, K., Ji, B., Wang, Y., & Liu, Y. (2014) · Oncology Reports · doi:10.3892/or.2014.3418 · Cited by 21 · see citing works
“Accumulating evidence have demonstrated that ADAM10 is involved in cancer cell progression and metastasis (21-23,31-35).”
BackgroundInfluentialADAM10 mediates the house dust mite‐induced release of chemokine ligand CCL20 by airway epithelium
Post, S., Rozeveld, D., Jonker, M. R., et al. (2015) · Allergy · doi:10.1111/all.12730 · Cited by 21 · see citing works
“Cytokines/chemokines, growth factors, and their receptors are typical substrates of the a disintegrin and metalloproteinase (ADAMs) family, membrane-anchored proteases that are able to cleave the extracellular domains of membrane-bound proteins (10, 11).”
BackgroundSelf-citationmiR-449a inhibits proliferation and invasion by regulating ADAM10 in hepatocellular carcinoma.
Liu, S., Liu, K., Zhang, W., et al. (2016) · PubMed · Cited by 20 · see citing works
RetractedADAM28: Another ambivalent protease in cancer
Hubeau, C., Rocks, N., & Cataldo, D. D. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.08.031 · Cited by 20 · see citing works
“Twenty-two ADAMs have been reported in human while 32 ADAMs have been identified in mouse [2].”
BackgroundGiudice, S. D., Luca, V. D., Parizadeh, S., Russo, D., Luini, A., & Martino, R. D. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.833663 · Cited by 19 · see citing works
“MMPs are a family of 23 proteins, divided into four classes based on their substrate specificity, whose extracellular secretion occurs in a Golgi-dependent fashion (Klein and Bischoff, 2011b).”
BackgroundADAM Metalloprotease-Released Cancer Biomarkers
Herrlich, P. A., & Herrlich, A. (2017) · Trends in cancer · doi:10.1016/j.trecan.2017.05.001 · Cited by 20 · see citing works
Ectodomain shedding by ADAM proteases as a central regulator in kidney physiology and disease
Meyer‐Schwesinger, C., Seipold, L., & Säftig, P. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2021.119165 · Cited by 19 · see citing works
Duan, Y., Long, J., Chen, J., et al. (2016) · Experimental Cell Research · doi:10.1016/j.yexcr.2016.10.004 · Cited by 19 · see citing works
Yang, H., & Khalil, R. A. (2022) · Advances in pharmacology · doi:10.1016/bs.apha.2021.11.002 · Cited by 18 · see citing works
Jhilta, A., Jadhav, K., Singh, R., Ray, E., Kumar, A., Singh, A., & Verma, R. K. (2024) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.4c00385 · Cited by 18 · see citing works
Vascular Pathology as a Potential Therapeutic Target in SCI
Benton, R. L., & Hagg, T. (2011) · Translational Stroke Research · doi:10.1007/s12975-011-0128-7 · Cited by 18 · see citing works
“This class of proteins is an essential orchestrator of biological processes, including extracellular matrix remodeling, migration, and activation of cleavage-dependent proteins such as TNFα and Notch [72, 76, 128, 145].”
BackgroundDrosophila sperm proteome evolution
Rettie, E. C., & Dorus, S. (2012) · Spermatogenesis · doi:10.4161/spmg.21748 · Cited by 17 · see citing works
Adam10 haploinsufficiency causes freckle‐like macules in Hairless mice
Tharmarajah, G., Faas, L., Reiß, K., Säftig, P., Young, A. R., & Raamsdonk, C. D. V. (2012) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2012.01032.x · Cited by 17 · see citing works
“Adams are zinc-binding metalloproteases that are membrane bound and have a large number of potential cleavage targets (Klein and Bischoff, 2010).”
BackgroundDiagnostic and prognostic value of a disintegrin and metalloproteinase-17 in patients with gliomas
Wu, B., Sha, L., Wang, Y., et al. (2014) · Oncology Letters · doi:10.3892/ol.2014.2582 · Cited by 17 · see citing works
“ADAMs are a class of membrane-anchored cell surface proteins, which function in proteolysis, the release of bioactive cytokines, cell adhesion, integration, migration and signal transduction (15).”
BackgroundUpregulated expression of ADAM12 is associated with progression of oral squamous cell carcinoma
Shiiba, M. (2012) · International Journal of Oncology · doi:10.3892/ijo.2012.1339 · Cited by 17 · see citing works
Martin, A. C. B. M., Cardoso, A. C. F., Selistre-de-Araújo, H. S., & Cominetti, M. R. (2015) · Cell Adhesion & Migration · doi:10.4161/19336918.2014.994917 · Cited by 16 · see citing works
“The ADAM (A Disintegrin And Metalloproteinase) family of proteins comprises a group of multifunctional proteins that play important roles in many biological processes, such as cell fusion, cell adhesion, proteolysis, and in some diseases as well, including cancer.(2,3) These type I transmembrane proteins are character…”
BackgroundEphrin-A1 and the sheddase ADAM12 are upregulated in COVID-19
Mendoza, R., Saha, N., Momeni, A., et al. (2021) · Heliyon · doi:10.1016/j.heliyon.2021.e07200 · Cited by 16 · see citing works
“ADAMs (A Disintegrin And Metalloproteases) are transmembrane metalloproteases that process and shed the ectodomains of membraneanchored growth factors, cytokines and receptors [19].”
Proteases in Cancer: Significance for Invasion and Metastasis
Sloane, B. F., List, K., Fingleton, B., & Matrisian, L. M. (2013) · Springer eBooks · doi:10.1007/978-3-7091-0885-7_15 · Cited by 19 · see citing works
“These family members are thought to be especially important in cell adhesion events such as sperm-egg fusion (Klein and Bischoff 2011).”
BackgroundFejza, A., Camicia, L., Poletto, E., Carobolante, G., Mongiat, M., & Andreuzzi, E. (2021) · Cancers · doi:10.3390/cancers13112759 · Cited by 16 · see citing works
MA, B., Zhang, H., Bai, X., et al. (2016) · Oncology Reports · doi:10.3892/or.2016.4667 · Cited by 15 · see citing works
“The a disintegrin and metalloproteases (ADAMs), a family of zinc-dependent transmembrane proteins, contain a metalloprotease and a disintegrin-like domain (9-11) and are closely associated with the degradation of the basement membrane, cell migration, cell fusion and signal transduction (12,13), thus playing important…”
BackgroundStructure, regulatory factors and cancer-related physiological effects of ADAM9
Haoyuan, M., & Yanshu, L. (2020) · Cell Adhesion & Migration · doi:10.1080/19336918.2020.1817251 · Cited by 15 · see citing works
“[122] When the ADAM9 gene was knocked out, the mice showed vitality and fertility, and showed no pathological changes.”
BackgroundLiu, H., YANG, Q.-C., Shen, Y., et al. (2014) · Molecular Medicine Reports · doi:10.3892/mmr.2014.2802 · Cited by 15 · see citing works
“…(ADAM) family, ADAM17, termed tumor necrosis factor-α converting enzyme (TACE), is the primary secretase responsible for releasing the soluble form of tumor necrosis factor-α from the plasma membrane and is the primary sheddase for multiple epidermal growth factor receptor (EGFR) pro-ligands (1,2).”
Escalona, R. M., Chan, E., Kannourakis, G., Findlay, J. K., & Ahmed, N. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19020450 · Cited by 15 · see citing works
“ADAMs on the other hand, are commonly known for their proteolytic activity required for the ectdomain shedding of growth factors and cytokines crucial for cell signaling associated with cancer cell proliferation, adhesion on ECM, migration and angiogenesis [78,82,83,133].”
Background
- Authors
- Klein, T., & Bischoff, R.
- Affiliations
- University of Groningen (NL)
- Corresponding author
- Bischoff, Rainer
- ORCID
- Bischoff, Rainer
- Venue
- Journal of Proteome Research
- Publisher
- American Chemical Society (ACS)
- Published
- 2011-01-07
- Volume
- 10
- Issue
- 1
- Pages
- 17-33
- ISSN
- 1535-3893 (ISSN-L)
- 1535-3907
- OpenAlex
- W2485983537
- Cited by
- 179
- References
- 0
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 18 · 2020: 14 · 2019: 13 · 2018: 8 · 2017: 9 · 2016: 19 · 2015: 15 · 2014: 19 · 2013: 9 · 2012: 19
- FWCI
- 3.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Proteome Research (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Oncology › Peptidase Inhibition and Analysis
- Keywords
- ADAMS, metzincins, metalloprotease domain, proteolytic activity, protein structure, metastasis, inflammation, neurological disorders, asthma, functional redundancy
- MeSH terms
- Animals, Humans, Protein Conformation, Mice, 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
