The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family
The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family in...
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| Veröffentlicht in: | Genome Biology 2015-05, Vol.16 (1), p.113-113, Article 113 |
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| description | The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future. |
| doi_str_mv | 10.1186/s13059-015-0676-3 |
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The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future.</description><identifier>ISSN: 1465-6906</identifier><identifier>ISSN: 1474-7596</identifier><identifier>EISSN: 1474-760X</identifier><identifier>EISSN: 1465-6906</identifier><identifier>EISSN: 1465-6914</identifier><identifier>DOI: 10.1186/s13059-015-0676-3</identifier><identifier>PMID: 26025392</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>active sites ; ADAM protein ; ADAM Proteins - genetics ; ADAM Proteins - metabolism ; ADAMTS-1 protein ; Analysis ; Animals ; Arthritis ; Arthritis - genetics ; Cancer ; carcinogenesis ; Cardiovascular diseases ; Cardiovascular Diseases - genetics ; Cartilage ; Cartilage oligomeric matrix protein ; Catalytic Domain ; Cell adhesion & migration ; Chondroitin sulfate ; Collagen ; Disease Models, Animal ; Disintegrins - genetics ; Disintegrins - metabolism ; domain ; Endopeptidases - genetics ; Endopeptidases - metabolism ; Enzymes ; Epidermal growth factor ; Evolution, Molecular ; Extracellular matrix ; Extracellular Matrix - metabolism ; family ; Gene Expression Regulation ; Genes ; Genetic aspects ; Genetic disorders ; genome ; Genomes ; Humans ; inflammation ; Insects ; Localization ; Matrix protein ; Maximum likelihood method ; metalloproteinases ; Metastases ; Metastasis ; Morphogenesis ; Multigene Family ; Neoplasms - genetics ; Peptides ; Phylogenetics ; Physiological aspects ; Physiology ; Procollagen ; Proteases ; Protein Family Review ; Proteinase ; Proteins ; Proteoglycans ; Structure-function relationships ; Substrate Specificity ; Therapeutic applications ; therapeutics ; Thrombospondin ; Thrombospondins - genetics ; Thrombospondins - metabolism ; Tumorigenesis ; zinc</subject><ispartof>Genome Biology, 2015-05, Vol.16 (1), p.113-113, Article 113</ispartof><rights>COPYRIGHT 2015 BioMed Central Ltd.</rights><rights>2015. This work is licensed under http://creativecommons.org/licenses/by/4.0 (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Kelwick et al.; licensee BioMed Central. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c661t-4fe69216484d9493e2072d5c07dc4f38f4815e916aee7909696ab99effaa3e463</citedby><cites>FETCH-LOGICAL-c661t-4fe69216484d9493e2072d5c07dc4f38f4815e916aee7909696ab99effaa3e463</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448532/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448532/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26025392$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kelwick, Richard</creatorcontrib><creatorcontrib>Desanlis, Ines</creatorcontrib><creatorcontrib>Wheeler, Grant N</creatorcontrib><creatorcontrib>Edwards, Dylan R</creatorcontrib><title>The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family</title><title>Genome Biology</title><addtitle>Genome Biol</addtitle><description>The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future.</description><subject>active sites</subject><subject>ADAM protein</subject><subject>ADAM Proteins - genetics</subject><subject>ADAM Proteins - metabolism</subject><subject>ADAMTS-1 protein</subject><subject>Analysis</subject><subject>Animals</subject><subject>Arthritis</subject><subject>Arthritis - genetics</subject><subject>Cancer</subject><subject>carcinogenesis</subject><subject>Cardiovascular diseases</subject><subject>Cardiovascular Diseases - genetics</subject><subject>Cartilage</subject><subject>Cartilage oligomeric matrix protein</subject><subject>Catalytic Domain</subject><subject>Cell adhesion & migration</subject><subject>Chondroitin sulfate</subject><subject>Collagen</subject><subject>Disease Models, Animal</subject><subject>Disintegrins - genetics</subject><subject>Disintegrins - metabolism</subject><subject>domain</subject><subject>Endopeptidases - genetics</subject><subject>Endopeptidases - metabolism</subject><subject>Enzymes</subject><subject>Epidermal growth factor</subject><subject>Evolution, Molecular</subject><subject>Extracellular matrix</subject><subject>Extracellular Matrix - metabolism</subject><subject>family</subject><subject>Gene Expression Regulation</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic disorders</subject><subject>genome</subject><subject>Genomes</subject><subject>Humans</subject><subject>inflammation</subject><subject>Insects</subject><subject>Localization</subject><subject>Matrix protein</subject><subject>Maximum likelihood method</subject><subject>metalloproteinases</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Morphogenesis</subject><subject>Multigene Family</subject><subject>Neoplasms - genetics</subject><subject>Peptides</subject><subject>Phylogenetics</subject><subject>Physiological aspects</subject><subject>Physiology</subject><subject>Procollagen</subject><subject>Proteases</subject><subject>Protein Family Review</subject><subject>Proteinase</subject><subject>Proteins</subject><subject>Proteoglycans</subject><subject>Structure-function relationships</subject><subject>Substrate Specificity</subject><subject>Therapeutic applications</subject><subject>therapeutics</subject><subject>Thrombospondin</subject><subject>Thrombospondins - genetics</subject><subject>Thrombospondins - metabolism</subject><subject>Tumorigenesis</subject><subject>zinc</subject><issn>1465-6906</issn><issn>1474-7596</issn><issn>1474-760X</issn><issn>1465-6906</issn><issn>1465-6914</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>KPI</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkl1rFDEUhgdRbK3-AG9kwJv2Ymq-M7kRhtaPYouiK3gXsjMnuykzyTbJqP33Zt1aXG8khITkeV_OObxV9RyjU4xb8SphirhqEOYNElI09EF1iJlkjRTo28PtXfBGKCQOqicpXSOEFSPicXVABCKcKnJYfV6soe7Ou6vFl_q4q89dcj7DKjpfGz_UV5DNOIZNDBmcNwnqHy6v68U6hmkZ0ib4oZBTyM6mk9qayY23T6tH1owJnt2dR9XXt28WZ--by4_vLs66y6YXAueGWRCKYMFaNiimKBAkycB7JIeeWdpa1mIOCgsDIBVSQgmzVAqsNYYCE_Soer3z3czLCYYefI5m1JvoJhNvdTBO7_94t9ar8F0zxlpOSTE4vjOI4WaGlPXkUg_jaDyEOWmCEKKccsz_i2LRcslKF1v05T_odZijL5PQpLTIy5ayUKc7amVG0M7bUErsyxpgcn3wYF157zjDXFH0u9iTPUFhMvzMKzOnpD98uthn8Y7tY0gpgr0fCkZ6mxy9S44uydHb5GhaNC_-nua94k9U6C_ADLxS</recordid><startdate>20150530</startdate><enddate>20150530</enddate><creator>Kelwick, Richard</creator><creator>Desanlis, Ines</creator><creator>Wheeler, Grant N</creator><creator>Edwards, Dylan R</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>KPI</scope><scope>IAO</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20150530</creationdate><title>The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family</title><author>Kelwick, Richard ; Desanlis, Ines ; Wheeler, Grant N ; Edwards, Dylan R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c661t-4fe69216484d9493e2072d5c07dc4f38f4815e916aee7909696ab99effaa3e463</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>active sites</topic><topic>ADAM protein</topic><topic>ADAM Proteins - genetics</topic><topic>ADAM Proteins - metabolism</topic><topic>ADAMTS-1 protein</topic><topic>Analysis</topic><topic>Animals</topic><topic>Arthritis</topic><topic>Arthritis - genetics</topic><topic>Cancer</topic><topic>carcinogenesis</topic><topic>Cardiovascular diseases</topic><topic>Cardiovascular Diseases - genetics</topic><topic>Cartilage</topic><topic>Cartilage oligomeric matrix protein</topic><topic>Catalytic Domain</topic><topic>Cell adhesion & migration</topic><topic>Chondroitin sulfate</topic><topic>Collagen</topic><topic>Disease Models, Animal</topic><topic>Disintegrins - genetics</topic><topic>Disintegrins - metabolism</topic><topic>domain</topic><topic>Endopeptidases - genetics</topic><topic>Endopeptidases - metabolism</topic><topic>Enzymes</topic><topic>Epidermal growth factor</topic><topic>Evolution, Molecular</topic><topic>Extracellular matrix</topic><topic>Extracellular Matrix - metabolism</topic><topic>family</topic><topic>Gene Expression Regulation</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic disorders</topic><topic>genome</topic><topic>Genomes</topic><topic>Humans</topic><topic>inflammation</topic><topic>Insects</topic><topic>Localization</topic><topic>Matrix protein</topic><topic>Maximum likelihood method</topic><topic>metalloproteinases</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Morphogenesis</topic><topic>Multigene Family</topic><topic>Neoplasms - genetics</topic><topic>Peptides</topic><topic>Phylogenetics</topic><topic>Physiological aspects</topic><topic>Physiology</topic><topic>Procollagen</topic><topic>Proteases</topic><topic>Protein Family Review</topic><topic>Proteinase</topic><topic>Proteins</topic><topic>Proteoglycans</topic><topic>Structure-function relationships</topic><topic>Substrate Specificity</topic><topic>Therapeutic applications</topic><topic>therapeutics</topic><topic>Thrombospondin</topic><topic>Thrombospondins - genetics</topic><topic>Thrombospondins - metabolism</topic><topic>Tumorigenesis</topic><topic>zinc</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kelwick, Richard</creatorcontrib><creatorcontrib>Desanlis, Ines</creatorcontrib><creatorcontrib>Wheeler, Grant N</creatorcontrib><creatorcontrib>Edwards, Dylan R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Global Issues</collection><collection>Gale Academic OneFile Select</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medicine (ProQuest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genome Biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kelwick, Richard</au><au>Desanlis, Ines</au><au>Wheeler, Grant N</au><au>Edwards, Dylan R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family</atitle><jtitle>Genome Biology</jtitle><addtitle>Genome Biol</addtitle><date>2015-05-30</date><risdate>2015</risdate><volume>16</volume><issue>1</issue><spage>113</spage><epage>113</epage><pages>113-113</pages><artnum>113</artnum><issn>1465-6906</issn><issn>1474-7596</issn><eissn>1474-760X</eissn><eissn>1465-6906</eissn><eissn>1465-6914</eissn><abstract>The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>26025392</pmid><doi>10.1186/s13059-015-0676-3</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | active sites ADAM protein ADAM Proteins - genetics ADAM Proteins - metabolism ADAMTS-1 protein Analysis Animals Arthritis Arthritis - genetics Cancer carcinogenesis Cardiovascular diseases Cardiovascular Diseases - genetics Cartilage Cartilage oligomeric matrix protein Catalytic Domain Cell adhesion & migration Chondroitin sulfate Collagen Disease Models, Animal Disintegrins - genetics Disintegrins - metabolism domain Endopeptidases - genetics Endopeptidases - metabolism Enzymes Epidermal growth factor Evolution, Molecular Extracellular matrix Extracellular Matrix - metabolism family Gene Expression Regulation Genes Genetic aspects Genetic disorders genome Genomes Humans inflammation Insects Localization Matrix protein Maximum likelihood method metalloproteinases Metastases Metastasis Morphogenesis Multigene Family Neoplasms - genetics Peptides Phylogenetics Physiological aspects Physiology Procollagen Proteases Protein Family Review Proteinase Proteins Proteoglycans Structure-function relationships Substrate Specificity Therapeutic applications therapeutics Thrombospondin Thrombospondins - genetics Thrombospondins - metabolism Tumorigenesis zinc |
| title | The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family |
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