ADAMTS9: Difference between revisions

Latest revision as of 22:30, 1 January 2025

ADAMTS9 is a member of the ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) family of proteins. This family is characterized by a combination of metalloproteinase and disintegrin domains, and is involved in a variety of biological processes, including extracellular matrix (ECM) remodeling, angiogenesis, and cell migration.

Structure[edit]

ADAMTS9 is a large, multi-domain protein that includes the following domains:

Propeptide domain: This domain is involved in the regulation of the enzyme's activity. It is cleaved to activate the enzyme.
Metalloproteinase domain: This domain contains the catalytic site responsible for the proteolytic activity of the enzyme. It requires a zinc ion for its activity.
Disintegrin-like domain: This domain is thought to mediate interactions with other proteins, particularly those in the ECM.
Thrombospondin type 1 repeats (TSR): ADAMTS9 contains multiple TSRs, which are involved in binding to ECM components and modulating cell-matrix interactions.
Cysteine-rich domain: This domain may play a role in substrate recognition and binding.
Spacer domain: This domain contributes to the overall structure and function of the protein.

Function[edit]

ADAMTS9 is involved in the processing of various ECM components, including proteoglycans such as aggrecan and versican. It plays a critical role in ECM remodeling, which is essential for normal development and tissue homeostasis. ADAMTS9 is also implicated in the regulation of angiogenesis, the process by which new blood vessels form from pre-existing vessels.

Role in Development[edit]

During embryonic development, ADAMTS9 is expressed in various tissues and is essential for normal organogenesis. It is particularly important in the development of the cardiovascular system, kidneys, and limbs.

Role in Disease[edit]

ADAMTS9 has been associated with several pathological conditions, including:

Cancer: Altered expression of ADAMTS9 has been observed in various cancers, where it may influence tumor progression and metastasis.
Arthritis: Due to its role in ECM degradation, ADAMTS9 may contribute to the breakdown of cartilage in osteoarthritis.
Obesity and Metabolic syndrome: Genetic studies have linked variants in the ADAMTS9 gene with susceptibility to obesity and related metabolic disorders.

Genetics[edit]

The ADAMTS9 gene is located on chromosome 3p14.3. It is composed of multiple exons and encodes a protein of approximately 1,930 amino acids. The expression of ADAMTS9 is regulated at both the transcriptional and post-transcriptional levels.

Clinical Significance[edit]

Mutations or dysregulation of ADAMTS9 can lead to developmental abnormalities and contribute to the pathogenesis of various diseases. Understanding the precise role of ADAMTS9 in these processes is an area of active research, with potential implications for the development of therapeutic interventions.

Research Directions[edit]

Current research on ADAMTS9 focuses on elucidating its specific substrates and interaction partners, understanding its regulation, and exploring its potential as a therapeutic target in diseases such as cancer and arthritis.

External Links[edit]

Template:ADAMTS family

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-<br>= ADAMTS9 =
+{{DISPLAYTITLE:ADAMTS9}}
+{{Infobox protein
+| name = ADAMTS9
+| image = <!-- No image available -->
+| caption =
+| symbol = ADAMTS9
+| alt_symbols =
+| hgnc_id = 211
+| omim_id = 606145
+| uniprot_id = Q9P2N4
+| chromosome = 3
+| arm = p
+| band = 14.3
+}}
-'''ADAMTS9''' is a member of the ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) family of zinc-dependent proteases. These enzymes are involved in the processing of extracellular matrix components and have roles in various physiological and pathological processes.
+'''ADAMTS9''' is a member of the [[ADAMTS]] (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) family of [[proteins]]. This family is characterized by a combination of [[metalloproteinase]] and [[disintegrin]] domains, and is involved in a variety of biological processes, including [[extracellular matrix]] (ECM) remodeling, [[angiogenesis]], and [[cell migration]].
-== Structure ==
+==Structure==
-ADAMTS9, like other members of the ADAMTS family, is characterized by a multi-domain structure. It contains a signal peptide, a propeptide region, a metalloproteinase domain, a disintegrin-like domain, a thrombospondin type 1 motif (TSR), and several other domains that contribute to its function and regulation. The presence of multiple TSRs is a hallmark of the ADAMTS family, which distinguishes them from other metalloproteinases.
+ADAMTS9 is a large, multi-domain protein that includes the following domains:
-== Function ==
+* '''Propeptide domain''': This domain is involved in the regulation of the enzyme's activity. It is cleaved to activate the enzyme.
-ADAMTS9 is involved in the degradation of proteoglycans, which are major components of the extracellular matrix. It specifically cleaves aggrecan, a key proteoglycan in cartilage, and versican, which is found in various tissues. This proteolytic activity is crucial for tissue remodeling, development, and repair processes.
+* '''Metalloproteinase domain''': This domain contains the catalytic site responsible for the proteolytic activity of the enzyme. It requires a [[zinc]] ion for its activity.
+* '''Disintegrin-like domain''': This domain is thought to mediate interactions with other proteins, particularly those in the ECM.
+* '''Thrombospondin type 1 repeats (TSR)''': ADAMTS9 contains multiple TSRs, which are involved in binding to ECM components and modulating cell-matrix interactions.
+* '''Cysteine-rich domain''': This domain may play a role in substrate recognition and binding.
+* '''Spacer domain''': This domain contributes to the overall structure and function of the protein.
-ADAMTS9 also plays a role in angiogenesis, the formation of new blood vessels, by modulating the extracellular environment and influencing cell-matrix interactions. It has been implicated in the regulation of cell migration and proliferation, processes that are essential during development and wound healing.
+==Function==
+ADAMTS9 is involved in the processing of various ECM components, including [[proteoglycans]] such as [[aggrecan]] and [[versican]]. It plays a critical role in ECM remodeling, which is essential for normal development and tissue homeostasis. ADAMTS9 is also implicated in the regulation of angiogenesis, the process by which new blood vessels form from pre-existing vessels.
-== Clinical Significance ==
+===Role in Development===
-Mutations or dysregulation of ADAMTS9 have been associated with several diseases. For instance, alterations in ADAMTS9 expression have been linked to cancer progression, as the enzyme can influence tumor microenvironment and metastasis. Additionally, ADAMTS9 has been studied in the context of cardiovascular diseases, where its role in extracellular matrix remodeling is critical.
+During embryonic development, ADAMTS9 is expressed in various tissues and is essential for normal organogenesis. It is particularly important in the development of the [[cardiovascular system]], [[kidneys]], and [[limbs]].
-Research has also suggested a potential involvement of ADAMTS9 in metabolic disorders, such as obesity and type 2 diabetes, although the mechanisms are not fully understood. The enzyme's activity in adipose tissue and its influence on insulin signaling pathways are areas of active investigation.
+===Role in Disease===
+ADAMTS9 has been associated with several pathological conditions, including:
-== Genetic Studies ==
+* '''[[Cancer]]''': Altered expression of ADAMTS9 has been observed in various cancers, where it may influence tumor progression and metastasis.
-Genetic studies have identified ADAMTS9 as a susceptibility locus for several complex traits. Genome-wide association studies (GWAS) have linked variants in the ADAMTS9 gene with conditions such as polycystic ovary syndrome (PCOS) and certain forms of glaucoma. These findings highlight the diverse roles of ADAMTS9 in human health and disease.
+* '''[[Arthritis]]''': Due to its role in ECM degradation, ADAMTS9 may contribute to the breakdown of cartilage in [[osteoarthritis]].
+* '''[[Obesity]] and [[Metabolic syndrome]]''': Genetic studies have linked variants in the ADAMTS9 gene with susceptibility to obesity and related metabolic disorders.
-== Research Directions ==
+==Genetics==
-Ongoing research aims to further elucidate the specific substrates and regulatory mechanisms of ADAMTS9. Understanding how this enzyme is controlled at the molecular level could lead to novel therapeutic strategies for diseases where ADAMTS9 activity is dysregulated. Additionally, the development of specific inhibitors or modulators of ADAMTS9 activity is an area of interest for drug development.
+The '''ADAMTS9''' gene is located on chromosome 3p14.3. It is composed of multiple exons and encodes a protein of approximately 1,930 amino acids. The expression of ADAMTS9 is regulated at both the transcriptional and post-transcriptional levels.
-== References ==
+==Clinical Significance==
-* Apte, S. S. (2009). A disintegrin-like and metalloprotease (reprolysin-type) with thrombospondin type 1 motif (ADAMTS) superfamily: Functions and mechanisms. ''Journal of Biological Chemistry'', 284(46), 31493-31497.
+Mutations or dysregulation of ADAMTS9 can lead to developmental abnormalities and contribute to the pathogenesis of various diseases. Understanding the precise role of ADAMTS9 in these processes is an area of active research, with potential implications for the development of therapeutic interventions.
-* Kelwick, R., Desanlis, I., Wheeler, G. N., & Edwards, D. R. (2015). The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family. ''Genome Biology'', 16, 113.
-* Mead, T. J., & Apte, S. S. (2018). ADAMTS proteins in human disorders. ''Matrix Biology'', 71-72, 225-239.
-{{Medical-stub}}
+==Research Directions==
+Current research on ADAMTS9 focuses on elucidating its specific substrates and interaction partners, understanding its regulation, and exploring its potential as a therapeutic target in diseases such as cancer and arthritis.
+==See Also==
+* [[ADAMTS family]]
+* [[Extracellular matrix]]
+* [[Metalloproteinase]]
+==External Links==
+* [https://www.uniprot.org/uniprot/Q9P2N4 UniProt entry for ADAMTS9]
+* [https://www.genecards.org/cgi-bin/carddisp.pl?gene=ADAMTS9 GeneCards entry for ADAMTS9]
+{{ADAMTS family}}
+[[Category:Proteins]]
+[[Category:Enzymes]]
+[[Category:Human proteins]]
+[[Category:Chromosome 3]]