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ADAMTS7, an enzyme involved in protein degradation, is encoded by the ADAMTS7 gene located on chromosome 15q24.2.
Answer: True
Explanation: The ADAMTS7 gene, which encodes the ADAMTS7 enzyme, is situated on chromosome 15 at band 15q24.2. The enzyme itself is involved in protein degradation processes.
The ADAMTS7 gene consists of approximately 10 exons.
Answer: False
Explanation: The ADAMTS7 gene comprises 25 exons, not approximately 10.
The ADAMTS7 protein is a small peptide chain composed of fewer than 500 amino acids.
Answer: False
Explanation: The ADAMTS7 protein is a large molecule, consisting of approximately 1686 amino acids, significantly more than 500.
The ancillary domain of ADAMTS7 is highly conserved across different ADAMTS family members and lacks thrombospondin motifs.
Answer: False
Explanation: The ancillary domain of ADAMTS7 exhibits significant variability among ADAMTS family members and contains eight thrombospondin (TSP) type 1 motifs, rather than lacking them.
The thrombospondin (TSP) type 1 motifs in ADAMTS7's ancillary domain are involved in interactions with the extracellular matrix.
Answer: True
Explanation: The thrombospondin (TSP) type 1 motifs, along with the spacer domain in ADAMTS7's ancillary region, are crucial for mediating its tight interaction with the extracellular matrix.
The eight thrombospondin (TSP) type 1 motifs in ADAMTS7 are primarily involved in its catalytic activity.
Answer: False
Explanation: The eight thrombospondin (TSP) type 1 motifs within ADAMTS7's ancillary domain are primarily involved in mediating interactions with the extracellular matrix, not its catalytic activity.
The proteinase domain of ADAMTS7 contains a signal peptide, prodomain, metalloproteinase domain, and disintegrin-like domain.
Answer: True
Explanation: The proteinase domain of ADAMTS7 comprises a signal peptide, a prodomain, a metalloproteinase domain, and a disintegrin-like domain. These sub-domains are integral to the enzyme's function.
ADAMTS7's gene is located on chromosome 15, band 15q24.2, and it contains 25 exons.
Answer: True
Explanation: The ADAMTS7 gene is located on chromosome 15, specifically at band 15q24.2, and comprises 25 exons.
ADAMTS7's ancillary domain contains eight thrombospondin type 1 motifs and is crucial for anchoring the enzyme in the extracellular matrix.
Answer: True
Explanation: The ancillary domain of ADAMTS7 contains eight thrombospondin (TSP) type 1 motifs and is pivotal for anchoring the enzyme to the extracellular matrix.
What is the full name for the enzyme ADAMTS7?
Answer: A disintegrin and metalloproteinase with thrombospondin motifs 7
Explanation: ADAMTS7 is an acronym denoting 'A disintegrin and metalloproteinase with thrombospondin motifs 7'.
Where is the human ADAMTS7 gene located?
Answer: Chromosome 15, band 15q24.2
Explanation: The human ADAMTS7 gene is located on chromosome 15 at the specific band 15q24.2.
How many exons make up the ADAMTS7 gene?
Answer: 25
Explanation: The ADAMTS7 gene comprises 25 exons.
What is the approximate length of the ADAMTS7 protein in amino acids?
Answer: Approximately 1686 amino acids
Explanation: The ADAMTS7 protein is a large molecule, consisting of approximately 1686 amino acids.
What feature characterizes the ancillary domain of ADAMTS7 compared to its proteinase domain?
Answer: It varies significantly and contains eight thrombospondin type 1 motifs.
Explanation: Unlike the conserved proteinase domain, the ancillary domain of ADAMTS7 exhibits significant variability and comprises eight thrombospondin (TSP) type 1 motifs.
What is the function of the thrombospondin (TSP) type 1 motifs and spacer domain in ADAMTS7?
Answer: To facilitate tight interaction with the extracellular matrix.
Explanation: The thrombospondin (TSP) type 1 motifs and spacer domain within ADAMTS7's ancillary region are pivotal for anchoring the enzyme to the extracellular matrix, facilitating its interaction with the tissue environment.
What is the role of the TSP type 1 motifs and spacer domain within ADAMTS7?
Answer: Anchoring the enzyme to the extracellular matrix.
Explanation: The thrombospondin (TSP) type 1 motifs and spacer domain are pivotal for anchoring ADAMTS7 to the extracellular matrix, facilitating its functional localization.
Which sub-domains constitute the proteinase domain of ADAMTS7?
Answer: Signal peptide, prodomain, metalloproteinase domain, and disintegrin-like domain
Explanation: The proteinase domain of ADAMTS7 comprises the signal peptide, prodomain, metalloproteinase domain, and disintegrin-like domain.
The primary enzymatic function of ADAMTS7 is to synthesize cartilage oligomeric matrix protein (COMP) and TIMP1.
Answer: False
Explanation: ADAMTS7's primary enzymatic function is not synthesis, but rather the catalytic degradation of cartilage oligomeric matrix protein (COMP) and Tissue Inhibitor of Metalloproteinases 1 (TIMP1).
The metalloproteinase domain of ADAMTS7 contains a cysteine-switch motif essential for binding zinc ions.
Answer: True
Explanation: The metalloproteinase domain of ADAMTS7 features a cysteine-switch motif, which is critical for binding the zinc ion necessary for its proteolytic activity.
A pharmacophore model suggests the metalloproteinase domain of ADAMTS7 has primarily hydrogen bond acceptor sites.
Answer: False
Explanation: A pharmacophore model indicates that the metalloproteinase domain of ADAMTS7 possesses four hydrogen bond donor sites and three hydrogen bond acceptor sites, not primarily acceptor sites.
ADAMTS7 requires calcium ions (Ca2+) for its proteolytic activity.
Answer: False
Explanation: As a metalloproteinase, ADAMTS7 requires zinc ions (Zn2+) for its proteolytic activity, not calcium ions.
ADAMTS7 degrades TIMP1, which normally inhibits matrix metalloproteinases.
Answer: True
Explanation: ADAMTS7 degrades TIMP1 (Tissue Inhibitor of Metalloproteinases 1). TIMP1 normally functions to inhibit matrix metalloproteinases, consequently, ADAMTS7's degradation of TIMP1 may indirectly influence matrix remodeling.
Which two key proteins does ADAMTS7 primarily catalyze the degradation of?
Answer: Cartilage oligomeric matrix protein (COMP) and TIMP1
Explanation: ADAMTS7 primarily catalyzes the degradation of cartilage oligomeric matrix protein (COMP) and Tissue Inhibitor of Metalloproteinases 1 (TIMP1).
Which motif within the metalloproteinase domain is crucial for ADAMTS7's catalytic activity involving zinc ions?
Answer: Cysteine-switch motif
Explanation: The cysteine-switch motif within the metalloproteinase domain is essential for binding the zinc ion required for ADAMTS7's proteolytic function.
According to the pharmacophore model, how many hydrogen bond acceptor sites are suggested for the metalloproteinase domain of ADAMTS7?
Answer: Three
Explanation: A pharmacophore model suggests the metalloproteinase domain of ADAMTS7 possesses three hydrogen bond acceptor sites.
What metal ion is essential for the proteolytic function of ADAMTS7?
Answer: Zinc (Zn2+)
Explanation: As a metalloproteinase, ADAMTS7 utilizes zinc ions (Zn2+) for its proteolytic catalysis, specifically for the degradation of its substrates like COMP.
What is the functional consequence of ADAMTS7 degrading TIMP1?
Answer: It decreases the inhibition of matrix metalloproteinases.
Explanation: By degrading TIMP1, which normally inhibits matrix metalloproteinases, ADAMTS7 indirectly leads to decreased inhibition of these enzymes, potentially affecting extracellular matrix remodeling.
ADAMTS7 expression is restricted to specific tissues like cartilage and bone.
Answer: False
Explanation: ADAMTS7 exhibits ubiquitous expression, meaning it is found across a wide range of tissues and cell types, not restricted to cartilage and bone.
ADAMTS7 plays a role in mediating cell migration in vascular smooth muscle cells (VSMCs).
Answer: True
Explanation: ADAMTS7 is instrumental in mediating cell migration within vascular smooth muscle cells (VSMCs), a process relevant to vascular pathologies.
In mouse models, Adamts7 deficiency resulted in increased neointima formation after vascular injury.
Answer: False
Explanation: Experiments involving wire-induced injury in Adamts7-deficient mice demonstrated a marked reduction, not an increase, in neointima formation.
What is characteristic of ADAMTS7 expression in human tissues?
Answer: It is expressed ubiquitously across many tissues and cell types.
Explanation: ADAMTS7 exhibits ubiquitous expression, meaning it is found in numerous tissues and cell types throughout the human body, indicating broad physiological relevance.
In vascular smooth muscle cells (VSMCs), ADAMTS7 is known to play a key role in:
Answer: Cell migration
Explanation: ADAMTS7 is instrumental in mediating cell migration within vascular smooth muscle cells (VSMCs), a critical process implicated in the pathogenesis of conditions such as atherosclerosis and restenosis.
Studies involving wire-induced injury in mice showed that Adamts7 deficiency led to:
Answer: Reduced neointima formation.
Explanation: Experiments utilizing wire-induced injury in Adamts7-deficient mice demonstrated a marked reduction in neointima formation, suggesting a role in preventing vascular remodeling post-injury.
ADAMTS7 has been implicated in the development of arthritis and an increased risk of coronary artery disease.
Answer: True
Explanation: Research indicates that ADAMTS7 is associated with the pathogenesis of arthritis and contributes to an elevated risk of developing coronary artery disease.
Adamts7 deficiency in mouse models led to an increase in atherosclerotic lesion formation.
Answer: False
Explanation: In hyperlipidemic mouse models, Adamts7 deficiency resulted in a marked reduction, not an increase, in atherosclerotic lesion formation, indicating a protective effect.
Genome-wide association studies (GWAS) have linked ADAMTS7 to a reduced risk of coronary artery disease.
Answer: False
Explanation: Genome-wide association studies have identified ADAMTS7 as a genetic locus linked to an increased risk, not a reduced risk, of coronary artery disease.
Associations between ADAMTS7 gene polymorphisms and coronary artery calcification have been observed, particularly in Hispanic populations.
Answer: True
Explanation: Significant associations have been established between single nucleotide polymorphisms (SNPs) in the ADAMTS7 gene and coronary artery calcification, notably within Hispanic populations, indicating a role for ADAMTS7 in this process.
ADAMTS7 is included in multi-locus genetic risk scores for coronary artery disease.
Answer: True
Explanation: ADAMTS7 is among the 27 genetic loci incorporated into multi-locus genetic risk scores utilized to identify individuals at elevated risk for coronary artery disease events.
Which of the following conditions is NOT explicitly associated with ADAMTS7 in the provided text?
Answer: Diabetes Mellitus
Explanation: The provided text explicitly associates ADAMTS7 with cancer, arthritis, and coronary artery disease. Diabetes Mellitus is not mentioned in relation to ADAMTS7.
What was the effect of Adamts7 deficiency on atherosclerosis in mouse models?
Answer: Significantly reduced lesion formation.
Explanation: In hyperlipidemic mouse models, Adamts7 deficiency resulted in a marked reduction in atherosclerotic lesion formation, indicating a protective role.
What have Genome-Wide Association Studies (GWAS) identified ADAMTS7 as concerning coronary artery disease?
Answer: A genetic locus associated with increased risk of CAD
Explanation: Genome-wide association studies have identified ADAMTS7 as a genetic locus linked to an increased risk of coronary artery disease, underscoring ADAMTS7's role in cardiovascular health.
Which population group showed significant associations between ADAMTS7 gene SNPs and coronary artery calcification?
Answer: Hispanic populations
Explanation: Significant associations between ADAMTS7 gene single nucleotide polymorphisms (SNPs) and coronary artery calcification have been observed particularly within Hispanic populations.
In normal tissues, ADAMTS7 expression levels are positively correlated with certain microRNAs (miRNAs).
Answer: False
Explanation: In normal tissues, a negative correlation exists between ADAMTS7 expression and certain miRNAs. This correlation is altered or absent in disease tissues.
Mutations in the ADAMTS7 gene have been reported exclusively in individuals of European descent.
Answer: False
Explanation: Mutations in the ADAMTS7 gene have been reported exclusively in individuals of Asian descent, not European descent.
ADAMTS7 is considered a potential target for therapeutic interventions in managing arthritis.
Answer: True
Explanation: ADAMTS7 is critically involved in the pathogenesis of arthritis, positioning it as a potential therapeutic target for interventions aimed at managing joint inflammation and degradation.
In osteoarthritis pathogenesis, ADAMTS7 is part of a molecular axis involving FGF2, p65, miR-105, and Runx2.
Answer: True
Explanation: In osteoarthritis pathogenesis, ADAMTS7 is indeed part of a specific molecular axis that involves FGF2, p65, miR-105, and Runx2. This intricate network contributes to the disease's progression.
ADAMTS7 forms a negative feedback loop with TNF-α in osteoarthritis, reducing inflammation.
Answer: False
Explanation: ADAMTS7 engages in a positive feedback loop with TNF-α in osteoarthritis pathogenesis. Specifically, ADAMTS7 can stimulate TNF-α, which subsequently may further promote ADAMTS7 activity, thereby exacerbating the inflammatory cycle in OA.
ADAMTS7 is considered a potential oncogene, with mutations found exclusively in Asian populations.
Answer: True
Explanation: ADAMTS7 is considered a potential oncogene, and mutations have been reported exclusively in individuals of Asian descent, suggesting specific implications for cancer pathogenesis and targeted therapies in this demographic.
How does the relationship between ADAMTS7 and certain miRNAs differ between normal and disease tissues?
Answer: A negative correlation exists in normal tissues but is altered or absent in disease tissues.
Explanation: In normal tissues, a negative correlation exists between ADAMTS7 expression and certain miRNAs. However, this correlation is altered or absent in disease tissues, indicating disruption of miRNA-target interactions.
ADAMTS7 mutations have been reported to occur exclusively in which population group?
Answer: Asian descent
Explanation: Mutations in the ADAMTS7 gene have been reported exclusively in individuals of Asian descent.
In osteoarthritis pathogenesis, ADAMTS7 is involved in a feedback loop with which inflammatory cytokine?
Answer: Tumor Necrosis Factor-alpha (TNF-α)
Explanation: In osteoarthritis pathogenesis, ADAMTS7 engages in a positive feedback loop with Tumor Necrosis Factor-alpha (TNF-α), contributing to the inflammatory cycle.
ADAMTS7's potential role as an oncogene, particularly in Asian populations, suggests relevance for:
Answer: Targeted therapies for certain cancers
Explanation: ADAMTS7's potential oncogenic role, especially noted in Asian populations, indicates its relevance for developing targeted therapies for specific types of cancer.
ADAMTS7 was initially discovered through studies of protein crystallization.
Answer: False
Explanation: ADAMTS7 was initially identified via a yeast two-hybrid screen, utilizing the epidermal growth factor (EGF) domain of COMP as bait, not through protein crystallization studies.
Inhibiting ADAMTS7 activity is proposed as a potential strategy to prevent coronary artery disease.
Answer: True
Explanation: Given ADAMTS7's role in promoting atherosclerosis, its inhibition is posited as a potential atheroprotective strategy in humans, suggesting it as a target for preventing coronary artery disease.
The expression profiles of ADAMTS7 and specific miRNAs might serve as diagnostic tools for certain diseases.
Answer: True
Explanation: The expression patterns of ADAMTS7 and specific miRNAs hold potential as diagnostic biomarkers, possibly aiding in the differentiation between normal and diseased tissues, such as in cancer.
Understanding ADAMTS7 binding sites is important for developing new therapeutic targets.
Answer: True
Explanation: Classifying the binding sites of ADAMTS7 is crucial for the development of novel therapeutic targets. Precise understanding of its binding sites facilitates the design of targeted inhibitors for conditions associated with ADAMTS7 activity.
Studies showed that individuals with higher genetic risk scores involving ADAMTS7 experienced less benefit from statin therapy.
Answer: False
Explanation: Studies utilizing genetic risk scores that included ADAMTS7 revealed that individuals with higher genetic risk scores derived enhanced clinical benefit from statin therapy, indicating that genetic factors associated with ADAMTS7 may influence response to these medications.
The Malmö Diet and Cancer study was one of the trials used to evaluate genetic risk scores involving ADAMTS7.
Answer: True
Explanation: The Malmö Diet and Cancer study was indeed cited as one of the community cohort studies used in evaluating the multi-locus genetic risk scores that incorporate ADAMTS7.
ADAMTS7's role in cardiovascular disease suggests it is not a viable target for therapeutic intervention.
Answer: False
Explanation: Conversely, ADAMTS7's established role in cardiovascular disease pathogenesis underscores its potential as a viable target for therapeutic intervention, offering potential avenues for prevention and management.
The identification of ADAMTS7 involved a yeast two-hybrid screen using the epidermal growth factor (EGF) domain of COMP as bait.
Answer: True
Explanation: ADAMTS7 was initially identified via a yeast two-hybrid screen, employing the epidermal growth factor (EGF) domain of COMP as bait.
How was ADAMTS7 initially identified in research?
Answer: Via a yeast two-hybrid screen using the EGF domain of COMP.
Explanation: ADAMTS7 was initially identified through a yeast two-hybrid screen employing the epidermal growth factor (EGF) domain of COMP as bait.
The role of ADAMTS7 in atherosclerosis suggests that inhibiting it could be:
Answer: Atheroprotective
Explanation: Given ADAMTS7's role in promoting atherosclerosis, inhibiting its activity is proposed to be atheroprotective, suggesting potential therapeutic benefits for cardiovascular disease.
Why is classifying the binding sites of ADAMTS7 considered important?
Answer: For the development of new therapeutic targets.
Explanation: Classifying the binding sites of ADAMTS7 is crucial for the development of novel therapeutic targets. Precise understanding of its binding sites facilitates the design of targeted inhibitors.
ADAMTS7 is included in multi-locus genetic risk scores for coronary artery disease. What benefit did individuals with higher scores show from statin therapy?
Answer: Enhanced clinical benefit
Explanation: Studies revealed that individuals with higher genetic risk scores incorporating ADAMTS7 derived enhanced clinical benefit from statin therapy, indicating a potential influence on treatment response.
Which of the following studies was mentioned in relation to genetic risk scores involving ADAMTS7?
Answer: Malmö Diet and Cancer study
Explanation: The Malmö Diet and Cancer study was cited as one of the community cohort studies used in evaluating genetic risk scores involving ADAMTS7.
The association of ADAMTS7 with cardiovascular disease implies its potential as a target for:
Answer: Preventing or managing cardiovascular conditions
Explanation: ADAMTS7's established role in cardiovascular disease presents potential therapeutic avenues for the prevention or management of these conditions.
The identification of ADAMTS7 was linked to which protein's epidermal growth factor (EGF) domain?
Answer: COMP
Explanation: The initial identification of ADAMTS7 was linked to the epidermal growth factor (EGF) domain of Cartilage Oligomeric Matrix Protein (COMP) during a yeast two-hybrid screen.