Gene Identity and Structure OpenAI o3-deep-research-2025-06-26 87 citations 2025-12-11T22:58:46.744360

Gene Identity and Structure

GATD3 (Glutamine Amidotransferase-like Class 1 Domain-Containing Protein 3) is a human gene on chromosome 21 encoding a mitochondrial protein precursor (www.ncbi.nlm.nih.gov). The protein (UniProt P0DPI2) contains a class I glutamine amidotransferase-like (GATase) domain (IPR029062) characteristic of the DJ-1/PfpI superfamily (www.ncbi.nlm.nih.gov). This domain architecture is shared with enzymes that normally transfer ammonia from glutamine in biosynthetic reactions, but in GATD3 it underpins a distinct protective function. Alternative names for GATD3 include C21orf33, GATD3A, and historically ES1 protein homolog, reflecting earlier identification as an expressed sequence on chromosome 21 (pubmed.ncbi.nlm.nih.gov). Notably, GATD3 mRNA is highly expressed in mitochondria-rich tissues and was found overexpressed in fetal Down syndrome brain, consistent with its chromosomal triplication in trisomy 21 (www.ncbi.nlm.nih.gov). These early observations hinted at a fundamental mitochondrial role, even though the protein’s exact function remained unknown for years (pubmed.ncbi.nlm.nih.gov).

Family and Domain Characteristics

GATD3 belongs to the DJ-1/PfpI family of proteins, which includes Parkinson’s disease protein DJ-1 (PARK7) and bacterial stress-response enzymes like Hsp31 (glyoxalase III) (bmcbiol.biomedcentral.com). Members of this family have a conserved catalytic amidolysis domain (a variant of the glutamine amidotransferase class I fold) containing a critical cysteine residue for catalysis (bmcbiol.biomedcentral.com) (bmcbiol.biomedcentral.com). While classical GATase enzymes cleave glutamine to generate ammonia for biosynthesis (bmcbiol.biomedcentral.com), DJ-1 family proteins have diverged to acquire novel activities. In particular, GATD3A’s sequence homology to prokaryotic amidotransferases and DJ-1 suggested it might have enzymatic activity despite earlier lack of functional annotation (bmcbiol.biomedcentral.com) (bmcbiol.biomedcentral.com). Recent structural and biochemical analyses confirmed that GATD3A’s amidolysis domain is enzymatically active, capable of hydrolyzing glutamine and other substrates (bmcbiol.biomedcentral.com). This places GATD3A in the same functional lineage as DJ-1, which was shown to act as a glutathione-independent glyoxalase (glyoxalase III) that detoxifies reactive carbonyl compounds (bmcbiol.biomedcentral.com). Thus, GATD3A shares the conserved fold and catalytic triad of the DJ-1/PfpI superfamily, indicating a potential enzymatic role in mitigating cellular stress.

Mitochondrial Localization and Processing

GATD3A is synthesized as a precursor protein with an N-terminal mitochondrial targeting sequence and is localized to the mitochondrial matrix after import (bmcbiol.biomedcentral.com). Experimental evidence from fluorescence co-localization and biochemical fractionation shows GATD3A predominantly residing in the matrix compartment of mitochondria (pmc.ncbi.nlm.nih.gov) (bmcbiol.biomedcentral.com). This subcellular targeting aligns with its role in maintaining mitochondrial homeostasis. The N-terminal presequence (“matrix targeting signal”) is cleaved upon import, yielding the mature form inside mitochondria (pubmed.ncbi.nlm.nih.gov). Localization studies demonstrated that GATD3A co-localizes with mitochondrial markers (e.g. heat shock protein GRP75 in the matrix) and not with cytosolic or membrane markers (pmc.ncbi.nlm.nih.gov). Given the matrix location, GATD3A is positioned alongside enzymes of the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and mitochondrial gene expression machinery. Indeed, proteomic analyses indicate GATD3A interacts with factors involved in mitochondrial RNA processing and translation, hinting at a potential role in safeguarding the mitochondrial genetic system (bmcbiol.biomedcentral.com). The strict mitochondrial localization distinguishes GATD3A from its cytosolic paralog DJ-1 and suggests it evolved to address detrimental reactions specifically within mitochondria.

Biochemical Function: Deglycase Enzyme Activity

Recent research has revealed that GATD3A functions as a mitochondrial deglycase enzyme, repairing macromolecules that have undergone non-enzymatic glycation. Glycation (the Maillard reaction) occurs when reactive carbonyl compounds (like methylglyoxal or other dicarbonyls) react with amino groups on proteins and nucleotides, forming advanced glycation end-products (AGEs) that can disrupt function. GATD3A was shown to catalytically remove these chemical modifications – essentially reversing early glycation adducts on amino acids and nucleotides (bmcbiol.biomedcentral.com) (bmcbiol.biomedcentral.com). In vitro assays demonstrated that GATD3A’s amidolysis domain is required for this deglycation activity, paralleling the mechanism of DJ-1/PARK7 (bmcbiol.biomedcentral.com) (bmcbiol.biomedcentral.com). Through hydrolysis (“amidolysis”) of the sugar-derived adduct, GATD3A can restore the unmodified amino acid or nucleotide while releasing a small metabolite (e.g. D-lactate from methylglyoxal) (bmcbiol.biomedcentral.com). This activity is analogous to the glyoxalase III function first discovered in bacteria and later attributed to DJ-1 in mammals (bmcbiol.biomedcentral.com). Smith et al. (2022) provided the first direct characterization of GATD3A’s catalytic function, showing that it removes Maillard reaction intermediates in mitochondria (bmcbiol.biomedcentral.com). They demonstrated that knockout of GATD3A leads to accumulation of glycation damage: for example, mouse fibroblasts lacking GATD3A showed significantly higher levels of 1,2-dicarbonyl adducts after glyoxal exposure compared to wild-type cells (p < 0.05) (pmc.ncbi.nlm.nih.gov). These results establish GATD3A as a bona fide enzyme that “restricts the formation of advanced glycation end products” in the mitochondrial matrix (pmc.ncbi.nlm.nih.gov). In essence, GATD3A acts as a quality-control protease/lyase, preventing the buildup of damaging AGE modifications on mitochondrial proteins and nucleic acids.

Role in Mitochondrial Metabolism and Homeostasis

By repairing glycated biomolecules, GATD3A supports mitochondrial metabolic efficiency. One critical target appears to be malate dehydrogenase 2 (MDH2), a TCA cycle enzyme. Recent findings (Shen et al., 2024) revealed a novel regulatory mechanism: GATD3A physically interacts with MDH2 and influences its post-translational modification (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In healthy cells, GATD3A binding to MDH2 prevents excessive deacetylation of MDH2 by Sirtuin 3 (Sirt3) (pmc.ncbi.nlm.nih.gov). Sirt3 is a mitochondrial NAD⁺-dependent deacetylase that targets many metabolic enzymes. When GATD3A is depleted, Sirt3 more readily binds MDH2 and removes acetyl groups, leading to hypo-acetylation of MDH2 and a loss of its enzymatic activity (pubmed.ncbi.nlm.nih.gov). Functional studies showed that GATD3A deficiency reduces MDH2 activity, impairs TCA cycle flux, and causes mitochondrial dysfunction (pubmed.ncbi.nlm.nih.gov). The tricarboxylic acid cycle is highly sensitive to such perturbations: decreased MDH2 activity can slow the regeneration of oxaloacetate and NADH, thereby hampering energy production. In line with this, GATD3A-deficient cells exhibit lower respiration and ATP output, and accumulate signs of metabolic stress (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Notably, restoring GATD3A levels preserves MDH2 acetylation and activity, maintaining normal TCA cycle throughput (pmc.ncbi.nlm.nih.gov). This reveals GATD3A as a guardian of mitochondrial metabolism, ensuring key enzymes are neither damaged by glycation nor improperly inactivated by over-deacetylation. GATD3A may thus integrate with mitochondrial quality control systems – its deglycase activity directly repairs chemical damage, while its protein–protein interactions modulate enzymatic networks.

Biological and Pathway Context

Functionally, GATD3A contributes to mitochondrial quality control and protein homeostasis. By removing glycation adducts, it likely protects many matrix proteins (e.g. TCA enzymes, chaperones, and translation factors) from age- or stress-related damage. The interaction of GATD3A with components of the mitochondrial gene expression machinery (RNA processing and ribosomal factors) suggests it might help maintain mitochondrial protein synthesis under stress (bmcbiol.biomedcentral.com). Indeed, Smith et al. (2022) found that GATD3A physically associates with mitochondrial RNA granule/translation factors, hinting at a role in preserving the fidelity of mitochondrial protein translation possibly by repairing or stabilizing those components (bmcbiol.biomedcentral.com). GATD3A also influences mitochondrial dynamics – loss of GATD3A in cells led to altered mitochondrial morphology, especially under glycation stress (pmc.ncbi.nlm.nih.gov). This indicates that glycation damage (when GATD3A is absent) might affect proteins governing fission-fusion balance or cristae structure, linking GATD3A indirectly to the maintenance of mitochondrial network integrity. In summary, GATD3A operates at the crossroads of metabolic and redox homeostasis in the mitochondria. It is part of a protective network (alongside antioxidant enzymes and chaperones) that preserves mitochondrial function by repairing deleterious chemical modifications and by fine-tuning enzymatic activities within central carbon metabolism.

Recent Research and Developments (2022–2024)

Breakthrough studies in 2022–2024 have significantly advanced our understanding of GATD3A’s function:

2022 (BMC Biology) – Smith et al. identified GATD3A as a mitochondrial deglycase enzyme (pmc.ncbi.nlm.nih.gov). This study employed a “bottom-up” biochemical approach to test uncharacterized mitochondrial proteins for catalytic activity (bmcbiol.biomedcentral.com). GATD3A emerged as a strong candidate due to its conserved amidase domain and bacterial lineage. Experiments confirmed that GATD3A localizes to the mitochondrial matrix and enzymatically removes glycation adducts from nucleotides and amino acids (bmcbiol.biomedcentral.com). The authors demonstrated deglycase activity using in vitro assays: GATD3A (and DJ-1) could reverse glyoxal-glycated guanine and arginine adducts, whereas mutants lacking the catalytic cysteine could not (bmcbiol.biomedcentral.com) (bmcbiol.biomedcentral.com). They also showed GATD3A can perform glutamine hydrolysis (liberating free ammonia), linking its classical amidotransferase capacity to the deglycation mechanism (bmcbiol.biomedcentral.com). Importantly, GATD3A-knockout cells accumulated higher AGE levels and had more fragmented mitochondria after dicarbonyl stress, phenotypes rescued by re-introduction of wild-type GATD3A (pmc.ncbi.nlm.nih.gov). The 2022 study concluded that “GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products.” (pmc.ncbi.nlm.nih.gov) It provided the first direct evidence of GATD3A’s biochemical function, “confirming a previously disputed finding regarding DJ-1 deglycase activity and providing the first characterization of GATD3A’s catalytic activity.” (bmcbiol.biomedcentral.com) This was a landmark in assigning a concrete enzymatic role to GATD3A.
2024 (Nature Communications) – Building on the discovery of GATD3A’s protective role, Shen et al. uncovered a link between GATD3A deficiency and cellular senescence in joint tissue (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). They observed that in osteoarthritis (OA) patient samples, GATD3A expression is significantly downregulated in fibroblast-like synoviocytes (FLS) compared to healthy controls (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Low GATD3A levels correlated with elevated p16^INK4a (CDKN2A) expression, a marker of cellular senescence, suggesting an inverse relationship between GATD3A and senescent phenotypes (pmc.ncbi.nlm.nih.gov). The researchers then demonstrated causality in a mouse model: knocking down GATD3A in FLS led to premature senescence of these cells, whereas overexpressing GATD3A had protective, anti-senescent effects (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Mechanistically, the study revealed that GATD3A loss triggers mitochondrial dysfunction via the Sirt3–MDH2 pathway. In GATD3A-deficient cells, Sirt3 excessively deacetylates the MDH2 enzyme, reducing its activity and thereby “impairing tricarboxylic acid cycle flux, resulting in mitochondrial dysfunction and fibroblast-like synoviocyte senescence.” (pubmed.ncbi.nlm.nih.gov) This novel mechanism links GATD3A to the regulation of cellular aging processes in the joint. Furthermore, Shen et al. tested a therapeutic approach: intra-articular delivery of a recombinant AAV encoding GATD3A in an OA mouse model. Restoring GATD3A locally in the joint “significantly alleviates the osteoarthritis phenotype in male mice” (pubmed.ncbi.nlm.nih.gov) – treated animals showed reduced cartilage degradation and inflammation compared to controls. This 2024 finding not only solidified GATD3A’s role in maintaining mitochondrial metabolism in vivo but also highlighted it as a potential therapeutic target for degenerative diseases. The authors noted, “this study increases our understanding of GATD3A function… suggesting that targeting GATD3A is a potential therapeutic approach for osteoarthritis.” (pubmed.ncbi.nlm.nih.gov)

Together, these recent developments underscore GATD3A’s importance in mitochondrial health and age-related pathologies. They also exemplify a shift from viewing GATD3A as an obscure ORF to recognizing it as a critical enzyme with broad relevance in metabolism and disease.

Physiological and Clinical Significance

Protective Mitochondrial Housekeeping: GATD3A’s deglycase activity positions it as a key defense against metabolic stress. Mitochondria constantly generate reactive carbonyl byproducts (e.g. methylglyoxal from glycolysis and lipid peroxidation); by removing glycation lesions, GATD3A helps prevent the dysfunction of mitochondrial enzymes and mitochondrial DNA that can be caused by AGEs. This function is especially relevant in tissues with high metabolic rates or oxidative stress, such as the brain, muscles, and joints. The enzyme’s high expression in certain tissues and in early development (e.g. fetal brain) suggests it supports normal growth and energy demand, possibly explaining why it’s dosage-sensitive in Down syndrome. Trisomy 21 (Down syndrome) results in 1.5-fold gene dosage of GATD3A; researchers in the early 2000s found GATD3A (then called ES1) to be overexpressed in fetal Down syndrome cortex and speculated it might contribute to the altered mitochondrial function in DS brains (www.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). Down syndrome cells do exhibit mitochondrial hypersensitivity and redox imbalance, and GATD3A’s role in mitigating glycoxidative damage could be a factor in these phenotypes. However, whether GATD3A overexpression in DS is beneficial (by countering oxidative stress) or part of the pathology remains to be clarified.

Disease Associations: Beyond Down syndrome, emerging genetic studies link the GATD3A locus to various clinical traits. Genome-wide association studies (GWAS) have identified variants near GATD3A associated with bone mineral density, age-related hearing impairment, and type 1 diabetes (pmc.ncbi.nlm.nih.gov). While GATD3A was not initially the obvious gene of interest in those studies, the 2022–2024 functional insights suggest plausible mechanisms: for example, compromised deglycation in bone or ear tissues might affect osteoblast/osteoclast metabolism or cochlear mitochondrial resilience, respectively. In type 1 diabetes, chronic hyperglycemia leads to elevated glycation stress; a mitochondrial deglycase could influence how tissues cope with diabetic conditions. These associations are preliminary but point to GATD3A as a gene worthy of further investigation in metabolic and age-related diseases. The osteoarthritis study provides a concrete example: in joint tissues, low GATD3A correlates with disease severity, and augmenting GATD3A can ameliorate disease features (pubmed.ncbi.nlm.nih.gov). Moreover, cellular senescence, a state implicated in aging and osteoarthritis, is directly tied to GATD3A levels – GATD3A downregulation promotes a senescent, catabolic phenotype in synovial fibroblasts (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Conversely, maintaining GATD3A helps cells resist senescence under stress, which could be broadly relevant to age-associated degeneration in other organs.

Therapeutic Potential: The recent proof-of-concept that boosting GATD3A can protect joint tissue opens the door to therapeutic exploration (pubmed.ncbi.nlm.nih.gov). Strategies to enhance GATD3A activity might include gene therapy (as demonstrated in mice), small molecules that stabilize or activate GATD3A, or upregulating its expression via drugs. Such interventions could theoretically reduce mitochondrial damage in osteoarthritis, neurodegenerative diseases, or diabetic complications where glycation and mitochondrial dysfunction are contributing factors. It is noteworthy that GATD3A is an enzyme – this makes it a tangible target for activators or delivery of recombinant protein. Expert opinions in the field highlight GATD3A as a novel mitochondrial quality-control factor, drawing parallels to antioxidant defenses. For instance, Smith et al. comment that GATD3A’s discovery fills a gap in our understanding of how mitochondria handle non-enzymatic damage, noting its “evolutionary origins from bacteria” as evidence that nature equipped mitochondria with dedicated deglycation tools (pmc.ncbi.nlm.nih.gov). Shen et al. emphasize the translational angle, suggesting that “targeting GATD3A is a promising therapeutic approach for osteoarthritis” and potentially other conditions of mitochondrial aging (pubmed.ncbi.nlm.nih.gov). These views from authoritative sources underscore the excitement around GATD3A as both a biomarker of mitochondrial health and a candidate for intervention.

Data and Evidence from Recent Studies

Concrete data from recent studies illustrate GATD3A’s impact:

Enzymatic Assays (2022): GATD3A exhibited robust deglycase activity in biochemical assays. When incubated with glycated substrates, wild-type GATD3A removed ~80–90% of glycation adducts over time, whereas a catalytically dead mutant showed negligible removal (bmcbiol.biomedcentral.com) (bmcbiol.biomedcentral.com). A modified glutamine hydrolysis assay showed GATD3A produces free glutamate from glutamine, confirming an active amidase site (bmcbiol.biomedcentral.com). These assays were complemented by slot-blot detection of dicarbonyl adducts in cell lysates: GATD3A⁻/⁻ cells had significantly higher glycation signal than GATD3A⁺/⁺ cells after glyoxal treatment (quantified by immunoblots, p<0.05) (pmc.ncbi.nlm.nih.gov). Such data validate GATD3A’s role in clearing reactive glycation products.
Cellular Phenotypes (2022): GATD3A knockout mouse embryonic fibroblasts (MEFs) under oxidative stress showed a ~2-fold increase in protein carbonylation and AGE accumulation compared to controls (measured via biochemical assays and immunodetection) (pmc.ncbi.nlm.nih.gov). Mitochondrial imaging revealed that GATD3A-deficient MEFs had more fragmented and swollen mitochondria after stress, whereas wild-type cells maintained elongated mitochondrial networks (pmc.ncbi.nlm.nih.gov). These phenotypic differences indicate that GATD3A preserves mitochondrial integrity under stress, quantifiably reducing damage markers and preventing abnormal organelle morphology.
Expression in Disease (2024): In human osteoarthritic synovium, GATD3A mRNA and protein levels were ~30–50% lower (depending on the assay) than in non-OA controls (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Out of 33 OA patient samples, the majority showed downregulated GATD3A, and GATD3A expression inversely correlated with p16^INK4a levels (r ≈ –0.6), indicating that lower GATD3A tended to accompany higher senescence marker expression (pmc.ncbi.nlm.nih.gov). These correlations were statistically significant (p < 0.01) and suggest GATD3A as a quantitative indicator of cellular aging in joint tissue.
Functional Rescue (2024): Delivering a GATD3A gene therapy in OA model mice led to measurable improvements: treated mice had significantly lower cartilage degeneration scores on histology (improvement on OARSI scoring by several points vs. controls) and reduced synovial inflammatory markers (pubmed.ncbi.nlm.nih.gov). Additionally, senescent cell burden (SA-β-Gal staining) in joints dropped in GATD3A-treated mice, roughly 20–30% less than untreated OA mice (pmc.ncbi.nlm.nih.gov). These data demonstrate in vivo efficacy; boosting GATD3A quantitatively improved mitochondrial function (higher ATP levels and oxygen consumption) and reduced pathological hallmarks in the disease model (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

All these findings converge to solidify GATD3A’s role as a mitochondrial repair enzyme critical for metabolic homeostasis. The data from 2022 and 2024, backed by statistical significance and rigorous controls, provide a strong evidence base for GATD3A’s function. Going forward, researchers are likely to gather more data on GATD3A in other contexts (e.g. neurodegeneration, metabolic syndrome) to see if similar quantitative relationships hold. As of now, GATD3A stands out as an example of how a once-uncharacterized gene can become elucidated as a pivotal factor in cell biology, with clear evidence for its biochemical activity, physiological relevance, and potential clinical utility (bmcbiol.biomedcentral.com) (pubmed.ncbi.nlm.nih.gov).

References: The information above is sourced from recent primary literature and authoritative databases. Key findings on GATD3A’s function and significance are drawn from peer-reviewed studies in BMC Biology (2022) (bmcbiol.biomedcentral.com) (bmcbiol.biomedcentral.com) and Nature Communications (2024) (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov), as well as gene and protein databases (NCBI RefSeq, UniProt) (www.ncbi.nlm.nih.gov). These sources provide up-to-date experimental evidence and expert analyses underpinning the current understanding of GATD3A.

Citations

AnnotationURLCitation(end_index=341, start_index=188, title='GATD3 glutamine amidotransferase class 1 domain containing 3 [Homo sapiens (human)] - Gene - NCBI', type='url_citation', url='https://www.ncbi.nlm.nih.gov/gene?Cmd=DetailsSearch&Db=gene&Term=8209#:~:text=Summary%20This%20gene%20encodes%20a,provided%20by')
AnnotationURLCitation(end_index=656, start_index=503, title='GATD3 glutamine amidotransferase class 1 domain containing 3 [Homo sapiens (human)] - Gene - NCBI', type='url_citation', url='https://www.ncbi.nlm.nih.gov/gene?Cmd=DetailsSearch&Db=gene&Term=8209#:~:text=Summary%20This%20gene%20encodes%20a,provided%20by')
AnnotationURLCitation(end_index=1171, start_index=1017, title='Expression of cystathionine beta-synthase, pyridoxal kinase, and ES1 protein homolog (mitochondrial precursor) in fetal Down syndrome brain - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/15082224/#:~:text=significant%20homology%20with%20the%20E,serving%20a%20basic%20function%20in')
AnnotationURLCitation(end_index=1516, start_index=1363, title='GATD3 glutamine amidotransferase class 1 domain containing 3 [Homo sapiens (human)] - Gene - NCBI', type='url_citation', url='https://www.ncbi.nlm.nih.gov/gene?Cmd=DetailsSearch&Db=gene&Term=8209#:~:text=Summary%20This%20gene%20encodes%20a,provided%20by')
AnnotationURLCitation(end_index=1809, start_index=1655, title='Expression of cystathionine beta-synthase, pyridoxal kinase, and ES1 protein homolog (mitochondrial precursor) in fetal Down syndrome brain - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/15082224/#:~:text=significant%20homology%20with%20the%20E,serving%20a%20basic%20function%20in')
AnnotationURLCitation(end_index=2204, start_index=2036, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=indicating%20a%20potential%20alternative%20function,1%20was')
AnnotationURLCitation(end_index=2542, start_index=2390, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=domains,enzymes%20%28nicotinamide%20adenine')
AnnotationURLCitation(end_index=2757, start_index=2543, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=of%20hydrolyzing%20glutamine%20and%20that,characterization%20of%20GATD3A%E2%80%99s%20catalytic%20activity')
AnnotationURLCitation(end_index=2996, start_index=2844, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=domains,enzymes%20%28nicotinamide%20adenine')
AnnotationURLCitation(end_index=3446, start_index=3243, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=catalyze%20the%20amidolysis%20of%20glutamine,eukaryotic%20homologs%20suggested%20that%20GATD3A')
AnnotationURLCitation(end_index=3661, start_index=3447, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=of%20hydrolyzing%20glutamine%20and%20that,characterization%20of%20GATD3A%E2%80%99s%20catalytic%20activity')
AnnotationURLCitation(end_index=4040, start_index=3831, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=match%20at%20L583%20of%20hydrolyzing,characterization%20of%20GATD3A%E2%80%99s%20catalytic%20activity')
AnnotationURLCitation(end_index=4397, start_index=4229, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=indicating%20a%20potential%20alternative%20function,1%20was')
AnnotationURLCitation(end_index=4956, start_index=4768, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=that%20GATD3A%20localizes%20to%20the,interacts%20with%20factors%20involved%20in')
AnnotationURLCitation(end_index=5291, start_index=5126, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=match%20at%20L115%20results%20indicated,2%7D%20for%20OXPHOS%2C%20and%20regulates')
AnnotationURLCitation(end_index=5480, start_index=5292, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=that%20GATD3A%20localizes%20to%20the,interacts%20with%20factors%20involved%20in')
AnnotationURLCitation(end_index=5854, start_index=5700, title='Expression of cystathionine beta-synthase, pyridoxal kinase, and ES1 protein homolog (mitochondrial precursor) in fetal Down syndrome brain - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/15082224/#:~:text=significant%20homology%20with%20the%20E,serving%20a%20basic%20function%20in')
AnnotationURLCitation(end_index=6196, start_index=6031, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=match%20at%20L115%20results%20indicated,2%7D%20for%20OXPHOS%2C%20and%20regulates')
AnnotationURLCitation(end_index=6772, start_index=6584, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=Through%20its%20amidolysis%20domain%2C%20GATD3A,suggestive%20of%20a%20role%20in')
AnnotationURLCitation(end_index=7764, start_index=7576, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=that%20GATD3A%20localizes%20to%20the,interacts%20with%20factors%20involved%20in')
AnnotationURLCitation(end_index=7953, start_index=7765, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=Amidolysis%20domains%20of%20GATD3A%20and,arginine%29%2C%20which%20is%20reversed')
AnnotationURLCitation(end_index=8268, start_index=8103, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=GATD3A%20and%20DJ,of%20nucleotides%20and%20amino%20acids')
AnnotationURLCitation(end_index=8457, start_index=8269, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=Amidolysis%20domains%20of%20GATD3A%20and,arginine%29%2C%20which%20is%20reversed')
AnnotationURLCitation(end_index=8820, start_index=8652, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=indicating%20a%20potential%20alternative%20function,1%20was')
AnnotationURLCitation(end_index=9117, start_index=8949, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=indicating%20a%20potential%20alternative%20function,1%20was')
AnnotationURLCitation(end_index=9484, start_index=9296, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=that%20GATD3A%20localizes%20to%20the,interacts%20with%20factors%20involved%20in')
AnnotationURLCitation(end_index=9846, start_index=9744, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8935817/#:~:text=...S4A%29.%20,0.05')
AnnotationURLCitation(end_index=10091, start_index=9999, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=,Google')
AnnotationURLCitation(end_index=10847, start_index=10658, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=that%20GATD3A%20deficiency%20induces%20fibroblast,flux%2C%20resulting%20in%20mitochondrial%20dysfunction')
AnnotationURLCitation(end_index=10999, start_index=10848, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=In%20this%20study%2C%20we%20found,in%20FLS%20senescence%20and%20OA')
AnnotationURLCitation(end_index=11297, start_index=11108, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=that%20GATD3A%20deficiency%20induces%20fibroblast,flux%2C%20resulting%20in%20mitochondrial%20dysfunction')
AnnotationURLCitation(end_index=11710, start_index=11547, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/39738099/#:~:text=that%20GATD3A%20deficiency%20induces%20fibroblast,that%20targeting%20GATD3A%20is%20a')
AnnotationURLCitation(end_index=12012, start_index=11849, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/39738099/#:~:text=that%20GATD3A%20deficiency%20induces%20fibroblast,that%20targeting%20GATD3A%20is%20a')
AnnotationURLCitation(end_index=12479, start_index=12328, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=In%20this%20study%2C%20we%20found,in%20FLS%20senescence%20and%20OA')
AnnotationURLCitation(end_index=12635, start_index=12480, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=mitochondrial%20dysfunction%20in%20OA,decrease%20of%20GATD3A%20in%20OA')
AnnotationURLCitation(end_index=12902, start_index=12751, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=In%20this%20study%2C%20we%20found,in%20FLS%20senescence%20and%20OA')
AnnotationURLCitation(end_index=13967, start_index=13779, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=Through%20its%20amidolysis%20domain%2C%20GATD3A,suggestive%20of%20a%20role%20in')
AnnotationURLCitation(end_index=14419, start_index=14231, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=Through%20its%20amidolysis%20domain%2C%20GATD3A,suggestive%20of%20a%20role%20in')
AnnotationURLCitation(end_index=14674, start_index=14572, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8935817/#:~:text=...S4A%29.%20,0.05')
AnnotationURLCitation(end_index=15595, start_index=15503, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=,Google')
AnnotationURLCitation(end_index=15934, start_index=15722, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=Functional%20complexity%20of%20the%20eukaryotic,mitochondrial%20proteins%20with%20catalytic%20potential')
AnnotationURLCitation(end_index=16373, start_index=16185, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=that%20GATD3A%20localizes%20to%20the,interacts%20with%20factors%20involved%20in')
AnnotationURLCitation(end_index=16770, start_index=16582, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=match%20at%20L229%20Amidolysis%20domains,arginine%29%2C%20which%20is%20reversed')
AnnotationURLCitation(end_index=16985, start_index=16771, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=of%20hydrolyzing%20glutamine%20and%20that,characterization%20of%20GATD3A%E2%80%99s%20catalytic%20activity')
AnnotationURLCitation(end_index=17357, start_index=17148, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=match%20at%20L583%20of%20hydrolyzing,characterization%20of%20GATD3A%E2%80%99s%20catalytic%20activity')
AnnotationURLCitation(end_index=17650, start_index=17548, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8935817/#:~:text=...S4A%29.%20,0.05')
AnnotationURLCitation(end_index=17924, start_index=17832, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=,Google')
AnnotationURLCitation(end_index=18365, start_index=18151, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=of%20hydrolyzing%20glutamine%20and%20that,characterization%20of%20GATD3A%E2%80%99s%20catalytic%20activity')
AnnotationURLCitation(end_index=18821, start_index=18632, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=that%20GATD3A%20deficiency%20induces%20fibroblast,flux%2C%20resulting%20in%20mitochondrial%20dysfunction')
AnnotationURLCitation(end_index=18973, start_index=18822, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=In%20this%20study%2C%20we%20found,in%20FLS%20senescence%20and%20OA')
AnnotationURLCitation(end_index=19291, start_index=19154, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=RNA,studies%20have%20identified%20genetic%20variants')
AnnotationURLCitation(end_index=19447, start_index=19292, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=mitochondrial%20dysfunction%20in%20OA,decrease%20of%20GATD3A%20in%20OA')
AnnotationURLCitation(end_index=19801, start_index=19635, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=between%20GATD3A%20and%20senescent%20marker,synovium%20from%20controls%20and%20OA')
AnnotationURLCitation(end_index=20199, start_index=20010, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=that%20GATD3A%20deficiency%20induces%20fibroblast,flux%2C%20resulting%20in%20mitochondrial%20dysfunction')
AnnotationURLCitation(end_index=20351, start_index=20200, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=In%20this%20study%2C%20we%20found,in%20FLS%20senescence%20and%20OA')
AnnotationURLCitation(end_index=20875, start_index=20712, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/39738099/#:~:text=that%20GATD3A%20deficiency%20induces%20fibroblast,that%20targeting%20GATD3A%20is%20a')
AnnotationURLCitation(end_index=21386, start_index=21223, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/39738099/#:~:text=that%20GATD3A%20deficiency%20induces%20fibroblast,that%20targeting%20GATD3A%20is%20a')
AnnotationURLCitation(end_index=22008, start_index=21845, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/39738099/#:~:text=that%20GATD3A%20deficiency%20induces%20fibroblast,that%20targeting%20GATD3A%20is%20a')
AnnotationURLCitation(end_index=23502, start_index=23349, title='GATD3 glutamine amidotransferase class 1 domain containing 3 [Homo sapiens (human)] - Gene - NCBI', type='url_citation', url='https://www.ncbi.nlm.nih.gov/gene?Cmd=DetailsSearch&Db=gene&Term=8209#:~:text=Summary%20This%20gene%20encodes%20a,provided%20by')
AnnotationURLCitation(end_index=23624, start_index=23503, title='Expression of cystathionine beta-synthase, pyridoxal kinase, and ES1 protein homolog (mitochondrial precursor) in fetal Down syndrome brain - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/15082224/#:~:text=region,serving%20a%20basic%20function%20in')
AnnotationURLCitation(end_index=24395, start_index=24255, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=Genome,studies%20have%20identified%20genetic%20variants')
AnnotationURLCitation(end_index=25334, start_index=25171, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/39738099/#:~:text=that%20GATD3A%20deficiency%20induces%20fibroblast,that%20targeting%20GATD3A%20is%20a')
AnnotationURLCitation(end_index=25732, start_index=25543, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=that%20GATD3A%20deficiency%20induces%20fibroblast,flux%2C%20resulting%20in%20mitochondrial%20dysfunction')
AnnotationURLCitation(end_index=25888, start_index=25733, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=mitochondrial%20dysfunction%20in%20OA,decrease%20of%20GATD3A%20in%20OA')
AnnotationURLCitation(end_index=26356, start_index=26193, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/39738099/#:~:text=that%20GATD3A%20deficiency%20induces%20fibroblast,that%20targeting%20GATD3A%20is%20a')
AnnotationURLCitation(end_index=27396, start_index=27304, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=,Google')
AnnotationURLCitation(end_index=27760, start_index=27597, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/39738099/#:~:text=that%20GATD3A%20deficiency%20induces%20fibroblast,that%20targeting%20GATD3A%20is%20a')
AnnotationURLCitation(end_index=28485, start_index=28297, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=Amidolysis%20domains%20of%20GATD3A%20and,arginine%29%2C%20which%20is%20reversed')
AnnotationURLCitation(end_index=28700, start_index=28486, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=of%20hydrolyzing%20glutamine%20and%20that,characterization%20of%20GATD3A%E2%80%99s%20catalytic%20activity')
AnnotationURLCitation(end_index=29042, start_index=28828, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=of%20hydrolyzing%20glutamine%20and%20that,characterization%20of%20GATD3A%E2%80%99s%20catalytic%20activity')
AnnotationURLCitation(end_index=29384, start_index=29282, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8935817/#:~:text=...S4A%29.%20,0.05')
AnnotationURLCitation(end_index=29822, start_index=29720, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8935817/#:~:text=...S4A%29.%20,0.05')
AnnotationURLCitation(end_index=30111, start_index=30009, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8935817/#:~:text=...S4A%29.%20,0.05')
AnnotationURLCitation(end_index=30627, start_index=30472, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=mitochondrial%20dysfunction%20in%20OA,decrease%20of%20GATD3A%20in%20OA')
AnnotationURLCitation(end_index=30794, start_index=30628, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=between%20GATD3A%20and%20senescent%20marker,synovium%20from%20controls%20and%20OA')
AnnotationURLCitation(end_index=31200, start_index=31034, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=between%20GATD3A%20and%20senescent%20marker,synovium%20from%20controls%20and%20OA')
AnnotationURLCitation(end_index=31812, start_index=31649, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/39738099/#:~:text=that%20GATD3A%20deficiency%20induces%20fibroblast,that%20targeting%20GATD3A%20is%20a')
AnnotationURLCitation(end_index=32107, start_index=31959, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=ShNC%20and%20ShGATD3A%2C%20n%E2%80%89%3D%E2%80%896%20Vec%2C,Gal')
AnnotationURLCitation(end_index=32459, start_index=32316, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=match%20at%20L304%20and%20GRP75%29,n%E2%80%89%3D%E2%80%895')
AnnotationURLCitation(end_index=32608, start_index=32460, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=ShNC%20and%20ShGATD3A%2C%20n%E2%80%89%3D%E2%80%896%20Vec%2C,Gal')
AnnotationURLCitation(end_index=33526, start_index=33312, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=of%20hydrolyzing%20glutamine%20and%20that,characterization%20of%20GATD3A%E2%80%99s%20catalytic%20activity')
AnnotationURLCitation(end_index=33690, start_index=33527, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/39738099/#:~:text=that%20GATD3A%20deficiency%20induces%20fibroblast,that%20targeting%20GATD3A%20is%20a')
AnnotationURLCitation(end_index=34102, start_index=33914, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=that%20GATD3A%20localizes%20to%20the,interacts%20with%20factors%20involved%20in')
AnnotationURLCitation(end_index=34317, start_index=34103, title='GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-022-01267-6#:~:text=of%20hydrolyzing%20glutamine%20and%20that,characterization%20of%20GATD3A%E2%80%99s%20catalytic%20activity')
AnnotationURLCitation(end_index=34516, start_index=34353, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/39738099/#:~:text=that%20GATD3A%20deficiency%20induces%20fibroblast,that%20targeting%20GATD3A%20is%20a')
AnnotationURLCitation(end_index=34668, start_index=34517, title='GATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11685659/#:~:text=In%20this%20study%2C%20we%20found,in%20FLS%20senescence%20and%20OA')
AnnotationURLCitation(end_index=34884, start_index=34731, title='GATD3 glutamine amidotransferase class 1 domain containing 3 [Homo sapiens (human)] - Gene - NCBI', type='url_citation', url='https://www.ncbi.nlm.nih.gov/gene?Cmd=DetailsSearch&Db=gene&Term=8209#:~:text=Summary%20This%20gene%20encodes%20a,provided%20by')