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Appears in Networks 4

In-Edges 30

deg(complex(a(MESH:Proteins), a(MESH:Ubiquitin))) increases a(MESH:Ubiquitin) View Subject | View Object

Following degradation of the substrate, short peptides are released along with free and reusable ubiquitin. PubMed:14556719

composite(a(CHEBI:ATP), p(HGNC:UBA1)) increases act(a(MESH:Ubiquitin)) View Subject | View Object

Initially, the ubiquitin-activating enzyme E1 activates ubiquitin in an ATP-requiring reaction to generate a high-energy thiol ester intermediate, E1-S~ubiquitin, where ubiquitin is bound to an internal E1 Cys residue PubMed:14556719

complex(a(CHEBI:ATP), p(HGNC:UBA1)) increases act(a(MESH:Ubiquitin)) View Subject | View Object

An E1 enzyme must first activate ubiquitin, a highly conserved, 76 amino acid polypeptide, in an ATP-dependent manner. PubMed:24457024

complex(a(CHEBI:ATP), p(HGNC:UBA1)) increases act(a(MESH:Ubiquitin)) View Subject | View Object

E1s are multidomain enzymes that must activate ubiquitin and efficiently transfer it to the E2 active site PubMed:24457024

a(GO:"Lewy body") association a(MESH:Ubiquitin) View Subject | View Object

We soon found that DF2 strongly stained cortical and brain stem Lewy bodies in brain sections from “diffuse Lewy body disease” (Kuzuhara et al. 1988), as originally described by Kenji Kosaka (1978), who proposed that some elderly subjects dying with dementia had many cortical Lewy bodies PubMed:22908190

a(GO:"Lewy body") association a(MESH:Ubiquitin) View Subject | View Object

The DF2 immunoreactivity of Lewy bodies led us to search for similar DF2-positive inclusions, and we found that Lewy-like bodies in motor neurons in amyotrophic lateral sclerosis (ALS; Murayama et al. 1990a) and Pick bodies in Pick’s disease (Murayama et al. 1990b) were strongly reactive; the latter stained also for tau, whereas the former stained neither for tau nor a-synuclein. PubMed:22908190

a(GO:"Pick body") association a(MESH:Ubiquitin) View Subject | View Object

The DF2 immunoreactivity of Lewy bodies led us to search for similar DF2-positive inclusions, and we found that Lewy-like bodies in motor neurons in amyotrophic lateral sclerosis (ALS; Murayama et al. 1990a) and Pick bodies in Pick’s disease (Murayama et al. 1990b) were strongly reactive; the latter stained also for tau, whereas the former stained neither for tau nor a-synuclein. PubMed:22908190

a(GO:"neurofibrillary tangle") association a(MESH:Ubiquitin) View Subject | View Object

In AD cortical sections, we observed that NFTs and dystrophic neurites (Fig. 1) and, unexpectedly, granulovacuolar changes (Fig. 1, inset) were intensely immunolabeled by the DF2 monoclonal. When mild fixation conditions were used, innumerable neuropil threads were also detected. PubMed:22908190

a(HBP:"dystrophic neurite") association a(MESH:Ubiquitin) View Subject | View Object

In AD cortical sections, we observed that NFTs and dystrophic neurites (Fig. 1) and, unexpectedly, granulovacuolar changes (Fig. 1, inset) were intensely immunolabeled by the DF2 monoclonal. When mild fixation conditions were used, innumerable neuropil threads were also detected. PubMed:22908190

a(HBP:"paired helical filaments") association a(MESH:Ubiquitin) View Subject | View Object

Besides the characteristic “PHF smear,” they also labeled a very small protein of ~8 kDa. Hiroshi Mori named these monoclonal antibodies DF (Dementia Filament) 1 and 2, of which the latter (DF2) was used for subsequent characterization (Mori et al. 1987). PubMed:22908190

a(MESH:"Neuropil Threads") association a(MESH:Ubiquitin) View Subject | View Object

In AD cortical sections, we observed that NFTs and dystrophic neurites (Fig. 1) and, unexpectedly, granulovacuolar changes (Fig. 1, inset) were intensely immunolabeled by the DF2 monoclonal. When mild fixation conditions were used, innumerable neuropil threads were also detected. PubMed:22908190

composite(a(CHEBI:ATP), p(HGNC:UBA1)) increases act(a(MESH:Ubiquitin)) View Subject | View Object

The first step is activation of the carboxyl terminus of Ub by an E1 protein (i.e., a Ub-activating enzyme), which consumes ATP. PubMed:22908190

path(HBP:"granulovacuolar degeneration") association a(MESH:Ubiquitin) View Subject | View Object

In AD cortical sections, we observed that NFTs and dystrophic neurites (Fig. 1) and, unexpectedly, granulovacuolar changes (Fig. 1, inset) were intensely immunolabeled by the DF2 monoclonal. When mild fixation conditions were used, innumerable neuropil threads were also detected. PubMed:22908190

path(HBP:"granulovacuolar degeneration") association a(MESH:Ubiquitin) View Subject | View Object

In addition, DF2 intensely labeled the classical granulovacuolar changes in the hippocampus in AD and other neurodegenerative disorders (Fig. 1, inset). PubMed:22908190

Out-Edges 17

a(MESH:Ubiquitin) regulates bp(GO:macroautophagy) View Subject | View Object

For instance, ubiquitin can recruit other factors to mediate various cellular responses such as signaling, gene regulation, endocytosis, macro-autophagy, and DNA repair PubMed:24457024

a(MESH:Ubiquitin) regulates bp(GO:"DNA repair") View Subject | View Object

For instance, ubiquitin can recruit other factors to mediate various cellular responses such as signaling, gene regulation, endocytosis, macro-autophagy, and DNA repair PubMed:24457024

act(a(MESH:Ubiquitin)) increases complex(a(MESH:Ubiquitin), p(HGNC:UBA1)) View Subject | View Object

Initially, the ubiquitin-activating enzyme E1 activates ubiquitin in an ATP-requiring reaction to generate a high-energy thiol ester intermediate, E1-S~ubiquitin, where ubiquitin is bound to an internal E1 Cys residue PubMed:14556719

a(MESH:Ubiquitin) regulates bp(GO:signaling) View Subject | View Object

For instance, ubiquitin can recruit other factors to mediate various cellular responses such as signaling, gene regulation, endocytosis, macro-autophagy, and DNA repair PubMed:24457024

a(MESH:Ubiquitin) regulates bp(GO:endocytosis) View Subject | View Object

For instance, ubiquitin can recruit other factors to mediate various cellular responses such as signaling, gene regulation, endocytosis, macro-autophagy, and DNA repair PubMed:24457024

act(a(MESH:Ubiquitin)) regulates bp(GO:"cellular homeostasis") View Subject | View Object

This function is crucial for cellular homeostasis because failure to activate ubiquitin, as seen by the chemical inhibition of E1 activity in the cell, results in the almost immediate shutdown of the entire UPS PubMed:24457024

a(MESH:Ubiquitin) association a(HBP:"paired helical filaments") View Subject | View Object

Besides the characteristic “PHF smear,” they also labeled a very small protein of ~8 kDa. Hiroshi Mori named these monoclonal antibodies DF (Dementia Filament) 1 and 2, of which the latter (DF2) was used for subsequent characterization (Mori et al. 1987). PubMed:22908190

a(MESH:Ubiquitin) association a(GO:"neurofibrillary tangle") View Subject | View Object

In AD cortical sections, we observed that NFTs and dystrophic neurites (Fig. 1) and, unexpectedly, granulovacuolar changes (Fig. 1, inset) were intensely immunolabeled by the DF2 monoclonal. When mild fixation conditions were used, innumerable neuropil threads were also detected. PubMed:22908190

a(MESH:Ubiquitin) association a(HBP:"dystrophic neurite") View Subject | View Object

In AD cortical sections, we observed that NFTs and dystrophic neurites (Fig. 1) and, unexpectedly, granulovacuolar changes (Fig. 1, inset) were intensely immunolabeled by the DF2 monoclonal. When mild fixation conditions were used, innumerable neuropil threads were also detected. PubMed:22908190

a(MESH:Ubiquitin) association path(HBP:"granulovacuolar degeneration") View Subject | View Object

In AD cortical sections, we observed that NFTs and dystrophic neurites (Fig. 1) and, unexpectedly, granulovacuolar changes (Fig. 1, inset) were intensely immunolabeled by the DF2 monoclonal. When mild fixation conditions were used, innumerable neuropil threads were also detected. PubMed:22908190

a(MESH:Ubiquitin) association path(HBP:"granulovacuolar degeneration") View Subject | View Object

In addition, DF2 intensely labeled the classical granulovacuolar changes in the hippocampus in AD and other neurodegenerative disorders (Fig. 1, inset). PubMed:22908190

a(MESH:Ubiquitin) association a(MESH:"Neuropil Threads") View Subject | View Object

In AD cortical sections, we observed that NFTs and dystrophic neurites (Fig. 1) and, unexpectedly, granulovacuolar changes (Fig. 1, inset) were intensely immunolabeled by the DF2 monoclonal. When mild fixation conditions were used, innumerable neuropil threads were also detected. PubMed:22908190

a(MESH:Ubiquitin) association a(GO:"Lewy body") View Subject | View Object

We soon found that DF2 strongly stained cortical and brain stem Lewy bodies in brain sections from “diffuse Lewy body disease” (Kuzuhara et al. 1988), as originally described by Kenji Kosaka (1978), who proposed that some elderly subjects dying with dementia had many cortical Lewy bodies PubMed:22908190

a(MESH:Ubiquitin) association a(GO:"Lewy body") View Subject | View Object

The DF2 immunoreactivity of Lewy bodies led us to search for similar DF2-positive inclusions, and we found that Lewy-like bodies in motor neurons in amyotrophic lateral sclerosis (ALS; Murayama et al. 1990a) and Pick bodies in Pick’s disease (Murayama et al. 1990b) were strongly reactive; the latter stained also for tau, whereas the former stained neither for tau nor a-synuclein. PubMed:22908190

a(MESH:Ubiquitin) association a(GO:"Pick body") View Subject | View Object

The DF2 immunoreactivity of Lewy bodies led us to search for similar DF2-positive inclusions, and we found that Lewy-like bodies in motor neurons in amyotrophic lateral sclerosis (ALS; Murayama et al. 1990a) and Pick bodies in Pick’s disease (Murayama et al. 1990b) were strongly reactive; the latter stained also for tau, whereas the former stained neither for tau nor a-synuclein. PubMed:22908190

act(a(MESH:Ubiquitin)) increases complex(a(MESH:Ubiquitin), p(HGNC:UBA2)) View Subject | View Object

Second, there is conjugation of the ATP-activated Ub to an E2 protein (i.e., a Ub-conjugating enzyme). PubMed:22908190

a(MESH:Ubiquitin) increases tloc(a(MESH:Proteins), fromLoc(GO:cytoplasm), toLoc(GO:"multivesicular body")) View Subject | View Object

Ubiquitin, the crucial signal for efficient sorting of proteins into the MVB (Babst et al. 1997), initiates this process, which is mediated by a group of ESCRT complexes (endosomal sorting complex required for transport; Hurley 2010). PubMed:22908190

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.