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a(MESH:Proteins)

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Entity

Name
Proteins
Namespace
MeSH
Namespace Version
20181007
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/01c9daa61012b37dd0a1bc962521ba51a15b38f1/external/mesh-names.belns

Appears in Networks 7

The Ubiquitin Proteasome System in Neurodegenerative Diseases: Sometimes the Chicken, Sometimes the Egg v1.0.0

Perilous journey: a tour of the ubiquitin–proteasome system v1.0.0

Interplay of pathogenic forms of human tau with different autophagic pathways v1.0.1

Molecular chaperones and regulation of tau quality control: strategies for drug discovery in tauopathies v1.0.0

Clearance of Amyloid Beta and Tau in Alzheimer’s Disease:from Mechanisms to Therapy v1.0.1

The Ubiquitin–Proteasome System and the Autophagic–Lysosomal System in Alzheimer Disease v1.0.0

Autophagy and the ubiquitin-proteasome system: collaborators in neuroprotection v1.0.0

In-Edges 40

complex(a(MESH:"Molecular Chaperones"), a(MESH:Proteins)) hasComponent a(MESH:Proteins) View Subject | View Object

Appears in Networks:

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

Appears in Networks:

complex(a(MESH:Proteins), a(MESH:Ubiquitin), p(HGNC:UBA3)) hasComponent a(MESH:Proteins) View Subject | View Object

Appears in Networks:

a(CHEBI:ATP) increases tloc(a(MESH:Proteins), fromLoc(GO:cytosol), toLoc(HBP:"20 S Proteasome")) View Subject | View Object

Another key early finding was that the cleavage of the ubiquitin chain from the substrate was ATP-dependent and was coupled to the translocation of the protein substrate into the 20S core PubMed:24457024

Appears in Networks:

complex(a(GO:"proteasome complex"), a(MESH:Proteins)) hasComponent a(MESH:Proteins) View Subject | View Object

Appears in Networks:

complex(a(GO:"proteasome complex"), a(MESH:Proteins)) increases tloc(a(MESH:Proteins), fromLoc(GO:cytosol), toLoc(HBP:"20 S Proteasome")) View Subject | View Object

Thus, the binding of substrate to the 26S and its concomitant translocation into the 20S results in the activation of Rpn11 through a conformational change. PubMed:24457024

Appears in Networks:

complex(a(MESH:Proteins), a(MESH:Ubiquitin), p(HGNC:UBA2), p(HGNC:UBA3)) hasComponent a(MESH:Proteins) View Subject | View Object

Appears in Networks:

act(p(HGNC:PSMD14)) increases tloc(a(MESH:Proteins), fromLoc(GO:cytosol), toLoc(HBP:"20 S Proteasome")) View Subject | View Object

This activity promotes both the recycling of chains back into the free cellular pool of ubiquitin and creates space for the protein substrate to enter the 20S core. PubMed:24457024

Appears in Networks:

bp(GO:macroautophagy) increases deg(a(MESH:Proteins)) View Subject | View Object

In fact, increased macroautophagy may be responsible for the increase in the degradation of long-lived proteins that we observed for both mutant forms of tau under these conditions (Fig. 3b) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Multivesicular Bodies
Confidence
High
MeSH
Brain

p(MGI:Mapt, var("p.Ala152Thr")) increases deg(a(MESH:Proteins)) View Subject | View Object

Cells expressing tau-A152T displayed significantly higher rates of intracellular protein degradation than the other cells under basal conditions (Fig. 3a) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Intracellular Space
Confidence
High
MeSH
Brain

p(MGI:Mapt, var("p.Ala152Thr")) increases deg(a(MESH:Proteins)) View Subject | View Object

A similar significant increase in protein degradation was observed in response to serum removal in cells expressing either of the mutants (Fig. 3b) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Intracellular Space
Confidence
Low
MeSH
Brain

p(MGI:Mapt, var("p.Ala152Thr")) increases deg(a(MESH:Proteins)) View Subject | View Object

In fact, increased macroautophagy may be responsible for the increase in the degradation of long-lived proteins that we observed for both mutant forms of tau under these conditions (Fig. 3b) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Multivesicular Bodies
Confidence
High
MeSH
Brain

p(MGI:Mapt, var("p.Pro301Leu")) increases deg(a(MESH:Proteins)) View Subject | View Object

A similar significant increase in protein degradation was observed in response to serum removal in cells expressing either of the mutants (Fig. 3b) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Intracellular Space
Confidence
Low
MeSH
Brain

p(MGI:Mapt, var("p.Pro301Leu")) increases deg(a(MESH:Proteins)) View Subject | View Object

In fact, increased macroautophagy may be responsible for the increase in the degradation of long-lived proteins that we observed for both mutant forms of tau under these conditions (Fig. 3b) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Multivesicular Bodies
Confidence
High
MeSH
Brain

bp(HBP:Proteostasis) regulates a(MESH:Proteins) View Subject | View Object

All proteins, including tau, are subject to extensive regulation by the cellular quality control pathways, which carefully control the balance between protein expression and turnover to maintain healthy protein homeostasis (or proteostasis) PubMed:21882945

Appears in Networks:

complex(a(MESH:Proteins), p(FPLX:HSP90)) hasComponent a(MESH:Proteins) View Subject | View Object

Appears in Networks:

complex(a(MESH:Proteins), p(FPLX:HSP90)) increases deg(a(MESH:Proteins)) View Subject | View Object

Moreover, these compounds were found to prolong binding of Hsp90 to a model substrate, which was sufficient to promote its degradation [142] PubMed:21882945

Appears in Networks:

complex(a(MESH:Proteins), p(HGNC:STUB1), p(INTERPRO:"Heat shock protein 70 family")) hasComponent a(MESH:Proteins) View Subject | View Object

Appears in Networks:

complex(a(MESH:Proteins), p(INTERPRO:"Heat shock protein 70 family")) hasComponent a(MESH:Proteins) View Subject | View Object

Appears in Networks:

a(MESH:"Tight Junctions") decreases tloc(a(MESH:Proteins), fromLoc(MESH:Brain), toLoc(MESH:Blood)) View Subject | View Object

However, some proteins fail to be transported out of the brain through intercellular tight junctions, and can only be transported into blood by transporters expressed in the capillary endothelium PubMed:29626319

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a(MESH:"Ubiquitin-Protein Ligases") increases deg(a(MESH:Proteins)) View Subject | View Object

Under physiological conditions, UPS, located in the cytosol and the nucleus in eukaryotic cells, as a major intracellular short-lived protein degradation system (Schwartz and Ciechanover 2009), mediates the clearance of misfolded or other abnormally modified proteins with the help of ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), ubiquitin ligase (E3), and the 26S proteasome for the sake of preventing the accumulation of toxic substances (Shang and Taylor 2011) PubMed:29626319

Appears in Networks:
Annotations
MeSH
Cell Nucleus
MeSH
Cytosol

bp(GO:"proteasome-mediated ubiquitin-dependent protein catabolic process") regulates deg(a(MESH:Proteins)) View Subject | View Object

Under physiological conditions, UPS, located in the cytosol and the nucleus in eukaryotic cells, as a major intracellular short-lived protein degradation system (Schwartz and Ciechanover 2009), mediates the clearance of misfolded or other abnormally modified proteins with the help of ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), ubiquitin ligase (E3), and the 26S proteasome for the sake of preventing the accumulation of toxic substances (Shang and Taylor 2011) PubMed:29626319

Appears in Networks:
Annotations
MeSH
Cell Nucleus
MeSH
Cytosol

p(FPLX:UBE2) increases deg(a(MESH:Proteins)) View Subject | View Object

Under physiological conditions, UPS, located in the cytosol and the nucleus in eukaryotic cells, as a major intracellular short-lived protein degradation system (Schwartz and Ciechanover 2009), mediates the clearance of misfolded or other abnormally modified proteins with the help of ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), ubiquitin ligase (E3), and the 26S proteasome for the sake of preventing the accumulation of toxic substances (Shang and Taylor 2011) PubMed:29626319

Appears in Networks:
Annotations
MeSH
Cell Nucleus
MeSH
Cytosol

p(HGNC:PSMD7) increases deg(a(MESH:Proteins)) View Subject | View Object

Under physiological conditions, UPS, located in the cytosol and the nucleus in eukaryotic cells, as a major intracellular short-lived protein degradation system (Schwartz and Ciechanover 2009), mediates the clearance of misfolded or other abnormally modified proteins with the help of ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), ubiquitin ligase (E3), and the 26S proteasome for the sake of preventing the accumulation of toxic substances (Shang and Taylor 2011) PubMed:29626319

Appears in Networks:
Annotations
MeSH
Cell Nucleus
MeSH
Cytosol

p(HGNC:UBA1) increases deg(a(MESH:Proteins)) View Subject | View Object

Under physiological conditions, UPS, located in the cytosol and the nucleus in eukaryotic cells, as a major intracellular short-lived protein degradation system (Schwartz and Ciechanover 2009), mediates the clearance of misfolded or other abnormally modified proteins with the help of ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), ubiquitin ligase (E3), and the 26S proteasome for the sake of preventing the accumulation of toxic substances (Shang and Taylor 2011) PubMed:29626319

Appears in Networks:
Annotations
MeSH
Cell Nucleus
MeSH
Cytosol

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

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") increases tloc(a(MESH:Proteins), fromLoc(GO:cytosol), toLoc(GO:"lysosomal lumen")) View Subject | View Object

In CMA, cytosolic proteins containing a KFERQ motif (including proteins pathogenic in some neurodegenerative diseases) are selectively targeted by certain chaperones to the lysosomal lumen for degradation (Arias et al. 2011). PubMed:22908190

Appears in Networks:

bp(GO:"proteasomal protein catabolic process") decreases a(MESH:Proteins) View Subject | View Object

Interdependence of the proteasome and lysosomal system is also suggested by observations that, when proteasome activity is inhibited, proteins accumulate that become substrates for autophagy (Fortun et al. 2003) PubMed:22908190

Appears in Networks:

bp(GO:endocytosis) positiveCorrelation a(MESH:Proteins) View Subject | View Object

Accelerated endocytosis also increases protein and lipid accumulation in endosomes and slows lysosomal degradation of endocytic cargoes (Cataldo et al. 2008), leading to lysosomal instability and neurodegeneration, as discussed below. PubMed:22908190

Appears in Networks:
Annotations
MeSH
Endosomes

complex(GO:"ESCRT complex") regulates 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

Appears in Networks:

complex(a(GO:"late endosome"), a(GO:autophagosome), a(GO:lysosome)) increases deg(a(MESH:Proteins)) View Subject | View Object

Sequestered material within autophagosomes is digested when lysosomes or late endosomes fuse with the outer membrane of the autophagosome (Gordon et al. 1988). PubMed:22908190

Appears in Networks:

complex(a(GO:"proteasome regulatory particle"), p(MESH:Proteins, pmod(Ub))) increases tloc(a(MESH:Proteins), fromLoc(GO:"proteasome regulatory particle"), toLoc(HBP:"20 S Proteasome")) View Subject | View Object

Ubiquitinated target proteins bind to the 19S cap (RP), which has a Ub binding site and ATPase activity, and this leads to cleavage of Ub moieties from the target by deubiquitinating enzymes, unfolds the polypeptides and sends them to the narrow channel of the 20S core particle. PubMed:22908190

Appears in Networks:

act(p(HGNC:RAB5A)) positiveCorrelation a(MESH:Proteins) View Subject | View Object

It is this abnormal rab5 activation that causes protein and lipid accumulation in endosomes, slowed lysosomal degradation of endocytic cargoes,endosome swelling (Cataldo et al. 2008), and disrupted retrograde transport of endosomes (S Kim and RA Nixon, unpubl.). PubMed:22908190

Appears in Networks:

tloc(a(MESH:Proteins), fromLoc(GO:intracellular), toLoc(GO:lysosome)) increases deg(a(MESH:Proteins)) View Subject | View Object

The substrate-chaperone complex is then targeted to the lysosome by binding to lysosome-associated membrane protein 2A (LAMP-2A) which carries out receptor-mediated translocation of the substrate into the lysosome for degradation [11,13] PubMed:18930136

Appears in Networks:

bp(GO:"chaperone-mediated autophagy") increases tloc(a(MESH:Proteins), fromLoc(GO:cytoplasm), toLoc(GO:"lysosomal lumen")) View Subject | View Object

Microautophagy consists of direct engulfment of small volumes of cytosol by lysosomes [10], whereas chaperone-mediated autophagy (CMA) involves selective, receptor-mediated translocation of proteins into the lysosomal lumen [11]. PubMed:18930136

Appears in Networks:

bp(GO:autophagy) increases tloc(a(MESH:Proteins), fromLoc(GO:cytoplasm), toLoc(GO:lysosome)) View Subject | View Object

“Autophagy”, literally “self-eating”, describes a catabolic process in which cell constituents such as organelles and proteins are delivered to the lysosomal compartment for degradation. PubMed:18930136

Appears in Networks:

bp(GO:autophagy) increases deg(a(MESH:Proteins)) View Subject | View Object

“Autophagy”, literally “self-eating”, describes a catabolic process in which cell constituents such as organelles and proteins are delivered to the lysosomal compartment for degradation. PubMed:18930136

Appears in Networks:
Annotations
MeSH
Lysosomes

complex(a(MESH:Proteins), p(HGNC:HSPA8)) hasComponent a(MESH:Proteins) View Subject | View Object

Appears in Networks:

p(HGNC:LAMP2) increases tloc(a(MESH:Proteins), fromLoc(GO:intracellular), toLoc(GO:lysosome)) View Subject | View Object

The substrate-chaperone complex is then targeted to the lysosome by binding to lysosome-associated membrane protein 2A (LAMP-2A) which carries out receptor-mediated translocation of the substrate into the lysosome for degradation [11,13] PubMed:18930136

Appears in Networks:

rxn(reactants(a(MESH:Proteins)), products(a(CHEBI:oligopeptide))) hasReactant a(MESH:Proteins) View Subject | View Object

Appears in Networks:

Out-Edges 4

tloc(a(MESH:Proteins), fromLoc(GO:cytosol), toLoc(HBP:"20 S Proteasome")) increases act(p(HGNC:PSMD14)) View Subject | View Object

Thus, the binding of substrate to the 26S and its concomitant translocation into the 20S results in the activation of Rpn11 through a conformational change. PubMed:24457024

Appears in Networks:

a(MESH:Proteins) positiveCorrelation act(p(HGNC:RAB5A)) View Subject | View Object

It is this abnormal rab5 activation that causes protein and lipid accumulation in endosomes, slowed lysosomal degradation of endocytic cargoes,endosome swelling (Cataldo et al. 2008), and disrupted retrograde transport of endosomes (S Kim and RA Nixon, unpubl.). PubMed:22908190

Appears in Networks:

a(MESH:Proteins) positiveCorrelation bp(GO:endocytosis) View Subject | View Object

Accelerated endocytosis also increases protein and lipid accumulation in endosomes and slows lysosomal degradation of endocytic cargoes (Cataldo et al. 2008), leading to lysosomal instability and neurodegeneration, as discussed below. PubMed:22908190

Appears in Networks:
Annotations
MeSH
Endosomes

tloc(a(MESH:Proteins), fromLoc(GO:intracellular), toLoc(GO:lysosome)) increases deg(a(MESH:Proteins)) View Subject | View Object

The substrate-chaperone complex is then targeted to the lysosome by binding to lysosome-associated membrane protein 2A (LAMP-2A) which carries out receptor-mediated translocation of the substrate into the lysosome for degradation [11,13] PubMed:18930136

Appears in Networks:

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BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

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.