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p(HGNC:HSPA8)

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Entity

Name
HSPA8
Namespace
hgnc
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

Appears in Networks 11

A chaperome subnetwork safeguards proteostasis in aging and neurodegenerative disease. v1.0.0

A Quantitative Chaperone Interaction Network Reveals the Architecture of Cellular Protein Homeostasis Pathways v1.0.0

Tau degradation: the ubiquitin-proteasome system versus the autophagy-lysosome system. v1.0.0

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

Extracellular Tau and Its Potential Role in the Propagation of Tau Pathology v1.0.0

TAU and Interaction Partners v1.2.5

TAU Interactions Section of NESTOR

Alzheimer’s disease and the autophagic-lysosomal system v1.0.0

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

Protein aggregation can inhibit clathrin-mediated endocytosis by chaperone competition v1.0.0

Carboxy terminus heat shock protein 70 interacting protein reduces tau-associated degenerative changes v1.0.0

In-Edges 25

complex(p(HGNC:BAG1), p(HGNC:HSPA8)) hasComponent p(HGNC:HSPA8) View Subject | View Object

Appears in Networks:

bp(MESH:Aging) decreases p(HGNC:HSPA8) View Subject | View Object

Four genes that are significantly repressed both in AD and HD (HSP90AB1, HSPA8, HSPA14, and TCP1) are also repressed in aging (Figure 6B). PubMed:25437566

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

path(MESH:"Alzheimer Disease") decreases p(HGNC:HSPA8) View Subject | View Object

Four genes that are significantly repressed both in AD and HD (HSP90AB1, HSPA8, HSPA14, and TCP1) are also repressed in aging (Figure 6B). PubMed:25437566

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

path(MESH:"Huntington Disease") decreases p(HGNC:HSPA8) View Subject | View Object

Four genes that are significantly repressed both in AD and HD (HSP90AB1, HSPA8, HSPA14, and TCP1) are also repressed in aging (Figure 6B). PubMed:25437566

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

complex(p(HGNC:HSPA8), p(INTERPRO:"Chaperone DnaJ")) hasComponent p(HGNC:HSPA8) View Subject | View Object

Appears in Networks:

complex(p(HGNC:AR), p(HGNC:HSPA8)) hasComponent p(HGNC:HSPA8) View Subject | View Object

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complex(p(HGNC:BAG2), p(HGNC:HSPA8), p(HGNC:STUB1), p(INTERPRO:"Heat shock protein 70 family")) hasComponent p(HGNC:HSPA8) View Subject | View Object

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complex(p(HGNC:BAG3), p(HGNC:HSPA8)) hasComponent p(HGNC:HSPA8) View Subject | View Object

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complex(p(HGNC:BAG4), p(HGNC:HSPA8)) hasComponent p(HGNC:HSPA8) View Subject | View Object

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complex(p(HGNC:BAG5), p(HGNC:HSPA8)) hasComponent p(HGNC:HSPA8) View Subject | View Object

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complex(p(HGNC:FKBP4), p(HGNC:HSPA8)) hasComponent p(HGNC:HSPA8) View Subject | View Object

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complex(p(HGNC:FKBP5), p(HGNC:HSPA8)) hasComponent p(HGNC:HSPA8) View Subject | View Object

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complex(p(HGNC:HSPA8), p(HGNC:SIRT6)) hasComponent p(HGNC:HSPA8) View Subject | View Object

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complex(p(HGNC:HSPA8), p(HGNC:SUGT1)) hasComponent p(HGNC:HSPA8) View Subject | View Object

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complex(p(HGNC:HSPA8), p(INTERPRO:"BAG domain superfamily")) hasComponent p(HGNC:HSPA8) View Subject | View Object

Appears in Networks:

complex(p(HGNC:HSPA8), p(HGNC:STUB1)) hasComponent p(HGNC:HSPA8) View Subject | View Object

Appears in Networks:

composite(p(HGNC:HSPA8), p(HGNC:STUB1), p(HGNC:UBE2D2)) hasComponent p(HGNC:HSPA8) View Subject | View Object

Appears in Networks:

act(complex(GO:microtubule)) negativeCorrelation act(p(HGNC:HSPA8)) View Subject | View Object

The location of the hsc70-binding site in the tau MTBR suggests that hsc70 cannot bind microtubule-associated tau. The location of the hsc70-binding site also suggests that hsc70 might compete with tubulin or microtubules for binding to tau. Our data implicating I308/V309 in tau’s binding to hsp70 similarly suggest that tau cannot bind simultaneously to hsp70 and microtubules. However, unlike hsc70, which does not associate directly with tubulin or microtubules (Gache et al. 2005), hsp70 binds microtubules, presumably through its N-terminus (Sanchez et al. 1994). This would allow hsp70 to simultaneously bind to tau through its C-terminal substrate-binding domain and to microtubules through its N-terminus. PubMed:18500754

Appears in Networks:

p(HBP:"microtubule-binding region") association p(HGNC:HSPA8) View Subject | View Object

The location of the hsc70-binding site in the tau MTBR suggests that hsc70 cannot bind microtubule-associated tau. The location of the hsc70-binding site also suggests that hsc70 might compete with tubulin or microtubules for binding to tau. Our data implicating I308/V309 in tau’s binding to hsp70 similarly suggest that tau cannot bind simultaneously to hsp70 and microtubules. However, unlike hsc70, which does not associate directly with tubulin or microtubules (Gache et al. 2005), hsp70 binds microtubules, presumably through its N-terminus (Sanchez et al. 1994). This would allow hsp70 to simultaneously bind to tau through its C-terminal substrate-binding domain and to microtubules through its N-terminus. PubMed:18500754

Appears in Networks:

composite(p(HGNC:HSPA8), p(HGNC:LAMP2)) hasComponent p(HGNC:HSPA8) View Subject | View Object

Appears in Networks:

complex(p(HGNC:HSPA8), p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)), p(HGNC:STUB1)) hasComponent p(HGNC:HSPA8) View Subject | View Object

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

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complex(a(HBP:"protein aggregates"), p(HGNC:HSPA8)) hasComponent p(HGNC:HSPA8) View Subject | View Object

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path(MESH:"Protein Aggregation, Pathological") decreases act(p(HGNC:HSPA8)) View Subject | View Object

Here, we show that diverse disease-associated aggregates se- quester the highly abundant major chaperone heat shock cognate protein 70 (HSC70) to the point of functional collapse of an essential cellular process, clathrin-mediated endocytosis (CME). PubMed:24706768

Appears in Networks:

complex(p(HGNC:HSPA8), p(HGNC:MAPT, pmod(Ub)), p(HGNC:STUB1)) hasComponent p(HGNC:HSPA8) View Subject | View Object

Appears in Networks:

Out-Edges 13

p(HGNC:HSPA8) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

This functional screen identified 18 genes (Figure 3D), corresponding to ten ATP-dependent chaperones, HSC70 (hsp-1), HSP90 (daf-21), and eight subunits of the CCT/TRiC chaperonin complex; the co-chaperones, HSP40 (dnj-12) and CDC37 (cdc-37); and the TPR-domain pro- tein STI1 that upon knockdown significantly enhanced A b 42 pro- teotoxicity (Figure 3D). PubMed:25437566

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

p(HGNC:HSPA8) increases bp(GO:"protein folding") View Subject | View Object

Knockdown of daf-21 (HSP90) or hsp-1 (HSC70) led to increased paralysis in 45% and 44% of day 6 animals, respectively, and knockdown of TPR co-chaper- ones tpr-1 and dnj-12 resulted in 70% impairment (Figure S4D). PubMed:25437566

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

p(HGNC:HSPA8) increases a(HBP:"huntingtin aggregates") View Subject | View Object

These included all subunits of the CCT/TRiC complex (except CCT5); HSP40 and HSP70 family members DNAJA1 (HDJ-2), DNAJA4, HSPA8 (HSC70), and HSPA14 (Figures 5B and 5C); and the TPR-domain APC/C subunits CDC23 and CDC27 that, upon knockdown, led to significantly elevated aggregation (Figure S5B). PubMed:25437566

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease
MeSH
Huntington Disease
MeSH
Parkinson Disease

p(HGNC:HSPA8) regulates complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

In addition, recent work has demonstrated that Hsc70, the constitutive cytosolic form of Hsp70s, also dynamically regulates the association of tau with microtubules PubMed:21882945

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act(p(HGNC:HSPA8)) increases deg(p(HGNC:MAPT)) View Subject | View Object

In fact, recent work from our group has shown that inhibition of the ATPase activity of Hsp70/Hsc70 promotes proteasomal degradation of tau; whereas activation results in tau accumulation [117] PubMed:21882945

Appears in Networks:

p(HGNC:HSPA8) association p(HBP:"microtubule-binding region") View Subject | View Object

The location of the hsc70-binding site in the tau MTBR suggests that hsc70 cannot bind microtubule-associated tau. The location of the hsc70-binding site also suggests that hsc70 might compete with tubulin or microtubules for binding to tau. Our data implicating I308/V309 in tau’s binding to hsp70 similarly suggest that tau cannot bind simultaneously to hsp70 and microtubules. However, unlike hsc70, which does not associate directly with tubulin or microtubules (Gache et al. 2005), hsp70 binds microtubules, presumably through its N-terminus (Sanchez et al. 1994). This would allow hsp70 to simultaneously bind to tau through its C-terminal substrate-binding domain and to microtubules through its N-terminus. PubMed:18500754

Appears in Networks:

act(p(HGNC:HSPA8)) negativeCorrelation act(complex(GO:microtubule)) View Subject | View Object

The location of the hsc70-binding site in the tau MTBR suggests that hsc70 cannot bind microtubule-associated tau. The location of the hsc70-binding site also suggests that hsc70 might compete with tubulin or microtubules for binding to tau. Our data implicating I308/V309 in tau’s binding to hsp70 similarly suggest that tau cannot bind simultaneously to hsp70 and microtubules. However, unlike hsc70, which does not associate directly with tubulin or microtubules (Gache et al. 2005), hsp70 binds microtubules, presumably through its N-terminus (Sanchez et al. 1994). This would allow hsp70 to simultaneously bind to tau through its C-terminal substrate-binding domain and to microtubules through its N-terminus. PubMed:18500754

Appears in Networks:

p(HGNC:HSPA8) increases deg(p(HGNC:MAPT)) View Subject | View Object

Evidence suggests that CMA can degrade tau via the chaperone heat shock cognate of 70 kDa (Hsc70), which recognizes KFERQ-like motifs and transfers its substrates via LAMP-2 into the lysosome [47] PubMed:29758300

Appears in Networks:

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

CMA is a process in which proteins harboring a pentapeptide motif related to the sequence KFERQ are specifically recognized by a cytosolic chaperone, the heat shock cognate protein of 70 kDa (hsc70). PubMed:18930136

Appears in Networks:

p(HGNC:HSPA8) increases complex(a(MESH:Proteins), p(HGNC:HSPA8)) 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

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p(HGNC:HSPA8) increases bp(GO:"clathrin-dependent endocytosis") View Subject | View Object

Importantly, aggregate-driven CME inhibition is reversible and can be rescued by nominally increasing HSC70 levels. PubMed:24706768

Appears in Networks:

p(HGNC:HSPA8) increases bp(GO:"clathrin-dependent endocytosis") View Subject | View Object

Although internalized transferrin levels remained un- changed in cells with near-normal amounts of HSC70, cells with over a 50% reduction in HSC70 expression had significant CME inhibition (compare Fig. 2 E and D ), with a 51 ± 17% decrease in internalized transferrin fluorescence compared with nondepleted cells. PubMed:24706768

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p(HGNC:HSPA8) increases bp(GO:"clathrin coat disassembly") View Subject | View Object

. Be- yond maintaining the general solubility of the CME machinery, HSC70 is specifically required for both the disassembly of the clathrin coat from endocytosed vesicles (20, 29 – 31) and in the recycling of coat components back to the plasma membrane. PubMed:24706768

Appears in Networks:

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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.