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p(HGNC:MAPT, var("p.Ala152Thr"))

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Entity

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

Appears in Networks 5

MMP-9 and MMP-2 Contribute to Neuronal Cell Death in iPSC Models of Frontotemporal Dementia with MAPT Mutations v1.0.0

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

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

Caenorhabditis elegans models of tauopathy v1.0.0

Tau in physiology and pathology v1.0.0

In-Edges 7

composite(a(CHEBI:rotenone), p(HGNC:MAPT, var("p.Ala152Thr"))) hasComponent p(HGNC:MAPT, var("p.Ala152Thr")) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT) hasVariant p(HGNC:MAPT, var("p.Ala152Thr")) View Subject | View Object

Appears in Networks:

composite(a(CHEBI:sirolimus), p(HGNC:MAPT, var("p.Ala152Thr"))) hasComponent p(HGNC:MAPT, var("p.Ala152Thr")) View Subject | View Object

Appears in Networks:

composite(a(CHEBI:staurosporine), p(HGNC:MAPT, var("p.Ala152Thr"))) hasComponent p(HGNC:MAPT, var("p.Ala152Thr")) View Subject | View Object

Appears in Networks:

p(HGNC:MAPT, pmod(Ph)) positiveCorrelation p(HGNC:MAPT, var("p.Ala152Thr")) View Subject | View Object

For example, in tau A152T iPSC-derived cortical neurons, total and phosphorylated Tau levels are elevated, particularly the insoluble forms [133], which is associated with decreases in UPS function as measured by total polyubiquitinated proteins and an upregulation of macroautophagy markers. PubMed:29758300

Appears in Networks:

path(MESH:"Supranuclear Palsy, Progressive") association p(HGNC:MAPT, var("p.Ala152Thr")) View Subject | View Object

Another MAPT polymorphism (A152T) was recently identified in patients diagnosed with progressive supranuclear palsy (PSP) (72–74). PubMed:29191965

Appears in Networks:

path(MESH:"Supranuclear Palsy, Progressive") positiveCorrelation p(HGNC:MAPT, var("p.Ala152Thr")) View Subject | View Object

Interestingly, the PSP-associated tau mutation A152T is localized far away from the repeat domain but still decreases the binding of tau to microtubules and therefore promotes microtubule assembly less efficiently PubMed:26631930

Appears in Networks:

Out-Edges 33

p(HGNC:MAPT, var("p.Ala152Thr")) increases p(HGNC:MAP2) View Subject | View Object

Four weeks after terminal differentiation, 80% of cells were positive for the neuron-specific marker MAP2, and there was no significant difference between control and patient neurons (Figure S2A) PubMed:27594586

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) causesNoChange a(GO:"symmetric, GABA-ergic, inhibitory synapse") View Subject | View Object

The percentages of VGLUT1-positive excitatory and GABA-positive inhibitory neurons were similar in neuronal cultures differentiated from control and patient iPSCs (Figures S2B and S2C) PubMed:27594586

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) causesNoChange p(HGNC:SLC17A7) View Subject | View Object

The percentages of VGLUT1-positive excitatory and GABA-positive inhibitory neurons were similar in neuronal cultures differentiated from control and patient iPSCs (Figures S2B and S2C) PubMed:27594586

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) causesNoChange p(HGNC:MAPT) View Subject | View Object

Moreover, the total expression levels of tau and PSD-95 were the same in 1-month-old neurons derived from control and patient iPSCs (Figure 1B) PubMed:27594586

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) causesNoChange p(HGNC:DLGAP4) View Subject | View Object

Moreover, the total expression levels of tau and PSD-95 were the same in 1-month-old neurons derived from control and patient iPSCs (Figure 1B) PubMed:27594586

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) causesNoChange bp(MESH:"Membrane Potentials") View Subject | View Object

The resting membrane potential did not differ among neurons differentiated from all iPSC lines (Figure S2D) PubMed:27594586

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) causesNoChange bp(GO:"neuron differentiation") View Subject | View Object

Thus, both molecular and electrophysiological analyses suggest MAPT mutations do not affect early neuronal differentiation PubMed:27594586

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) increases act(p(HGNC:MMP9)) View Subject | View Object

Tau-A152T neurons had >10-fold higher level and activity of secreted MMP-9 than control neurons (Figures 2A and 2B), as did MAPT IVS10+16 neurons to a lesser extent (Figures 2C and 2D) PubMed:27594586

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) increases sec(p(HGNC:MMP9)) View Subject | View Object

Tau-A152T neurons had >10-fold higher level and activity of secreted MMP-9 than control neurons (Figures 2A and 2B), as did MAPT IVS10+16 neurons to a lesser extent (Figures 2C and 2D) PubMed:27594586

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) increases sec(p(HGNC:MMP9)) View Subject | View Object

The level of secreted MMP-9 and MMP-2 was also increased in cortical neurons derived from a published iPSC line with the tau-A152T mutation (Fong et al., 2013) (Figures 2E and 2F) PubMed:27594586

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) increases act(p(HGNC:MMP9)) View Subject | View Object

It is worth noting that the level and activity of secreted MMP-9 in tau- A152T neurons is also substantially higher than that in MAPT IVS10+16 neurons (Figure 2) PubMed:27594586

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) increases sec(p(HGNC:MMP9)) View Subject | View Object

It is worth noting that the level and activity of secreted MMP-9 in tau- A152T neurons is also substantially higher than that in MAPT IVS10+16 neurons (Figure 2) PubMed:27594586

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) increases sec(p(HGNC:MMP2)) View Subject | View Object

The level of secreted MMP-9 and MMP-2 was also increased in cortical neurons derived from a published iPSC line with the tau-A152T mutation (Fong et al., 2013) (Figures 2E and 2F) PubMed:27594586

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) increases act(p(HGNC:MMP2)) View Subject | View Object

It is worth noting that the level and activity of secreted MMP-9 in tau- A152T neurons is also substantially higher than that in MAPT IVS10+16 neurons (Figure 2) PubMed:27594586

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) increases sec(p(HGNC:MMP2)) View Subject | View Object

It is worth noting that the level and activity of secreted MMP-9 in tau- A152T neurons is also substantially higher than that in MAPT IVS10+16 neurons (Figure 2) PubMed:27594586

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) increases r(HGNC:MMP9) View Subject | View Object

This increase is likely in part due to transcriptional regulation, since the mRNA levels of MMP-9 and MMP-2 in tau-A152T and MAPT IVS10+16 neurons were higher than in control neurons (Figure S2J) PubMed:27594586

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) increases r(HGNC:MMP9) View Subject | View Object

MMP-9/MMP-2 mRNA levels in tau-A152T and MAPT IVS10+16 neurons were significantly higher than that in control neurons (Figure S2J), and rapamycin increased these levels (p < 0.01) (Figure 3C) PubMed:27594586

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) increases r(HGNC:MMP2) View Subject | View Object

This increase is likely in part due to transcriptional regulation, since the mRNA levels of MMP-9 and MMP-2 in tau-A152T and MAPT IVS10+16 neurons were higher than in control neurons (Figure S2J) PubMed:27594586

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) increases r(HGNC:MMP2) View Subject | View Object

MMP-9/MMP-2 mRNA levels in tau-A152T and MAPT IVS10+16 neurons were significantly higher than that in control neurons (Figure S2J), and rapamycin increased these levels (p < 0.01) (Figure 3C) PubMed:27594586

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) increases bp(GO:"neuron death") View Subject | View Object

We found that, indeed, TUJ1+ neurons showed reduced survival as measured by TUNEL analysis (Figure 3A) PubMed:27594586

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) increases p(FPLX:ERK, pmod(Ph)) View Subject | View Object

The level of phosphorylated ERK (p-ERK) was significantly increased in tau-A152T neurons and to a lesser extent in MAPT IVS10+16 patient neurons (Figure 4A) PubMed:27594586

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) increases a(HBP:HBP00045) View Subject | View Object

Interestingly, this ratio is also increased, but to a lesser extent, in tau-A152T neurons (Figure S3F) PubMed:27594586

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) decreases a(HBP:HBP00044) View Subject | View Object

Interestingly, this ratio is also increased, but to a lesser extent, in tau-A152T neurons (Figure S3F) PubMed:27594586

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) decreases deg(p(MGI:Mapt)) View Subject | View Object

Tau-A152T displayed very similar degradation dynamics, although this mutation slightly reduced tau’s rates of lysosomal degradation (20% inhibition) when compared with WT tau (Fig. 1a,b). PubMed:29024336

Appears in Networks:
Annotations
MeSH
Lysosomes
Confidence
High
MeSH
Brain

p(HGNC:MAPT, var("p.Ala152Thr")) positiveCorrelation p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

For example, in tau A152T iPSC-derived cortical neurons, total and phosphorylated Tau levels are elevated, particularly the insoluble forms [133], which is associated with decreases in UPS function as measured by total polyubiquitinated proteins and an upregulation of macroautophagy markers. PubMed:29758300

Appears in Networks:

p(HGNC:MAPT, var("p.Ala152Thr")) decreases bp(GO:"proteasome-mediated ubiquitin-dependent protein catabolic process") View Subject | View Object

For example, in tau A152T iPSC-derived cortical neurons, total and phosphorylated Tau levels are elevated, particularly the insoluble forms [133], which is associated with decreases in UPS function as measured by total polyubiquitinated proteins and an upregulation of macroautophagy markers. PubMed:29758300

Appears in Networks:

p(HGNC:MAPT, var("p.Ala152Thr")) increases bp(GO:macroautophagy) View Subject | View Object

For example, in tau A152T iPSC-derived cortical neurons, total and phosphorylated Tau levels are elevated, particularly the insoluble forms [133], which is associated with decreases in UPS function as measured by total polyubiquitinated proteins and an upregulation of macroautophagy markers. PubMed:29758300

Appears in Networks:

p(HGNC:MAPT, var("p.Ala152Thr")) association path(MESH:"Supranuclear Palsy, Progressive") View Subject | View Object

Another MAPT polymorphism (A152T) was recently identified in patients diagnosed with progressive supranuclear palsy (PSP) (72–74). PubMed:29191965

Appears in Networks:

p(HGNC:MAPT, var("p.Ala152Thr")) positiveCorrelation path(MESH:"Supranuclear Palsy, Progressive") View Subject | View Object

Interestingly, the PSP-associated tau mutation A152T is localized far away from the repeat domain but still decreases the binding of tau to microtubules and therefore promotes microtubule assembly less efficiently PubMed:26631930

Appears in Networks:

p(HGNC:MAPT, var("p.Ala152Thr")) decreases complex(a(GO:microtubule), p(HGNC:MAPT)) View Subject | View Object

Interestingly, the PSP-associated tau mutation A152T is localized far away from the repeat domain but still decreases the binding of tau to microtubules and therefore promotes microtubule assembly less efficiently PubMed:26631930

Appears in Networks:

p(HGNC:MAPT, var("p.Ala152Thr")) decreases bp(GO:"microtubule polymerization") View Subject | View Object

Interestingly, the PSP-associated tau mutation A152T is localized far away from the repeat domain but still decreases the binding of tau to microtubules and therefore promotes microtubule assembly less efficiently PubMed:26631930

Appears in Networks:

p(HGNC:MAPT, var("p.Ala152Thr")) increases a(HBP:"Tau oligomers") View Subject | View Object

In addition, this A152T tau enhances the formation of oligomers but not fibres PubMed:26631930

Appears in Networks:

p(HGNC:MAPT, var("p.Ala152Thr")) decreases act(p(HGNC:MAPT)) View Subject | View Object

Some tau mutations (such as A152T and R5H) may cause loss of tau function as well (as discussed above) PubMed:26631930

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.