INT101810

From wiki-pain
Jump to: navigation, search
Context Info
Confidence 0.53
First Reported 2002
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 7
Total Number 11
Disease Relevance 4.12
Pain Relevance 0.29

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

nucleus (NFE2L2, KEAP1) cytoplasm (NFE2L2, KEAP1) cytosol (NFE2L2)
endoplasmic reticulum (KEAP1) nucleolus (KEAP1) plasma membrane (NFE2L2)
Anatomy Link Frequency
hinge 2
nucleus 1
NFE2L2 (Homo sapiens)
KEAP1 (Homo sapiens)
Pain Link Frequency Relevance Heat
cINOD 3 95.72 Very High Very High Very High
tolerance 3 87.76 High High
antidepressant 1 60.80 Quite High
anticonvulsant 1 58.12 Quite High
Inflammation 9 45.48 Quite Low
Mechanosensation 1 44.12 Quite Low
Acute pain 1 34.64 Quite Low
Glutamate 8 33.52 Quite Low
Pain 5 5.00 Very Low Very Low Very Low
Osteoarthritis 5 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Stress 84 99.84 Very High Very High Very High
INFLAMMATION 8 95.00 High High
Cancer 323 85.80 High High
Targeted Disruption 13 84.56 Quite High
Toxicity 21 84.00 Quite High
Lung Cancer 164 81.04 Quite High
Heat Stress Disorders 1 77.04 Quite High
Non-small-cell Lung Cancer 72 74.88 Quite High
Lifespan 16 73.04 Quite High
Apoptosis 26 68.40 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
When oxidants are present, KEAP1 no longer interacts with NRF2, which moves into the nucleus and induces the expression of the proteins that protect the cell against oxidants and toxins.
NRF2 Binding (interacts) of KEAP1 in nucleus
1) Confidence 0.53 Published 2006 Journal PLoS Medicine Section Abstract Doc Link PMC1584412 Disease Relevance 0.70 Pain Relevance 0
The Kelch repeats of KEAP1 bind the Neh2 domain of NRF2, whereas the IVR and BTB domains are required for the redox-sensitive regulation of NRF2 through a series of reactive cysteines present throughout this region [22].
NRF2 Binding (bind) of KEAP1
2) Confidence 0.41 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.44 Pain Relevance 0
Expression of the wild-type KEAP1 in H838 cells stably expressing an ARE reporter completely abolished ARE reporter activity, whereas overexpression of the KEAP1 mutant construct did not, suggesting that the somatic mutations hamper the association between KEAP1 and NRF2 and consequently activate NRF2.
NRF2 Binding (association) of KEAP1
3) Confidence 0.39 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.75 Pain Relevance 0
Redox-sensitive interaction between KIAA0132 and Nrf2 mediates indomethacin-induced expression of gamma-glutamylcysteine synthetase.
Nrf2 Binding (interaction) of KIAA0132
4) Confidence 0.37 Published 2002 Journal Free Radic. Biol. Med. Section Title Doc Link 11909699 Disease Relevance 0.10 Pain Relevance 0.19
Under normal conditions, cells maintain low constitutive levels of Nrf2-target genes through constant ubiquitination and degradation of Nrf2, which is accomplished by the Keap1-dependent E3 ubiquitin ligase complex.
Nrf2 Binding (accomplished) of Keap1-dependent
5) Confidence 0.28 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0 Pain Relevance 0
Binding to one molecule of Keap1 via the high affinity 79ETGE82 motif within the Neh2 domain of Nrf2 provides the “hinge” through which the transcription factor can move in space relatively freely.
Nrf2 Binding (Binding) of Keap1 in hinge
6) Confidence 0.21 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878012 Disease Relevance 0.38 Pain Relevance 0
In addition to Nrf2, Keap1 has been reported to associate with several other proteins in mammalian cells.
Nrf2 Binding (associate) of Keap1
7) Confidence 0.20 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878012 Disease Relevance 0.13 Pain Relevance 0
The modification of cysteine residues within Keap1 is postulated to cause a conformational change in the protein that disrupts the interaction between Keap1 and the low affinity 29DLG31 motif within Nrf2, perturbing the ability of Keap1 to direct the ubiquitination and proteasomal degradation of the transcription factor (8).
Nrf2 Binding (interaction) of Keap1
8) Confidence 0.20 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878012 Disease Relevance 0.14 Pain Relevance 0
The “hinge and latch” model of Nrf2 regulation proposes that two distinct binding sites in Nrf2 facilitate the interaction with a Keap1 dimer (8).
Nrf2 Binding (interaction) of Keap1 in hinge
9) Confidence 0.20 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878012 Disease Relevance 0.38 Pain Relevance 0
For example, Keap1 associates with PGAM5, which reportedly tethers Keap1 and Nrf2 to the outer membrane of the mitochondria (16, 17), implying that the Keap1·Nrf2 complex may be well placed to sense the disruption of mitochondrial function and subsequent elevated generation of reactive oxygen species that can contribute to the onset of oxidative stress.
Nrf2 Binding (associates) of Keap1 associated with stress
10) Confidence 0.18 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878012 Disease Relevance 0.15 Pain Relevance 0
Without such stresses, Nrf2 is normally repressed by the oxidative stress sensor Keap1 [38], which binds and degrades Nrf2 through the ubiquitin-proteasome system.
Nrf2 Binding (binds) of Keap1 associated with stress
11) Confidence 0.00 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2822842 Disease Relevance 0.96 Pain Relevance 0.10

General Comments

This test has worked.

Personal tools
Namespaces

Variants
Actions
Navigation
Toolbox