INT131598

Context Info Confidence 0.65 First Reported 2006 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 2 Total Number 3 Disease Relevance 1.27 Pain Relevance 0.08

nucleus (Keap1, Nfe2l2) cytoplasm (Keap1, Nfe2l2) endoplasmic reticulum (Keap1) plasma membrane (Nfe2l2) DNA binding (Nfe2l2)

Keap1 (Mus musculus) Nfe2l2 (Mus musculus)

Pain Link Frequency Relevance Heat Paracetamol 3 82.64 Analgesic 1 25.00

Disease Link Frequency Relevance Heat Stress 46 99.96 Cancer 12 98.24 Toxicity 1 75.00 Congenital Anomalies 1 66.88 Aging 2 62.56 Targeted Disruption 6 61.52 Death 2 60.72 Sprains And Strains 2 5.00 Chronic Disease 2 5.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Nrf2 is a key regulator of many detoxifying enzyme genes, and cytoplasmic protein Keap1 represses the Nrf2 activity under quiescent conditions.

Keap1 Negative_regulation (represses) of Nrf2

1) Confidence 0.65 Published 2006 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 16293230 Disease Relevance 0.14 Pain Relevance 0

Under conditions of oxidative stress, KEAP1 loses its ability to limit NRF2 protein accumulation and to block NRF2 from transcribing its target genes.

KEAP1 Negative_regulation (block) of NRF2 associated with stress

2) Confidence 0.36 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2898415 Disease Relevance 0.47 Pain Relevance 0.08

A second notable difference between KEAP1 and CRIF1 negative regulation of NRF2 is that KEAP1 can bind to, ubiquitinate, and drive proteasomal degradation of full-length NRF2 only at the N-terminal region of NRF2, whereas CRIF1 can bind and ubiquitinate and may drive proteasomal degradation of full-length NRF2 through both ends of the protein.

KEAP1 Negative_regulation (regulation) of NRF2

3) Confidence 0.16 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2898415 Disease Relevance 0.66 Pain Relevance 0

General Comments

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