INT336768

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Context Info
Confidence 0.78
First Reported 2010
Last Reported 2010
Negated 4
Speculated 0
Reported most in Body
Documents 1
Total Number 25
Disease Relevance 2.82
Pain Relevance 0.19

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

peptidase activity (ERAP2) endoplasmic reticulum (ERAP2)
Anatomy Link Frequency
lymphocytes 4
band 2
reticulum 2
developmental stages 1
ERAP2 (Homo sapiens)
Pain Link Frequency Relevance Heat
spinal inflammation 25 97.72 Very High Very High Very High
Inflammation 75 94.44 High High
Inflammatory response 25 44.64 Quite Low
Disease Link Frequency Relevance Heat
Reprotox - General 1 25 99.08 Very High Very High Very High
Eclampsia 150 98.60 Very High Very High Very High
Targeted Disruption 150 98.10 Very High Very High Very High
Low Back Pain 25 97.72 Very High Very High Very High
Hypertension 25 97.12 Very High Very High Very High
Cancer 75 96.44 Very High Very High Very High
INFLAMMATION 100 94.44 High High
Epstein-barr Virus 25 91.88 High High
Infection 25 88.08 High High
Hepatitis 25 87.36 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The presence of functional ERAP2 and the resulting high levels of MHC class I may be beneficial in some situations (e.g., in response to tumors or pathogens) yet detrimental in others (e.g., in the case of auto-immunity).
Gene_expression (presence) of ERAP2 associated with cancer
1) Confidence 0.78 Published 2010 Journal PLoS Genetics Section Body Doc Link PMC2954825 Disease Relevance 0.76 Pain Relevance 0
Additionally, AB-heterozygotes only produce full-length ERAP2, in seemingly smaller quantities compared to AA-homozygotes (the intensity of the full-length ERAP2 band in AB-heterozygotes is 35% and 50% that of AA-homozygotes for the two antibodies, respectively).
Gene_expression (produce) of ERAP2 in band
2) Confidence 0.78 Published 2010 Journal PLoS Genetics Section Body Doc Link PMC2954825 Disease Relevance 0 Pain Relevance 0
Therefore, based on our results, the ERAP2 genotype should be accounted for in interpreting ERAP2 studies, especially those focused on ERAP2 expression and ERAP2 protein function.
Gene_expression (expression) of ERAP2
3) Confidence 0.78 Published 2010 Journal PLoS Genetics Section Body Doc Link PMC2954825 Disease Relevance 0.09 Pain Relevance 0
We found that ERAP2 expressed from Haplotype B undergoes differential splicing and encodes a truncated protein, leading to nonsense-mediated decay of the mRNA.
Gene_expression (expressed) of ERAP2
4) Confidence 0.78 Published 2010 Journal PLoS Genetics Section Abstract Doc Link PMC2954825 Disease Relevance 0 Pain Relevance 0
In any case, note that truncated ERAP2 protein (60 kDa) could not be detected in this experiment (Figure S4).
Neg (not) Gene_expression (detected) of ERAP2
5) Confidence 0.78 Published 2010 Journal PLoS Genetics Section Body Doc Link PMC2954825 Disease Relevance 0.08 Pain Relevance 0
In light of the differences in ERAP2 expression from the A versus B haplotypes, what are the biological consequences of lower ERAP2 protein levels in AB and BB individuals?
Gene_expression (expression) of ERAP2
6) Confidence 0.78 Published 2010 Journal PLoS Genetics Section Body Doc Link PMC2954825 Disease Relevance 0.10 Pain Relevance 0
We used LCLs because ERAP2 is highly expressed in lymphocytes [45] and this cell type is particularly relevant for studies of MHC class I presentation.
Gene_expression (expressed) of ERAP2 in lymphocytes
7) Confidence 0.78 Published 2010 Journal PLoS Genetics Section Body Doc Link PMC2954825 Disease Relevance 0.09 Pain Relevance 0
Nevertheless, several studies have previously identified associations between SNPs in this genomic region and changes in ERAP2 expression and splicing [40]–[43].
Gene_expression (expression) of ERAP2
8) Confidence 0.78 Published 2010 Journal PLoS Genetics Section Body Doc Link PMC2954825 Disease Relevance 0.07 Pain Relevance 0
This analysis revealed that AA-homozygote cells produce only full-length ERAP2 (120 kDa), while BB-homozygote cells produce no detectable ERAP2 protein (Figure 4).
Neg (no) Gene_expression (produce) of ERAP2
9) Confidence 0.68 Published 2010 Journal PLoS Genetics Section Body Doc Link PMC2954825 Disease Relevance 0 Pain Relevance 0
This analysis revealed that AA-homozygote cells produce only full-length ERAP2 (120 kDa), while BB-homozygote cells produce no detectable ERAP2 protein (Figure 4).
Gene_expression (produce) of ERAP2
10) Confidence 0.68 Published 2010 Journal PLoS Genetics Section Body Doc Link PMC2954825 Disease Relevance 0 Pain Relevance 0
This result is consistent with the reduced MHC class I cell-surface expression observed after transient knock-down of ERAP1 or ERAP2 in cultured cells [48], the reduced MHC class I cell-surface expression seen in ERAP1-knock-out mice [54]–[56], [61], and our observation that ERAP1 is not upregulated to compensate for ERAP2 deficiency in cells from BB-homozygotes (Text S1).
Gene_expression (deficiency) of ERAP2 associated with targeted disruption
11) Confidence 0.67 Published 2010 Journal PLoS Genetics Section Body Doc Link PMC2954825 Disease Relevance 0.42 Pain Relevance 0
Effects of ERAP2 variants on MHC class I presentation
Gene_expression (variants) of ERAP2
12) Confidence 0.67 Published 2010 Journal PLoS Genetics Section Body Doc Link PMC2954825 Disease Relevance 0.15 Pain Relevance 0
Additionally, AB-heterozygotes only produce full-length ERAP2, in seemingly smaller quantities compared to AA-homozygotes (the intensity of the full-length ERAP2 band in AB-heterozygotes is 35% and 50% that of AA-homozygotes for the two antibodies, respectively).
Gene_expression (produce) of ERAP2 in band
13) Confidence 0.67 Published 2010 Journal PLoS Genetics Section Body Doc Link PMC2954825 Disease Relevance 0 Pain Relevance 0
Here, we present genetic and functional evidence that another gene with a fundamental role in MHC class I presentation, endoplasmic reticulum aminopeptidase 2 (ERAP2), has also evolved under balancing selection and contains a variant that affects antigen presentation.
Gene_expression (presentation) of ERAP2 in reticulum
14) Confidence 0.67 Published 2010 Journal PLoS Genetics Section Abstract Doc Link PMC2954825 Disease Relevance 0 Pain Relevance 0
It is possible, though unlikely, that other tissues and/or developmental stages utilize alternate mechanisms that lead to the generation of ERAP2 protein from both haplotypes.
Gene_expression (generation) of ERAP2 in developmental stages
15) Confidence 0.60 Published 2010 Journal PLoS Genetics Section Body Doc Link PMC2954825 Disease Relevance 0 Pain Relevance 0
Therefore, based on our results, the ERAP2 genotype should be accounted for in interpreting ERAP2 studies, especially those focused on ERAP2 expression and ERAP2 protein function.
Gene_expression (expression) of ERAP2
16) Confidence 0.60 Published 2010 Journal PLoS Genetics Section Body Doc Link PMC2954825 Disease Relevance 0.09 Pain Relevance 0
Nevertheless, our data suggest that 25% of the population are AA homozygotes and generate abundant amounts of ERAP2 protein in lymphocytes, 50% are heterozygotes and generate reduced amounts of ERAP2 protein, and 25% are BB homozygotes and generate no or virtually no ERAP2 protein.
Neg (no) Gene_expression (generate) of ERAP2 in lymphocytes
17) Confidence 0.60 Published 2010 Journal PLoS Genetics Section Body Doc Link PMC2954825 Disease Relevance 0.07 Pain Relevance 0
Therefore, Haplotype A-expressed ERAP2 is consistently spliced to contain the standard exon 10, while Haplotype B-expressed ERAP2 is spliced to contain the extended version of exon 10.
Gene_expression (expressed) of ERAP2
18) Confidence 0.60 Published 2010 Journal PLoS Genetics Section Body Doc Link PMC2954825 Disease Relevance 0.06 Pain Relevance 0
Nevertheless, our data suggest that 25% of the population are AA homozygotes and generate abundant amounts of ERAP2 protein in lymphocytes, 50% are heterozygotes and generate reduced amounts of ERAP2 protein, and 25% are BB homozygotes and generate no or virtually no ERAP2 protein.
Gene_expression (generate) of ERAP2 in lymphocytes
19) Confidence 0.60 Published 2010 Journal PLoS Genetics Section Body Doc Link PMC2954825 Disease Relevance 0.06 Pain Relevance 0
Therefore, Haplotype A-expressed ERAP2 is consistently spliced to contain the standard exon 10, while Haplotype B-expressed ERAP2 is spliced to contain the extended version of exon 10.
Gene_expression (expressed) of ERAP2
20) Confidence 0.60 Published 2010 Journal PLoS Genetics Section Body Doc Link PMC2954825 Disease Relevance 0.06 Pain Relevance 0

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