INT113219

Context Info Confidence 0.35 First Reported 2003 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 12 Total Number 13 Disease Relevance 9.77 Pain Relevance 0.46

cytosol (TNFRSF25) signal transduction (TNFRSF25) extracellular region (TNFRSF25) plasma membrane (TNFRSF25)

Anatomy Link Frequency liver 1 HeLa 1 colon 1 band 1 TNFRSF25 (Homo sapiens)

Pain Link Frequency Relevance Heat rheumatoid arthritis 72 89.80 cytokine 55 86.80 Paracetamol 1 86.12 cINOD 1 78.92 Inflammation 82 68.56 agonist 2 34.72 Multiple sclerosis 12 27.12 methotrexate 39 5.00 Kinase C 21 5.00 Etanercept 20 5.00

Disease Link Frequency Relevance Heat Apoptosis 191 100.00 Death 30 100.00 Colon Cancer 6 100.00 Autoimmune Disease 68 99.86 Autoimmune Hepatitis 338 99.80 Disease 126 99.76 Systemic Lupus Erythematosus 8 99.60 Hypergammaglobulinemia 4 99.34 Diabetes Mellitus 185 96.60 Rheumatoid Arthritis 173 89.80

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Protein

Mutation

Event

Anatomy

Negation

Speculation

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Disease term

The uncommon A allele is strongly associated with the HLA-A1-B8-DR3-DQ2 haplotype [18], and is also associated with both autoimmune diseases and the high TNF producer phenotype [19].

DR3 Binding (associated) of associated with autoimmune disease

1) Confidence 0.35 Published 2008 Journal Current Genomics Section Body Doc Link PMC2691664 Disease Relevance 0.49 Pain Relevance 0.23

The receptor binds to DR3, DR4, DR5, ER6 and ER8 motifs of the general nuclear receptor binding site, which have been identified in enhancer and promoter regions of some of the genes regulated [reviewed in [1]].

DR3 Binding (binds) of

2) Confidence 0.25 Published 2004 Journal Nucl Recept Section Body Doc Link PMC406421 Disease Relevance 0 Pain Relevance 0.09

Therefore, recruitment to the HRE and activation of DR3- and DR5-dependent transcription by this factor does not involve a direct association with the receptors and appears to require DREAM–DNA interactions.

DR3 Binding (recruitment) of

3) Confidence 0.20 Published 2005 Journal Nucleic Acids Research Section Body Doc Link PMC1084319 Disease Relevance 0 Pain Relevance 0

Also showing the specificity of the binding of DREAM to the DR3 sequence, an anti-DREAM antibody caused a supershift of the DREAM-DR3 retarded band (Figure 1C).

DR3 Binding (binding) of in band

4) Confidence 0.20 Published 2005 Journal Nucleic Acids Research Section Body Doc Link PMC1084319 Disease Relevance 0.07 Pain Relevance 0

To test the importance of these interactions in the transactivating effect of DREAM on hormone receptor mediated transcription, we used DREAM with mutations at the LCDs (Figure 6A) and assessed their activity on the DR3-TK and R-140 reporters in HeLa cells.

DR3 Binding (activity) of in HeLa

5) Confidence 0.20 Published 2005 Journal Nucleic Acids Research Section Body Doc Link PMC1084319 Disease Relevance 0.14 Pain Relevance 0

Since the affinity of binding of the receptor to the DRE was lower than to a DR3, the CAT activity was also examined after the overexpression of VDR.

DR3 Binding (binding) of

6) Confidence 0.20 Published 2005 Journal Nucleic Acids Research Section Body Doc Link PMC1084319 Disease Relevance 0.07 Pain Relevance 0

Figure 1E compares binding of VDR and RXR with the DR3 and the DRE.

DR3 Binding (compares) of

7) Confidence 0.17 Published 2005 Journal Nucleic Acids Research Section Body Doc Link PMC1084319 Disease Relevance 0.06 Pain Relevance 0

Overlap between HLA class II associations has been seen between AIDs, with DR3 also being associated with GD, SLE and HT, therefore, being termed the ‘autoimmunity haplotype’ (See Table 1 for list of common AID HLA class II associations).

DR3 Binding (associated) of associated with autoimmune disease, systemic lupus erythematosus and disease

8) Confidence 0.15 Published 2007 Journal Current Genomics Section Body Doc Link PMC2647156 Disease Relevance 1.20 Pain Relevance 0.06

Therefore, TR3 translocation from the nucleus may initiate the apoptotic cascade in colon cancer cells by stimulating other cytosolic proapoptotic molecules to associate with mitochondria.

TR3 Binding (associate) of in colon associated with colon cancer and apoptosis

9) Confidence 0.14 Published 2003 Journal Cancer Res. Section Abstract Doc Link 14500374 Disease Relevance 0.93 Pain Relevance 0.08

Autoantibodies and autoantigens in autoimmune hepatitis: important tools in clinical practice and to study pathogenesis of the disease Autoimmune hepatitis (AIH) is a chronic necroinflammatory disease of the liver characterized by hypergammaglobulinemia, characteristic autoantibodies, association with HLA DR3 or DR4 and a favorable response to immunosuppressive treatment.

DR3 Binding (association) of in liver associated with hypergammaglobulinemia, autoimmune hepatitis and disease

10) Confidence 0.08 Published 2004 Journal J Autoimmune Dis Section Title Doc Link PMC544946 Disease Relevance 1.54 Pain Relevance 0

Taking into consideration the genetic markers, it has been found that the association between HLA DR3 and AIH-2 is rather weaker than that reported in AIH-1, while an association between HLA DQ2 and AIH-2 has been reported [14,18,33,34].

DR3 Binding (association) of associated with autoimmune hepatitis

11) Confidence 0.06 Published 2004 Journal J Autoimmune Dis Section Body Doc Link PMC544946 Disease Relevance 1.84 Pain Relevance 0

When they bind their specific death receptor, apoptotic signals are transmitted in the cell and a caspase cascade is activated within seconds of ligand binding, inducing apoptosis in a very rapid way.

death receptor Binding (bind) of associated with apoptosis and death

12) Confidence 0.01 Published 2010 Journal Mediators of Inflammation Section Body Doc Link PMC2903979 Disease Relevance 1.75 Pain Relevance 0

The general signaling pathway that is activated through death receptor binding begins with the generation of ceramide, produced by acid sphingomyelinase.

death receptor Binding (binding) of associated with death

13) Confidence 0.01 Published 2010 Journal Mediators of Inflammation Section Body Doc Link PMC2903979 Disease Relevance 1.68 Pain Relevance 0

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