INT141054

Context Info Confidence 0.40 First Reported 2007 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 14 Total Number 16 Disease Relevance 3.65 Pain Relevance 1.22

nucleus (NFATC1) DNA binding (NFATC1) cytoplasm (NFATC1)

Anatomy Link Frequency NFAT 1 NFATC1 (Homo sapiens)

Pain Link Frequency Relevance Heat opioid receptor 7 98.80 antagonist 16 91.44 agonist 12 88.96 Opioid 4 78.72 Morphine 3 78.20 cytokine 107 77.36 Kappa opioid receptor 1 75.44 Paracetamol 3 75.00 mu opioid receptor 2 75.00 Endocannabinoid 1 71.00

Disease Link Frequency Relevance Heat Respiratory Syncytial Virus 348 99.68 Acquired Immune Deficiency Syndrome Or Hiv Infection 987 98.92 Stress 3 96.24 Breast Cancer 13 79.52 Cancer 97 57.68 Hypercalcemia 42 54.96 Fibromyalgia 18 49.04 Down Syndrome 4 44.64 Peripheral Arterial Disease 4 32.12 Hyperplasia 4 24.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

We found that AM404 inhibited both the binding to DNA and the transcriptional activity of endogenous NFAT and the transcriptional activity driven by the over expressed fusion protein Gal4-NFAT (1-415).

NFAT Binding (binding) of

1) Confidence 0.40 Published 2007 Journal Biochem. Pharmacol. Section Abstract Doc Link 17196940 Disease Relevance 0 Pain Relevance 0.24

Interestingly also, NFATc1 and NF-?

NFATc1 Binding (also) of

2) Confidence 0.16 Published 2010 Journal Calcif Tissue Int Section Body Doc Link PMC2964465 Disease Relevance 0.42 Pain Relevance 0

NFATc1 is thus downstream of several “signaling modules” and integrates them, whereas NF-?

NFATc1 Binding (integrates) of

3) Confidence 0.16 Published 2010 Journal Calcif Tissue Int Section Body Doc Link PMC2964465 Disease Relevance 0.38 Pain Relevance 0

B/NFATc1, which is shown here to respond to the RSV analogues, they do not allow a full understanding of our data.

NFATc1 Binding (respond) of associated with respiratory syncytial virus

4) Confidence 0.16 Published 2010 Journal Calcif Tissue Int Section Body Doc Link PMC2964465 Disease Relevance 0.73 Pain Relevance 0.12

NFAT was found to bind to three sequences of the mu-opioid receptor promoter, located at nucleotides -1064, -785, and -486.

NFAT Binding (bind) of in NFAT associated with opioid receptor

5) Confidence 0.15 Published 2008 Journal Mol. Pharmacol. Section Abstract Doc Link 18463202 Disease Relevance 0 Pain Relevance 0.73

The IL-11 promoter region contains two putative NFAT binding sites

NFAT Binding (binding) of

6) Confidence 0.07 Published 2010 Journal Molecular Human Reproduction Section Body Doc Link PMC2816169 Disease Relevance 0 Pain Relevance 0

Moreover, using a specific inhibitor, INCA-6, which is known to block the interaction between calcineurin and NFAT (Roehrl et al., 2004), we have shown that inhibiting NFAT signalling can block PROK1-PROKR1 mediated expression of IL-11.

NFAT Binding (interaction) of

7) Confidence 0.07 Published 2010 Journal Molecular Human Reproduction Section Body Doc Link PMC2816169 Disease Relevance 0 Pain Relevance 0.07

flank region we identified two correctly orientated putative NFAT binding sites at 1.642 and 5.138 kb from the start codon for IL-11 (Fig. 1D).

NFAT Binding (binding) of

8) Confidence 0.07 Published 2010 Journal Molecular Human Reproduction Section Body Doc Link PMC2816169 Disease Relevance 0 Pain Relevance 0

Using a highly stringent search we have identified two correctly orientated putative NFAT binding sites within the IL-11 promoter.

NFAT Binding (binding) of

9) Confidence 0.07 Published 2010 Journal Molecular Human Reproduction Section Body Doc Link PMC2816169 Disease Relevance 0 Pain Relevance 0.07

In addition to binding to the enhancer, NFAT binding at positions +169 to +181 has been reported to activate transcription [59,60,136].

NFAT Binding (binding) of

10) Confidence 0.06 Published 2009 Journal Retrovirology Section Body Doc Link PMC2805609 Disease Relevance 0.52 Pain Relevance 0

NFAT can bind DNA as a high affinity dimer or as a lower affinity monomer [127-129].

NFAT Binding (bind) of

11) Confidence 0.06 Published 2009 Journal Retrovirology Section Body Doc Link PMC2805609 Disease Relevance 0.14 Pain Relevance 0

Although this site can bind NFAT in vitro, this site was later shown not to be necessary for NFAT-mediated activation of the HIV-1 LTR [131,132].

NFAT Binding (bind) of associated with acquired immune deficiency syndrome or hiv infection

12) Confidence 0.06 Published 2009 Journal Retrovirology Section Body Doc Link PMC2805609 Disease Relevance 0.24 Pain Relevance 0

NFAT binds the NF-?

NFAT Binding (binds) of

13) Confidence 0.06 Published 2009 Journal Retrovirology Section Body Doc Link PMC2805609 Disease Relevance 0.23 Pain Relevance 0

Instead, NFAT binds the NF-?

NFAT Binding (binds) of

14) Confidence 0.06 Published 2009 Journal Retrovirology Section Body Doc Link PMC2805609 Disease Relevance 0.31 Pain Relevance 0

NFAT proteins frequently cooperate with other transcription factor families when bound to adjacent sites within a promoter.

NFAT Binding (bound) of

15) Confidence 0.06 Published 2009 Journal Retrovirology Section Body Doc Link PMC2805609 Disease Relevance 0.17 Pain Relevance 0

In addition to binding to the enhancer, NFAT binding at positions +169 to +181 has been reported to activate transcription [59,60,136].

NFAT Binding (binding) of

16) Confidence 0.04 Published 2009 Journal Retrovirology Section Body Doc Link PMC2805609 Disease Relevance 0.52 Pain Relevance 0

General Comments

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