INT175219

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Context Info
Confidence 0.27
First Reported 2003
Last Reported 2005
Negated 0
Speculated 2
Reported most in Body
Documents 31
Total Number 33
Disease Relevance 4.51
Pain Relevance 0.53

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

nuclear envelope (NUP62) small molecule metabolic process (NUP62) carbohydrate metabolic process (NUP62)
transmembrane transport (NUP62) cytoplasm (NUP62) nucleocytoplasmic transport (NUP62)
Anatomy Link Frequency
K48 3
brain 1
adult brain 1
reticulocyte 1
NUP62 (Homo sapiens)
Pain Link Frequency Relevance Heat
Neuritis 64 93.36 High High
Eae 32 64.24 Quite High
Kinase C 32 12.08 Low Low
Pain 4 5.00 Very Low Very Low Very Low
Nerve growth factor 1 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Disease 429 100.00 Very High Very High Very High
Neurodegenerative Disease 128 97.88 Very High Very High Very High
Neuritis 64 93.36 High High
Bone Disease 73 93.12 High High
Neurological Disease 32 92.20 High High
Shock 160 91.00 High High
Amyloid Plaque 96 84.60 Quite High
Autoimmune Disease 32 81.40 Quite High
Organ Transplantation 32 79.92 Quite High
Death 33 76.60 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The p62/SQSTM1 protein binds non-covalently to ubiquitin, co-localizing with ubiquitinated inclusions in several human diseases characterized by altered protein aggregation [10].
p62 Binding (binds) of associated with disease
1) Confidence 0.27 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1297578 Disease Relevance 0.40 Pain Relevance 0
Our results revealed
that proteins that bound to p62’s UBA domain could not be pulled down by
agarose beads alone, indicating that the agarose-immobilised p62 UBA peptide
had binding specificity.


p62 Binding (bound) of
2) Confidence 0.21 Published 2003 Journal Biol Proced Online Section Body Doc Link PMC302190 Disease Relevance 0 Pain Relevance 0
The individual protein synthesized from each plasmid DNA was retested for its ability to bind p62’s UBA domain.
p62 Binding (bind) of
3) Confidence 0.21 Published 2003 Journal Biol Proced Online Section Body Doc Link PMC302190 Disease Relevance 0 Pain Relevance 0
Proteins that specifically interact with the UBA domain
of p62 were isolated by interaction with agarose-immobilised p62-UBA peptide
(amino acid 387-436 of p62) (5 mg) for 2 hours at 4ºC, then washed three times
in washing buffer (25 mM Tris pH 7.6, 100 mM NaCl, 1% NP-40). 
p62 Binding (interact) of
4) Confidence 0.21 Published 2003 Journal Biol Proced Online Section Body Doc Link PMC302190 Disease Relevance 0 Pain Relevance 0
A second set of proteins identified in the screen that bind to p62’s UBA domain are associated with brain development, including homeobox protein Meis2 and unc51 like kinase II (Table 1).
p62 Binding (bind) of in brain
5) Confidence 0.21 Published 2003 Journal Biol Proced Online Section Body Doc Link PMC302190 Disease Relevance 0.82 Pain Relevance 0.19
The individual protein synthesized from each
plasmid DNA chosen was screened for its ability to bind p62’s UBA domain. 
p62 Binding (bind) of
6) Confidence 0.21 Published 2003 Journal Biol Proced Online Section Body Doc Link PMC302190 Disease Relevance 0 Pain Relevance 0
We chose 6
pools (pool # 2, 4, 8, 14, 20, 21) because of their stronger signal to
specifically identify which individual protein pool in the mixed pools has the
ability to bind to p62’s UBA domain. 
p62 Binding (bind) of
7) Confidence 0.21 Published 2003 Journal Biol Proced Online Section Body Doc Link PMC302190 Disease Relevance 0 Pain Relevance 0
Furthermore, the in vivo interaction of HSP70 and p62 was confirmed by transfecting myc-tagged HSP70 into HEK 293 cells in the presence of the proteasome inhibitor MG132 and subjecting cell lysates to p62 immunoprecipitation and Western blot with anti-myc antibody (Fig. 8C).
p62 Binding (interaction) of
8) Confidence 0.21 Published 2003 Journal Biol Proced Online Section Body Doc Link PMC302190 Disease Relevance 0 Pain Relevance 0
We have developed a method
that will enable identification of protein(s) that interact with p62’s UBA
domain.


p62 Binding (interact) of
9) Confidence 0.21 Published 2003 Journal Biol Proced Online Section Body Doc Link PMC302190 Disease Relevance 0 Pain Relevance 0
To
confirm the interaction with p62’s UBA domain, the final resulting individual
proteins were used in the coupled TNT/p62 UBA pull down assays. 
p62 Binding (interaction) of
10) Confidence 0.21 Published 2003 Journal Biol Proced Online Section Body Doc Link PMC302190 Disease Relevance 0 Pain Relevance 0
In order to identify proteins that bind to p62’s UBA domain,
p62 UBA pull down assays were performed. 
p62 Binding (bind) of
11) Confidence 0.21 Published 2003 Journal Biol Proced Online Section Body Doc Link PMC302190 Disease Relevance 0 Pain Relevance 0
It is not surprising that 5 more clones showed binding ability with p62’s UBA domain since there are 100 cDNAs in each positive individual pool and some of them could have lower binding ability and therefore showed weak signal in the mixed protein pool.
p62 Binding (binding) of
12) Confidence 0.21 Published 2003 Journal Biol Proced Online Section Body Doc Link PMC302190 Disease Relevance 0 Pain Relevance 0
Positive mixed protein pools were selected and individual pools were retested
for its ability to bind p62’s UBA domain. 
p62 Binding (bind) of
13) Confidence 0.21 Published 2003 Journal Biol Proced Online Section Body Doc Link PMC302190 Disease Relevance 0 Pain Relevance 0
Using the rabbit reticulocyte lysate in vitro expression cloning system, we have successfully identified eleven proteins in the human adult brain that interact with the UBA domain of p62, and the majority of the eleven proteins are associated with neurodegenerative disorders, such as Alzheimer’s disease.
p62 Binding (interact) of in adult brain associated with disease and neurodegenerative disease
14) Confidence 0.21 Published 2003 Journal Biol Proced Online Section Body Doc Link PMC302190 Disease Relevance 0.19 Pain Relevance 0
Proteins that specifically interact with the UBA domain
of p62 were isolated by interaction with agarose-immobilised p62-UBA peptide
(amino acid 387-436 of p62) (5 mg) for 2 hours at 4ºC, then washed three times
in washing buffer (25 mM Tris pH 7.6, 100 mM NaCl, 1% NP-40). 
p62 Binding (interaction) of
15) Confidence 0.21 Published 2003 Journal Biol Proced Online Section Body Doc Link PMC302190 Disease Relevance 0 Pain Relevance 0
The resulting proteins were assayed to
determine their binding ability with p62’s UBA domain. 
p62 Spec (determine) Binding (ability) of
16) Confidence 0.16 Published 2003 Journal Biol Proced Online Section Body Doc Link PMC302190 Disease Relevance 0 Pain Relevance 0
The specific type of polyubiquitin chain recognized by p62’s UBA domain is not yet known and studies are underway lab to determine p62’s interaction with specific polyubiquitin chains, however, our preliminary studies suggest that p62’s UBA domain may recognize K63 linked polyubiquitin chains.
p62 Binding (recognize) of
17) Confidence 0.16 Published 2003 Journal Biol Proced Online Section Body Doc Link PMC302190 Disease Relevance 0.12 Pain Relevance 0
In order to understand whether the proteins identified in our screen bind to the p62’s UBA domain through lysine 48 (K48), polyubiquitin K48 chains were added to the p62 UBA pull down assay (Fig. 6).
p62 Binding (bind) of in K48
18) Confidence 0.16 Published 2003 Journal Biol Proced Online Section Body Doc Link PMC302190 Disease Relevance 0.33 Pain Relevance 0
Out of the five proteins, four proteins (# 2, 3, 4, and 5) showed reduced binding ability with p62’s UBA domain when polyubiquitin K48 chains were included (Fig. 6A, 6B).
p62 Binding (binding) of in K48
19) Confidence 0.16 Published 2003 Journal Biol Proced Online Section Body Doc Link PMC302190 Disease Relevance 0.08 Pain Relevance 0
The proteins identified here suggest that p62’s UBA domain has the ability to interact with multiple proteins that play important roles in neurodegenerative diseases.
p62 Binding (interact) of associated with neurodegenerative disease
20) Confidence 0.16 Published 2003 Journal Biol Proced Online Section Body Doc Link PMC302190 Disease Relevance 0.52 Pain Relevance 0

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