INT298884

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Context Info
Confidence 0.45
First Reported 2010
Last Reported 2010
Negated 0
Speculated 1
Reported most in Body
Documents 1
Total Number 25
Disease Relevance 9.82
Pain Relevance 0.14

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

Golgi apparatus (RAB7A) GTPase activity (RAB7A) lysosome (RAB7A)
Anatomy Link Frequency
face 1
nervous system 1
RAB7A (Homo sapiens)
RAB7A - L129F (4)
Pain Link Frequency Relevance Heat
imagery 125 95.36 Very High Very High Very High
Pain 75 65.52 Quite High
Demyelination 25 41.76 Quite Low
Peripheral nervous system 25 27.00 Quite Low
Congenital analgesia 25 5.00 Very Low Very Low Very Low
Nerve growth factor 25 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Disease 1900 100.00 Very High Very High Very High
Neurological Disease 50 98.64 Very High Very High Very High
Paraplegia 25 97.88 Very High Very High Very High
Choroideremia 25 97.36 Very High Very High Very High
Charcot Marie Tooth Disease 150 96.36 Very High Very High Very High
Intellectual Impairment 25 95.80 Very High Very High Very High
Motor Neuron Diseases 25 95.16 Very High Very High Very High
Atrophic Muscular Disorders 25 94.00 High High
Spinocerebellar Ataxia Type 2 25 83.84 Quite High
Syndrome 50 77.92 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Wild-type Rab7 reversibly associates with the cytosolic face of late endosomes, lysosomes and autophagosomes and shows a diffuse vesicular pattern that largely overlaps with the late-endosomal/lysosomal marker LAMP2 (Fig. 5A, top) and the acidotropic dye LysoTracker Red (data not shown) as expected (6).
Rab7 Binding (associates) of in face
1) Confidence 0.45 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.51 Pain Relevance 0
Of particular note is the repositioning of the carboxylate group of D128, which in the wild-type Rab7 makes pseudo Watson–Crick pairing interactions with the guanine base of the nucleotide.
Rab7 Binding (interactions) of
2) Confidence 0.45 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0 Pain Relevance 0
Disease-causing mutations cause quantitative changes in Rab7 interactions
Rab7 Binding (interactions) of associated with disease
3) Confidence 0.45 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.44 Pain Relevance 0
As RILP specifically binds GTP-bound Rab7, the amount of Rab7 associated with RILP in this assay represents the GTP-bound fraction.
Rab7 Binding (binds) of
4) Confidence 0.45 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.26 Pain Relevance 0
The net effect of unregulated activation and inactivation is a subtle increase in the duration of association of active Rab7 with target membranes and an increase in the GTP-bound, active fraction (Figs. 3, 4, and 5).


Rab7 Binding (association) of
5) Confidence 0.45 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.41 Pain Relevance 0
First, we determined that Rab7 wild-type and disease mutants bound roughly the same amount of GTP following stripping of endogenous bound nucleotide (Fig. 3A).
Rab7 Spec (determined) Binding (bound) of associated with disease
6) Confidence 0.45 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.37 Pain Relevance 0
The structure of full-length L129F Rab7 bound to the non-hydrolysable GTP analog GppNHp was solved to 2.8 Å by molecular replacement (MR) using wild-type Rab7 as a search model (Table 1).
L129F Rab7 (L129F) Binding (bound) of
7) Confidence 0.39 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.24 Pain Relevance 0
Rab7 effectors specifically recognize the switch regions when Rab GTPases are in the GTP-bound conformation.
Rab7 Binding (recognize) of
8) Confidence 0.35 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.34 Pain Relevance 0
Membrane cycling in mutant Rab7 is uncoupled from GTP hydrolysis
Rab7 Binding (cycling) of
9) Confidence 0.35 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.41 Pain Relevance 0
We determined the crystal structure of GTP-bound L129F mutant Rab7 at 2.8 Å resolution revealing an alteration to the nucleotide binding pocket, but no impact on the catalytic region of Rab7.
Rab7 (L129F) Binding (bound) of
10) Confidence 0.35 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.95 Pain Relevance 0.07
Surprisingly, despite evidence of unregulated activation, Rab7 disease mutants have normal subcellular localization and associate normally with LAMP2 (Fig. 5B) and LysoTracker Red (data not shown).
Rab7 Binding (associate) of associated with disease
11) Confidence 0.35 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.56 Pain Relevance 0
Rab7 mutations cause a quantitative but not qualitative change in interaction with effector proteins
Rab7 Binding (interaction) of
12) Confidence 0.35 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.76 Pain Relevance 0
In addition, mutations in previously known Rab7 interactors have been implicated in multiple neurological diseases: REP-1 in choroideremia (44,45), GDI in X-linked mental retardation (46), p150glued in distal spinobulbar muscular atrophy (47), ?
Rab7 Binding (interactors) of associated with atrophic muscular disorders, intellectual impairment, neurological disease and choroideremia
13) Confidence 0.35 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.99 Pain Relevance 0
Consistent with augmented activity, mutant Rab7 shows significantly enhanced interaction with a subset of effector proteins.
Rab7 Binding (interaction) of
14) Confidence 0.35 Published 2010 Journal Human Molecular Genetics Section Abstract Doc Link PMC2830827 Disease Relevance 0.46 Pain Relevance 0.05
We present the 2.8 Å crystal structure of GTP-bound L129F mutant Rab7 which reveals normal conformations of the effector binding regions and catalytic site, but an alteration to the nucleotide binding pocket that is predicted to alter GTP binding.
Rab7 (L129F) Binding (bound) of
15) Confidence 0.35 Published 2010 Journal Human Molecular Genetics Section Abstract Doc Link PMC2830827 Disease Relevance 0.35 Pain Relevance 0.03
Notably, two of the novel Rab7 interacting proteins we identified have been implicated in human diseases affecting the nervous system.
Rab7 Binding (interacting) of in nervous system associated with disease
16) Confidence 0.34 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.81 Pain Relevance 0
As predicted by our structural data, the complement of interactors in wild-type and mutant Rab7 is qualitatively identical, although there is significantly enhanced interaction of mutant Rab7 with a subset of effector proteins.
Rab7 Binding (interaction) of
17) Confidence 0.34 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.27 Pain Relevance 0
The profiles of proteins identified in wild-type and mutant Rab7 were qualitatively identical, suggesting that Rab7 mutants bind to the same complement of interactors as wild-type Rab7 (Fig. 4A and B, Supplementary Material, Fig.
Rab7 Binding (bind) of
18) Confidence 0.34 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.11 Pain Relevance 0
To more broadly address the impact of disease-causing Rab7 mutations on interaction with binding partners, we used an unbiased proteomics approach to examine the protein–protein interactions in wild-type and mutant Rab7.
Rab7 Binding (interaction) of associated with disease
19) Confidence 0.34 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.43 Pain Relevance 0
We identified several putative novel Rab7 interacting proteins as well as previously known Rab7 interactors (Table 2).
Rab7 Binding (interacting) of
20) Confidence 0.34 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.12 Pain Relevance 0

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